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Male Infertility
Moderators
• Dr Sujoy Dasgupta
Panelists
• Dr Kaushiki Roy
• Dr Rohit Gutgutia
• Dr Saurav Prakash Maity
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
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
Male Infertility- Mild or Severe?
• TMSC= Total Motile sperm count = Sperm
concentration x total volume x total motility (TM)
• TMSC >5/ 10/ 20 million
What next?
• Straightaway donor sperm IUI
• Antioxidants for 3-6 months and repeat test
• Directly ICSI with self sperms
• Investigate in details
Prolonged use of antioxidants?
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.
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.
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 )
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)
Ultrasound showing varicocele
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.
Surgery for Varicocele (EUA, 2018)
• Grade 3 varicocele
• Ipsilateral testicular atrophy
• Abnormal semen parameters
• No other fertility factors in the couple
In couples seeking fertility with ART, varicocele repair
• may offer improvement in semen parameters
• may decrease level of ART needed
Male factor- IUI/ IVF/ICSI?
• Assess
1. Tubal factor
2. Ovarian reserve
3. Duration of Infertility
4. Age of the female partner
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?
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
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.
Double Ejaculate often produces
better quality of sperms
• 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?
Genetic changes- what to do?
45, XY rob (14, 21), (q10, q10)
Robertsonian Translocation
46,XYqh-
Normal variant (polymorphism)
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
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 cetrifugation)
Round cells Nil
What next?
• Straightaway donor sperm IUI
• Testicular FNAC?
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
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
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
Hormone treatment vs ART
• Priority for natural conception
• Other indications of ART- female partners
• Age of female partners
• Time to pregnancy
• Cost
Case 2- FNAC
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
Case 3- FNAC
“No sperms”
46,XX; SRY positive
Case 4- FNAC
• LH 30.10, FSH 43.70, E2 38.48, Testo 432
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)
If previous FNAC showed unfavourable
report?
Diagnosis Chance of sperm retrieval by
Micro TESE
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)
Y chromosome microdeletion
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.
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
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
What to assess?
• Abstinence period
• Completeness of collection
• Usual amount of ejaculate
• Exclude retrograde ejaculation- Post
masturbation urine
• Suspect obstructive pathology- TRUS
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)
Cases of CBAVD- TRUS and CFTR mutation
Partner testing needed
Partner testing NOT needed
What to do?
• Antibiotics?
• Culture?
• Anything else?
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
“Pus Cells” and ART outcome
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 16.56 million/ ml TMSC 33.12 million
Normal Morphology 5% Abnormal Morphology 95%
Vitality 32% Round cells Nil
• Treated for “male factor” with antioxidants
• Unexplained subfertility
• Conceived naturally, delivered
A silly question?
Reliance of Semen “Reference Range”
Limitations of WHO Semen Analysis
Guideline
• 5 percentile and time-to-pregnancy (TTP) concept
• Not true reference values but recommends
acceptable levels.
• Day to day variation
• Functional ability of the sperms?
Treatment burden for MALE
infertility falls on FEMALE
Male Infertility Panel Discussion by Dr Sujoy Dasgupta

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Male Infertility Panel Discussion by Dr Sujoy Dasgupta

  • 1. Male Infertility Moderators • Dr Sujoy Dasgupta Panelists • Dr Kaushiki Roy • Dr Rohit Gutgutia • Dr Saurav Prakash Maity
  • 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.
  • 8.
  • 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)
  • 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 cetrifugation) 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 • Age of female partners • Time to pregnancy • Cost
  • 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. Case 4- FNAC • LH 30.10, FSH 43.70, E2 38.48, Testo 432
  • 34. 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)
  • 35. If previous FNAC showed unfavourable report? Diagnosis Chance of sperm retrieval by Micro TESE 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)
  • 37. 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.
  • 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. 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
  • 40. What to assess? • Abstinence period • Completeness of collection • Usual amount of ejaculate • Exclude retrograde ejaculation- Post masturbation urine • Suspect obstructive pathology- TRUS
  • 41. 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)
  • 42. Cases of CBAVD- TRUS and CFTR mutation Partner testing needed Partner testing NOT needed
  • 43.
  • 44. What to do? • Antibiotics? • Culture? • Anything else?
  • 45. 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
  • 46. “Pus Cells” and ART outcome
  • 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 36 million/ ml Total Motility 46% Progressive Motility 33% Non progressive Motility 13% Immotile 54% Motile Sperm Count 16.56 million/ ml TMSC 33.12 million Normal Morphology 5% Abnormal Morphology 95% Vitality 32% Round cells Nil • Treated for “male factor” with antioxidants • Unexplained subfertility • Conceived naturally, delivered A silly question?
  • 48. Reliance of Semen “Reference Range”
  • 49. Limitations of WHO Semen Analysis Guideline • 5 percentile and time-to-pregnancy (TTP) concept • Not true reference values but recommends acceptable levels. • Day to day variation • Functional ability of the sperms?
  • 50. Treatment burden for MALE infertility falls on FEMALE