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Infertilit Infertilit y y Zeev Blumenfeld, M.D. Zeev Blumenfeld, M.D. Reproductive Endocrinology, Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care Campus, Faculty of Medicin Rambam Health Care Campus, Faculty of Medicin Technion- Israel Institute of Technology (IIT) Technion- Israel Institute of Technology (IIT) Haifa, Israel Haifa, Israel

InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

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Page 1: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

InfertilityInfertilityInfertilityInfertility

Zeev Blumenfeld, M.D.Zeev Blumenfeld, M.D.

Reproductive Endocrinology,Reproductive Endocrinology, Dept. Obstetrics & GynecologyDept. Obstetrics & Gynecology

Rambam Health Care Campus, Faculty of Medicine,Rambam Health Care Campus, Faculty of Medicine,Technion- Israel Institute of Technology (IIT)Technion- Israel Institute of Technology (IIT)

Haifa, IsraelHaifa, Israel

Zeev Blumenfeld, M.D.Zeev Blumenfeld, M.D.

Reproductive Endocrinology,Reproductive Endocrinology, Dept. Obstetrics & GynecologyDept. Obstetrics & Gynecology

Rambam Health Care Campus, Faculty of Medicine,Rambam Health Care Campus, Faculty of Medicine,Technion- Israel Institute of Technology (IIT)Technion- Israel Institute of Technology (IIT)

Haifa, IsraelHaifa, Israel

Page 2: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care
Page 3: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

DefinitionsDefinitionsDefinitionsDefinitions

• Infertility– Inability to conceive after one year of

unprotected intercourse (6 months for women over 35?)

• Fertility– Ability to conceive

• Fecundity– Ability to carry to delivery

• Infertility– Inability to conceive after one year of

unprotected intercourse (6 months for women over 35?)

• Fertility– Ability to conceive

• Fecundity– Ability to carry to delivery

Page 4: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

StatisticsStatisticsStatisticsStatistics• 80% of couples will conceive within 1 year of

unprotected intercourse• ~86% will conceive within 2 years• ~14-20% of US couples are infertile by definition

(~3 million couples)• Origin:

– Female factor ~40%– Male factor ~30%– Combined ~30%

• 80% of couples will conceive within 1 year of unprotected intercourse

• ~86% will conceive within 2 years• ~14-20% of US couples are infertile by definition

(~3 million couples)• Origin:

– Female factor ~40%– Male factor ~30%– Combined ~30%

Page 5: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

EtiologiesEtiologiesEtiologiesEtiologies

• Sperm disorders 30%

• Anovulation/oligo-ovulation 30%

• Tubal disease 15%

• Unexplained 15%

• Cx factors 5%

• Peritoneal factors 5%

• Sperm disorders 30%

• Anovulation/oligo-ovulation 30%

• Tubal disease 15%

• Unexplained 15%

• Cx factors 5%

• Peritoneal factors 5%

Page 6: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care
Page 7: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Associated FactorsAssociated FactorsAssociated FactorsAssociated Factors• PID• Endometriosis • Ovarian aging• Spermatic varicocoele• Toxins • Previous abdominal surgery (adhesions)• Cervical/uterine abnormalities• Cervical/uterine surgery• Fibroids

• PID• Endometriosis • Ovarian aging• Spermatic varicocoele• Toxins • Previous abdominal surgery (adhesions)• Cervical/uterine abnormalities• Cervical/uterine surgery• Fibroids

Page 8: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Emotional & Educational NeedsEmotional & Educational NeedsEmotional & Educational NeedsEmotional & Educational Needs

• Disease of couples, not individuals

• Feelings of guilt

• Where to go for information?

• Options

• Feelings of frustration and anger

• Support groups (e.g. Resolve)

• Disease of couples, not individuals

• Feelings of guilt

• Where to go for information?

