Male infertility guide for gynaecologists
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Invited lecture delivered by Dr Sujoy Dasgupta in a webinar organized by Emcure IVA division, held in April, 2020
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Male infertility guide for gynaecologists
- 1. Male Infertility- What a Gynaec should know Sujoy Dasgupta MBBS (Gold Medalist, Hons) MS (OBGY- Gold Medalist) DNB (New Delhi) MRCOG (London) Advanced ART Course for Clinicians (NUHS, Singapore) Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata Managing Committee Member, Bengal Obstetric & Gynaecological Society (BOGS) Secretary, Subfertility and Reproductive Endocrinology Committee, BOGS Convener and Faculty, Spectrum MRCOG Course Member, Male Infertility, Special Interest Group, ASPIRE, Singapore Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019
- 4. Esteves S C. Clinical relevance of routine semen analysis and controversies surrounding the 2010 World Health Organization criteria for semen examination. Int Braz J Urol. 2014; 40: 443-53
- 5. Esteves S C. Clinical relevance of routine semen analysis and controversies surrounding the 2010 World Health Organization criteria for semen examination. Int Braz J Urol. 2014; 40: 443-53
- 7. Murray KS, et al. The effect of the new 2010 World Health Organization criteria for semen analyses on male infertility. Fertil Steril 2012;98:1428–31 • The 2010 reference values result in some infertile men being reclassified as fertile if status is based on semen analysis alone. • This may lead to fewer men being referred for proper infertility evaluation or treatment.
- 8. Limitations of WHO 2010 Semen Analysis • 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
- 13. Issues in Semen Collection • Privacy • Relaxation • Bed • Partner • Washing facility
- 14. Still Difficult • Ask- Why Difficulty • Erection issue- Sildenafil (50)/ Tadalafil (10)/ Verdenafil (10)
- 15. Still Difficult • Ask- Why Difficulty • Erection issue • Vibroejaculator
- 16. Still Difficult • Ask- Why Difficulty • Erection issue • Vibroejaculator • Coitus interruptus • Nontoxic condom
- 17. Still Difficult • Ask- Why Difficulty • Erection issue • Vibroejaculator • Coitus interruptus • Nontoxic condom • Home Collection • Urine (In RE) • Prostatic Massage • Electroejaculation
- 18. Still Difficult • Ask- Why Difficulty • Erection issue • Vibroejaculator • Coitus interruptus • Nontoxic condom • Home Collection • Urine (In RE) • Prostatic Massage • Electroejaculation • TESA
- 19. Consider- freezing of the Sperm • In difficult cases
- 20. Case-Study
- 21. Case-Study
- 22. Case Scenario 1
- 26. What to do • Empirical Antibiotics? • Method of collection • Hand washing before collection • Special Tests- Round cells vs Pus cells • History • Culture of semen • Prostatic Massage- Culture
- 27. EUA Guideline, 2018 • The clinical significance of an increased concentration of leukocytes in the ejaculate is controversial. • Although leukocytospermia is a sign of inflammation, it is not necessarily associated with bacterial or viral infections. • More leukocytes found in men with prostatitis compared to those without inflammation
- 28. MAGI (Male Accessory Gland Infection)
- 29. Case-Study • 36-yr-old Bank Manager • Primary Infertility • Apparently unexplained infertility • Pus cells in semen • Culture negative • Pain during intercourse • Severe Phimosis • Pus cells disappeared after circumcision • Conception after OI with CC
- 30. Case Scenario 2
- 31. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 12 million/ ml Total Motility 42% Progressive Motility 17% Non progressive Motility 25% Immotile 58% Motile Sperm Count 20.16 million Normal Morphology 4% Vitality 62% Round cells Nil
- 32. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 12 million/ ml Total Motility 42% Progressive Motility 17% Non progressive Motility 25% Immotile 58% Motile Sperm Count 20.16 million Normal Morphology 4% Vitality 62% Round cells Nil
- 33. Mild Male Factor • Difficult to define • Sperm Concentration (SC) >5 million/ ml • TMSC= Total Motile sperm count = SC x total volume x TM >5/10/20 million
- 35. Mild male Factor • Investigations? • Antioxidants • CC • Other adjuvants
- 36. EUA, 2018; NICE, 2013
- 37. Lifestyle changes 1. Heat exposure to scrotum 2. Obesity 3. Food habit 4. Smoking 5. Alcohol 6. Anabolic steroids 7. Chronic scrotal fungal dermatitis
- 38. Oxidative Stress in Sub-fertility 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.
- 39. Free Radicals (Oxidants) Free radical is charged unstable molecule that have at least one unpaired electron in their outer orbit.
