Gab Kovacs International Medical Director Monash IVF Hawthorn Victoria Australia
Declared speakers fees from MSD and Bayer being a stakeholder in Monash IVF ISIS FERTILITY ACT
L1 In vitro fertilization and factors affecting success Professor Gab Kovacs AM International Medical Director Monash IVF
Date Footer
Date Footer
Date Footer
How to improve your ART
success rates
bull Based on an ldquoEvidence Based Reviewrdquo
bull 48 Chapters- each written by a leading expert
bull Written in late 2010
bull Published by Cambridge University Press
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
L1 In vitro fertilization and factors affecting success Professor Gab Kovacs AM International Medical Director Monash IVF
Date Footer
Date Footer
Date Footer
How to improve your ART
success rates
bull Based on an ldquoEvidence Based Reviewrdquo
bull 48 Chapters- each written by a leading expert
bull Written in late 2010
bull Published by Cambridge University Press
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Date Footer
Date Footer
Date Footer
How to improve your ART
success rates
bull Based on an ldquoEvidence Based Reviewrdquo
bull 48 Chapters- each written by a leading expert
bull Written in late 2010
bull Published by Cambridge University Press
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Date Footer
Date Footer
How to improve your ART
success rates
bull Based on an ldquoEvidence Based Reviewrdquo
bull 48 Chapters- each written by a leading expert
bull Written in late 2010
bull Published by Cambridge University Press
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Date Footer
How to improve your ART
success rates
bull Based on an ldquoEvidence Based Reviewrdquo
bull 48 Chapters- each written by a leading expert
bull Written in late 2010
bull Published by Cambridge University Press
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
How to improve your ART
success rates
bull Based on an ldquoEvidence Based Reviewrdquo
bull 48 Chapters- each written by a leading expert
bull Written in late 2010
bull Published by Cambridge University Press
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Patient preparation (1)- Hormonal screening and Ultrasound
bull AMH- ndash predicts ovarian response
ndash Warns of likely OHSS
ndash Can be measured any time in cycle
bull Thyroid screening
bull Pelvic ultrasound ndash Antral follicle count (AFC)
ndash Uterine abnormalities- fibroids polyps senechiae
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Patient preparation (2)- surgery bull Hysteroscopy- If pathology suspected
bull Fibroids- ndash Submucous ndash Definite
ndash Intramural- Maybe
ndash Subserous- no
bull Laparoscopy- not routinely ndash If hydrosalpinges present
bull Salpingectomy and tubal occlusion performed prior to the IVF treatment improve subsequent pregnancy rates
ndash Endometrioma Dermoids
bull May be beneficial to remove
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Patient preparation (3)- Vitamins and other nutrients
bull There is evidence on the effects of folic acid and iodine supplementation preconception and during pregnancy
bull There is limited evidence as to the effect of other micronutrients on improving pregnancy rates and obstetric outcomes
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Patient Preparation (4) Weight control
bull Thinness and obesity have a negative impact on reproduction
bull Not just for getting pregnant but staying pregnant and having a healthy child
bull Weight control andor reduction will improve chances of success
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Patient preparation (5)-Thrombophilia screening
bull Haematological- suggested tests ndash Protein C Protein S ndash Antithrombin ndash Lupus anticoagulant ndash Anti Cardiolipinis ndash Factor 5 Leyden ndash Prothrombin Gene mutation ndash Fasting homocysteine ndash Full Blood Examination platelet count
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Patient preparation (6)-Immunological Screening
bull Antinuclear factor
bull Antithyroid antibodies
bull Anti gastric parietal cell antibodies
bull Antigliadin transglutaminase
bull Antiovarian antibodies
bull Natural Killer Cells (NKC)
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Patient preparation (7) Immunological Screening NK
Cells bull NK cells are lymphocytes with a CD3-CD56+ phenotypic profile
bull produce cytokines (IFN-γ TNF-β IL-10 and GM-CSF)
bull Can be tested in Blood or Endometrium-
ndash What is ldquonormalrdquo
bull treatment with immune therapy (on an empirical basis) is not necessarily confined to women with high NK cells
bull No conclusive evidence for any benefit
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Conclusion Immunological Thrombophilia
bull No good evidence that these factors are significant
bull No definite evidence that treatment of any of these factors improves outcomes
bull (steroids anticoagulants albumin intralipid)
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Patient Preparation (7)- Metformin in PCOS
bull The current evidence would support the use of metformin as an adjunct to IVF treatment ndash particularly in the context of the long agonist
protocol
ndash as adjunct to the short antagonist protocol requires further clarification
bull metformin may not necessarily improve the bdquotake home baby rate‟ but reduces the incidence of moderate-severe OHSS
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Stimulation Regimens
bull No significant difference between Agonist and Antagonist
bull Marginal benefits for hMG vs rFSH
bull Pretreatment with OC
ndash Benefits exceed disadvantages
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Stimulation regimens- poor responders
bull DHEA-
bull Limited evidence that DHEA may improve oocyte numbers quality
bull LH addback-
bull Maybe some subgroups
bull Growth Hormone
bull Some evidence for benefit RCT in progress
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Rationale for using LH ldquoadd-backrdquo
bull FSH and LH both secreted in natural ovulatory cycle bull During natural menstrual cycles FSH levels initially rise and
then primarily under the influence of oestradiol decline whereas LH is secreted in pulses rising during the mid follicular phase of the cycle
bull With the use of
ndash rFSH
ndash Agonistantagonist protocols levels of LH very low (lt12IUL)
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Summary- role of LH addback bull In women with HH it is generally accepted that LH supplementation is