• Options

• Feelings of frustration and anger

• Support groups (e.g. Resolve)

Page 9: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Overview of EvaluationOverview of EvaluationOverview of EvaluationOverview of Evaluation• Female

– Ovary– Tube – Corpus– Cervix– Peritoneum

• Male– Sperm count and function– Ejaculate characteristics, immunology– Anatomic anomalies

• Female – Ovary– Tube – Corpus– Cervix– Peritoneum

• Male– Sperm count and function– Ejaculate characteristics, immunology– Anatomic anomalies

Page 10: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

The Most Important Factor in The Most Important Factor in the Evaluation of the Infertile the Evaluation of the Infertile

Couple Is:Couple Is:

The Most Important Factor in The Most Important Factor in the Evaluation of the Infertile the Evaluation of the Infertile

Couple Is:Couple Is:

Page 11: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

HISTORYHISTORYHISTORYHISTORY

Page 12: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

History-GeneralHistory-GeneralHistory-GeneralHistory-General

• Both couples should be present• Age• Previous pregnancies by each partner• Length of time without pregnancy• Sexual history

– Frequency and timing of intercourse– Use of lubricants– Impotence, anorgasmia, dyspareunia– Contraceptive history

• Both couples should be present• Age• Previous pregnancies by each partner• Length of time without pregnancy• Sexual history

– Frequency and timing of intercourse– Use of lubricants– Impotence, anorgasmia, dyspareunia– Contraceptive history

Page 13: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

History-MaleHistory-MaleHistory-MaleHistory-Male

• History of pelvic infection

• Radiation, toxic exposures (include drugs)

• Mumps

• Testicular surgery/injury

• Excessive heat exposure (spermicidal)

• History of pelvic infection

• Radiation, toxic exposures (include drugs)

• Mumps

• Testicular surgery/injury

• Excessive heat exposure (spermicidal)

Page 14: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

History-FemaleHistory-FemaleHistory-FemaleHistory-Female

• Previous female pelvic surgery

• PID

• Appendicitis

• IUD use

• Ectopic pregnancy history

• DES (?relation to infertility)

• Endometriosis

• Previous female pelvic surgery

• PID

• Appendicitis

• IUD use

• Ectopic pregnancy history

• DES (?relation to infertility)

• Endometriosis

Page 15: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Mechanical/Pelvic factor infertilityMechanical/Pelvic factor infertilityDistal tubal occlusionDistal tubal occlusion

Mechanical/Pelvic factor infertilityMechanical/Pelvic factor infertilityDistal tubal occlusionDistal tubal occlusion

PID - 13% post PIDx1 - 39% post PIDx2 - 75% post PIDx3EndometriosisSurgical injuryPeritoneal infection

PID - 13% post PIDx1 - 39% post PIDx2 - 75% post PIDx3EndometriosisSurgical injuryPeritoneal infection

Page 16: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

History-FemaleHistory-FemaleHistory-FemaleHistory-Female

• Irregular menses, amenorrhea, detailed menstrual history

• Vasomotor symptoms • Stress• Weight changes• Exercise• Cervical and uterine surgery

• Irregular menses, amenorrhea, detailed menstrual history

• Vasomotor symptoms • Stress• Weight changes• Exercise• Cervical and uterine surgery

Page 17: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

When Not to Pursue an When Not to Pursue an Infertility EvaluationInfertility Evaluation

When Not to Pursue an When Not to Pursue an Infertility EvaluationInfertility Evaluation

• Patient not sexually-active

• Patient not in long-term relationship?

• Patient declines treatment at this time

• Couple does not meet the definition of an infertile couple

• Patient not sexually-active

• Patient not in long-term relationship?