- 40. COQ-10 1) Co-Q10 is concentrated in the mitochondrial mid-piece of sperm & is involved in energy production – Improves sperm kinetic features 2) Prevents oxidative stress & lipid peroxidation of sperm membranes. Lycopene 1) Found in high concentrations in testes & seminal plasma. daily supplementation of Lycopene improves sperm concentration, motility & morphology. L- Carnitine 1) L-carnitine is a naturally occurring antioxidant responsible for energy production. 2) It provides energetic substrates to sperm epididymis, which positively affects sperm motility, maturation & spermatogenesis process. Glutathione 1) Considerable amount of glutathione is present in seminal fluid & protects sperm against oxidative damage. 2) Glutathione deficiency can lead to instability of the mid-piece of sperm, resulting in defective motility. L-Arginine 1) L-Arginine is a biochemical precursor in the synthesis of putrescine, spermidine & spermine which are essential for sperm motility. Methylcobalamine 1) 39% of men with abnormal semen analysis have methylcobalamine deficiency. 2) Methylcobalamine supplementation improves sperm concentration, total sperm count , sperm motility.
- 42. 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. Published 2019 Mar 14. • In this review, there is low-quality evidence from seven small randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. • Low-quality evidence suggests that clinical pregnancy rates may also increase. • Overall, there is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal upsets but the evidence is of very low quality. • Subfertilte couples should be advised that overall, the current evidence is inconclusive.
- 43. When to repeat the semen analysis? • Mild- After 3 months • Severe/ Azoospermia- As soon as possible • (NICE, 2013)
- 44. After 3 months of antioxidants here Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 18 million/ ml Total Motility 41% Progressive Motility 26% Non progressive Motility 15% Immotile 59% Motile Sperm Count 14.76 million Normal Morphology 5% Vitality 62% Round cells Nil
- 45. After 3 months of antioxidants here Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 18 million/ ml Total Motility 41% Progressive Motility 26% Non progressive Motility 15% Immotile 59% Motile Sperm Count 14.76 million Normal Morphology 5% Vitality 62% Round cells Nil
- 46. Case Scenario 3
- 47. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 8 million/ ml Total Motility 30% Progressive Motility 16% Non progressive Motility 14% Immotile 70% Motile Sperm Count 4.8 million Normal Morphology 3% Vitality 62% Round cells Nil
- 48. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 8 million/ ml Total Motility 30% Progressive Motility 16% Non progressive Motility 14% Immotile 70% Motile Sperm Count 4.8 million Normal Morphology 3% Vitality 62% Round cells Nil
- 49. IUI/ ICSI? • Assess 1. Tubal factor 2. Ovarian reserve 3. Duration of Infertility 4. Age of the female partner
- 50. TMSC and motility– cut offs TMSC PR/CYCLE 10–20 million 18.29% 5–10 million 5.63% <5million 2.7% TMSC should be 5-10 million If less than 5 million counsel and do IUI (Guven et al, 2008;Abdelkader & Yeh, 2009)
- 51. Post wash and decide • “Trial IUI” • IMSC <1 million and morphology <4%
- 53. Double Ejaculate • obtaining a second semen sample when the motile sperm yield of the first semen sample is 1 million to 5 million significantly increases the total motile sperm count in the final inseminate.
- 54. Oligospermia and IUI • TMSC 5-10 mil- Do IUI 4-6 cycles • TMSC <5 mil- Counsel before IUI 1. Double Ejaculate 2. Post wash- IMSC 3. IMSC >1 mil → Further IUI 4. IMSC <1 mil → see Morphology
- 56. Tubal Patency before IUI? • If no risk factors for tubal block- 3 cycles of IUI, then tubal patency test • If risk factors- tubal patency first • With severe male factor chance of tubal factor- infertility decreases
- 57. Case-Study • 32-yrs-old IT Professional • Already received antioxidants • Uncontrolled diabetes was diagnosed after finding OAT • 5 cm (large) epididymal cyst/ Spermatocele • IUI was planned • Natural conception
- 58. While the occurrence of epididymal cysts in this cohort is unexplained, our observation that these cysts are not associated with infertility will be useful for those clinicians counseling patients observed to have these structures.
- 59. Case Scenario 4
- 60. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 1.5 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 1.2 million/ ml Total Motility 30% Progressive Motility 16% Non progressive Motility 14% Immotile 70% Motile Sperm Count 0.54 million Normal Morphology 1% Vitality 34% Round cells Nil
- 61. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 1.5 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 1.2 million/ ml Total Motility 30% Progressive Motility 16% Non progressive Motility 14% Immotile 70% Motile Sperm Count 0.54 million Normal Morphology 1% Vitality 34% Round cells Nil
- 62. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 1.5 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 1.2 million/ ml Total Motility 30% Progressive Motility 16% Non progressive Motility 14% Immotile 70% Motile Sperm Count 0.54 million Normal Morphology 1% Vitality 34% Round cells Nil
- 63. Severe OAT • IUI –Donor Sperm? • HSG- Bilateral tube blocked • AMH 0.9 ng/ml • Husband 42, wife 38 • Trying for pregnancy for 5 years • Antioxidants ???
