Male Infertility - How Gynaecologists can manage?
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Dr. Sujoy Dasgupta is a clinical director at the Genome Fertility Centre in Kolkata and has extensive qualifications and accolades in reproductive medicine. The document discusses male infertility, its assessment, treatment options, and various cases illustrating the complexities and successes in managing male fertility issues. It highlights the significance of semen analysis, lifestyle modifications, and the role of antioxidants in improving fertility outcomes.
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Male Infertility - How Gynaecologists can manage?
- 1. Dr Sujoy Dasgupta MBBS (Gold Medalist, Hons) MS (OBGY- Gold Medalist) DNB (New Delhi) MRCOG (London) Advanced ART Course for Clinicians (NUHS, Singapore) M Sc, Sexual and Reproductive Medicine (South Wales, UK) Clinical Director, Genome Fertility Centre, Kolkata Managing Committee Member, BOGS, 2024-25 Clinical Examiner, MRCOG Part 3 Examination Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019 Delivered, Dr Kamini Rao Oration, AICOG, 2024 Peer reviewer- Fertility & Sterility, BMJ Case reports, JOGI, Clinical Urology, Journal of Men’s Health Male Infertility- How Gynaecologists Can Manage?
- 2. Do we understand- “Male Infertility?”
- 3. Men’s fertility potential depends on female factors • Assessment of tests and treatments for the male is challenging due to inconsistent endpoints and the observation that many of these endpoints are dependent upon and measured from the female partner. • Ideally, the endpoint for fertility trials should be "live birth or cumulative live birth” (WHO, 2021)
- 4. Limitations of WHO 2010 Guideline • Based on parameters in a large group of fertile men along with defined confidence intervals from recent fathers with known time-to-pregnancy (TTP). • The WHO does not consider the values set as true reference values but recommends or suggests acceptable levels. • Day to day variation • Functional ability of the sperms?
- 5. We cannot treat We bypass
- 6. Disclaimer • Written inform consent from all the patients • Conflict of interest- None
- 7. Case 1
- 9. Case 2 Collection Method Masturbation Total Motility 41% Abstinence 4 days Progressive Motility 26% Collection Complete Non progressive Motility 15% Volume 2 ml Immotile 59% Viscosity Normal Motile Sperm Count 14.76 million Liquefaction Time 45 minutes Normal Morphology 5% pH 7.6 Abnormal Morphology 95% Sperm Concentration 18 million/ ml Vitality 62% Sperm count 36 million/ ejaculate Round cells Nil
- 10. Case 2 Collection Method Masturbation Total Motility 41% Abstinence 4 days Progressive Motility 26% Collection Complete Non progressive Motility 15% Volume 2 ml Immotile 59% Viscosity Normal Motile Sperm Count 14.76 million Liquefaction Time 45 minutes Normal Morphology 5% pH 7.6 Abnormal Morphology 95% Sperm Concentration 18 million/ ml Vitality 62% Sperm count 36 million/ ejaculate Round cells Nil
- 12. Points to note in semen report Volume 1.4 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.2 Sperm Concentration 16 million/ ml Sperm count 39 million/ ejaculate Total Motility 42% Progressive Motility 30% Non progressive Motility 12% Immotile 58% Normal Morphology 4% Vitality 54% Round cells Nil 1 2 3 4 5 6
- 13. Case 3 Collection Method Masturbation Total Motility 46% Abstinence 4 days Progressive Motility 33% Collection Complete Non progressive Motility 13% Volume 2 ml Immotile 54% Viscosity Normal Motile Sperm Count 33.12 million Liquefaction Time 45 minutes Normal Morphology 5% pH 7.6 Vitality 32% Sperm Concentration 36 million/ ml Pus cells 10-12/hpf
- 14. Case 3 Collection Method Masturbation Total Motility 46% Abstinence 4 days Progressive Motility 33% Collection Complete Non progressive Motility 13% Volume 2 ml Immotile 54% Viscosity Normal Motile Sperm Count 33.12 million Liquefaction Time 45 minutes Normal Morphology 5% pH 7.6 Vitality 32% Sperm Concentration 36 million/ ml Pus cells 10-12/hpf