• Patient declines treatment at this time

• Couple does not meet the definition of an infertile couple

Page 18: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Physical Exam-MalePhysical Exam-MalePhysical Exam-MalePhysical Exam-Male

• Size of testicles

• Testicular descent

• Varicocoele

• Outflow abnormalities (hypospadias, etc)

• Size of testicles

• Testicular descent

• Varicocoele

• Outflow abnormalities (hypospadias, etc)

Page 19: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care
Page 20: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Physical Exam-FemalePhysical Exam-FemalePhysical Exam-FemalePhysical Exam-Female

• Pelvic masses

• Uterosacral nodularity

• Abdominopelvic tenderness

• Uterine enlargement

• Thyroid exam

• Uterine mobility

• Cervical abnormalities

• Pelvic masses

• Uterosacral nodularity

• Abdominopelvic tenderness

• Uterine enlargement

• Thyroid exam

• Uterine mobility

• Cervical abnormalities

Page 21: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Overall Guidelines for Work-upOverall Guidelines for Work-up Overall Guidelines for Work-upOverall Guidelines for Work-up

• Work- up can usually be accomplished in 1-2 cycles [“Cycle Evaluation”]

• Timing of tests

• Don’t over test

• Cut to the chase, i.e. proceed with laparoscopy if adhesive disease is likely

• Work- up can usually be accomplished in 1-2 cycles [“Cycle Evaluation”]

• Timing of tests

• Don’t over test

• Cut to the chase, i.e. proceed with laparoscopy if adhesive disease is likely

Page 22: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Work-up by Organ UnitWork-up by Organ Unit

Page 23: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

OvaryOvary

Page 24: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Ovarian FunctionOvarian FunctionOvarian FunctionOvarian Function

• Document ovulation:– BBT– Luteal phase progesterone – LH surge– Endom. Bx

• If POF suspected, perform FSH• TSH, PRL, adrenal functions if indicated

• The only convincing proof of ovulation is pregnancy

• Document ovulation:– BBT– Luteal phase progesterone – LH surge– Endom. Bx

• If POF suspected, perform FSH• TSH, PRL, adrenal functions if indicated

• The only convincing proof of ovulation is pregnancy

Page 25: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Ovarian FunctionOvarian FunctionOvarian FunctionOvarian Function

• Three main types of dysfunction– Hypogonadotrophic, hypoestrogenic

(central)– Normogonadotropic,normoestrogenic

(e.g. PCOS)– Hypergonadotrophic, hypoestrogenic

(POF)

• Three main types of dysfunction– Hypogonadotrophic, hypoestrogenic

(central)– Normogonadotropic,normoestrogenic

(e.g. PCOS)– Hypergonadotrophic, hypoestrogenic

(POF)

Page 26: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

BBTBBTBBTBBT• Cheap and easy, but…

Inconsistent resultsRetrospective May delay timely diagnosis and treatment98% of women will ovulate within 3 days

of the nadirBiphasic profiles can also be seen with

LUF syndrome

• Cheap and easy, but…Inconsistent resultsRetrospective May delay timely diagnosis and treatment98% of women will ovulate within 3 days

of the nadirBiphasic profiles can also be seen with

LUF syndrome

Page 27: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Luteal Phase ProgesteroneLuteal Phase ProgesteroneLuteal Phase ProgesteroneLuteal Phase Progesterone

Pulsatile release, thus single level may not be useful unless elevated

Performed 7 days after presumptive ovulation

Done properly, >15 ng/ml consistent with ovulation

Pulsatile release, thus single level may not be useful unless elevated

Performed 7 days after presumptive ovulation

Done properly, >15 ng/ml consistent with ovulation

Page 28: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Urinary LH KitsUrinary LH KitsUrinary LH KitsUrinary LH Kits

Sensitive and accuratePositive test precedes ovulation by ~24

hours, so useful for timing intercourseDownside: price, obsession with

timing of intercourse

Sensitive and accuratePositive test precedes ovulation by ~24

hours, so useful for timing intercourseDownside: price, obsession with

timing of intercourse

Page 29: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Endometrial BiopsyEndometrial Biopsy Endometrial BiopsyEndometrial Biopsy Invasive, but the only reliable way to diagnose

