Invited lecture by Dr Sujoy Dasgupta in a Webinar organized by Emcure IVA Division held in May, 2021

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
Case Discussion on Male Infertility

2. 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

3. WHO Standard 2010
1
2
3
4
5
6

4. 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
• Functional ability of the sperms?

5. 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)

6. Significance of SDF
• Live birth after IUI/ IVF/ ICSI- ?
• Oocytes can repair the damaged DNA
• Lack of standardization
• Lack of definitive treatment
Should not be routine (ASRM, 2020)

8. From which Laboratory?

9. Issues in Semen Collection
• Privacy
• Relaxation
• Bed
• Partner
• Washing facility

10. Issues in Semen Collection
• Ask- Why Difficulty
• Erection issue
• Vibroejaculator
• Coitus interruptus
• Nontoxic condom
• Home Collection
• Urine (In RE)
• Prostatic Massage
• Electroejaculation
• TESA

11. Leukocytospermia

12. 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

13. “Mild” Male Factor
• TMSC= Total Motile sperm count = Sperm
concentration x total volume x total motility (TM)
• TMSC >5/ 10/ 20 million

14. Mild Male Factor
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)

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

16. Severe Male Factor
• 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)

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, Finesteride,
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. 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

25. 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)

26. 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

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

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

30. 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.

31. • 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.

32. IUI, IVF or ICSI?
Criteria TMSC Treatment
Pre wash TMSC > 5 million IUI
Pre wash TMSC 1 - 5 million IVF
Pre wash TMSC <1 million ICSI

33. 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

34. 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
• ICSI- Ejaculated sperms vs testicular sperms
(TESE)

35. Azoospermia (OA>NOA)

36. FNAC- role?
• “Trial TESA”
• 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

37. Predictors of sperm retrieval?
• No reliable positive prognostic factors
• FSH and Testicular Size- No
• The only negative prognostic factor is the
presence of AZFa and AZFb microdeletions.
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%

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

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

40. Ejaculation Problems
• DM
• Spinal cord Injury
• Neurological diseases
• Obstruction
• Surgery to bladder neck
• Medication- SSRI, PDE-5 blockers, alpha-
blockers

42. Strategies in Ejaculatory
disorders
• Pharmacotherapy
• Vibroejaculator
• Post-masturbation urine (PMU)- After
alkalinization- IUI/ IVF/ ICSI
• Elactroejaculation
• TESA

43. Case Discussions
•Written informed consent was taken
from ALL the patients
•Confidentiality maintained

44. Case 1
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
• Unexplained subfertility
• Treated for “male factor” with antioxidants
• Conceived with OI with CC first cycle

45. Case 2
• 36-yr-old Bank
Manager
• Apparently
unexplained
infertility
• Persistent Pus cells
in semen
• Culture negative
• Pain during
intercourse

46. Case 2 (Contd)
• No pus cells after circumcision
• Conceived after OI with CC

47. Case 3
• Primary subfertility
• Persistent mild male factor
• Stopped smoking
• Concentration 10-14 million/ml, TM 30-38%
over last one year
• Not willing for IUI
• H/O repeated attacks of Tinea crusis (jock-
itch)

48. Case 3 (Contd)
• Local and systemic antifgungal by dermatologist
• Semen could not be retested
• Conceived spontaneously

49. Case 4a
• 42-yr male, office
worker
• Severe OAT
• Hypergonadotrophic
hypogonadism
• Twin brother having
same problem
• Can’t afford ICSI
• Opted for IUI (D)
• Lost to follow up

50. Case 4b
• 28 years
• Nonobstructive azoospermia
• Testo 74.47, LH 17.25, FSH 29.91
• H/O Laparotomy for GI perforation , 17 yr age

51. Case 4b (Contd)
• Endocrinologist started TRT
• 3 cycles IUI (D) failed
• Conceived after first cycle of IVF with donor
sperms- now 24/40, twin pregnancy

52. Case 5
• 35 yr-old businessman
• Azoospermia
• Referred for TESE-ICSI
• Refused donor sperms
• FSH 31.2
• LH 6.2
• Testo 90
• Estradiol 96.2
• T:E2 <10:1