- 15. Case 3 (Contd) • Apparently unexplained infertility • Male- 36 years • No apparent risk factors for infertility • Ignore • Antibiotics (empirically) • Culture of semen • Further tests
- 16. Disclosed “pain during intercourse” • Diagnosed to be diabetic • Pus cells disappeared after circumcision • Conceived after OI
- 17. Male Accessory Gland Infection (MAGI)
- 18. Leucocytospermia EUA, 2018; ASRM, 2020; Vignera et al., J Med Microbiology, 2014 • The clinical significance is controversial. • Special Tests- Round cells vs Pus cells • Method of collection • Hand washing before collection • Culture of semen • Antibiotics- only when documented infections • Routine antibiotics- can harm • Consider prostatic fluid culture
- 19. Case 4 • 26 yr, smoker • Concentration 14 million/ml, motility 35%, pus cells 8-10/ hpf • Acute Rt scrotal pain • After antibiotics- symptoms subsided, semen became normal • Conceived after IUI+
- 20. “Pus Cells” and ART outcome
- 21. Case 5 • Trying for pregnancy for 3 years • Woman- regular cycle, no dysmenorrhoea • AMH 2.8 ng/ml; tubes patent in HSG • Semen- “normozoospermia” as per WHO • Do further tests in male partner • Give some medicines
- 23. Treatment options for high DFI (Agarwal et al., World J Mens Health. 2020) • ICSI with TESA • MACS, IMSI • Varicocelectomy • Treat infection • Control weight, diabetes • Quit smoking • Antioxidants • Frequent ejaculation
- 24. SDF Testing Indications Infertile men with: • Repeated IUI or IVF failure • Recurrent spontaneous miscarriages (ESHRE, 2018) • Previous low fertilization, cleavage or blastulation rate • Varicocele with normozoospermia • Advanced male age (>40 y) Significance of SDF • Live birth after IUI/ IVF/ ICSI- ? • Oocytes can repair the damaged DNA • Lack of standardization • Lack of definitive treatment
- 25. Don’t advise any test if you do not know what to do with the result !!!
- 26. Oxidative Stress in Subfertility I n f e r t i l i t y Oxidative stress (OS) is an imbalance in a cell’s production of Free radicals( oxidants) of intrinsic or extrinsic origin, and its ability to reduce them with scavengers.
- 28. Smits RM, Mackenzie-Proctor R, Yazdani A, Stankiewicz MT, Jordan V, Showell MG. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2019;3(3):CD007411. • May improve live birth rates • Clinical pregnancy rates may also increase • Overall, there is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal upsets • Subfertilte couples should be advised that overall, the current evidence is inconclusive.
- 29. • In some studies, AS was found to be beneficial in reversing OS- related sperm dysfunction and improving pregnancy rates. • The most commonly used preparations, either as monotherapy or in combination as multi-AS, were: vitamin E (400 mg), carnitines (500–1000 mg), vitamin C (500–1000 mg), CoQ10 (100–300 mg), NAC (600 mg), zinc (25–400 mg), folic acid (0.5 mg), selenium (200 mg), and lycopene (6–8 mg). • Still debatable due to the heterogeneity in study designs and the multifactorial genesis of infertility.
- 30. Case 6 • P0+2, all early miscarriage, no H/O subfertility • Female-28, Male- 34 • Karyotypes of both normal • Female- 3-D USS, APLA, TSH, sugar- normal • DFI 40% • Advised TESA-ICSI or donor sperms elsewhere because of high SDF • Subclinical varicocele • Conceived spontaneously, delivered
- 31. Case 7 Collection Method Masturbation Total Motility 35% Abstinence 4 days Progressive Motility 17% Collection Complete Non progressive Motility 18% Volume 2 ml Immotile 65% Viscosity Normal Motile Sperm Count 8.4 million Liquefaction Time 45 minutes Normal Morphology 3% pH 7.6 Vitality 62% Sperm Concentration 12 million/ ml Round cells Nil
- 32. Case 7 Collection Method Masturbation Total Motility 35% Abstinence 4 days Progressive Motility 17% Collection Complete Non progressive Motility 18% Volume 2 ml Immotile 65% Viscosity Normal Motile Sperm Count 8.4 million Liquefaction Time 45 minutes Normal Morphology 3% pH 7.6 Vitality 62% Sperm Concentration 12 million/ ml Round cells Nil
- 33. What’s next? • Detailed evaluation? • How severe? • Repeat semen analysis? • Some “medicines”? • Lifestyle changes?