LPD ??Is LPD a genuine disorder??? Pregnancy loss rate <1% Perform around 2 days before expected

menstruation (= day 28 by definition) Lag of >2 days is consistent with LPD Must be done in two different cycles to confirm

diagnosis of LPD

Invasive, but the only reliable way to diagnose LPD

??Is LPD a genuine disorder??? Pregnancy loss rate <1% Perform around 2 days before expected

menstruation (= day 28 by definition) Lag of >2 days is consistent with LPD Must be done in two different cycles to confirm

diagnosis of LPD

Page 30: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Fallopian TubesFallopian Tubes

Page 31: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Tubal FunctionTubal FunctionTubal FunctionTubal Function

Evaluate tubal patency whenever there is a history of PID, endometriosis or other adhesiogenic condition

Kartagener’s syndrome can be associated with decreased tubal motility

Tests HSG Laparoscopy Falloposcopy (not widely available)

Evaluate tubal patency whenever there is a history of PID, endometriosis or other adhesiogenic condition

Kartagener’s syndrome can be associated with decreased tubal motility

Tests HSG Laparoscopy Falloposcopy (not widely available)

Page 32: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Hysterosalpingography (HSG)Hysterosalpingography (HSG)Hysterosalpingography (HSG)Hysterosalpingography (HSG)

Radiologic procedure requiring contrastPerformed optimally in early proliferative phase

(avoids pregnancy)Low risk of PID except if previous history of PID

(give prophylactic doxycycline or consider laparoscopy)

Oil-based contrast Higher risk of anaphylaxis than H2O-based May be associated with fertility rates

Radiologic procedure requiring contrastPerformed optimally in early proliferative phase

(avoids pregnancy)Low risk of PID except if previous history of PID

(give prophylactic doxycycline or consider laparoscopy)

Oil-based contrast Higher risk of anaphylaxis than H2O-based May be associated with fertility rates

Page 33: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Hysterosalpingography (HSG)Hysterosalpingography (HSG)Hysterosalpingography (HSG)Hysterosalpingography (HSG)

• Can be uncomfortable

• Pregnancy test is advisable

• Can detect intrauterine and tubal disorders but not always definitive

• Can be uncomfortable

• Pregnancy test is advisable

• Can detect intrauterine and tubal disorders but not always definitive

Page 34: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

LaparoscopyLaparoscopy LaparoscopyLaparoscopy

• Invasive; requires OR or office setting• Can offer diagnosis and treatment in one sitting• Not necessary in all patients• Uses (examples):

– Lysis of adhesions– Diagnosis and excision of endometriosis– Myomectomy – Tubal reconstructive surgery

• Invasive; requires OR or office setting• Can offer diagnosis and treatment in one sitting• Not necessary in all patients• Uses (examples):

– Lysis of adhesions– Diagnosis and excision of endometriosis– Myomectomy – Tubal reconstructive surgery

Page 35: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

FalloposcopyFalloposcopyFalloposcopyFalloposcopy

• Hysteroscopic procedure with cannulation of the Fallopian tubes

• Can be useful for diagnosis of intraluminal pathology

• Promising technique but not yet widespread

• Hysteroscopic procedure with cannulation of the Fallopian tubes

• Can be useful for diagnosis of intraluminal pathology

• Promising technique but not yet widespread

Page 36: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Uterine CorpusUterine Corpus

Page 37: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

CorpusCorpusCorpusCorpus• Asherman Syndrome

– Diagnosis by HSG or hysteroscopy– Usually s/p D+C, myomectomy, other intrauterine

surgery– Associated with hypo/amenorrhea, recurrent miscarriage

• Fibroids, Uterine Anomalies– Rarely associated with infertility– Work-up:

• Ultrasound • Hysteroscopy• Laparoscopy

• Asherman Syndrome– Diagnosis by HSG or hysteroscopy– Usually s/p D+C, myomectomy, other intrauterine

surgery– Associated with hypo/amenorrhea, recurrent miscarriage

• Fibroids, Uterine Anomalies– Rarely associated with infertility– Work-up:

