Male Infertility- What works and what does not

Male infertility is NOT a single disease. Therefore, the investigations and treatment are not straightforward. Every case should be managed on an individualized basis.
1. Physical examination can pick out congenital bilateral absent vas deferens (CBAVD- which can be associated with lethal disease in the baby, cystic fibrosis.
2. Bifid urethra (opening of penis split into two) and hypospadias (opening of penis located too low) although not common, can be encountered (as we experienced) and treated surgically as they can create problem in deposition of sperms in the vagina.
3. Undescended testicles (testes not present inside the scrotum since birth) even in adults can be managed by orchidopexy operation (bringing down them to scrotum)
4. If varicocele is detected only by ultrasound that should not be treated surgically.
5. If obstruction occurs at the level of ejaculatory ducts (small ducts near the prostate gland), that can be surgically treated to achieve natural pregnancy.
6. Simple treatment of fungal infection in the groin (Jock itch), control of diabetes and lifestyle changes (avoiding heat exposure to the scrotum) can improve sperm count.
7. In severe male infertility, treatment should not be delayed as sperm parameters can decrease further.
8. There is emerging evidence that hormone therapy can help to improve sperm count in selective cases.
9. If a sperm problem occurs because of the diseases of the pituitary gland, usually IUI or IVF are not needed.
10. Even men with Azoospermia (zero sperm count) can become biological fathers by collecting sperm from the testicles (TESA or TESE).
11. Indiscriminate use of FNAC or testicular biopsy in azoospermia should be stopped.
12. Men with abnormal karyotypes like Klinefelter syndrome or translocation should consider PGT (preimplantation genetic testing - testing the embryos for genetic disease) to prevent transmission of the disease to the babies.

Feeling privileged to have delivered a talk on "Male Infertility- What works and what does not" in a CME organised by Lupin Diagnostics Limited on 22 August 2025.

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, 2025-26 Executive Committee Member, ISAR Bengal , 2024-26 Clinical Examiner, MRCOG Part 3 Examination Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, Lond on, 2019 Delivered, Dr Kamini Rao Oration, AICOG, 2024 Published original articles (10), case reports (4) and review articles (5) in various National and International journals. Contributed to chapters in 8 books . Peer-reviewer in in various National and International journals. Male Infertility: What works and what doesn’t

2. Is this man “infertile”? 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 4% pH 7.6 Vitality 62% Sperm Concentration 12 million/ ml Round cells Nil Married for 5 yr Just planning for pregnancy Female 28 Male 32 Definition of “Infertility”?

3. Why semen is not an ideal test? Men’s fertility potential depends on female factors Ideally, the endpoint for fertility trials should be "live birth or cumulative live birth” (WHO, 2021) Day to day variation Functional ability of the sperms? WHO recommendation Based on 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.

4. We cannot treat We bypass

5. Is this abnormal report? 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 Normozoospermia

6. WHO reference ranges

7. 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

8. Does the Lab matter?

9. From which Laboratory?

10. Leucocytospermia 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 Ignore Antibiotics (empirically) Culture of semen Further tests

11. Disclosed “pain during intercourse” Diagnosed to be diabetic Pus cells disappeared after circumcision Conceived after OI

12. 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

13. Male Accessory Gland Infection (MAGI)

14. MAGI- an example 26 yr, smoker Concentration 14 million/ml, motility 35%, pus cells 8-10/ hpf Acute Rt scrotal pain; tender epididymis Rt side After antibiotics- symptoms subsided, semen became normal Conceived after IUI

15. Advanced Lab tests? 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- Antioxidants?

16. Sperm DNA Fragmentation

17. 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 Should not be routine (ASRM, 2020; ESHRE, 2023)

18. Treatment options for high DFI ( Agarwal et al., World J Mens Health. 2020) ICSI with TESA MACS, IMSI Varicocelectomy for clinical varicocele Treat infection Control weight, diabetes Quit smoking Antioxidants Frequent ejaculation

19. Frequency of intercourse Timed intercourse- “ sexual frequency ” within the 6 days preceding ovulation could affect the probability of conception 1 Sexual intercourse daily/every other day/ twice during the fertility window 2 Conception rate lower if intercourse only once 2 Frequent ejaculations do not affect sperm quality and may even be beneficial 3 Wilcox AJ, et al. NEJM 1995;333: 1517-1521. ESHRE, 2023 Agarwal A, et al. Urology 2016;94: 102-110. NICE,, 2013 4

