DR. RABI NARAYAN SATAPATHYASST.PROFESSORDEPT. OF OBST.& GYNAECOLOGYSCB MEDICAL COLLEGE, [email protected]
Relative Prevalence Of The Etiologies Of Infertility
10% 10%
40-50%
25-40%
Both male & femalefactor
Female factor
Male factor
Unexplainedinfertility
Incidence of Male Infertility is increasing ! !Incidence of Male Infertility is increasing ! !
PRESENTATION OF MALE INFERTILITYPRESENTATION OF MALE INFERTILITY
ABNORMAL SEMEN PROFILEABNORMAL SEMEN PROFILE MALE SEXUAL DYSFUNCTION MALE SEXUAL DYSFUNCTION
AZOOSPERMIA AZOOSPERMIA ERECTILE DYSFUNCTION ERECTILE DYSFUNCTION
OLIGOSPERMIA OLIGOSPERMIA EJACUALATORY DYSFUNCTION EJACUALATORY DYSFUNCTION
ASTHENOSPERMIA ASTHENOSPERMIA RETROGRADE EJACULATION RETROGRADE EJACULATION
TERATOZOOSPERMIA TERATOZOOSPERMIA PREMATURE EJACULATION PREMATURE EJACULATION
HIGH LEUCOCYTE COUNT HIGH LEUCOCYTE COUNT LOCAL ANATOMICAL DEFECTLOCAL ANATOMICAL DEFECT
COMBINATIONCOMBINATION
PretesticularPretesticular TesticularTesticular PosttesticularPosttesticular
EndocrineEndocrine Hypogonadotropic hypogonadismHypogonadotropic hypogonadism
Hypothyroidism, Hypothyroidism,
Hyperprolatinaemia Hyperprolatinaemia
DiabetesDiabetes
Coital disordersCoital disorders Erectile dysfunctionErectile dysfunction
Ejaculatory failureEjaculatory failure
GeneticGenetic Klinefelter’s Syndrome Klinefelter’s Syndrome
Y chromosome deletionY chromosome deletion
Immotile cilia syndromeImmotile cilia syndrome
Congenital Congenital CryptorchidismCryptorchidism
Infective (orchitis)Infective (orchitis)
Antispermatogenic agentsAntispermatogenic agents Heat, Chemotherapy, Drugs, Heat, Chemotherapy, Drugs,
IrradiationIrradiation
Vascular Vascular TorsionTorsion
VaricoceleVaricocele
Immunological Immunological
IdiopathicIdiopathic
ObstructiveObstructive EpididymalEpididymal
CongenitalCongenital
InfectiveInfective
VasalVasal
Genetic: Cystic fibrosisGenetic: Cystic fibrosis
Aquired: VasectomyAquired: Vasectomy
Ejaculatory duct obstructionEjaculatory duct obstruction
Epididymal hostilityEpididymal hostility Epididymal asthenospermiaEpididymal asthenospermia
Accessory gland Accessory gland
infectioninfection
ImmunologicalImmunological IdiopathicIdiopathic
Post vasectomyPost vasectomy
ETIOLOGICAL FACTORS IN MALE INFERTILITYETIOLOGICAL FACTORS IN MALE INFERTILITY
CAUSECAUSE PERCENTAGEPERCENTAGE
No demonstrable causeNo demonstrable cause
Idiopathic abnormal semenIdiopathic abnormal semen
VaricoceleVaricocele
Infectious factorsInfectious factors
Immunologic factorImmunologic factor
Other acquired factorsOther acquired factors
Congenital factorsCongenital factors
Sexual factorsSexual factors
Endocrine disturbances Endocrine disturbances
48.5%48.5%
26.4%26.4%
12.3%12.3%
6.6%6.6%
3.1%3.1%
2.6%2.6%
2.1%2.1%
1.7%1.7%
0.6%0.6%
Frequency of Etiologies in Male Factor InfertilityFrequency of Etiologies in Male Factor Infertility
WHO Study 1994, Eshre Capri Workshop Group (7057 men)WHO Study 1994, Eshre Capri Workshop Group (7057 men)
EVALUATION OF MALE EVALUATION OF MALE INFERTILITYINFERTILITY HistoryHistory
Physical examination Physical examination
Semen analysis Semen analysis
Additional proceduresAdditional procedures
- Sperm function tests- Sperm function tests - Immunological tests- Immunological tests - Semen culture- Semen culture - Hormone assays - Hormone assays - Testicular biopsy- Testicular biopsy - Chromosomal analysis - Chromosomal analysis - Vasography- Vasography - Scrotal ultrasound- Scrotal ultrasound - Transrectal ultrasound (TRU)- Transrectal ultrasound (TRU) - DNA integrity tests - DNA integrity tests