- 34. Male Infertility- Mild or Severe? • TMSC= Total Motile sperm count = • Sperm concentration x total volume x total motility (16 mil/ml x 1.4 ml x 42%) • TMSC >5/ 10/ 20 million
- 35. Mild Male Factor • Investigations- NOT usually recommended • Antioxidants • CC • Other adjuvant Lifestyle changes 1. Heat exposure to scrotum 2. Obesity 3. Food habit 4. Smoking 5. Alcohol 6. Anabolic steroids 7. Chronic scrotal fungal dermatitis (EUA, 2018; ASRM, 2020)
- 36. When to repeat semen analysis? • Mild problems- After 3 months • Severe problems- ASAP (NICE, 2013; EUA, 2018; ASRM, 2020)
- 37. Case 7 details • Persistent mild male factor • Stopped smoking • Not willing for IUI • H/O repeated attacks of Tinea crusis • Dermatology referral • Topical and systemic antifungal • Sperm parameters normalized • Conceived spontaneously, miscarried 12/40
- 38. Case 8 Collection Method Masturbation Total Motility 46% Abstinence 4 days Progressive Motility 33% Collection Complete Non progressive Motility 13% Volume 2 ml Immotile 54% Viscosity Normal Motile Sperm Count 33.12 million Liquefaction Time 45 minutes Normal Morphology 3% pH 7.6 Vitality 32% Sperm Concentration 36 million/ ml Round cells Nil
- 39. Case 8 Collection Method Masturbation Total Motility 46% Abstinence 4 days Progressive Motility 33% Collection Complete Non progressive Motility 13% Volume 2 ml Immotile 54% Viscosity Normal Motile Sperm Count 33.12 million Liquefaction Time 45 minutes Normal Morphology 2% pH 7.6 Vitality 32% Sperm Concentration 36 million/ ml Round cells Nil
- 40. Isolated teratozoospermia • Isolated abnormal morphology is not the indication for ART Penn HA, Windsperger A, Smith Z, et al. Fertil Steril. 2011; 95(7):2320–3.
- 41. Case 9 Collection Method Masturbation Total Motility 30% Abstinence 4 days Progressive Motility 16% Collection Complete Non progressive Motility 14% Volume 1.5 ml Immotile 70% Viscosity Normal Motile Sperm Count 0.54 million Liquefaction Time 45 minutes Normal Morphology 1% pH 7.6 Vitality 34% Sperm Concentration 1.2 million/ ml Round cells Nil
- 42. Case 9 Collection Method Masturbation Total Motility 30% Abstinence 4 days Progressive Motility 16% Collection Complete Non progressive Motility 14% Volume 1.5 ml Immotile 70% Viscosity Normal Motile Sperm Count 0.54 million Liquefaction Time 45 minutes Normal Morphology 1% pH 7.6 Vitality 34% Sperm Concentration 1.2 million/ ml Round cells Nil
- 43. Severe male factor- What’s next? • Donor sperm IUI • Antioxidants for 3-6 months, then review • ICSI directly?
- 44. Case 9 details • 2012- Initially 1.2 mil/ml, then 4 million/ ml • 2013- 0.5 mil/ml • Years after years- different brands of antioxidants, CC • 2016- Azospermia (repeatedly) • 2016- FNAC- hypospermatogenesis • 2018- FSH 5.36, LH 4.6, Testo 537, E2 26 • Testicular size normal • Karyo 46,XY; Y chromosome- no microdeletion • 2019- TESE- No sperms obtained, ICSI done with donor sperms- conceived, delivered
- 45. Severe Male Factor- if not left untreated ??? • Overall, 16 (24.6%) of 65 patients with severe oligozoospermia developed azoospermia. • Two (3.1%)patients with moderate oligozoospermia developed azoospermia • None of the patients with mild oligozoospermia developed azoospermia.