- 64. • 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.
- 65. Treatment should NOT be delayed • Antioxidants • Consider freezing • Investigate the cause • ICSI • In extreme cases- may need preparation for TESA
- 66. • As in azoospermia, in extreme cases of oligozoospermia (spermatozoa < 1 million/mL), there is an increased incidence of obstruction of the male genital tract and genetic abnormalities.
- 67. Investigation is needed • If sperm concentration < 5 million/ml
- 68. History Taking • Lifestyle • Medical history- Diabetes, Mumps, Cancer • Surgical history- Hernia, Orchidopexy, Pituitary Surgery • Drugs history- Sulphasalazine, cytotoxic drugs, steroids • Sexual history
- 69. Orchidopexy for B/L Undescended Testicles
- 70. Physical Examination • General body habitus, secondary sex characters, gynaecomastia • Testicular size and consistency • Varicocele • May diagnose serious disorders
- 72. Self testicular Examination • Atrophic Testes • H/O undescended testicles • Testicular microcalcification
- 74. Investigations Endocrine- If nonobstructive pathology is suspected • FSH, LH, Testosterone, sugar Genetic testing- 1. Karyotyping, Y chromosome microdeletion- If testicular failure 2. CFTR testing- If CBAVD Urological- • USG Scrotum- 1. Clinically abnormal findings 2. Tight scrotum (Cremasteric reflex) 3. Post-orchistis (Mumps) NOT for Varicocele detection • TRUS- If obstructive pathology/ ejaculatory problem suspected
- 75. Severe OAT/ Azoospermia Volume/ pH of semen Normal Low testicular volume FSH, LH, Testosterone, blood sugar FSH high LH Normal/ high Testosterone normal/low Karyotyping YMD FSH// LH Low Testosterone low Pituitary Imaging FSH/LH Low Testosterone high Anabolic steroid abuse Prolactin, TSH if clinically suspected Volume/ pH of semen low Normal testicular volume Scrtotal USG TRUS CFTR
- 76. Severe OAT/ Azoospermia Volume/ pH of semen Normal Low testicular volume FSH, LH, Testosterone, blood sugar FSH high LH Normal/ high Testosterone normal/low Karyotyping YMD FSH// LH Low Testosterone low Pituitary Imaging FSH/LH Low Testosterone high Anabolic steroid abuse Prolactin, TSH if clinically suspected Volume/ pH of semen low Normal testicular volume Scrtotal USG TRUS CFTR
- 77. Severe OAT/ Azoospermia Volume/ pH of semen Normal Low testicular volume FSH, LH, Testosterone, blood sugar FSH high LH Normal/ high Testosterone normal/low Karyotyping YMD FSH// LH Low Testosterone low Pituitary Imaging FSH/LH Low Testosterone high Anabolic steroid abuse Prolactin, TSH if clinically suspected Volume/ pH of semen low Normal testicular volume Scrtotal USG TRUS CFTR
- 78. Severe OAT/ Azoospermia Volume/ pH of semen Normal Low testicular volume FSH, LH, Testosterone, blood sugar FSH high LH Normal/ high Testosterone normal/low Karyotyping YMD FSH// LH Low Testosterone low Pituitary Imaging FSH/LH Low Testosterone high Anabolic steroid abuse Prolactin, TSH if clinically suspected Volume/ pH of semen low Normal testicular volume Scrtotal USG TRUS CFTR
- 79. Severe OAT/ Azoospermia Volume/ pH of semen Normal Low testicular volume FSH, LH, Testosterone, blood sugar FSH high LH Normal/ high Testosterone normal/low Karyotyping YMD FSH// LH Low Testosterone low Pituitary Imaging FSH/LH Low Testosterone high Anabolic steroid abuse Prolactin, TSH if clinically suspected Volume/ pH of semen low Normal testicular volume Scrtotal USG TRUS CFTR
- 80. Severe OAT/ Azoospermia Volume/ pH of semen Normal Low testicular volume FSH, LH, Testosterone, blood sugar FSH high LH Normal/ high Testosterone normal/low Karyotyping YMD FSH// LH Low Testosterone low Pituitary Imaging FSH/LH Low Testosterone high Anabolic steroid abuse Prolactin, TSH if clinically suspected Volume/ pH of semen low Fructose Negative Normal testicular volume Scrtotal USG TRUS CFTR
- 81. In this case • FSH 15.21 IU/L (normal 1-10) • LH 12.8 IU/L (normal 1-10) • Testosterone 159 ng/dl (normal 200-800 )
- 83. Estrogen in male? • Estradiol , normal range- 10-40 pg/ml • If T:E2 ratio <10 (T- ng/dl, E2- pg/ml), consider Aromatase Inhibitors (Anastrozole 1 mg/day or letrozole 2.5 mg/day)
- 84. Asian J Andr, 2019. A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility
- 85. Case-study • 42-yr male, office worker • Brother also having primary infertility • Hypergonadotrophic hypogonadism • Opted for IUI (D) • Lost to follow up
- 86. Case Scenario 5
- 87. 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 Round cells Nil
- 88. 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 Round cells Nil
- 89. Assess • Abstinence period • Completeness of collection • Usual amount of ejaculate • Exclude retrograde ejaculation • Post-masturbation urine • Suspect obstructive pathology- TRUS
- 90. Surgical Sperm Retrieval in Azoospermia (OA>NOA)
- 91. Case Study • 38-yr, IT worker • B/L vas not palpable clinically
- 92. CFTR testing was done after trial TESA confirmed presence of motile sperms
- 93. Case Scenario 6
- 94. 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 Round cells Nil
- 95. Collection Method Masturbation Abstinence 2 days Collection Complete Volume 3.0 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.8 Sperm Concentration Nil Round cells Nil
- 96. Predictors of sperm retrieval? • FSH • Testicular Size • No reliable positive prognostic factors guarantee sperm recovery for patients with non-obstructive azoospermia. • The only negative prognostic factor is the presence of AZFa and AZFb microdeletions.