HISTORYHISTORY
Age and duration of marriage Age and duration of marriage Occupation –hyperthermia, pesticides, bicycling, stressOccupation –hyperthermia, pesticides, bicycling, stress H/O childhood problems – Cryptorchidism – surgery H/O childhood problems – Cryptorchidism – surgery
Delayed pubertyDelayed puberty Medical History – Mumps, syphilis, leprosy, tuberculosis Medical History – Mumps, syphilis, leprosy, tuberculosis
Chronic respiratory diseases –Chronic respiratory diseases –
Young’s syndrome – epididymal obstruction Young’s syndrome – epididymal obstruction
Immotile cilia syndrome – Sperms are immotile Immotile cilia syndrome – Sperms are immotile
Cystic fibrosis – Congenital absence of VASCystic fibrosis – Congenital absence of VAS
Endocrine disorder, diabetes, hypothyroidism, Endocrine disorder, diabetes, hypothyroidism,
Renal failure, Liver disease, hypertension, multiple sclerosisRenal failure, Liver disease, hypertension, multiple sclerosis
HISTORY (Contd…)HISTORY (Contd…)
Surgical & Traumatic History – Damage of VAS – Surgical & Traumatic History – Damage of VAS – Hernia, Hernia,
Orchidopexy, Vasectomy, Trauma, Torsion, Spinal cord Orchidopexy, Vasectomy, Trauma, Torsion, Spinal cord injuryinjury
Sexual history – Timing, frequency ,conception windowSexual history – Timing, frequency ,conception window H/O–Erectile & Ejaculatory problem - H/O–Erectile & Ejaculatory problem -
Nocturnal penile trumescence (NPT)Nocturnal penile trumescence (NPT) Family history – Family history – History of smoking, alcohol, radiation, heavy metals, History of smoking, alcohol, radiation, heavy metals,
estrogen exposureestrogen exposure Drugs – Antipsychotic, Antihypertensives, Cimetidine Drugs – Antipsychotic, Antihypertensives, Cimetidine
Anticonvulsants, Sex steroids, Environmental Anticonvulsants, Sex steroids, Environmental exposures exposures
PHYSICAL EXAMINATION PHYSICAL EXAMINATION
General – Obesity, Secondary sexual character , gynaecomastia, Body General – Obesity, Secondary sexual character , gynaecomastia, Body habitus, Thyroid gland, Galactorrhoea, Visual field defect, Features of habitus, Thyroid gland, Galactorrhoea, Visual field defect, Features of endocrinopathyendocrinopathy
Per abdomen – Scar of hernia, lymph node Per abdomen – Scar of hernia, lymph node Local examination Local examination * Scrotum- hernia, hydrocele, varicocele * Scrotum- hernia, hydrocele, varicocele * Testes – Present or absent * Testes – Present or absent Size (18-20ml)Size (18-20ml) Sensation Sensation * Penis – Hypospadius, phimosis * Penis – Hypospadius, phimosis * Epididymis & VAS – Presence, feel, presence of cyst * Epididymis & VAS – Presence, feel, presence of cyst
* Rectal examination* Rectal examination
Varicocele
SEMEN ANALYSIS (WHO 1999) SEMEN ANALYSIS (WHO 1999)
Volume Volume > 2ml > 2ml
pH pH 7.2-7.8 7.2-7.8
Sperm concentration Sperm concentration ≥≥ 20milion/ml20milion/ml
Total sperm count Total sperm count ≥≥ 40milion40milion
Motility Motility ≥≥ 50% with normal 50% with normal
morphology morphology
MorphologyMorphology ≥≥ 30% normal forms 30% normal forms
WBCWBC < 1 X 10 < 1 X 1066 / ml / ml
MAR test MAR test < 10% spermatozoa with < 10% spermatozoa with
adherent particle adherent particle
SEMEN ANALYSISSEMEN ANALYSIS
ENDTZ test can distinguish between leukocytes & ENDTZ test can distinguish between leukocytes &
immature germ cells (both round cells) immature germ cells (both round cells)