20. Can we categorize male infertility? Collection Method Masturbation Total Motility 30% Abstinence 4 days Progressive Motility 15% Collection Complete Non progressive Motility 15% Volume 2 ml Immotile 70% Viscosity Normal Motile Sperm Count 4.2 million Liquefaction Time 45 minutes Normal Morphology 2% pH 7.6 Vitality 62% Sperm Concentration 14 million/ ml Round cells Nil Oligo - Astheno-Terato - (zoo)- spermia (OAT)

21. 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

22. Mild Male Factor Investigations- NOT usually recommended Antioxidants CC Other adjuvant Lifestyle changes Heat exposure to scrotum Obesity Food habit Smoking Alcohol Anabolic steroids Chronic scrotal fungal dermatitis (EUA, 2018; ASRM, 2020)

23. Does this man need any treatment? 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 Isolated teratospermia is not the indication for ART Exception? Penn HA, Windsperger A, Smith Z, et al. Fertil Steril . 2011; 95(7):2320–3.

24. Is it mild or severe? 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 Donor sperm IUI Antioxidants for 3-6 months, then review ICSI directly

25. When to repeat semen analysis? Mild problems- After 3 months Severe problems- ASAP (NICE, 2013; EUA, 2018; ASRM, 2020)

26. 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 . Consider freezing the sperms

27. Oxidative Stress in Subfertility Infertility OXIDANT PRODUCTION ANTIOXIDANT DEFENCES SYSTEM 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. Overzealous use of antioxidants 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

29. Evidence for antioxidants 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. In some studies, AS was found to be beneficial in reversing OS-related sperm dysfunction and improving pregnancy rates. Still debatable due to the heterogeneity in study designs and the multifactorial genesis of infertility. 

30. Severe male factor- What’s next? Donor sperm IUI Antioxidants ICSI directly? Investigate in details √ History Physical Examination Hormone Assay Imaging Genetic Tests

31. Sperm abnormality- 1 st sign of testicular cancer 31 yrs Came for IUI (D) Too reluctant for physical examination Malignant teratoma - treated by orchidectomy and chemotherapy

32. 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)

33. “Reflective practice” 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

34. Previously fathered a baby- Is semen analysis needed? Secondary subfertility Koch’s abscess in Right testicle Repeated I/D Finally right orchidectomy Azoospermia TRUS- Right ejaculatory duct cystic and widely dilated

35. 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

36. Darren et al. Male infertility – The other side of the equation . 2017 Varicocele Vas derens Testicular location

37. Does this varicocele need surgery? 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.

38. 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

39. Surgery for Varicocele (EUA, 2018) Grade 3 varicocele Ipsilateral testicular atrophy Pain Abnormal semen parameters No other fertility factors in the couple

40. In couples seeking fertility with ART, varicocele repair may offer improvement in semen parameters may decrease level of ART needed

41. Grade III varicocele - Surgery needed? 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

42. 46,X,Yqh- Grade III varicocele ? Female- Grade IV endometriosis AMH 0.9 ng /ml

43. What went wrong? 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.

44. 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

45. Bilateral cryotorchidism in adults?

46. Is there any abnormality? Transverse testicular ectopia  (TTE) or crossed testicular ectopia (CTE) 46,X,Yqh-

47. Can it create problem?

48. Testicular Dysgenesis Syndrome (TDS) Sharpe et al;, Fertil Steril , 2008

49. Anything wrong here?

50. Imaging Scrotal ultrasound Clinically abnormal findings- mass/ atrophy Tight scrotum ( Cremasteric reflex) Obese patient NOT for Varicocele detection NOT the replacement for clinical examination (EUA, 2018; ASRM, 2020) Transrectal ultrasound ( TRUS ) Low volume and pH of semen Ejaculatory disorders (EUA, 2018; ASRM, 2020)

51. “Abnormal” scrotal ultrasound Epididymal cyst Microlithiasis Testicular prosthesis 54

52. Hormone Evaluation FSH, LH, testosterone, HbA1C FSH, LH low Testosterone low Hypogonadotropic hypodonadism Pituitary MRI Testosterone normal/ high Androgen excess Exogenous testosterone Congenital adrenal hyperplasia (CAH) Testicular adrenal rest tumors (TARTs) History, Endocrinology referral 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 55

53. Testosterone supplementation? Any other medical therapy? FSH 25.21 IU/L (normal 1-10) LH 16.8 IU/L (normal 1-10) Testosterone 159 ng /dl (normal 200-800)

54. 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) Sperm concentration <5 million/ml Azoospermia Testicular atrophy Elevated FSH Karyotype Y chromosome microdeletion

55. Genetic defect ≠ Donor sperm Genetic counseling PGT-SR- preimplantation genetic testing for structural rearrangements (previously- called PGD) Prenatal invasive testing (EUA, 2021; ASRM/AUA, 2024)

56. TMSC PR/CYCLE 10–20 million 18.29% 5–10 million 5.63% <5million 2.7% Guven et al, 2008;Abdelkader & Yeh , 2009 Hamilton etral ., 2015 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?

