Ivited lecture by Dr Sujoy Dasgupta in the CME organized by ArEx Pharma

1. Dr Sujoy Dasgupta
MBBS (Gold Medalist, Hons)
MS (OBGY- Gold Medalist)
DNB (New Delhi)
MRCOG (London)
Advanced ART Course for Clinicians (NUHS, Singapore)
MSc, Sexual & Reproductive Medicine (South Wales, UK)
Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata
Managing Committee Member, Bengal Obstetric & Gynaecological Society
(BOGS)
Secretary, Subfertility and Reproductive Endocrinology Committee, BOGS
Clinical Examiner, MRCOG (Part 3) Examination
Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019
Role of Multivitamins & Antioxidants in
Managing Male Infertility

2. Do we understand-
“Male Infertility”

3. 1. Men’s fertility potential
depends on female factors
• Assessment of tests and treatments for the male is
challenging due to inconsistent endpoints and the
observation that many of these endpoints are
dependent upon and measured from the female
partner.
• Ideally, the endpoint for fertility trials should be
"live birth or cumulative live birth (WHO, 2021)

4. 2. Reliance on semen analysis

5. WHO, 2021

6. Limitations of WHO 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
• Functional ability of the sperms?

7. 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
1
2
3
4
5
6

8. 3. 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. 4. Laboratory Issues

13. From which Laboratory?

14. 5. We cannot treat
We bypass

15. Treatment burden for MALE
infertility falls on FEMALE

16. 6. Semen collection- may NOT
be so easy
• Privacy
• Relaxation
• Bed
• Partner
• Washing facility
• Ask- Why Difficulty
• Erection issue
• Vibroejaculator
• Coitus interruptus
• Nontoxic condom
• Home Collection
• Urine (In RE)
• Prostatic Massage
• Electroejaculation

17. 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
Impression- Normozoospermia
• Treated for “male factor” with antioxidants
• Unexplained subfertility
• Conceived with OI with hMG first cycle, delivered
7. Can we interpret properly?

18. 8. Is it infection in semen?

19. 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
• Consider urethral swab/ prostatic fluid culture
EUA, 2018; ASRM, 2020; Vignera et al., J Med Microbiology, 2014

20. “Pus Cells” and ART outcome

21. A story of “Pus cells”
• 36-yr
• Apparently
unexplained
infertility
• Persistent Pus cells
in semen
• Culture negative
• Pain during
intercourse
• Phimosis
• No pus cells after
circumcision
• Conceived after OI,
delivered

22. Antioxidants in “Pus cells in semen”

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

24. 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)

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

26. Pathological effect of ROS on
sperm function
High concentrations and prolonged
exposure to ROS causes extensive
damage to various integral cellular
biomolecules, including proteins,
lipids and nucleic acids, which
hampers multiple cellular functions
Hypertension induced
Oxidative stress in Male
infertility
Hypertension and the development of
oxidative stress. There is proliferation
of the vascular smooth muscles and
the narrowing of vascular lumen. The
narrowing of the vascular lumen
leads to increase in the generation of
ROS, thus causing oxidative stress.
Diabetes and impaired
sperm function.
Hyperglycaemia can
increase the production of
advanced glycation end
products, causing imbalance
in the ratio of ROS
generation and elimination
by antioxidants, thereby
resulting in the development
of oxidative stress
Diabetes mellitus
induced Oxidative
stress in Male infertility
Front. Reprod. Health 4:822257., February
2022, volume 4, 1-15

27. Reproductive Consequences of
ROS and Oxidative Stress
In-Vitro Fertilization (IVF) / Intracytoplasmic
Sperm Injection (ICSI) Outcomes:
• ICSI is also affected for an excessive presence
of ROS molecules in seminal plasma and
sperm.
• The damaged cell development generated by
oxidative stress, causing apoptosis and
embryo fragmentation.