Sperm vitality test: Sperm vitality test:
* Eosin Nigration test* Eosin Nigration test
* * Hypoosmotic swelling testHypoosmotic swelling test
* H33258 Flurochrome test* H33258 Flurochrome testFructose estimation-Absent in Ejaculatory duct obstructionFructose estimation-Absent in Ejaculatory duct obstruction
Split Ejaculate-Split Ejaculate-
Limitations of WHO criteria
Significant overlapping of sperm characteristics between fertile and infertile men
Sperm motility and concentration are more important than sperm morphology
Change of cut off values and introduction of new parameters are needed to differentiate between fertile and infertile men
Kiran P et al;Fertil Steril, vol 85,No 3,March 2006:629-34
MATURE SPERMATOZOA
SPERM FUNCTION TEST SPERM FUNCTION TEST
Sperm cervical mucus interactionsSperm cervical mucus interactions a. In Vivo – a. In Vivo – Post Coital TestPost Coital Test (Sim’s Hunner test) (Sim’s Hunner test) b. In Vitro – b. In Vitro – I. Sperm cervical mucus contact test (SCMC test)I. Sperm cervical mucus contact test (SCMC test) II. Tube test (Kremar test)II. Tube test (Kremar test) Hemizona test (Human zona binding assay) Hemizona test (Human zona binding assay) Hypoosmotic swelling testHypoosmotic swelling test Swim up testSwim up test Computerised assisted seminal analysis (CASA)Computerised assisted seminal analysis (CASA) Evidence of acrosomal reactionEvidence of acrosomal reaction
IMMUNOLOGICAL TESTS IMMUNOLOGICAL TESTS
Indications –
• Abnormal semen profile
• Abnormal cervical mucus sperm interaction
• Failed Vasectomy reversal
• Marked Agglutination (more than 10%)
Two Tests –
a. Immunobead testa. Immunobead test
b. MAR testb. MAR test
c. Others – TAT test, Kibrick’s test, Frankling Duke test, Isojama’s
test (Not done now a days)
MIXED AGGLUTINATION REACTION (MAR) TEST
Screening test for detection of antisperm antibodies on the surface of sperm head or tail.
Washed sperms from the patient are mixed with antibody coated RBC, (Sheep RBC + rabbit antibody)
These antibody will form mixed agglutinates with motile sperms carrying immunoglobulins
MAR test is positive when particulate binding is found in over 10% spermatozoa.
HORMONE ASSAYS HORMONE ASSAYS Indication-Indication- when Sperm count is less than 10 when Sperm count is less than 10
million/mlmillion/ml
FSHFSH LHLH TestosteroneTestosterone Estradiol Estradiol Prolactin Prolactin TSHTSH
HORMONAL CONTROL OF SPERMATOGENESISHORMONAL CONTROL OF SPERMATOGENESIS
HypothalamusHypothalamus
GGnnRHRH
Anterior PituitaryAnterior Pituitary
FSHFSH LHLH
Sertoli cellSertoli cell Leydig cellLeydig cell
InhibinInhibin ABGABG TT
ABG+TABG+T
- Ve- Ve - Ve- Ve
- Ve- Ve
SpermatogenesisSpermatogenesis and and spermsperm maturationmaturation
Hormones in different clinical Hormones in different clinical conditionsconditions
FINDINGS FINDINGS DIAGNOSISDIAGNOSIS
1.1. Azoospermia or OligospermiaAzoospermia or Oligospermia
Small testes Small testes
FSH - HighFSH - High
Primary testicular failure Primary testicular failure
(Severe tubular damage) (Severe tubular damage)
2. Azoospermia2. Azoospermia
Normal testicular volume Normal testicular volume
FSH – Normal level FSH – Normal level
i. Bilateral genital tract obstruction i. Bilateral genital tract obstruction
ii.Sertoli cell only syndrome ii.Sertoli cell only syndrome
3. FSH – Lower or undetectable 3. FSH – Lower or undetectable
LH – LowLH – Low
Testosterone – Low Testosterone – Low
Other evidences of androgen def. Other evidences of androgen def.