57. TMSC <5 mil/ml and IUI Counsel before IUI Double Ejaculate Kucuc et al., 2004; Oritz et al., 2016 “Trial IUI”- Post wash- IMSC Ombelet et al., 2014 IMSC >1 mil/ml → Further IUI IMSC <1 mil/ml → ICSI Donor sperm is NOT the only solution

58. Azoospermia (?Non-Obstructive) 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 Donor sperm IUI? Testicular FNAC/ Biopsy? TESA-ICSI directly?

59. 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

60. Problems with indiscriminate FNAC Repeat test showed SC 3-4 sperms/ hpf Repeat semen analysis- 58 mil/ml, TM 48%

61. Problems with indiscriminate FNAC 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

62. Stories of Hypo/Hypo 29 yr, Azoospermia Delayed puberty Anosmia MRI- B/L olfactory bulb absent Genetic tests advised, Lost to F/U. 32 yr, Azoospermia sudden loss of body hair, low libido Nonfunctioning Pituitary macroadenoma → Endoscopic surgery H/P Lymphocytic hypophysitis Started hCG f/b hMG by endocrinologist Sperm conc 1-2/ hpf 30 yr, Azoospermia 17 yr age, sudden testicular atrophy B/L testes 6 cc each MRI- Empty sella syndrome 65

63. How to manage- Hypo-Hypo? hCG 2000-5000 IU 3 times a week Serum testosterone should be checked every 1–2 months The sperm count should be monitored monthly Sperm parameters become normal within 6 months but sometimes it can take 24 months of time If hCG alone cannot restore spermatogenesis, FSH is added in the dose of 75-150 IU 3 times a week Often can father the baby at much lower sperm concentration EUA, 2021; ASRM/AUA, 2024

64. Spontaneous conception after treatment of hypo-hypo

65. Problems with indiscriminate FNAC FNAC- B/L maturation arrest FSH 37.2, LH 24.4, Testo 245.53, E2 37, ratio <10 Not keen for IVF-ICSI-PGT

66. 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

67. 47,XXY- Typical phenotype

68. Can we suspect KS here? 37 yr FSH 35.42, LH 10.13, testo 93, E2 14.45 Undiagnosed Diabetes Prev FNAC - Lt side- Sertoli Only Syndrome TESE – Rt side- No sperms, Lt side- Motile Sperms Chance of sperm retrieval in KS 20-70% (Kang et al., 2024)

69. Can KS be associated with RPL? Mosaic Klinefelter 47,XXY del(9)(q12.q34), del(x)(q27,q28)/ 47XXY/47XY

70. Autosome abnormalities 45,XY,rob (13;14)(q10;q10) Robertsonian Translocation Azoospermia 46,XY,t(15;17)(q10;q10) Reciprocal balanced Translocation Severe OAT

71. Testing the “embryos” PGT-SR report Amniocentesis

72. Autosomal translocations 46,XY,t(11;21)(p22;p11.2) 46,XY,t(13;18)(p11.2;p11.2) 46.XY,t(2;22)(q37;q11.21) 45, XY,rob (14;21)(q10;q10) 45,XY,rob (13;14)(q10;q10) 46,XY,t(3;6)(p21;p23)

73. Other structural rearrangements 46,XY,del(Y)(q11.23) Deletion 46,XY,dup(9)(q11-q12) Duplication (Partial trisomy ) 46,X,inv(Y)(q11q11) Inversion 46,XY,inv(3)(p25q21) Inversion Family History of Azoospermia in Own brother 2 maternal uncles 2 Cousin brothers (of same maternal aunt) 76

74. Are these genetic “abnormalities”? 46,XYqh- 46,XY,16qh+ 46,XY,22ps+ 46,XY,15ps+ 46,XYq+ 46,XY,9qh+ Keep geneticist on board

75. Problems with indiscriminate FNAC 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

76. Y chromosome microdeletion Most common genetic abnormality in infertile men (after KS) Rare if sperm conc >5 mil/ml 79