53. Case 5 (Contd)
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 USG at lower abd

54. Case 6
• Age 34
• Orchidopexy at 8 yr
age
• B/L testes atrophic,
found at superficial
inguinal ring
• Lost to F/U

55. Case 7
• 29 yr-old
• First medical consultation ONLY after diagnosis of
azoospermia

56. Case 8-10
• 25 yr
• Requested not to
disclose
cryptorchidism to
female partner
• 36 yr
• Initial c/o Erectile
dysfunction
• Subsequently-
azoospermia
• Conceived with IUI (D)
• 39 yr
• First time
disclosed while
evaluating
azoospermia

57. Case 11
• 31 yrs-old
• Came for IUI (D)
• Too reluctant for physical examination
• Malignant teratoma- treated by orchidectomy and chemotherapy

58. Case 12
• 34-yrs-old, Army-man, past smoker
• Repeated analysis- 100% immotile sperms
• Advised varicocelectomy outside
• No palpable varicocele
• Went for ICSI
• Ejaculated sperms- poor morphology
• TESA- ICSI done, Conceived but miscarried by 12 wk

59. Case 13
• 35 yrs
• Initially Azzospermia
• Subsequent- few motile sperms/ hpf
• FSH 12.6, LH 5.5, Testo 527
• ICSI done with ejaculated sperms, FET awaited

60. Case 14
• 34 yr, IT worker with azospermia
• Did 8 cycles of IUI (D) outside
• Semen- 0.5 ml. pH 6.8, Fructose NEGATIVE
• B/L vasa not palpable
• Renal USG normal

61. Case 14 (Contd)
• Trial TESA- B/L normotile sperms, (Lt>Rt)
• Lt TESE- few motile sperms obtained, frozen
• 2 cycles of ICSI done with fresh sperms by TESE
• 1st ICSI cycle- Biochemical pregnancy
• 2nd ICSI cycle- Now continuing pregnancy at 14 wk

62. Case 15
• 37 yr with azoospermia
• Volume 1 ml, pH 6.8,
Fructose- not mentioned
• FSH 3.34, LH 2.28,
Testo 457
• CBAVD
• Trial TESA done- motile
sperms obtained
• CFTR testing advised-
report awaited

63. Case 16-18
• 40 yr, CBAVD
• TRUS- Rt SV absent,
Lt SV very small
• FSH 3.8, Testo 353
• FNAC- B/L normal
spermatogenesis
• 35 yr, CBAVD
• TRUS- B/L SV
absent
• 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

64. Case 19
40-yrs-old IT Professional
Mild oligospermia (12 mil/ml)
5 cm (large) epididymal cyst/ Spermatocele
IUI was planned
Natural conception

65. Case 20
• 35 yr, office worker
• 2019- 1-2 sperms/ hpf
• 2019- FSH 24.88, LH 5.7, Testo 410
• 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. Case 21
• 26 yr
• Concentration 14
million/ml, motility
35%, pus cells 8-10/ hpf
• Occasional Rt scrotal
pain
• After antibiotics-
symptoms subsided,
semen became normal

67. Case 22
• 31 yr, Doctor
• Azoospermia repeatedly
• Volume 3 ml, pH 7.8,
Fructose positive
• FSH 17.77, LH 5.67,
Testo 7.24 nmol/l, E2
13.32

68. Case 22 (Contd)
• Trial TESE done
• B/L Maturation Arrest (no spermatid, only
spermatogonial cells)
• Finally decided for IUI (D)

69. Case 23
• 33 yr, teacher
• Mumps orchitis 20 yr age
• FSH 29.7 LH 6.49, Testo 219, E2 37, Ratio <10
• Letrozole started
• Planning for trial TESA

70. Case 24
• 36 yr, businessman
• Apparanetly unexplained
infertility
• Multiple cycles of OI
• C/O inability to deposit
sperms in the vagina
• Multiple operations for
hypospadias
• Conceived after 1st cycle
of IUI (H), delivered

71. Case 25
• 36 yr. carpenter
• FSH 44.83, Testo 5.12 nmol/L (Low), E2 17
• Referred for TRT
• Lost to F/U

72. Case 26
• 37 yr, businessman
• FSH 37.2, LH 24.4, Testo 245.53
• FNAC done before karyotyping- Maturation arrest (B/L)
• Both elder and younger brother are fertile
• Opted for IUI (D)

73. Case 27
• 29 yr, IT worker
• Presented with erectile dysfunction and low libido
• Could not produce semen despite repeated attempts
• Hypergonadotropic hypogonadism
• Referred for TRT
• Lost to F/U