Hypogonadism Hypogonadism
4. LH – High4. LH – High
Testosterone – High Testosterone – High Androgen receptor defect Androgen receptor defect
TESTICULAR BIOPSYTESTICULAR BIOPSY
Obstructive AzoospermiaObstructive Azoospermia Non Obstructive Azoospermia – To detect isolated Non Obstructive Azoospermia – To detect isolated
areas containing sperm cells for TESE – ICSIareas containing sperm cells for TESE – ICSI
Grading – Johonson’s Scoring System ( 1 – 10)Grading – Johonson’s Scoring System ( 1 – 10)
2 – Sertoli cell only2 – Sertoli cell only
3 – Spermatogonia3 – Spermatogonia
4,5 – Spermatocytes 4,5 – Spermatocytes
6,7 – Spermatids 6,7 – Spermatids
8,9,10 – Spermatozoa 8,9,10 – Spermatozoa
Histology Of Normal Testis
Histology of seminiferous tubule
GENETIC ANALYSIS GENETIC ANALYSIS
IndicationsIndications Azoospermia, Severe Oligozoospermia, Azoospermia, Severe Oligozoospermia,
VarietiesVarieties Klinefelter’s Syndrome (47XXY), Sex Reversal Klinefelter’s Syndrome (47XXY), Sex Reversal
Syndrome (46 – XX male) Syndrome (46 – XX male) Deletion of a part of Long arm of Y containing Deletion of a part of Long arm of Y containing
azoospermic factor (AZF) means Azoospermia azoospermic factor (AZF) means Azoospermia Mutation of specific gene like mutation of CFTR geneMutation of specific gene like mutation of CFTR gene
in cystic fibrosisin cystic fibrosis
Y Chromosome in Azoospermic men
Solid bars indicate presence of genetic material
Dashed regions indicate missing of genetic material in NOA men
Y-chromosome deletion in AZFb region indicates absence of sperms in sperm retrieval procedure
Sex Chromosome Abnormalities Leading Sex Chromosome Abnormalities Leading to Male Infertility to Male Infertility
Syndrome Karyotpe abnormalities Phenotype
Klinefelter’s syndrome 46, XY/47, XXY mosaic, 47, XXY – 49, XXXY
Male with increased height, small firm testes possibly female hair distribution
Mixed gonadal dysgensis 45, X/ 46, XY mosaic, possibly normal 46, XY
Male, female, or ambiguous genitalia, testis are streak
XX male syndrome 46, XX SRY translocation to the short arm of X
Male with Sertoli-cell-only on testis biopsy
XYY male 47, XYY Male, possibly increased height
TREATMENT MODALITIES OF MALE TREATMENT MODALITIES OF MALE INFERTILITYINFERTILITY
• General Measures General Measures
• Medical ManagementMedical Management
• Surgical Management:- Surgical Management:- Vasovasostomy, Epididymovasostomy, Vasovasostomy, Epididymovasostomy,
Repair of varicocele, Orchidopexy, Surgery forRepair of varicocele, Orchidopexy, Surgery for Hypospadius Hypospadius
• Artificial Insemination:-Artificial Insemination:- Intrauterine insemination (IUI)Intrauterine insemination (IUI)
• Assisted Reproductive Technology:-Assisted Reproductive Technology:- IVF & ET, IVF & ET,
Intracytoplasmic sperm injection (ICSI),Intracytoplasmic sperm injection (ICSI), PESA, MESA & PESA, MESA & TESE – TESE – ICSI, GIFT, ZIFTICSI, GIFT, ZIFT
• Management of Male Sexual DysfunctionManagement of Male Sexual Dysfunction
Medical ManagementMedical Management
• Hormonal – Hormonal – HCG, HMG, GHCG, HMG, GnnRH, Testosterone, CC, RH, Testosterone, CC,
Thyroxine, BromocryptineThyroxine, Bromocryptine
• Antibiotics, Corticosteroids, Aromatase inhibitorAntibiotics, Corticosteroids, Aromatase inhibitor
• Sperm Vitalising Agents – Sperm Vitalising Agents – Pentoxifylline, KallikreinPentoxifylline, Kallikrein
• Emperical TherapyEmperical Therapy
• AntioxidantsAntioxidants – In increased ROS – In increased ROS
Oxidative stress status in an ejaculate. Oxidative stress status in an ejaculate.