- 46. Severe male factor- What’s next? • Donor sperm IUI • Antioxidants • ICSI directly? • Investigate in details√ • History • Physical Examination • Hormone Assay • Imaging • Genetic Tests
- 47. Severe Male Factor is NOT ONLY a fertility problem • Diabetes • Cardiovascular diseases • Lymphoma, extragonadal germ cell tumours, peritoneal cancers • Repeated hospitalization • Increased mortality • Testicular Cancer Choy and Eisenberg, 2020; Bungum et al., 2018; Eisenberg et al., 2013; Jungwirth et al., 2018; Hotaling and Walsh, 2009 Self-Testicular Examination •Atrophic Testes •H/O undescended testicles •Testicular microcalcification (post-mumps or others)
- 48. Case 10 • 31 yrs • Came for IUI (D) • Too reluctant for physical examination • Malignant teratoma- treated by orchidectomy and chemotherapy • Later- adopted a baby
- 49. Revisiting History • Age • Duration of subfertility • Previous pregnancy- can have secondary male subfertility • Lifestyle • Occupation- Driving, IT, chemical industry (heavy metal, pesticides) • Medical history- Diabetes, Mumps, Cancer • Surgical history- Hernia, Orchidopexy, Pituitary Surgery, Bladder neck surgery • Drug history- Sulphasalazine, Finesteride, cytotoxic drugs, steroids • Sexual history- Low libido, ED
- 50. Case 10-11 • Secondary subfertility of 6 yrs • Previous- one male baby, 10 yrs, natural conception • Only female was evaluated initially (including Lap dye test) • Male- azoospermia on repeated occasions • Diabetic for 7 yrs, uncontrolled • Endocrine, imaging all normal • Lost to F/U • Secondary subfertility of 10 yrs • Previous- one male baby, 12 yrs, natural conception; followed by 2 TOP • Only female was evaluated initially- multiple cycles of OI with CC, letrozole, hMG • Varicocele surgery 10 yr ago • Male- Severe OAT on several occasions • Endocrine, imaging all normal • Planning for ICSI
- 51. Case 12 • Secondary subfertility • Koch’s abscess in Right testicle • Repeated I/D • Finally right orchidectomy • Azoospermia • TRUS- Right ejaculatory duct cystic and widely dilated • Waiting for TESA ICSI
- 52. Case 12 •Referred for TESA after investigations •Rt sided orchidopexy during appendicectomy at 18 yr •Subsequently Rt testis atrophied •Lt side operated after 6 months, could not be brought to scrotum, biopsied, seen by USG at lower abd
- 53. Darren et al. Male infertility – The other side of the equation . 2017
- 54. Case 13 • 34-yrs-old, Army-man, past smoker • Repeated analysis- 100% immotile sperms • Advised varicocelectomy outside • No palpable varicocele • Went for ICSI • Ejaculated sperms- poor morphology • TESA- ICSI done, Conceived but miscarried 14/40.
- 55. Varicocele- always CLINICAL Diagnosis (EUA, 2018) • Subclinical: not palpable or visible, but can be shown by special tests (Doppler ultrasound). • Grade 1: palpable during Valsava manoeuvre, but not otherwise. • Grade 2: palpable at rest, but not visible. • Grade 3: visible at rest
- 56. Surgery for Varicocele (EUA, 2018) • Grade 3 varicocele • Ipsilateral testicular atrophy • Pain • Abnormal semen parameters • No other fertility factors in the couple
- 57. In couples seeking fertility with ART, varicocele repair • may offer improvement in semen parameters • may decrease level of ART needed
- 58. Case 14 • 35 yr- Azoospermia • Lt undescended testis • 19 yr age- Lt orchidopexy • 21 yr age- left testicular cancer (mixed germ cell Tx)→ orchidectomy, f/b 3 cycles of chemotherapy (BPC) • 33 yr age-Papillary Ca Thyroid→ Total thyroidectomy and neck LN dissection f/b Radio-iodine. Now on Eltroxin 150 • FSH 27.14, LH 6.69, Testosterone 336 ng/dl, E2 26.0 pg/ml. • Female age 35
- 59. 46,X,Yqh- Case 15 • Female- Grade IV endometriosis • AMH 0.9 ng/ml
- 60. Case 16 • 42-yr male, office worker • Severe OAT • Hypergonadotrophic hypogonadism • Twin brother having same problem • Can’t afford ICSI • Opted for IUI (D) • Lost to follow up
- 61. Case 17 • 28 years • Nonobstructive azoospermia • Testo 74.47, LH 17.25, FSH 29.91 • H/O Laparotomy for GI perforation , 17 yr age • 3 cycles IUI (D) failed • Conceived after first cycle of IVF with donor sperms- now 24/40, twin pregnancy
- 62. Case 18 • 31 yr • Azoospermia • USG- Rt testis in lower abdomen, Lt testis in inguinal canal • FSH 13.40. LH 6.87. Testo 6.89. E2 <10.
