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Abnormal Semen- What next?
The document discusses abnormal semen analysis, including multiple semen reports with varying sperm parameters, and guidelines for further management based on the severity of male infertility. It emphasizes the role of antioxidants, lifestyle changes, and potential medical therapies while detailing the importance of further investigations in severe cases. Additionally, the document outlines the implications of abnormal findings and the need for appropriate follow-up actions such as donor sperm or specialized techniques for sperm retrieval.
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Abnormal Semen- What next?
- 1. Abnormal Semen Analysis- WhatNext? 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) Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata Managing Committee Member, BOGS, 2022-23 Executive Committee Member, ISAR Bengal, 2022-24 Clinical Examiner, MRCOG Part 3 Examination Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019
- 2. Semen Report 1 CollectionMethod 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
- 3. Semen Report 1 CollectionMethod 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
- 4.
- 5. When to repeatsemen analysis? • Mild problems- After 3 months • Severe problems- ASAP (NICE, 2013; EUA, 2018; ASRM, 2020)
- 6. Points to notein semen report Volume 1.4 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 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. Semen Report 2 Collection Method MasturbationTotal 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
- 9. Semen Report 2 Collection Method MasturbationTotal 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
- 10. Male Infertility- Mildor Severe? • TMSC= Total Motile sperm count = Sperm concentration x total volume x total motility • TMSC >5/ 10/ 20 million
- 11. 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)
- 12. I n fe r t i l i t y
- 13. Antioxidants Astaxanthin several-fold strongerantioxidant activity than vitamin E and b-carotene. potent antiperoxidation activity. Coenzyme Q10 Protects the cell membrane from lipid peroxidation. improves Total Antioxidant Capacity (TAC) concentrations and decreased Malondialdehyde (MDA) levels. L-Carnitine increases fatty acid transport into sperm mitochondria which are needed for sperm energy production. Lycopene antiproliferative, immunomodulatory, and anti-inflammatory effects that promote cell differentiation . Vitamin B9 (Folic Acid) Protects against mutations and DNA strand breaks. Regulates DNA methylation and gene expression prevents abnormal chromosomal replication and mitochondrial DNA deletions. Zinc role in signaling, enzymatic activities, sexual maturation and managing mitochondrial oxidative stress. improves chromatin integrity Selenium Suppresses testicular toxicity and modulate DNA repair.
- 15. Smits RM, Mackenzie-ProctorR, 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.
- 16. Semen Report 3 CollectionMethod 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
- 17. Semen Report 3 CollectionMethod 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
- 18. What next? • Straightawaydonor sperm IUI • Antioxidants for 3 months and repeat test • Investigate in details √
- 19. 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.
- 20. Severe Male Factoris 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)
- 21. 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
- 22. Darren et al.Male infertility – The other side of the equation . 2017
- 23. Varicocele- always CLINICALDiagnosis (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
- 24. Surgery for Varicocele (EUA,2018) • Grade 3 varicocele • Ipsilateral testicular atrophy • Abnormal semen parameters • No other fertility factors in the couple
- 25. Cryptorchidism in adults(EUA, 2018) • A palpable undescended testis should NOT be removed • Correction of B/L cryptorchidism, can lead to sperm production in previously azoospermic men
- 26. Imaging Scrotal ultrasound 1. Clinicallyabnormal 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)
- 27.
- 28. Sperm concentration <10million/ml Sexual dysfunction Clinically suspected endocrinopathy FSH, LH, Testosterone, HbA1C FSH/ LH low Testosterone low Serum Prolactin Pituitary Imaging FSH high LH high Testosterone low Global Testicular failure LH normal Testosterone normal Spermatogenesis defect LH high Testosterone normal Subclinical hypogonadism Prolactin, TSH if clinically suspected
- 29. Pituitary imaging- MRI •Anosmia, MRI- B/L olfactory bulb absent • Genetic tests advised, Lost to F/U.
- 30. Genetic testing • Spermconcentration <5 million/ml • Azoospermia • Testicular atrophy • Elevated FSH • Karyotyping • Y chromosome Microdeletion (YCM)
- 31. Hamilton et al.,2015 Criteria TMSC Treatment Pre wash TMSC > 5 million IUI Pre wash TMSC 1 - 5 million IVF Pre wash TMSC <1 million ICSI IUI, IVF or ICSI?