Pro-and anti-oxidative molecules have antagonistic Pro-and anti-oxidative molecules have antagonistic functions in semenfunctions in semen
Vasectomy Reversal
Vasovasostomy
Repair of Vericocele
Verecocelectomy-Testis is delivered to ligate internal spermatic veins
INTRAUTERINE INSEMINATION
(I U I)
Washed sperms are injected inside the
uterine cavity in stimulated cycle with proper monitoring of ovulation
Both fresh or frozen sperm can be used
Male: SEMINOPATHIES – OLIGOSPERMIA,
ASTHENOTERATOSPERMIA, LOW VOLUME SEMEN, HIGH VISCOUS SEMEN
ERECTILE FAILURE, EJACULATORY FAILURE, PREMATURE EJACULATION, RETROGRADE EJACULATION
Female: CERVICAL FACTOR ,OVULATORY
DYSFUNCTION,ENDOMETRIOSIS,VAGINISMUS UNEXPLAINED INFERTILITY IMMUNOLOGICAL INFFERTILITY
INDICATIONS OF I U I
STEPS OF INTRA-UTERINE INSEMINATION
Ensure tubal patency Semen analysis & culture
Ovarian stimulation Sperm Collection
Monitoring of ovarian Response & fixation of Sperm processingOvulation time
Insemination & Luteal support
SWIM – UP TECHNIQUESWIM – UP TECHNIQUE
Semen processing media(Ham’s F-10)Semen processing media(Ham’s F-10)
&&
SEMEN SAMPLESEMEN SAMPLE
INCUBATE AT 370C
30 MINUTE
Liquefied semen sample
Equal Quantity of MEDIA
Aspirate upper & middle part
In another centrifuge tube
Centrifuge at 2000 RPM
FOR 1 MINUTEDiscard supermatant & Leave pellet
Centrifugation
at 2000 RPM
15 minute
Mix
wellDiscard supernatant
& leave pellet
MEDIAPellet
Keep the tube inclined at 300
In incubator at 370c
For 45 minute
Layer 2 ml Media
Over Pellet
Add 0.5 ml. Semen processing media
& mix well
Sample ready for IUI
SINGLE LAYER DENSITY GRADIENT CENTRIFUGATION TECHNIQUE
* DENSITY GRADIENT MEDIA
* SPERM WASHING * SEMEN SAMPLE
MEDIA (Han’s F10)
INCUBATE AT 370C
30 MINUTE
Centrifugation
At 2000 RPM
LIQUEFIED SEMEN
D.G. Media
15 minute
Disard Supermatant Centrifugation at 2000 RPM Pellet with 2ml Add 2ml. Spermwashing
& Leave pellet 5 minute Spermwashing medium
Medium mix well with pellet Discard supermatant & leave pellet
Add 0.5 ml. Of sperm washing medium
Mix well with pellet
Pellet with
0.5 ml. Sperm washing medium
Keep at 370c
10-15 minute Sample ready for IUI
SWIM UP TECHNIQUE Vs LAYER TECHNIOUE Simple Less expensive Not suitable for
abnormal semen sample
Time consuming
Not so simple More expensive For seminopathy it is
better Less time is needed
RESULTS OF IUI
CLINICAL PREGNANCY – 10-25% IN AIH 20-40% IN AID
20-25% END IN MISCARRIAGE
Gamete Micromanipulation
P Z D-Partial Zona dissection
S U Z I-Subzonal dissection of sperm
I C SI-Intracytoplasmic sperm injection
Intracytoplasmic sperm Intracytoplasmic sperm injection (ICSI)injection (ICSI)
It involves the direct insertion of a single sperm cell into It involves the direct insertion of a single sperm cell into the cytoplasm of a single oocyte by micropuncturethe cytoplasm of a single oocyte by micropuncture
Indications – Indications –
Severe OATSevere OAT
ObstructiveObstructive azoospermiaazoospermia by MESA, PESA,TESA by MESA, PESA,TESA ````Nonobstructive azoospermiaNonobstructive azoospermia (NOA)(NOA) by TESE by TESE
