Dr Sujoy Dasgupta moderated a session of Case Discussion on "Subfertility" in a CME organized by Torrent in November, 2022

1. Discussion on “Subfertility”
Moderator
• Sujoy Dasgupta
Panelists
• Bidisha Roy
Chowdhury
• Dipanjan Bandhya
• Mayukh Chakraborty
• Partha Bhattacharyya
• Shobhan Deb Kalapahar

2. Dr Sujoy Dasgupta
MBBS (Gold Medalist, Hons)
MS (OBGY- Gold Medalist)
DNB (New Delhi)
MRCOG (London)
Advanced ART Course for Clinicians (NUHS, Singapore)
M Sc, Sexual and Reproductive Medicine (South Wales, UK)
Consultant: Reproductive Medicine, Genome Fertility
Centre, Kolkata
Clinical Examiner, MRCOG Part 3 Examination
Winner, Prof Geoffrey Chamberlain Award, RCOG World
Congress, London, 2019

5. DR MAYOUKH
CHAKRABORTY
MBBS, DGO, MD(PGI, Chandigarh)
Fellowship in Reproductive
Medicine,Kiel,Germany
ASSISTANT PROFESSOR, KPC MEDICAL
COLLEGE & HOSPITAL
VISITING CONSULTANT AMRI,
MUKUNDAPUR
ASSOCIATE CONSULTANT ANKURAN
IVF & FERTILITY CENTRE

6. Dr. Partha Bhattacharyya
MBBS, DGO, MS(O&G), MRCOG
Ob Gyn Specialist: Maniktala ESI Hospital,
Kolkata
Overseas Faculty: Lincoln University College,
Kuala Lumpur
Examiner, Part 3 MRCOG

7. MBBS,MS(G&O),DNB(G&O),FNB(REPRODUCTIVE
MEDICINE).
CONSULTANT,INSTITUTE OF REPRODUCTIVE
MEDICINE,SALTLAKE.
CONTRIBUTED CHAPTERS IN DIFFERENT
INFERTILITY BOOKS.
PRESENTED PAPERS IN DIFFERENT NATIONAL AND
INTERNATIONAL CONFERENCE.

9. Case Scenario 1
• Mrs BD, 26 yr- irregular
cycle since menarche
• BMI 30 Kg/M2
• HSG and semen
analysis- normal
• Ultrasound-

10. Line of management?
• Weight loss
• Ovulation induction
• Insulin sensitizers
 How?
 Any specific target?
 Which agent?
 How long?
 Follicular tracking?
 Metformin?
 Inositol?

11. Weight reduction
• BMI <27 kg/m2 for women trying to conceive
(NICE, 2013).
• “SMART” (sustainable, measurable,
achievable, realistic and timely) goal (ESHRE,
2018).
• 5-10% weight loss can have positive impact

12. Ovulation Induction- CC vs Letrozole
• Letrozole is considered as the first line of agent
in PCOS (ACOG, 2018; ESHRE, 2018).
• The PPCOS II (Pregnancy in PCOS) trial-
better pregnancy and live birth rates than CC (Legro
et al., 2014)
• More favourable molecular markers of
implantation in the endometrium than CC
(Mehdinejadiani et al., 2019; Miller et al., 2012; Ganesh et al., 2014).
• Less incidence of multiifollicular development
(Franik et al., 2018; Teede et al., 2018).

13. Monitoring of OI cycle
• CC cycle- to see response and risk of OHSS
(NICE, 2013)
• Letrozole- risk of multiple pregnancy 3-7%
(Fritz and Speroff, 2011).
• HOMP recorded with letrozole (Warraich and Vause,
2015).
• Midluteal serum progesterone – limited role
• TVS should be done in the first cycle of
Letrozole.

14. Metformin
Modest reduction in
weight
NOT recommended as appetite suppressant
(Morley et al., 2017)
Metformin + CC •May increase ovarian response to CC (NICE,
2013; Vandermolen et al., 2001; Hwu et al., 2005)
•The PPCOS I trial- Live birth rates
1. CC alone 22.5%
2. Metformin alone 7.2%
3. CC and Metformin 26.8% (Legro et al., 2007).
Metformin + Letrozole No Data
Metformin +
Gonadotropin
Significantly reduces the risks and severity of
OHSS (Huang et al., 2015; Palomba et al., 2013).
Consider Metformin For OVERWEIGHT PCOS, especially if NOT
responding to CC (ESHRE, 2018)

15. Inositol
• Combination of D-chiroinositol and
myoinositol- 40:1 ratio- improves ovulation
(Formuso et al., 2015; Monastra et al., 2017; Facchinetti et al., 2015).
• Use of inositol in PCOS should be considered
“experimental”, although some studies
showed promising results (ESHRE, 2018)

16. Mrs BD now reduced weight
• Current BMI 26 kg/m2
• Taken letrozole 5 mg/day for OI
• No dominant follicle developed
• Next step?