- 63. Case 19-24
- 64. Case 25-30
- 65. Case 31-32 Post-orchidopexy Almost normal count Post-orchidopexy Azoospermia
- 66. Cryptorchidism in adults (EUA, 2018) • In adulthood, a palpable undescended testis should NOT be removed because it still produces testosterone. • Correction of B/L cryptorchidism, even in adulthood, can lead to sperm production in previously azoospermic men • Perform testicular biopsy at the time of orchidopexy in adult- to detect germ cell neoplasia in situ
- 67. Case 33 Transverse testicular ectopia (TTE) or crossed testicular ectopia (CTE)
- 69. Case 35 • 36 yr • Apparently unexplained infertility • Multiple cycles of OI • C/O inability to deposit sperms in the vagina • Multiple operations for hypospadias • Conceived after 1st cycle of IUI (H), delivered
- 70. Case 36
- 71. Imaging Scrotal ultrasound 1. Clinically abnormal findings- mass/ atrophy 2. Tight scrotum (Cremasteric reflex) 3. Obese patient • NOT for Varicocele detection • NOT the replacement for clinical examination (EUA, 2018; ASRM, 2020) Transrectal ultrasound (TRUS) 1. Low volume and pH of semen 2. Ejaculatory disorders (EUA, 2018; ASRM, 2020)
- 72. Case 37 • Azoospermia initially • On the day of IVF- few sperms in the ejaculate • ICSI done • Conceived after 1st cycle • Twin- sIUFD, one live birth
- 73. Case 38-39
- 74. Epididymal cysts •NOT associated with infertility •Surgery may cause obstruction Weatherly D, et al. Epididymal Cysts: Are They Associated With Infertility? Am J Mens Health. 2018
- 75. Case 40 • Mumps orchitis 20 years age • Biopsied during TESA • No sperms obtained • Conceived with IVF with sperm donation
- 76. Case 41 • Left cryptorchidism (abdominal testis) • Lt orchidectomy at 12 yr • Testicular prosthesis • Azoospermia • Opted for AID
- 77. Hormone Evaluation Sperm concentration <10 million/ml Sexual dysfunction Clinically suspected endocrinopathy FSH, LH, testosterone, HbA1C FSH, LH low Testosterone low Hypogonadotropic hypodonadism Pituitary imaging FSH high LH high Testosterone low Global testicular failure LH normal Testosterone normal Spermatogenesis defect LH high Testosterone normal Sublinical hypogonadism PRL, TSH If clinically suspected
- 78. Role Of Medical Therapy (EUA, 2018, ASRM, 2020) Hypogonadotropic hypodonadism •hCG 2000-5000 IU 3 times a week •If hCG alone cannot restore spermatogenesis, FSH is added 75-150 IU 3 times a week •Serum testosterone and semen analysis every 1–2 months •Usual time to recover 6 – 12 months (may take 24 months) •Often conceives at lower sperm concentration Idiopathic Male infertility CC Tamoxifen Letrozole hCG All empirical Evidences? Testosterone supplementation Strongly CONTRAINDICATED Feedback inhibition on FSH, LH→ secondary hypogonadism Aromatase inhibitors (Letrozole, Anastrozole) If T:E2 ratio <10 (T- ng/dl, E2- pg/ml)
- 79. FSH Testosterone Semen Diagnosis Treatment APHRODITE Group 1 Low Low Abnormal including Azoos Hypogonadotropic hypogonadism hCG (+ FSH if needed) APHRODITE Group 2 Normal Normal (≥350 ng/dl) Abnormal including Azoos Reduced Gonadotropin action, functional hypogonadism FSH only APHRODITE Group 3 Normal Low Abnormal including Azoos Reduced Gonadotropin action, biochemical hypogonadism FSH (+hCG) APHRODITE Group 4 High Normal/ Low Abnormal including Azoos Functional hypogonadism hCG (+ FSH if needed) APHRODITE Group 5 Normal Normal (≥350 ng/dl) Normal Unexplained couple infertility ?FSH only APHRODITE Criteria, RBMO, 2024 Addressing male Patients with Hypogonadism and/or infeRtility Owing to altereD, Idiopathic TEsticular function
- 80. Genetic tests in testicular failure • The spermatozoa of infertile men show an increased rate of aneuploidy, structural chromosomal abnormalities, and DNA damage • Carrying the risk of passing genetic abnormalities to the next generation (AUA, 2018) • Karyotype • Y chromosome microdeletion
- 81. TMSC PR/CYCLE 10–20 million 18.29% 5–10 million 5.63% <5million 2.7% Guven et al, 2008;Abdelkader & Yeh, 2009 Criteria TMSC Treatment Pre wash TMSC > 5 million IUI Pre wash TMSC 1 - 5 million IVF Pre wash TMSC <1 million ICSI Male factor- IUI, IVF or ICSI?