Unexplained infertilityUnexplained infertility
Source of Sperms for ICSI
EJACULATED SPERMS
MESA: Microsurgical Epididymal sperm aspiration
PESA: Percutaneous Epididymal sperm aspiration
TESE: Testicular sperm extraction
TESA: Testicular sperm aspiration
Distribution of sperms in tubules of epididymis in obst. azoospermia Proximal part contains
maximum good sperms Distal part (identified by
yellow colour) contains less and damaged sperms
P E S A
M E S A
Testicular Fine Needle Aspiration (TESA--TFNA)
PercBiopsy
MULTIPLE LARGE TEST. BIOPSY
T E S E Microsurgical
Conventional
ICSI Laboratory
ICSI IS GOING ON (IRM, Kolkata)
RESULTS OF ICSIRESULTS OF ICSI
Fertilization rate - Fertilization rate - 60-70%60-70%
Pregnancy rate – Pregnancy rate – 20-40%20-40% /Embryo transfer /Embryo transfer
Male partner having abnormal karyotype in Male partner having abnormal karyotype in
Y-Chromosome micro deletion should undergo Y-Chromosome micro deletion should undergo genetic counselling before ICSIgenetic counselling before ICSI
TREATMENT OF OLIGOASTHENOTERATOZOOSPERMIA TREATMENT OF OLIGOASTHENOTERATOZOOSPERMIA (OAT)(OAT)
Infective
* Antibodies
Immunological
* Corticosteroid
* Condom
Endocrinal
* GnRH
* hCG
* hMG
* Testosterone
* CC
* Bromocryptine
* Thyroxin
Idiopathic
* CC
* Empirical
*Antioxidants
If FailsIf Fails
* IUI
*ART
TREATMENT OF AZOOSPERMIA
Azoospermia
Obstructive
* Surgery
* Epididymal sperm
Aspiration (MESA, PESA)
IVF-ET
GIFT
ZIFT
ICSI
* TESE – ICSI
* TDI
Non obstructive
* TESE – ICSI
* TDI
Endocrinal (Rare)
* GNRH
* HCG
* HMG
* CC
Treatment of Erectile and Ejaculatory Dysfunction Erectile Dysfunction
* Withdrawal of drugs
* Treatment of underlying cause * Psychosexual therapy * Local injection ,Vacuum pump * Transurethral pellet ,Penile implant * Sildenafil(Viagra),Tadalafil,Vardenafil
Ejaculatory Dysfunction * Psychosexual therapy * Vibrator * Electro-Ejaculation
Retrograde Ejaculation * Coitus in full bladder * Alphaadrenergic or cholinergic drugs * Insemination with post-voided urine after processing
Premature Ejaculation * Use of condom
* Pelvic Floor exercise * Squeeze techniques * IUI with ejaculated sperm
CONCLUSION
Male factor is involved up to half of infertile couples
Thorough evaluation is needed to detect the abnormality.
There are only few cases in practice where specific drug therapy is indicated
Though IUI is an effective procedure it has little role in severe OAT.
ICSI has revolutionized the management of male
infertility. But it is a very expensive procedure
CONCLUSION (Contd…)
Sexual dysfunction should always be enquired and be dealt with sympathy
Vibrator and Viagra are two effective tools available in ejaculatory and erectile failure
More research is needed to know paracrine regulation of spermatogenesis and to develop newer treatment to improve sperm parameters in VIVO
Irrespective of problems adoption of general measure is important in achieving pregnancy