28. Antioxidants
Astaxanthin several-fold stronger antioxidant 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.

29. Combined conventional/antioxidant "Astaxanthin"
treatment for male infertility: a double blind,
randomized trial
• To evaluate the treatment of male infertility with a strong natural antioxidant.
• 30 men with infertility of ≥12 months and female partners with no cause of
infertility.
• Astaxanthin 16 mg/day or placebo for 3 months were given.
• Effects of treatment on,
 Semen parameters
 Reactive oxygen species (ROS)
 Zona-free hamster oocyte test
 Serum hormones including testosterone, LH, FSH and Inhibin B, and spontaneous or IUI-induced
pregnancies were evaluated
Asian J Androl 2005; 7 (3):
LH: Luteinizing Hormone, FSH: Follicle Stimulating Hormone, IUI:

30. Results:
• ROS and Inhibin B decreased
significantly.
• Sperm linear velocity increased in
the Astaxanthin group.
• The results of the zona-free
hamster oocyte test* tended to
improve in the Astaxanthin group.
• A total pregnancy rate of 54.5 % in
the Astaxanthin group.
• The conception per month was 23.1
% in the Astaxanthin group.
*The hamster zona-free ovum test (HZFO test), or hamster test is a method for
diagnosing male infertility due to the inability of the sperm to penetrate the ova.
Semen characteristics and hormone results at
baseline and after 3 months of treatment.
Conclusion:
The present study suggests a positive effect of Astaxanthin on sperm parameters and fertility.
Asian J Androl 2005; 7 (3):

31. Coenzyme Q10 supplementation in infertile men with low-
grade varicocele: an open, uncontrolled pilot study
• To evaluate the antioxidant capacity of seminal plasma of infertile
men with varicocele.
• 38 patients were recruited.
• Patients underwent an oral supplementation with CoQ10 at a dosage
of 50 mg twice a day for 12 weeks.
• A semen analysis was performed at baseline and 3 months.
• Coenzyme Q10 therapy improved semen parameters and
antioxidant status.
Andrologia. 2014 Sep;46(7):805-7

32. The effect of L-Arginine of treatment for infertile men on
semen parameters
• The study is to determine the effect of oral supplement of L-Arginine on semen
parameters as a treatment for infertile men.
• Study conducted on 15 infertile men.
• L-arginine was given orally at a dose 1000 mg one capsule per day morning.
• All semen parameters were measured, such as semen volume, sperm count,
motility, pH, Vitality and normal morphology and abnormal shape.
• Biochemical tests like, GSH, MDA, IL-6, and CRP, were analyzed according
standard procedures.
Tikrit Journal of Pure Science Vol. 24 (5) 2019, 1-4. Glutathione (GSH), Malondialdehyde (MDA), Interleukin 6 (IL-6), and C- Reactive protein (CRP).

33. The mean & standard deviation of semen
parameters of infertile men before &
after treatment with L- Arginine
 Significant reduction in Sluggish, abnormal
sperm shape and non-motile sperm count
after treatment with L-Arginine.
 L-arginine which provides protection against oxidative stress.
 It protects spermatozoa against lipid peroxidation by increased the release of nitric oxide gas.
 Supplement of arginine per day to infertile men markedly increased sperm count and motility.
 Significant elevation in the concentration of Glutathione (GSH). A significant reductions in
the concentration of Malondialdehyde (MDA), Interleukin 6 (IL-6), and C- Reactive protein
(CRP).
Tikrit Journal of Pure Science Vol. 24 (5) 2019, 1-4

34. • 60 patients were included with 30 patients in
case and 30 patients in control groups.
• Homocysteine lowering agents were given (folic
acid 5mg, vitamin B12 500 microgram, vitamin
B6 5 mg )
• Homocysteine lowering agents were given for 6
weeks.
• Re-assessed homocysteine levels after 6 weeks.
• Outcome:
 Conceptions over a period of one year were
also noted.
• Results:
 homocysteine levels was 10.4 µmol/l
Int J Reprod Contracept Obstet Gynecol. 2013 Jun;2(2):165-171
To study the role of hyperhomocysteinemia in
unexplained infertility
Conclusions:
 Homocysteine lowering agents
have a favourable impact on the
outcomes.
 Their use is suggested in cases of
infertility associated with
hyperhomocysteinemia.