- 32. TMSC <5 mil/mland 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 5. No role of double insemination or any special washing technique ESHRE, 2018
- 33. Role Of MedicalTherapy (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) Idiopathic Male infertility CC Tamoxifen Letrozole hCG All empirical Evidences? Testosterone supplementation Feedback inhibition on FSH, LH→ secondary hypogonadism Aromatase inhibitors (Letrozole, Anastrozole) If T:E2 ratio <10 (T- ng/dl, E2- pg/ml)
- 34. Role Of MedicalTherapy (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) Idiopathic Male infertility CC Tamoxifen Letrozole hCG All empirical Evidences? Testosterone supplementation Feedback inhibition on FSH, LH→ secondary hypogonadism Aromatase inhibitors (Letrozole, Anastrozole) If T:E2 ratio <10 (T- ng/dl, E2- pg/ml)
- 35. Role Of MedicalTherapy (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) Idiopathic Male infertility CC Tamoxifen Letrozole hCG All empirical Evidences? Testosterone supplementation Feedback inhibition on FSH, LH→ secondary hypogonadism Aromatase inhibitors (Letrozole, Anastrozole) If T:E2 ratio <10 (T- ng/dl, E2- pg/ml)
- 36. Role Of MedicalTherapy (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) Idiopathic Male infertility CC Tamoxifen Letrozole hCG All empirical Evidences? Testosterone supplementation Feedback inhibition on FSH, LH→ secondary hypogonadism Aromatase inhibitors (Letrozole, Anastrozole) If T:E2 ratio <10 (T- ng/dl, E2- pg/ml)
- 37. Semen Report 4 CollectionMethod 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
- 38. Semen Report 4 CollectionMethod 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 cetrigugation) Round cells Nil
- 39. What next? • Straightawaydonor sperm IUI • Testicular FNAC
- 40. Problems with indiscriminateFNAC • Repeat test showed SC 2 mil/ml
- 41. FNAC- role? • Isolatedfoci 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
- 42. If previous FNACwas 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%
- 43. Surgical Sperm Retrieval(SSR) in Azoospermia (OA>NOA)
- 44. Predictors of spermretrieval? • 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.
- 45. In presence ofgenetic defect • Sperm Aneuploidy testing by FISH • PGT-SR (previously- PGD) • Prenatal invasive testing (EUA, 2018; ASRM, 2020)
- 46. Robertsonian Translocation 45, XYrob (14, 21), (q10, q10) Sperm FISH
- 47. Genetic abnormality ≠Donor sperms 46,XYqh- 46,XY,16qh+
- 48.
- 49. Semen Report 5 CollectionMethod 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
- 50. Semen Report 5 CollectionMethod 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
- 51. Assess • Abstinence period •Completeness of collection • Usual amount of ejaculate • Exclude retrograde ejaculation • Suspect obstructive pathology- TRUS
- 52. Congenital bilateral absenceof 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)
- 53. Cases of CBAVD-TRUS and CFTR mutation
- 54. Semen Report 6 CollectionMethod Masturbation Total Motility 0% Abstinence 4 days Progressive Motility 0% Collection Complete Non progressive Motility 0% Volume 2 ml Immotile 100% Viscosity Normal Motile Sperm Count Nil Liquefaction Time 45 minutes Normal Morphology 2% pH 7.6 Vitality 12% Sperm Concentration 18 million/ ml Round cells Nil
- 55. Semen Report 6 CollectionMethod Masturbation Total Motility 0% Abstinence 4 days Progressive Motility 0% Collection Complete Non progressive Motility 0% Volume 2 ml Immotile 100% Viscosity Normal Motile Sperm Count Nil Liquefaction Time 45 minutes Normal Morphology 2% pH 7.6 Vitality 12% Sperm Concentration 18 million/ ml Round cells Nil
- 56. Steps • Abstinence, frequencyof discharge • Place of collection • Look for vitality- HOS, Supravital staining • Repeat after proper abstinence • Can be associated with smoking, varicocele, Immotile Cilia Syndrome • Antioxidants ?
- 57. ICSI with Ejaculatevs Testicular sperms
- 58. Semen Report 7 Collection Method MasturbationTotal 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
- 59. Semen Report 7 Collection Method MasturbationTotal 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
- 60. Isolated teratozoospermia • Isolatedabnormal morphology is not the indication for ART Penn HA, Windsperger A, Smith Z, et al. Fertil Steril. 2011; 95(7):2320–3.
- 61. Semen Report 8 Collection Method MasturbationTotal 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
- 62. Semen Report 8 Collection Method MasturbationTotal 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
- 63. MAGI (Male AccessoryGland Infection) 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 • Phimosis • Consider prostatic fluid culture
- 64. Meticulous semenanalysis in a standard laboratory Physical examination and rational investigations Avoid non-evidence based drugs for long time Antioxidants- May be useful in mild problem Antioxidants- Not reliable in severe problem Donor sperm is NOT the only solution IUI or IVF/ICSI- depends on the overall assessment Take Home Messages
- 65. Treatment burden forMALE infertility falls on FEMALE