Panel discussion moderated by Dr Sujoy Dasgupta and Dr Sudip Basu on "Troubleshooting in Male Subfertility" in the Andrology Workshop organized by Special Interest Group (SIG) Andrology and Indian Fertility Society (IFS) West Bengal Chapter held on 11 June 2023 at Kolkata

1. Troubleshooting in Male Subfertility
Moderators
• Dr Sudip Basu
• Dr Sujoy Dasgupta
Panelists
• Dr Aindri Sanyal
• Dr Amitoj Atwal
• Dr Biplab Roy
Chowdhury
• Dr Rohit Gutgutia
• Dr S M Rahman
• Dr Suchetana Sengupta
Expert
• Dr K D Nayar
• Dr Venugopal M

2. Semen Report 1
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

3. Semen Report 1
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

4. Male Infertility- Mild or Severe?
• TMSC= Total Motile sperm count = Sperm
concentration x total volume x total motility (TM)
• TMSC >5/ 10/ 20 million

5. What next?
• Straightaway donor sperm IUI
• Antioxidants for 3-6 months and repeat test
• Directly ICSI with self sperms
• Investigate in details

6. Prolonged use of antioxidants?

7. 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.

9. 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.

10. Hormonal Investigations
• FSH 5.21 IU/L (normal 1-10)
• LH 6.8 IU/L (normal 1-10)
• Testosterone 159 ng/dl (normal 200-800 )

11. 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)
• If T:E2 ratio <10 (T- ng/dl, E2- pg/ml),
consider Aromatase Inhibitors (Letrozole,
Anastrozole) (EUA, 2018; AUA, 2018)

12. Ultrasound showing varicocele

13. 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.

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

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

16. Male factor- IUI/ IVF/ICSI?
• Assess
1. Tubal factor
2. Ovarian reserve
3. Duration of Infertility
4. Age of the female partner

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

18. TMSC <5 million
• “Trial IUI”
• See IMSC (inseminating motile sperm count)
IMSC Next action
> 1 million further 3-4 cycles of IUI
<1 million
Morphology ≥4% further IUI can be
attempted
Morphology <4% ICSI

19. Any other thing?
• 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.

20. Double Ejaculate often produces
better quality of sperms

21. • Sperm concentration <5
million/ml
• Azoospermia
• Testicular atrophy
• Elevated FSH
(EUA, 2018; ASRM/ AUA, 2020)
• Karyotyping
• Y chromosome
Microdeletion (YMD)
Genetic testing in severe male
subfertility?

22. Genetic changes- what to do?
45, XY rob (14, 21), (q10, q10)
Robertsonian Translocation
46,XYqh-
Normal variant (polymorphism)

23. Semen Report 2
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

24. Semen Report 2
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 cetrigugation)
Round cells Nil

25. What next?
• Straightaway donor sperm IUI
• Testicular FNAC?

26. FNAC- role?
ASRM/ AUA, 2020
• Consider TESA in indeterminate cases- NOT
NECESSARY
FSH >7.6 <7.6
Testicular long axis <4.6 cm >4.6 cm
89% chance of NOA 96% chance of OA

27. Case 1- FNAC
• Azoospermia- one occasion
• FNAC- B/L maturation arrest
• FSH 0.22, LH 0.34, Testo 139
• Pituitary MRI- normal
• Started hCG f/b FSH
• After 6 months- 2 mil/ml

28. 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, 2018; ASRM/AUA, 2020

29. Hormone treatment vs ART
• Priority for natural conception
• Other indications of ART- female partners
• Time to pregnancy
• Cost
• Age of female partners

30. Case 2- FNAC

31. Orchidectomy/ Orchidopexy in adult?
• 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
EUA, 2018

32. Case 3- FNAC
“No sperms”
46,XX; SRY positive

33. Can we refuse surgical sperm
retrieval?
• Testicular volume 8 cc each side
• Serum FSH 20.52
FSH, testicular size or other markers-
can NOT be used for prediction/ refusal
(EUA, 2018; ASRM/AUA, 2020)

34. If previous FNAC showed unfavourable
report?
Diagnosis Chance of sperm retrieval
Sertoli-cell-only syndrome
(Germ cell hypoplasia)
32%
Maturation arrest 66.7%
(Late MA> Early MA)
Hypospermatogenesis 100%
Tuberous sclerosis 33.3%
Mixed atrophy 95.2%
(Schwarzer, 2013)

35. Y chromosome microdeletion

36. Predictors of sperm retrieval?
• 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.

37. Semen Report 3
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

38. Semen Report 3
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

39. What to assess?
• Abstinence period
• Completeness of collection
• Usual amount of ejaculate
• Exclude retrograde ejaculation- Post
masturbation urine
• Suspect obstructive pathology- TRUS

40. 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/AUA, 2020)
• Partner testing if the man is carrier
• Indian prevalence- 1:10,000- 1:40,000 (Kapoor et al., 2006;
Prasad et al., 2010)

41. Cases of CBAVD- TRUS and CFTR mutation
Partner testing needed
Partner testing NOT needed

42. Semen Report 4
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

43. Semen Report 4
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

44. What to do?
• Isolated abnormal morphology is not the
indication for ART
Penn HA, Windsperger A, Smith Z, et al. Fertil Steril. 2011; 95(7):2320–3.

46. What to do?
• Antibiotics?
• Culture?
• Anything else?

47. EUA, 2018

48. MAGI (Male Accessory Gland Infection)
• The clinical significance of an increased
concentration of leukocytes in the ejaculate is
controversial.
• Special Tests- Round cells vs Pus cells
• Method of collection
• Hand washing before collection
• Culture of semen
• Antibiotics- only when documented infections
• Look for phimosis
• Consider prostatic fluid culture
EUA, 2018; ASRM, 2020; Vignera et al., J Med Microbiology, 2014

49. “Pus Cells” and ART outcome

50. Treatment burden for MALE
infertility falls on FEMALE