35. Clomiphene:
• An anti-estrogen drug that stimulate spermatogenesis.
• It is useful in idiopathic cases of male infertility.
• It can increase male fertility hormones (FSH and LH) and stimulate sperm
production.
• It is also useful in some hypogonadal, infertile men with low testosterone levels.
• The recommended dose for infertile men is 25 mg or 50 mg three times per week.
• Possible side effects include headache, nausea, vomiting, diarrhea, flushing and visual
disturbances such as blurred vision.
Empirical Therapies: Antiestrogen, Aromatase
Inhibitors
In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available
from: https://www.ncbi.nlm.nih.gov/books/NBK562258/

36. Tamoxifen:
• It is an estrogen receptor blocker that improve semen parameters,
when used together with clomiphene.
• It can improve sperm counts and other semen parameters in
infertile men.
• The usual dose is 10 mg twice a day.
• Possible side effects includes weight gain, edema, leg swelling,
nausea, skin rash and erectile dysfunction.

37. Aromatase Inhibitors (Anastrozole and Letrozole):
• Aromatase inhibitors are medications that block the conversion of
testosterone to estrogen.
• They are considered the treatment of choice for infertile males.
• They improve abnormal semen and hormonal parameters.
• The recommended dose of anastrozole is 1 mg three times a week,
while the dose of letrozole is 2.5 mg three times a week.
• The most common side effect reported with these medications is joint
pain and stiffness.

38. 10. Severe Male Factor is 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)

39. Sperm abnormality may be the
first symptom of testicular cancer
• 31 yrs
• Came for IUI (D)
• Malignant teratoma-
treated by orchidectomy
and chemotherapy

40. 11. Severe Male Factor- if not
left untreated ???
• Progressive decline in semen parameters

41. • 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.

42. 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, Finesteride,
cytotoxic drugs, steroids
• Sexual history- Low libido, ED

43. If previously fathered a baby?
• Secondary subfertility of 6 yrs
• Previous- one male baby, 10
yrs, natural conception
• Only female was evaluated
initially
• Male- azoospermia on
repeated occasions
• Diabetic for 7 yrs,
uncontrolled
• Endocrine, imaging all normal
• Lost to F/U
• Secondary subfertility of 10 yrs
• Previous- one male baby, 12
yrs, natural conception;
followed by 2 TOP
• Only female was evaluated
initially- multiple cycles of OI
with CC, letrozole, hMG
• Varicocele surgery 10 yr ago
• Male- Severe OAT on several
occasions
• Endocrine, imaging all normal
• Planning for ICSI

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

45. Prader’s Orchidometer

46. 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.

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

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

49. Varicocelectomy- How, when?
• Sclerotherapy
• Embolization
• Scrotal operation
• Inguinal operation
• Laparoscopic approach
• High ligation
• Microsurgical
varicocelectomy- most
effective method with
minimum risks of
complications and lower
recurrence rates (EUA, 2018)
Positive Predictive Factors
1. Grade 3 varicocele
2. TMSC ≥5 million
3. High SDF
Samplaski and Jarvi, 2016

50. Antioxidants in Varicocele

51. Congenital bilateral absence of
vas deferens (CBAVD)
• Semen- Volume <1.5 ml, pH <7.0, fructose negative
• TRUS
• 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)

52. Case of CBAVD

53. CFTR mutation present
• Fructose negative, pH 6.0,
Vol 0.5 ml
• B/L vasa absent
• TRUS- Absent Rt SV
• CFTR mutation present
• Wife- CFTR- no mutation

54. CBAVD is NOT uncommon
• 40 yr, CBAVD
• TRUS- Rt SV absent,
Lt SV very small
• FSH 3.8, Testo 353
• TESA- Motile sperms
• CFTR negative
• ICSI done, no
pregnancy
• 35 yr, CBAVD
• TRUS- B/L SV
absent
• IUI (D) twice,
Lost to F/U
• 33 yr, CBAVD diagnosed
during hydrocele Sx
• Subsequently
azoospermia
• TRUS- Rt SV absent, Lt
SV very small
• FSH 2.62, LH 8.79, Testo
406
• Did IUI (D), conceived