- 82. TMSC <5 mil/ml and IUI • Counsel before IUI 1. Double Ejaculate Kucuc et al., 2004; Oritz et al., 2016 2. “Trial IUI”- Post wash- IMSC Ombelet et al., 2014 3. IMSC >1 mil/ml → Further IUI 4. IMSC <1 mil/ml → ICSI
- 83. ICSI with Ejaculate vs Testicular sperms
- 84. Case 42 Collection Method Masturbation Abstinence 5 days Collection Complete Volume 3.0 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.8 Sperm Concentration Nil (even after centrifugation) Round cells Nil
- 85. Case 42 Collection Method Masturbation Abstinence 5 days Collection Complete Volume 3.0 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.8 Sperm Concentration Nil (even after centrifugation) Round cells Nil
- 86. Azoospermia- What’s next? • Donor sperm IUI? • Testicular FNAC/ Biopsy? • ICSI directly?
- 87. FNAC- role? • Isolated foci of spermatogenesis ASRM, 2020 • Consider TESA in indeterminate cases- NOT NECESSARY FSH >7.6 <7.6 Testicular long axis (cm) <4.6 >4.6 89% chance of NOA 96% chance of OA
- 89. Problems with indiscriminate FNAC • Repeat test showed SC 3-4 sperms/ hpf • Repeat semen analysis- 58 mil/ml, TM 48%
- 90. Case 42 (Contd) • Azoospermia- one occasion • FNAC- B/L maturation arrest • FSH 0.22, LH 0.34, Testo 549 • Pituitary MRI- normal • Started hMG • After 6 months- 2 mil/ml
- 91. Case 43 • 32 year • H/O delayed puberty • Was on TRT (17-23 yr age) • Gynaecomastia surgery, 22 yr • LH 0.06, FSH 0.02, Testo 0.63, PRL 1.18, TSH 2.48 • Low libido, ED • Anosmia • MRI- B/L olfactory bulb absent • Genetic tests advised • Lost to follow up
- 92. Case 44 • 30 yr, azoospermia • 17 yr age, sudden testicular atrophy, started testo 250 mg IM monthly injection from 23 yr age • B/L testes 6 cc each • FSH 1.11, LH 0.26, Testo 194 • ACTH, cortisol, PRL- all normal • Advised HRT • Lost to follow up
- 93. Case 45 • 35 yr • 2019- sudden loss of body hair, low libido→ nonfunctioning Pituitary macroadenoma → Endoscopic surgery H/P Lymphocytic hypophysitis • Sexual function and sec sex characters improved after Sx • On cortisol, L-thyroxine supplementation • Azoospermia diagnosed • Started hCG f/b hMG by endocrinologist • Sperm conc 1-2/ hpf after 4 months • After 8 months- 8 mil/ml • IUI planned
- 94. Case 46 • FNAC- B/L maturation arrest • FSH 37.2, LH 24.4, Testo 245.53, E2 37, ratio <10 • Not keen for IVF- ICSI-PGT
- 95. Case 46 (Contd)
- 96. Case 47
- 97. Case 48-51
- 98. Case 52-54
- 99. Sex Chromosome abnormalities • The most common - the Klinefelter’s syndrome (KS) • 47,XXY or 46,XY/47,XXY mosaicism • KS mosaic can have variable extent of germ cell production inside the testicles • Sperms carrying abnormalities in sex chromosomes (24,XY sperms) and autosomes (disomy for chromosomes 13, 18 and 21) • Needs PGT-A
- 100. Case 55-56 45, XY rob (14, 21), (q10, q10) Azoospermia Robertsonian Translocation 46,XY;t(2:22)(q37;q11.21) Severe OAT Reciprocal Translocation
- 101. Case 57 46,XY22ps+ • Oligospermia →Azoospermia • YCM normal • Spermes obtained by TESA Amniocentesis • Normal Karyo & CMA • Live born by 34/40
- 102. Case 58 • FISH- more accurate risk estimation of affected offspring • Limited role clinically • Only specific indication- Macrocephalia (Themset et al., 2009)
- 103. Case 59-62 46,XY,t(15:17) (q10;q10) 46,XY;t(2:22)(q37;q11.21) 45,XY,der(13;14)(q10;q10) 46,X,del(Y)(q11.23)
- 104. Case 63 46,XY, dup(9)(q11-q12) • Duplication of long arm of chromosome 9- partial trisomy • FNAC B/L Late maturation arrest • Family History of Azoospermia in a) Own brother b) 2 maternal uncles c) 2 Cousin brothers (of same maternal aunt)