74. Case 28-29
• 35 yr, Policeman
• FSH 19.26
• Trial TESA- Motile
sperms obtained
• ICSI done, conceived,
continuing at 10 wk
• 42 yr, Farmer
• FSH 5.7
• Trial TESE- No
sperms obtained
• Refused donor sperms

75. Case No 30
•45, XY rob (14, 21), (q10, q10)
•38 yr, businessman, azoospermic
•Diabetic for 10 yr

76. Case No 30 (Contd)
• Trial TESE- motile
sperms obtained,
sent for FISH
• ICSI 1st cycle done,
biochemical
pregnancy
• ICSI second cycle
attempted- empty
follicle syndrome,
TESE not done

77. Case No 31
• 35 yr, Teacher
• Mumps Orchitis 16 yr
of age
• Azoospermia
• FSH 29.65, LH 15.64
• FNAC- B/L
hypospermatogenesis
• 46,XY,16qh+
• Normal variant

78. Case No 32
• 32 yr, Office worker
• Prev relationship- surgical
TOP
• Azoospermia
• FSH 6.83, LH 3.69, Testo
631, E2 42.38 high
• 46,X,Y(q+)
• Large Y chromosome(Yq+)
- increased risk for
miscarriage
• Opted for IUI (D) for
financial constraint

79. Case No 33
• 35 yr, teacher
• Azoospermia
• FSH 30.73, LH 8.75,
Testo 120.51, E2 29.43,
T:E <10

80. Case 34-35
• 32 yr, Office Worker
• Azoospermia
• FSH 10.02, LH 3.90, Testo
453.4
• USG scrotum- Grade 3
varicocele
• Karyo- 46,XY
• Brother- azoospermic
• 30 yr, Lawyer
• Azoospermia
• FSH 4.78, LH 5.34, E2
26.37, Testo 208.3, Ratios
<10:1
• TRUS- Prostatitis
• USG Scrotum- Normal
• Karyo- 46, XY

81. Case 36
• 38 yr, policeman
• 1 million/ml, TM 10%
• Endocrine profile
normal
• Imaging unremarkable
• Karyo, 46, XY
• YMD- AZFc deletion
• ICSI done with
ejaculated sperms,
conceived, delivered

82. Case 37
• 39 yr, teacher
• 2012- 4 million/ ml; 2013- 0.5 mil/ml
• 2016- Azospermia (repeatedly)
• 2016- FNAC- hypospermatogenesis
• 2018- FSH 5.36, LH 4.6, Testo 537
• Testicular size normal
• 2019- TESE- No sperms obtained, ICSI done with donor sperms-
conceived, delivered

83. Case 38-39
• 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

84. Case 40
• 32, office worker
• 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 awaited

85. Case 41
• 35 yr, office worker
• 2019- 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 diagnosed
• Started hCG f/b hMG by endocrinologist
• Sperm conc 1-2/ hpf
• Advised to continue hMG

86. Case 42
• 38 yr, accountant
• Anejaculation during coitus
• Not used to masturbation
• Physical exam- unremarkable
• H/O circumcision 34 yrs
• Hormone profile, sugar- normal
• Did TESE-ICSI outside, failed
• Able to ejaculate with vibrator
• Normal semen
• Advised self-insemination (LH kit)
• Conceived, delivered

87. Case 43
• 40 yr, lecturer
• H/O neurological ds (?) by 32 yr → Secondary loss of ejaculation
• Post-masturbation urine- no sperms
• Vibroejaculator- failed
• Lt Testis atrophic, Rt testis normal
• Hormone profile, sugar- normal
• TESE-ICSI done twice
• Poor quality sperms
• No transferable embryos on D2 and D3 (female age 38)
• Donor gamete not acceptable

88. Case 44
• Came with “Primary
subfertility”
• Female factors normal (AMH,
HSG)
• Male- 32, Businessman
• Could not collect semen
• Disclosed- never had
consummation
• ED and anejaculation
• Hormonal profile, sugar-
normal
• Genitals- NAD
• Requested AID without
woman’s consent

89. Case 45
• P0+3, all early miscarriage, no H/O
subfertility
• Female- 32, Male- 35
• H/O unremarkable
• Karyotypes of both normal
• Femal- USG, APLA, TSH, sugar-
normal
• Advised ICSI elsewhere because of
high SDF
• Subclinical varicocele
• Male- Undiagnosed DM
• Blood sugar controlled
• Conceived spontaneously, cardiac
activity seen, now 10 wk

90.  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