• Ultrasound • Hysteroscopy• Laparoscopy

Page 38: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

CervixCervix

Page 39: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Cervical FunctionCervical FunctionCervical FunctionCervical Function

• Infection– Ureaplasma suspected

• Stenosis– S/P LEEP, Cryosurgery, Cone biopsy (probably

overstated)

• Immunologic Factors– Sperm-mucus interaction

• Infection– Ureaplasma suspected

• Stenosis– S/P LEEP, Cryosurgery, Cone biopsy (probably

overstated)

• Immunologic Factors– Sperm-mucus interaction

Page 40: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Cervical FunctionCervical FunctionCervical FunctionCervical Function

• Tests:– Culture for suspected pathogens – Postcoital test (PCT)

• Scheduled around 1-2d before ovulation (increased estrogen effect)

• 480 of male abstinence before test• No lubricants• Evaluate 8-12h after coitus (overnight is ok!)• Remove mucus from cervix (forceps, syringe)

• Tests:– Culture for suspected pathogens – Postcoital test (PCT)

• Scheduled around 1-2d before ovulation (increased estrogen effect)

• 480 of male abstinence before test• No lubricants• Evaluate 8-12h after coitus (overnight is ok!)• Remove mucus from cervix (forceps, syringe)

Page 41: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

SpinnbarkeitSpinnbarkeit FerningFerningLate follicular Late follicular phasephase

Watery, thin & Watery, thin & acellularacellular

Cervical MucusCervical Mucus

Page 42: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Cervical FunctionCervical FunctionCervical FunctionCervical Function

• PCT, continued (normal values in yellow)– Quantity (very subjective)– Quality (spinnbarkeit) (>8 cm)– Clarity (clear)– Ferning (branched)– Viscosity (thin)– WBC’s (~0)

– # progressively motile sperm/hpf (5-10/hpf)– Gross sperm morphology (WNL)

• PCT, continued (normal values in yellow)– Quantity (very subjective)– Quality (spinnbarkeit) (>8 cm)– Clarity (clear)– Ferning (branched)– Viscosity (thin)– WBC’s (~0)

– # progressively motile sperm/hpf (5-10/hpf)– Gross sperm morphology (WNL)

Male factorsMale factorsMale factorsMale factors

Page 43: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Problems with the PCT Problems with the PCT Problems with the PCT Problems with the PCT

• Subjective

• Timing varies; may need to be repeated

• In some studies, “infertile” couples with an abnormal PCT conceived successfully during that same cycle

• Subjective

• Timing varies; may need to be repeated

• In some studies, “infertile” couples with an abnormal PCT conceived successfully during that same cycle

Page 44: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

PeritoneumPeritoneum

Page 45: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Peritoneal FactorsPeritoneal FactorsPeritoneal FactorsPeritoneal Factors

• Endometriosis – 2x relative risk of infertility– Diagnosis (and best treatment) by laparoscopy – Can be familial; can occur in adolescents– Etiology unknown but likely multiple ones

• Retrograde menstruation• Immunologic factors• Genetics• Lymphatic or Hematogenic spread

– Medical options remain suboptimal

• Endometriosis – 2x relative risk of infertility– Diagnosis (and best treatment) by laparoscopy – Can be familial; can occur in adolescents– Etiology unknown but likely multiple ones

• Retrograde menstruation• Immunologic factors• Genetics• Lymphatic or Hematogenic spread

– Medical options remain suboptimal

Page 46: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Male FactorsMale Factors

Page 47: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Male FactorsMale FactorsMale FactorsMale Factors

• Serum T, FSH, PRL levels

• Semen analysis

• Testicular biopsy

• Sperm penetration assay (SPA)

• Serum T, FSH, PRL levels

• Semen analysis

• Testicular biopsy

• Sperm penetration assay (SPA)

Page 48: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Male Factors-Semen AnalysisMale Factors-Semen AnalysisMale Factors-Semen AnalysisMale Factors-Semen Analysis