- 107. Case 70 • 37 yr • Inguinal hernia operated Rt sided- 2 yr ago and Lt sided15 yr ago • B/L testes- 18 cc each • FSH 5.96. LH 4.74. Testo 212. Estradiol 14.22. • FNAC- Sertoli cell only
- 108. Y chromosome microdeletion (EUA, 2018) • Most common genetic defect in male infertility after KS • Never found in normozoospermic men • Highest frequency in azoospermic men (8-12%), followed by oligozoospermic (3-7%) men. • Extremely rare with a sperm concentration > 5 million/mL (~0.7%). • AZFa- Sertoli cell only syndrome • AZFb- maturation arrest • AZFc - variable phenotype
- 109. Negative YCM Report
- 110. Positive YCM report
- 111. Case 71-72
- 112. Case 73-74
- 113. Case 75
- 115. Case 77-79 46,X,del(Y)(q11.23) 46,X,del(Y)(q11.2) 46,X,+mar
- 116. Case 80 Mos45,X[12]/46,XY[28]; AZFa deleted
- 117. • 39 yr • FSH 25.4, LH 12.6, Estradiol 14, Testo 61. Case 81
- 118. Case 81 (Contd)
- 119. Case 83 • LH 30.10, FSH 43.70, E2 38.48, Testo 432
- 120. Genetic testing • Sperm concentration <5 million/ml • Azoospermia • Testicular atrophy • Elevated FSH • Karyotyping • Y chromosome Microdeletion (YCM)
- 121. In presence of genetic defect • PGT-SR (previously- PGD) • Prenatal invasive testing (EUA, 2018; ASRM, 2020)
- 122. Case 84 • 1 mil/ml • Diabetic • Idiopathic hypo/hypo • hCG and FSH started • Finally 16 mil/ml • 2 times IUI (H) • Both early miscarriage • APLA negative • Couple karyotype done 46,XY,t(3;7)(p25 ;q22)
- 123. Surgical Sperm Retrieval (SSR) in Azoospermia (OA>NOA)
- 124. Case 85-86 • 42 yr • FSH 43.56 • Karyo, YCM normal • Trial TESA- Motile sperms obtained • ICSI done, conceived, delivered 35/40 • 26 yr • FSH 5.7 • Karyo, YCM normal • Trial TESE- No sperms obtained • Refused donor sperms
- 125. Predictors of sperm retrieval? • FSH • Testicular Size • LH, Testosterone • BMI • AMH- semen, serum • Inhibin B- semen, serum • Age • Ultrasound parameters • No reliable positive prognostic factors guarantee sperm recovery for patients with NOA • The ONLY negative prognostic factor is the presence of AZFa and AZFb microdeletions.
- 126. Case 87 • 36 yr • FNAC B/L- Maturation arrest • Karyo, YCM done • Surgical sperm retrieval? 46,X,inv(Y)(p11q13)
- 128. If previous FNAC was done (Schwarzer, 2013) Diagnosis Chance of sperm retrieval (Micro-TESE >> TESE) Sertoli-cell-only syndrome (Germ cell hypoplasia) 32% Maturation arrest 66.7% Hypospermatogenesis 100% Tuberous sclerosis 33.3% Mixed atrophy 95.2%
- 129. Case 88 • 33 yr • Secondary anejaculation and ED • B/L abdominal testes • 3 yr age- attempted Rt orchidopexy but failed • 13 yr age- Left sided orchidopexy attempted but partial success. • 32 yr age- B/L orchidectomy after failed orchidopexy attempt
- 130. Case 89 Collection Method Masturbation Abstinence 2 days Collection Complete Volume 0.5 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 6.8 Sperm Concentration Nil (even after centrifugation) Round cells Nil
- 131. Case 89 (Contd) Collection Method Masturbation Abstinence 2 days Collection Complete Volume 0.5 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 6.8 Sperm Concentration Nil (even after centrifugation) Round cells Nil
- 132. Assess • Abstinence period • Completeness of collection • Usual amount of ejaculate • Exclude retrograde ejaculation • Suspect obstructive pathology- TRUS • Clinical assessment???