77. Look for type of YCM AZF c/d Variable phenotype TESE can be attempted AZF a/b Sertoli cell only Maturation arrest TESE should NOT be attempted 80

78. Our experience with YCM AZF a/b/c/d all deleted 3 AZF a/b/c deleted 3 AZFa only deleted 2 AZFb only deleted 2 AZFc only deleted 5 AZF b+c deleted 7 AZF c+d deleted 4 AZF b+c+d deleted 4 81

79. Can a man has Turner’s syndrome? Mos45,X[12]/46,XY[28] Mosaic- 45,X/46,XY (XY Turner’s or X0/XY)

80. Can a man have 46,XX? 46,XX SRY+ sex reversal (De La Chapelle syndrome)

81. Can a man have 46,XX? LH 30.10, FSH 43.70, E2 38.48, Testo 432 Karyo - 46,XX

82. Don’t advise Karyo alone Don’t interpret karyo alone 46,X,del(Y)(q11.22q11.23 )

83. 46,X+mar

84. Surgical Sperm Retrieval ( SSR ) in Azoospermia (OA>NOA)

85. Decide- if SSR can be done? 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

86. 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 .

87. 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%

88. Fructose negative azoospermia 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 Abstinence period Completeness of collection Usual amount of ejaculate Exclude retrograde ejaculation Suspect obstructive pathology- TRUS Clinical assessment???

89. Azoospermia - Low volume and/ or Fructose negative Vasa palpable Ejaculatory duct obstruction TRUS

90. Surgical Management in OA: When to refer? Vasovasostomy Vasoepididymostomy Transurethral resection of ejaculatory ducts in EDO Patent tract ≠ Conception Baker and Sabanegh , 2013

91. Azoospermia - Low volume and/ or Fructose negative Vasa palpable Ejaculatory duct obstruction TRUS Vasa NOT palpable CBAVD Why important?

92. 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, 2021; ASRM/AUA, 2024) Partner testing 25% chance of inheritance Indian prevalence- 1:10,000- 1:40,000 ( Kapoor et al., 2006; Prasad et al., 2010)

93. Should we miss a lethal disease? TRUS- B/L agenesis of seminal vesicles Male partner- CFTR carrier Fem ale partner- CFTR carrier PGT (M)- preimplantation genetic testing for Mendelian disorders (previously called PGD)

94. Our experience with CBAVD

95. Unilateral vas absent Usually fertile CFTR testing if no renal agenesis

96. Genetic testing CFTR testing in CBAVD Karyotyping Y chromosome Microdeletion (YCM)

97. Any other genetic testing?

98. Medical Therapy in Idiopathic Severe OAT/ NOA To improve chance of natural conception To improve the chance of sperm retrieval Sometimes, can lead to appearance of sperms in the ejaculate 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) Anti-estrogens (CC, Tamoxifen ) Block pituitary E2 receptors→ stimulate secretion of FSH, LH Men with normal FSH, low testosterone but normal T:E ratio Gonadotrophins “resetting” of the Gn receptors in testicles → improve the sensitivity of testicles to gonadotrophins may be increase intratesticular testosterone work better in case of eugonadism rather than high FSH If successful in raising FSH level 1.5 times baseline and testosterone 600-800 ng /dl, high success rate of microTESA ( Alkandari and Zini , 2021; Kumar, 2021; Holtermann et al., 2022; Dabaja and Schlegel, 2014; Holtermann et al., 2022; Anawalt , 2013; Flannigan and Schlegel, 2019; Ring et al., 2016; Chehab et al, 2015; Foran et al, 2023). Shiraishi et al., 2012)

99. APHRODITE Criteria, RBMO, 2024 A ddressing male P atients with H ypogonadism and/or infe R tility O wing to altere D , I diopathic TE sticular function 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

100. Dasgupta et al., Asian J Androl . 2024

101. Hormone treatment vs ART Priority for natural conception Other indications of ART- female partners Time to pregnancy Age of female partners, ovarian reserve Cost

102. All investigations in one go? 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 Karyo - 47,XXY Pituitary Incidentaloma

103. 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? No ART if female age <21 yr

104. 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

105. Semen analysis Mild problem Severe problem Lifestyle changes Antioxidants History Physical Exam Repeat semen ASAP 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

106. Treatment burden for MALE infertility falls on FEMALE

107. Disclaimer Written consent from all the patients 110

108. 111 This PPT will be available at: https://www.slideshare.net/SujoyDasgupta1 Mail ID- [email protected] ORCID ID- 0000-0002-8116-9312 Thank you Lupin Diagnostic