• Collected after 480 of abstinence

• Evaluated within one hour of ejaculation

• If abnormal parameters, repeat twice, 2 weeks apart

• Collected after 480 of abstinence

• Evaluated within one hour of ejaculation

• If abnormal parameters, repeat twice, 2 weeks apart

Page 49: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Normal Semen AnalysisNormal Semen AnalysisNormal Semen AnalysisNormal Semen Analysis

Quality Normal Value

Volume >1 cc

Concentration >2 x 106/cc

Initial ForwardMotility

>50%

Normal Morphology >60%

Quality Normal Value

Volume >1 cc

Concentration >2 x 106/cc

Initial ForwardMotility

>50%

Normal Morphology >60%

Page 50: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Male factor evaluationMale factor evaluationSpermiogramSpermiogram

Page 51: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Sperm Penetration AssaySperm Penetration AssaySperm Penetration AssaySperm Penetration Assay

• “Zona-free Hamster Ova Assay”

• Dynamic test of fertilization capacity of sperm

• Failure to penetrate at least 10% of zona-free ova consistent with male factor

• False positives and negatives exist

• “Zona-free Hamster Ova Assay”

• Dynamic test of fertilization capacity of sperm

• Failure to penetrate at least 10% of zona-free ova consistent with male factor

• False positives and negatives exist

Page 52: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Male factor Male factor Endocrine evaluationEndocrine evaluation

Page 53: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Male Factor EvaluationMale Factor EvaluationGeneticsGenetics

• CBAVD, CUAVD

Epididymal obstruction Ejaculatory duct obstruction

• Non-obstructive AZO

Severe OTA

• Non-Obstructive AZO

Severe OTA

CF gene mutations

Karyotype

Y-microdeletions

Page 54: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Treatment OptionsTreatment Options

Page 55: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Ovarian DisordersOvarian DisordersOvarian DisordersOvarian DisordersAnovulation

Clomiphene Citrate ± hCG FSH, hMG/hCG Induction + IUI (often done but unjustified)

PRLBromocriptine [ Parlodel,Parilac 1.25-10 mg/day, bid],Cabergoline [Dostinex 0.5 mg/week]], Octahydrobenzoquinoline [Norprolac 75-300g/day]TSR if macroadenoma

POF ?high-dose hMG (not very effective)

Anovulation Clomiphene Citrate ± hCG FSH, hMG/hCG Induction + IUI (often done but unjustified)

PRLBromocriptine [ Parlodel,Parilac 1.25-10 mg/day, bid],Cabergoline [Dostinex 0.5 mg/week]], Octahydrobenzoquinoline [Norprolac 75-300g/day]TSR if macroadenoma

POF ?high-dose hMG (not very effective)

Page 56: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Ovulatory DisordersOvulatory DisordersOvulatory DisordersOvulatory Disorders

• Central amenorrhea– CC first, then hMG– Pulsatile GnRH

• LPD– Progesterone suppositories during luteal phase– CC ± hCG

• Central amenorrhea– CC first, then hMG– Pulsatile GnRH

• LPD– Progesterone suppositories during luteal phase– CC ± hCG

Page 57: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Ovarian MatrixOvarian MatrixOvarian MatrixOvarian MatrixGonadotropins E2 Treatment

High Low ??high-dose hMG, r/oautoimmune diseases

WNL WNL CC ± hCG

Low Low CC first, then hMG

Gonadotropins E2 Treatment

High Low ??high-dose hMG, r/oautoimmune diseases

WNL WNL CC ± hCG

Low Low CC first, then hMG

Page 58: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Ovulatory factor Ovulatory factor Endocrine evaluationEndocrine evaluation

FSH LH E2 PRL

• Hypothalamic Insufficiency ↓ ↓ ↓ N

• Pituitary adenoma/ N/↓ N/↓ N/↓ N/↑

HyperPRLemia

• PCO N/low ↑ N N/↑

• Ovarian failure ↑ ↑ ↓ N

Page 59: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Ovulation InductionOvulation InductionOvulation InductionOvulation Induction