- 133. Case 89 (Contd) • TRUS- • B/L agenesis of seminal vesicles • Male partner- CFTR carrier • Female partner- CFTR carrier
- 134. Congenital bilateral absence of vas deferens (CBAVD) • Semen- Volume <1.5 ml, pH <7.0, fructose negative • TRUS • Renal ultrasound • Cystic fibrosis mutation (CFTR) testing (EUA, 2018; ASRM< 2020) • Partner testing • Indian prevalence- 1:10,000- 1:40,000 (Kapoor et al., 2006; Prasad et al., 2010)
- 135. CBAVD is NOT uncommon CFTR negative CFTR carrier; Wife- normal CFTR refused Both partners CFTR carrier CFTR negative CFTR carrier; Wife- normal
- 136. Genetic testing • CFTR testing in CBAVD • Karyotyping • Y chromosome Microdeletion (YCM)
- 137. Surgical Management of obstructive azoospermia • Vasovasostomy • Vasoepididymostomy • Transurethral resection of ejaculatory ducts in EDO • Patent tract ≠ Conception Baker and Sabanegh, 2013
- 138. Case 90 • Delayed puberty • Testo 100.86. FSH 28.33. LH 13.65. E2 27.83 • Testosterone injection started at puberty - sec sex charac, voice, genital size improved • MRI pitutary microadenoma • GH, TSH, Cortisol, PRL, - all normal
- 139. Targeted female investigations • If no risk factors for tubal block- 3 cycles of IUI, then tubal patency test • If risk factors- tubal patency first •Ovaries •Tubes- IUI or IVF/ICSI?
- 140. Meticulous semen analysis in a standard laboratory Physical examination and rational investigations Avoid non-evidence based drugs for long time Donor sperm is NOT the only solution IUI or ICSI- depends on the overall assessment Take Home Messages
- 141. Semen analysis Mild problem Severe problem 1. Lifestyle changes 2. Antioxidants 1. History 2. Physical Exam 3. Repeat semen ASAP 4. Hormonal evaluation Low FSH, LH Pituitary imaging hCG/ FSH supplementation High FSH Karyotype YCM ICSI TESA for azoospermia Donor sperms Repeat semen after 3 months Normal hormones Cannot afford ICSI No sperms in TESA S/O obstruction Idiopathic Obstructive Azoo TRUS CFTR test for CBAVD Pituitary failure Testicular failure
- 142. Semen analysis Mild problem Severe problem 1. Lifestyle changes 2. Antioxidants 1. History 2. Physical Exam 3. Repeat semen ASAP 4. Hormonal evaluation Low FSH, LH Pituitary imaging hCG/ FSH supplementation High FSH Karyotype YCM ICSI TESA for azoospermia Donor sperms Repeat semen after 3 months Normal hormones Cannot afford ICSI No sperms in TESA S/O obstruction Idiopathic Obstructive Azoo TRUS CFTR test for CBAVD Pituitary failure Testicular failure
- 143. Semen analysis Mild problem Severe problem 1. Lifestyle changes 2. Antioxidants 1. History 2. Physical Exam 3. Repeat semen ASAP 4. Hormonal evaluation Low FSH, LH Pituitary imaging hCG/ FSH supplementation High FSH Karyotype YCM ICSI TESA for azoospermia Donor sperms Repeat semen after 3 months Normal hormones Cannot afford ICSI No sperms in TESA S/O obstruction Idiopathic Obstructive Azoo TRUS CFTR test for CBAVD Pituitary failure Testicular failure
- 144. Semen analysis Mild problem Severe problem 1. Lifestyle changes 2. Antioxidants 1. History 2. Physical Exam 3. Repeat semen ASAP 4. Hormonal evaluation Low FSH, LH Pituitary imaging hCG/ FSH supplementation High FSH Karyotype YCM ICSI TESA for azoospermia Donor sperms Repeat semen after 3 months Normal hormones Cannot afford ICSI No sperms in TESA S/O obstruction Idiopathic Obstructive Azoo TRUS CFTR test for CBAVD Pituitary failure Testicular failure
- 145. Semen analysis Mild problem Severe problem 1. Lifestyle changes 2. Antioxidants 1. History 2. Physical Exam 3. Repeat semen ASAP 4. Hormonal evaluation Low FSH, LH Pituitary imaging hCG/ FSH supplementation High FSH Karyotype YCM ICSI TESA for azoospermia Donor sperms Repeat semen after 3 months Normal hormones Cannot afford ICSI No sperms in TESA S/O obstruction Idiopathic Obstructive Azoo TRUS CFTR test for CBAVD Pituitary failure Testicular failure
- 146. Semen analysis Mild problem Severe problem 1. Lifestyle changes 2. Antioxidants 1. History 2. Physical Exam 3. Repeat semen ASAP 4. Hormonal evaluation Low FSH, LH Pituitary imaging hCG/ FSH supplementation High FSH Karyotype YCM ICSI TESA for azoospermia Donor sperms Repeat semen after 3 months Normal hormones Cannot afford ICSI No sperms in TESA S/O obstruction Idiopathic Obstructive Azoo TRUS CFTR test for CBAVD Pituitary failure Testicular failure
- 147. Treatment burden for MALE infertility falls on FEMALE