55. 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

56. Cryptorchidism- Multidisciplinary
approach
• 28 years
• Nonobstructive azoospermia
• Testo 74.47, LH 17.25, FSH 29.91
• H/O Laparotomy for GI perforation , 17
yr age
• MRI advised by Urologist
• Endocrinologist started TRT
• 3 cycles IUI (D) failed
• Conceived after first cycle of IVF with
donor sperms- twin pregnancy,
spontaneous reduction to single tone

57. B/L cryoptorchidism in ADULTS!!!

58. Transverse testicular ectopia (TTE), or
crossed testicular ectopia (CTE)

59. Importance of history and examination
Rt sided orchidopexy during appendicectomy at 18 yr
Subsequently Rt testis atrophied
Lt side operated after 6 months, could not be brought to scrotum,
biopsied, seen by MRI (not seen in USG)

60. 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)

61. Epididymal cyst
NOT associated with infertility
Surgery may cause obstruction

62. Testicular microlithiasis
• Azoospermia
• FSH 17.77, LH 5.67, Testo 7.24
nmol/l, E2 13.32
• Trial TESE- B/L Maturation Arrest
• Finally decided for IUI (D)
•Mumps orchitis 20 yr age
•FSH 29.7 LH 6.49, Testo 219, E2 37, Ratio
<10
•Letrozole for 4 months → Azoospermia
persists
•Trial TESE- No sperms found-
•H/P- SCO (Sertoli cell Only)
•3 cycles IUI (D) failed, opts for IVF with
donor sperms
•Conceived, 12/40

63. 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

64. 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)

65. Ill effects of exogenous testosterone
• 35 yr,
• 2019- 1-2 sperms/ hpf
• 2019- FSH 24.88, LH 5.7, Testo 210
• Received testosterone
• 2020- azoospermia (vol 2.5 ml, pH 7.7)
• 2020- FSH 1.12, LH 0.73, Testo 812
• Rt vas felt, Lt vas absent
• Endocrinology referral → hCG + FSH

66. 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

67. Stories of Hypo/Hypo
• 32, yr, H/O delayed puberty
• Was on TRT (17-23 yr age)
• Gynaecomastia surgery, 22 yr
• LH 0.06, FSH 0.02, Testo 0.63, PRL
1.18, TSH 2.48
• Low libido, ED
• Anosmia, MRI- B/L olfactory bulb
absent
• Genetic tests advised, Lost to F/U.
•36 yr, Azoospermia
•sudden loss of body hair, low libido→
nonfunctioning Pituitary macroadenoma →
Endoscopic surgery H/P Lymphocytic
hypophysitis
•Sexual function and sec sex characters
improved after Sx
•On cortisol, L-thyroxine supplementation
•Azoospermia persists
•Started hCG f/b hMG by endocrinologist
•Sperm conc 1-2/ hpf
•Advised to continue hMG

68. Antioxidants in
severe male factor?

70. 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.

71. TMSC PR/CYCLE
 10–20 million 18.29%
 5–10 million 5.63%
 <5million 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
IUI, IVF or ICSI?

72. TMSC <5 mil/ml and 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

73. Antioxidants before IUI
Agarwal A, Majzoub A, 2017

74. Antioxidants before ART
Agarwal A, Majzoub A, 2017

75. Strategies in Severe OAT
• Donor sperm is NOT the solution
• Investigate the cause
• Consider freezing of the sperms
• Short “trial” of medical therapy
• Trial IUI- Double ejaculate, IMSC
• ICSI is the standard treatment

76. Ejaculate vs Testicular sperms

77. Surgical Sperm Retrieval (SSR) in
Azoospermia (OA>NOA)

78. Azoospermia- FNAC?
• Nonobstructive
Azoospermia- one
occasion
• FNAC- B/L maturation
arrest
• FSH 0.22, LH 0.34, Testo
549
• Pituitary MRI- normal
• Started hMG
• After 6 months- 2 mil/ml

79. Investigation depends on the plan
• B/L testes- 6 cc
each
• FNAC- B/L
maturation arrest
• FSH 37.2, LH 24.4,
Testo 245.53, E2
37, ratio <10
• Not keen for IVF-
ICSI

80. FNAC- role?
• Isolated foci of spermatogenesis
• “Trial TESA/TESE”
• If obtained, cryopreserve the sperms
ASRM, 2020
• FSH >7.6 AND testicular long axis <4.6 cm- 89% chance
of NOA
• FSH <7.6 AND testicular long axis >4.6 cm- 96% chance
of OA
• Consider TESA in indeterminate cases- NOT
NECESSARY

81. 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%

82. Predictors of sperm retrieval?
• 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 non-obstructive
azoospermia.
• The ONLY negative prognostic
factor is the presence of AZFa
and AZFb microdeletions.