• CC– 70% induction rate, ~40% pregnancy rate– Patients should typically be normoestrogenic– Induce menses and start on day 3-5– With dosages, antiestrogen effects dominate– Multifetal rates 5-10%– Monitor effects with PCT, pelvic exam

• CC– 70% induction rate, ~40% pregnancy rate– Patients should typically be normoestrogenic– Induce menses and start on day 3-5– With dosages, antiestrogen effects dominate– Multifetal rates 5-10%– Monitor effects with PCT, pelvic exam

Page 60: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Clomiphene CitrateClomiphene CitrateMechanism of ActionMechanism of Action

Page 61: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Response to clomipheneResponse to clomiphene

No responseNo response

OvulationOvulation & pregnancy& pregnancy

OvulationOvulation- no - no pregnancypregnancy

33%33%

Page 62: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Clomiphene CitrateClomiphene CitrateSide EffectsSide Effects

Clomiphene CitrateClomiphene CitrateSide EffectsSide Effects

Dysmucorrhea - 15%Hot flushes - 10%Abdominal pain - 5.5% (OHSS usually mild)Breast discomfort - 2%Nausea and vomiting - 2.2% Visual symptoms - 1.5%Headache - 1.3%Emotional liability and depression

Dysmucorrhea - 15%Hot flushes - 10%Abdominal pain - 5.5% (OHSS usually mild)Breast discomfort - 2%Nausea and vomiting - 2.2% Visual symptoms - 1.5%Headache - 1.3%Emotional liability and depression

Page 63: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

CC- Mechaniam of ActionCC- Mechaniam of Action

Page 64: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

hMG hMG (Pergonal,Menogon,Menopur)(Pergonal,Menogon,Menopur)

• LH +FSH (also FSH alone = Gonal-F,Puregon)• For patients with hypogonadotrophic

hypoestrogenism or normal FSH and E2 levels

• Close monitoring essential, including estradiol levels

• 60-80% pregnancy rates overall, lower for PCOS patients

• 10-15% multifetal pregnancy rate

• LH +FSH (also FSH alone = Gonal-F,Puregon)• For patients with hypogonadotrophic

hypoestrogenism or normal FSH and E2 levels

• Close monitoring essential, including estradiol levels

• 60-80% pregnancy rates overall, lower for PCOS patients

• 10-15% multifetal pregnancy rate

Page 65: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

hMG- Mechanism of ActionhMG- Mechanism of Action

Page 66: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Human GonadotropinsHuman GonadotropinsResultsResults

Human GonadotropinsHuman GonadotropinsResultsResults

• Group I

Cumulative pregnancy rate after 6 months

90%

• Group II

Cumulative pregnancy rate after 6 months

40%

• Group I

Cumulative pregnancy rate after 6 months

90%

• Group II

Cumulative pregnancy rate after 6 months

40%

Page 67: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

RisksRisks RisksRisks

CC Vasomotor symptoms Head Ache Ovarian enlargement Multiple gestation NO risk of SAb or

malformations

CC Vasomotor symptoms Head Ache Ovarian enlargement Multiple gestation NO risk of SAb or

malformations

hMGMultiple gestationOHSS (~1%)

– Can often be managed as outpatient

– Diuresis– Severe cases fatal if

untreated in ICU setting

hMGMultiple gestationOHSS (~1%)

– Can often be managed as outpatient

– Diuresis– Severe cases fatal if

untreated in ICU setting

Page 68: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Fallopian TubesFallopian TubesFallopian TubesFallopian Tubes

TuboplastyIVFGIFT, ZIFT not options

TuboplastyIVFGIFT, ZIFT not options

Page 69: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

CorpusCorpusCorpusCorpus

• Asherman syndrome– Hysteroscopic lysis of adhesions (scissor)– Postop Abx, E2

• Fibroids (rarely need treatment)– Myomectomy ( hysteroscopic, laparoscopic,

open)