needed for normal healthy follicular development and oocyte maturation
bull In a general population of normogonadotrophic women undergoing ART irrespective of whether a GnRH agonist or GnRH antagonist is co-administered the addition of r-hLH to treatment protocols does not appear to provide any additional benefits
bull Subgroups of normogonadotrophic women who may receive benefit from r-hLH supplementation for IVF and ICSI include the following
ndash women aged ge35 years and
ndash women who are hyporesponsive to FSH
The latter group of women may be further identified by specific genetic
biomarkers that are currently being investigated
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Monitoring
bull optimized by adopting an individualized patient-
centred approach to COH
bull selection of ndash appropriate COH protocol
ndash close monitoring of follicle growth and serum E2 levels
ndash adjustment of gonadotrophin dose to avoid hyper-response
ndash individualized timing of hCG injection
bull This approach to IVF can ndash improve oocyte and embryo quality pregnancy and implantation rates
ndash minimizes the risk of OHSS
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Monitoring
bull No evidence that intensive monitoring gives better results than a ldquominimalistrdquo approach
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndash Assisted hatching
ndash PGD
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Sperm preparation
bull Only use ICSI if indicated
bull Use most viable motile functional spermatozoa- IMSI Feldberg
bull Discontinuous gradient centrifugation or a new electrophoretic approach
bull Select least damaged DNA containing
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Laboratory aspects ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Metabolomics
ndash morphokinetics
ndash Assisted hatching
ndash PGD
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Addition of Co-factors
bull Has the potential to improve the development of zygotes to the blastocyst stage
bull Might mimic the autocrine and paracrine factors
bull Perhaps the use of microfluidic culture systems would be more applicable
bull Much research and controlled studies are required before these co factors can be routinely used
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Embryo Transfer- cleavage or blastocyst
bull When laboratory conditions are not ideal then it would be more appropriate to place the embryos into the uterus sooner than later
bull The available literature indicate that embryo transfer on day 5 is associated with better outcomes
bull Day 5 ET the preferred option with increasing move to single embryo transfer
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Metabolomics-
bull a non-invasive assessment of embryo culture media to aid in the prediction of embryo viability
bull determine more subtle embryo characteristics
bull rapid metabolic or metabolomic assessment tool will be part of the routine procedure used to select an embryo for transfer
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
bull Theory the differences between viable and sub-viable
embryos are reflected by metabolism activity
bull Take a small sample of the culture medium where the
embryo has been growing and measure amino acids etc
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
bull Eg glucose pyruvate amino amino acids
bull Currently several methods being trialled to measure these molecules Most popular is Near Infrared Spectoscopy (NIR)
bull Expected time-frame for commercial availability 1-2 years
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Laboratory aspects
ndash Sperm preparation and selection
ndash Culture media and culture of embryos
ndash Extended culture
ndash Embryo selection
bull Metabolomics
bull Morphokinetics
ndashAssisted hatching
ndash PGD
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Embryoscope
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
PRIMO VISION EVO
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Graphic representation of the considered embryo developmental events t2 t3 t4 t5 cc2 = t3-
t2 and s2 = t4-t3
Meseguer M et al Hum Reprod 2011262658-2671
copy The Author 2011 Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology All rights reserved For Permissions please email
journalspermissionsoupcom
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Could time-lapse embryo imaging reduce the need for biopsy and
PGS Swain JE J Assist Reprod Genet 2013 Jul 11
Multiple morphologic endpoint assessments and developmental timings and refinement of modeling systems may improve the predictive ability to determine embryonic aneuploidy
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Possible factors
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Embryo transfer
bull Dummy transfer beneficial
bull Position-mid fundus
bull Ultrasound monitoring
bull Catheter soft but malleable
bull Bed rest- no help
bull Intercourse may help
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
bull Patient preparation
bull Stimulation Regimens
bull Monitoring
bull Laboratory aspects
bull Embryo transfer
bull Ancillary treatment
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Ancillary treatments
bull Heparin Aspirin
bull Hormones ndash Estrogen
ndash Progestogens
ndash DHEA
bull Immunotherapy ndash Steroids
ndash IVIG Humira
bull Adjuvants ndash Chinese herbs
ndash Sidenafil
ndash Hyperbaric oxygen
ndash Acupuncture
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Immunological Thrombophilia
bull The best randomized controlled trials do not support the use of heparin and aspirin in aPL positive patients with IVF failure
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Hormone Supplements
bull On the basis of the currently best available evidence
bull The addition of E2 supplementation in the luteal phase does not improve IVF outcomes in long protocolantagonist cycles
ndash excluding antagonist trigger
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Prednisolone
bull Normal IVF patients do not significantly improve their chances of pregnancy when subjected to additional glucocorticoid treatment in the IVF cycle
bull In patients who present a previous autoimmune pathology and in whom it does seem that corticoid treatment might be beneficial
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological
Challenges 2011
bull Poor responders
bull Implantation failure ndash Embryo quality
bull Genetic
bull Developmental
ndash Endometrial receptivity
bull Hormonal
bull Immunological
bull Haematological