- 97. Trial TESA • No role of FNAC • If possible, freeze the sperms
- 98. Case-Example 1
- 99. Case-Example 2
- 100. Case-Example 3
- 101. YMD Report
- 102. If genetic defect • Sperm Aneuploidy testing by FISH • PGT-SR (previously- PGD)
- 103. Case Scenario 7
- 104. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 18 million/ ml Total Motility 0% Progressive Motility 0% Non progressive Motility 0% Immotile 100% Motile Sperm Count Nil Normal Morphology 2% Vitality 32% Round cells Nil
- 105. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 18 million/ ml Total Motility 0% Progressive Motility 0% Non progressive Motility 0% Immotile 100% Motile Sperm Count Nil Normal Morphology 2% Vitality 32% Round cells Nil
- 106. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 18 million/ ml Total Motility 0% Progressive Motility 0% Non progressive Motility 0% Immotile 100% Motile Sperm Count Nil Normal Morphology 2% Vitality 32% Round cells Nil
- 107. Steps • Abstinence, frequency of discharge • Place of collection • Reliability of the laboratory reports • Look for vitality- HOS, Supravital staining • Can be associated with smoking, varicocele, Immotile Cilia Syndrome • Antioxidants- ? • Repeat after proper abstinence • ICSI with viable sperms in semen • ICSI from testicular sperms
- 108. Case-Study • 34-yrs-old, Army-man, primary infertility • Repeated examination showed total asthenospermia • Past smoker • Ejaculated sperms- poor morphology • Advocated for TESA- ICSI done, conceived
- 109. Varicocele • Subclinical: not palpable or visible, but can be shown by special tests (Doppler ultrasound studies). • Grade 1: palpable during Valsava manoeuvre, but not otherwise. • Grade 2: palpable at rest, but not visible. • Grade 3: visible at rest.
- 111. Case Scenario 8
- 112. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 36 million/ ml Total Motility 46% Progressive Motility 33% Non progressive Motility 13% Immotile 54% Motile Sperm Count 33.12 million Normal Morphology 3% Vitality 32% Round cells Nil
- 113. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 36 million/ ml Total Motility 46% Progressive Motility 33% Non progressive Motility 13% Immotile 54% Motile Sperm Count 33.12 million Normal Morphology 3% Vitality 32% Round cells Nil
- 114. 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.
- 115. Case Scenario 9
- 116. Case-Study • 38-yrs-old, teacher, married for 5 years • Unable to ejaculate during coitus and also during masturbation since marriage • Nocturnal emission present • Diabetic on medication for last 8 years • Initially used to ejaculate during masturbation • Physical exam unremarkable • Vibroejaculator failed • Post-masturbation urine- No sperms
- 117. TRUS • TESA-ICSI done, conceived, delivered
- 118. Ejaculation Problems • DM • Spinal cord Injury • Neurological diseases • Obstruction • Medication- SSRI, PDE-5 blockers, alpha- blockers • Exclude- retrograde ejaculation
- 119. Retrograde Ejaculation • Exclude diabetes, neurological disorders, prostate disorders • Change medicines (alpha blocker) • Medical therapy • Vibroejaculator • IUI / ICSI with alkalinized urine • TESA- in extreme cases
- 121. Take Home Messages • Semen analysis must be done from reliable laboratories, following WHO 2010 standards • Single abnormal test must be repeated • Antioxidants should be offered in mild male factor problems • In severe problem, active investigation and treatment should not be delayed • Donor-Sperm is NOT the only solution