• Uterine anomalies (rarely need treatment)– Metroplasty, Hysteroscopy

• Asherman syndrome– Hysteroscopic lysis of adhesions (scissor)– Postop Abx, E2

• Fibroids (rarely need treatment)– Myomectomy ( hysteroscopic, laparoscopic,

open)

• Uterine anomalies (rarely need treatment)– Metroplasty, Hysteroscopy

Page 70: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

CervixCervixCervixCervix

• Repeat PCT to rule out inaccurate timing of test

• If cervicitis Abx

• If scant mucus low-dose estrogen

• Sperm motility issues (? Antisperm AB’s)– Steroids?– IUI

• Repeat PCT to rule out inaccurate timing of test

• If cervicitis Abx

• If scant mucus low-dose estrogen

• Sperm motility issues (? Antisperm AB’s)– Steroids?– IUI

Page 71: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Peritoneum (Endometriosis)Peritoneum (Endometriosis)Peritoneum (Endometriosis)Peritoneum (Endometriosis)• From a fertility standpoint, excision beats medical

management• Lysis of adhesions • GnRH-a (not a cure and has side effects, expense)• Danazol (side effects, cost)• Continuous OCP’s (poor fertility rates)• Chances of pregnancy highest within 6 m’s-1 year

after treatment

• From a fertility standpoint, excision beats medical management

• Lysis of adhesions • GnRH-a (not a cure and has side effects, expense)• Danazol (side effects, cost)• Continuous OCP’s (poor fertility rates)• Chances of pregnancy highest within 6 m’s-1 year

after treatment

Page 72: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Male FactorMale FactorMale FactorMale Factor

• Hypogonadotrophism– hMG– GnRH– CC, hCG results poor

• Varicocoele– Ligation? (no definitive data yet)

• Retrograde ejaculation– Ephedrine, imipramine– AIH with recovered sperm

• Hypogonadotrophism– hMG– GnRH– CC, hCG results poor

• Varicocoele– Ligation? (no definitive data yet)

• Retrograde ejaculation– Ephedrine, imipramine– AIH with recovered sperm

Page 73: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Male FactorMale FactorMale FactorMale Factor• Idiopathic oligospermia

– No effective treatment

– ?IVF

– donor insemination

• Idiopathic oligospermia

– No effective treatment

– ?IVF

– donor insemination

Page 74: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Unexplained InfertilityUnexplained InfertilityUnexplained InfertilityUnexplained Infertility• 5-10% of couples• Consider PRL, laparoscopy, other hormonal tests,

cultures, ASA testing, SPA if not done• Review previous tests for validity• Empiric treatment:

– Ovulation induction– Abx– IUI– Consider IVF and its variants

• Adoption

• 5-10% of couples• Consider PRL, laparoscopy, other hormonal tests,

cultures, ASA testing, SPA if not done• Review previous tests for validity• Empiric treatment:

– Ovulation induction– Abx– IUI– Consider IVF and its variants

• Adoption

Page 75: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

SummarySummarySummarySummary

• Infertility is a common problem• Infertility is a disease of couples• Evaluation must be thorough, but

individualized• Treatment is available, including IVF, but can

be expensive, invasive, and of limited efficacy in some cases

• Consultation with a expert reproductive endocrinologist is advisable

• Infertility is a common problem• Infertility is a disease of couples• Evaluation must be thorough, but

individualized• Treatment is available, including IVF, but can

be expensive, invasive, and of limited efficacy in some cases

• Consultation with a expert reproductive endocrinologist is advisable

Page 76: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care
Page 77: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care
Page 78: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care
Page 79: InfertilityInfertility Zeev Blumenfeld, M.D. Reproductive Endocrinology, Dept. Obstetrics & Gynecology Dept. Obstetrics & Gynecology Rambam Health Care

Thank you!