83. Genetic testing
• Sperm
concentration <5
million/ml
• Azoospermia
• Testicular atrophy
• Elevated FSH
• Karyotyping
• Y chromosome
Microdeletion
(YCM)
• CFTR testing- for
CBAVD

84. In presence of genetic defect
• Sperm Aneuploidy testing by FISH
• PGT-SR (previously- PGD) (EUA, 2018;
ASRM, 2020)

85. Alternative- Prenatal testing
(46,XY22ps+)

86. Klinefelter Syndrome
• 36 yr.
• FSH 44.83, Testo 5.12 nmol/L (Low), E2 17
• Not interested in ICSI
• Referred for TRT
• Lost to F/U

87. Klinefelter’s with normal phenotype
• 37 yr
• FSH 35.42, LH 10.13, testo 93, E2 14.45
• Undiagnosed Diabetes
• Prev FNAC- Lt side- Sertoli Only Syndrome
• TESE – Rt side- No sperms, Lt side- Motile Sperms

88. 46,XYqh-
• 35 yrs
• Initially Azoospermia
• Subsequent- few motile sperms/ hpf
• FSH 12.6, LH 5.5, Testo 527
• ICSI done with ejaculated sperms, delivered

89. Robertsonian Translocation
•45, XY rob (14, 21), (q10, q10)
•38 yr, NOA
•Diabetic for 10 yr

90. Sperm Aneuploidy test by FISH
• Trial TESE- motile
sperms obtained,
sent for FISH
• ICSI 1st cycle done,
biochemical
pregnancy
• ICSI second cycle
attempted- empty
follicle syndrome,
TESE not done

91. Genetic abnormality ≠ Donor sperms
• 35 yr
• Mumps Orchitis 16 yr
of age
• Azoospermia
• FSH 29.65, LH 15.64
• FNAC- B/L
hypospermatogenesis
• 46,XY,16qh+
• Normal variant
• ICSI done, now 28/40

92. AZF factor
• 32 yr
• Azoospermia
• FSH 10.02, LH 3.90, Testo
453.4
• USG scrotum- Grade 3
varicocele
• Varicose vein
• Karyo- 46,XY
• Brother- azoospermic
• 30 yr
• Azoospermia
• FSH 4.78, LH 5.34, E2 26.37, Testo
208.3, Ratios <10:1
• TRUS- Prostatitis
• USG Scrotum- Normal
• Karyo- 46, XY

93. Y chromosome Microdeletion
• 35 yr
• Azoospermia
• FSH 30.73, LH 8.75,
Testo 120.51, E2 29.43,
T:E <10

94. AZF-c- Good prognosis
• 38 yr
• 1 million/ml, TM 10%
• Endocrine profile normal
• Imaging unremarkable
• Karyo, 46, XY
• YMD- AZFc deletion
• ICSI done with ejaculated
sperms, 1st cycle beta hCG
negative
• Conceived after 2nd cycle
ICSI, now 32/40

95. More Genetic Abnormalities

96. Medical Therapy in Idiopathic
Azoospermia
• hCG, hMG, CC, Letrozole- Conflicting
results
• Antioxidants???

97. Antioxidants before SSR
Agarwal A, Majzoub A, 2017

98.  Meticulous semen analysis in a standard laboratory
 Physical examination and rational investigations
 Avoid non-evidence based drugs for long time
 Antioxidants- Useful in mild problem
 Antioxidants- Not reliable in severe problem
 Donor sperm is NOT the only solution
 IUI or ICSI- depends on the overall assessment
Take Home Messages