Dr. Sujoy Dasgupta is a reproductive medicine specialist who has extensive training and experience in India and abroad. He lists his qualifications and areas of practice. The document then discusses limitations of the 2010 WHO semen analysis guidelines, significance of sperm DNA fragmentation testing, definitions of mild and severe male factor infertility, and investigations and treatment approaches for various causes of male infertility including varicocele, congenital bilateral absence of vas deferens, cryptorchidism, hormonal abnormalities, and azoospermia. Key advice includes thorough evaluation and evidence-based therapies over long-term use of unproven drugs, and considering sperm retrieval and assisted reproduction rather than assuming donor sperm is the only option.

1. Dr 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
Visiting Consultant, RSV Hospital, Kolkata
Bhagirathi Neotia Women and Child Care centre
Woodlands Multispeciality Hospital, Kolkata
Managing Committee Member, Bengal Obstetric & Gynaecological Society (BOGS)
Secretary, Subfertility and Reproductive Endocrinology Committee, BOGS
Executive Committee Member, Indian Fertility Society (IFS)- West Bengal Chapter
Executive Committee Member, Indian Society for Assisted Reproduction (ISAR)- Bengal
Member, Endocrinology Committee, Federation of Obstetric and Gynaecological Societies of
India (FOGSI)
Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019
Male Infertility- Recent updates

2. Treatment burden for MALE
infertility falls on FEMALE

3. 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

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. 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

6. From which Laboratory?

8. Is “Routine” Semen
Analysis
ENOUGH?

9. Sperm DNA Fragmentation
(SDF)
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)

10. Significance of SDF
• Live birth after IUI/ IVF/ ICSI- ?
• Oocytes can repair the damaged DNA
• Lack of standardization
• Lack of definitive treatment

11. “Mild” Male Factor

12. What is “Mild”?
• TMSC= Total Motile sperm count
= Sperm concentration x total volume x total motility
• TMSC >5/ 10/ 20 million

13. Mild Male Factor
• Investigations- NOT
usually
recommended
• Repeat semen after 3
months (NICE, 2013; EUA,
2018; ASRM, 2020)
• 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)

14. Severe Male Factor

15. Male Infertility- A health-opportunity
• Diabetes
• Cardiovascular diseases
• Lymphoma, extragonadal germ cell tumours, peritoneal cancers
• Repeated hospitalization
• Increased mortality
Choy and Eisenberg, 2020; Bungum et al., 2018; Eisenberg et al., 2013; Jungwirth et al., 2018; Hotaling and Walsh, 2009

16. Self-Testicular
Examination
•Atrophic Testes
•H/O undescended testicles
•Testicular microcalcification

17. Revisiting History
• Age
• Duration of 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, cytotoxic drugs,
steroids
• Sexual history- Low libido, ED

18. Darren et al. Male infertility – The other side of the equation . 2017

19. Varicocele- always CLINICAL Diagnosis
• 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.

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

21. Congenital bilateral absence of
vas deferens (CBAVD)
• Semen- Volume <1.5 ml, pH <7.0, fructose negative
• Renal ultrasound
• CFTR testing (EUA, 2018; ASRM< 2020)
• Partner testing
• Indian prevalence- 1:10,000- 1:40,000 (Kapoor et al., 2006;
Prasad et al., 2010)

22. 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

23. 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)

24. Abnormal Imaging
Epididymal Cysts
• NOT associated with
infertility (Weatherly et al.,
2018)
Testicular Microlithiasis
• Premalignant condition (EUA,
2018)

25. Sperm concentration <10 million/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

26. Testosterone Supplementation?
• Should only be done in men with primary
hypogonadism, NOT interested in fertility (EUA, 2018;
EUA, 2016; AUA, 2018; CUA, 2015)
• They provide feedback inhibition on pituitary
gonadotrophins (FSH and LH) leading to
secondary hypogonadism (de Souza and Hallak, 2011; McBride and
Coward, 2016; WHO, 2010)

27. Alternative Strategy
• If T:E2 ratio <10
(T- ng/dl, E2- pg/ml),
consider Aromatase
Inhibitors (Letrozole,
Anastrozole)
EUA, 2018; AUA, 2018
Asian J Andr, 2019

28. Hypogonadotrophic Hypogonadism
• 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
EUA, 2018

29. Other hormonal therapies
Primary
hypogonadism
• SERM-
Clomiphene citrate
(CC), tamoxifen
AUA, 2018
Idiopathic Male
Subfertility
• CC, Tamoxifen, hCG,
Letrozole
• Empirical
• Level of evidences ?
EUA, 2018

30. I n f e r t i l i t y

32. 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.
• 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.

33. • 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.

34. IUI, IVF or ICSI?

35. TMSC and IUI – cut offs
TMSC PR/CYCLE
 10–20 million 18.29%
 5–10 million 5.63%
 <5 million 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

36. TMSC <5 million and IUI
• Counsel before IUI
1. Double Ejaculate Kucuc et al., 2004; Oritz et al., 2016
2. “Trial IUI”- Post wash- IMSC (Inseminating
motile sperm count) Ombelet et al., 2014
3. IMSC >1 million → Further IUI
4. IMSC <1 million → ICSI
5. No role of double insemination or any
special washing technique ESHRE., 2018

37. Strategies in severe oligo-astheno-
terato-zoospermia (OAT)
• Donor sperm is NOT the solution
• Investigate the cause
• Consider freezing of the sperms
• ICSI is the standard treatment

38. Ejaculate vs Testicular sperms

39. Azoospermia

40. Surgical Sperm Retrieval in
Azoospermia (OA>NOA)

41. Testicular FNAC- role?
• “Trial TESA”
• If obtained,
cryopreserve the
sperms
ASRM, 2020
• Diagnostic testicular
biopsy- NOT NECESSARY

42. 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%

43. 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.

44. Genetic testing
• Sperm
concentration <5
million/ml
• Azoospermia
• Testicular atrophy
• Elevated FSH
• Karyotyping
• Y chromosome
Microdeletion
(YMD)

45. In presence of genetic defect
• Sperm Aneuploidy testing by
fluorescent in situ hybridization (FISH)
• PGT-SR (previously called PGD) (EUA,
2018; ASRM, 2020)

46. Klinefelter’s syndrome

47. 45, XY rob (14, 21), (q10, q10)

48. YMD Report

49. AZF microdeletion

50. Testing for CFTR gene mutation in CBAVD

51.  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