17. If letrozole does NOT work?
• Try CC?
• Add insulin sensitizers?
• Try Gonadotropin?
• Advise LOD?
 Evidence for CC if letrozole
does not work ?
 hMG versus rFSH?
 Any specific precautions?
 To do or not at all?
 Pre-operative evaluation?
 Specific surgical precaution?

18. Gonadotropin in PCOS
• Second line of agent for women resistant to oral agents (NICE,
2013; ESHRE, 2018).
• Risk of OHSS and multiple pregnancy
• Step up regimen, starting with lower dose (37.5 to 75 IU/day)
and gradually increasing the dose
• Intense monitoring
• Trigger with hCG ONLY if 1-2 mature follicles (ESHRE, 2018).
• Theoretically- demerit of hMG- contains LH
• Meta-analysis- rates of ovulation, pregnancy, miscarriage, live
birth and OHSS- similar between FSH and hMG- (Weiss et al.,
2015).

19. Laparoscopic Ovarian Drilling (LOD)
• Second line of treatment as the
alternative to gonadotropin
(NICE, 2013; ESHRE, 2018).
• Commonly 3-6 punctures are
done in each ovary, avoiding the
tubal-ovarian interface
• Post-op spontaneous ovulation
rate 40-90% and 50% of them
conceive (Fritz and Speroff, 2011)
• Less incidence of multiple
pregnancy and OHSS
• Does not require extensive
monitoring
• Anaesthetic risks, risk of
adhesion formation and POF
(Lepine et al., 2017; ESHRE, 2018).
• Should have serum LH >10
IU/L and BMI <30 kg/m2
(Fritz and Speroff, 2011).
• Systematic review- LOD
was NOT superior to
gonadotropin therapy in
terms ovulation and
pregnancy rates (Farquhar et
al., 2012).

20. Mrs BD underwent LOD
• Subsequently responded to letrozole
• Taken 8 cycles of letrozole
• Failed to conceive
• Now wants to do IUI

21. Where IUI should be done?

22. Level 1 ART Clinic
• Preliminary investigations including diagnosis of
type, cause of infertility
• Only IUI is carried out as part of treatment.
• An application for registration shall be made by
the ART Clinics to the Appropriate Authority in
duplicate, in Form 3
• Application fee of: Rs 50,000
• Minimum staff requirement
01 Gynecologist with qualifications with at least 3
years of experience on Reproductive Medicine
01 Counselor with qualifications as specified

23. Requirements

24. Cycle day Tablet
Letrozole
Injection
hMG
Right Ovary Left Ovary Endometrial
thickness
D2 2.5 mg AFC 20 AFC 18 5 mm
D3 2.5 mg
D4 2.5 mg
D5 2.5 mg
D6 2.5 mg
D7 75 IU
D8 75 IU
D9 75 IU
D10
D11 14/2
13/2
12/5
14/3
11/2
7.5 mm
IUI stimulation started for Mrs BD

25. What to discuss with Mrs BD?
1. Proceed for IUI and add antagonist
2. Cancel IUI cycle and ask abstinence from
intercourse
3. Conversion to IVF

26. Cancellation versus conversion
• Discuss pros and cons of each option- cost
implications
• Risks of OHSS/ multiples are high if
1. Serum estradiol levels >900–1,400 pg/mL
2. >4-6 follicles ≥10–14 mm
3. >3 follicles ≥15 mm (ACOG, 2017; ESHRE, 2018).

27. Cycle day Tablet
Letrozole
Injectable Right
Ovary
Left
Ovary
Endometri
al
thickness
D2 2.5 mg AFC 20 AFC 18 5 mm
D3 2.5 mg
D4 2.5 mg
D5 2.5 mg
D6 2.5 mg
D10
D11 13/1 11/1 7 mm
D14 Inj hCG
(5000)
18/1 16/1 8.5 mm
D16 IUI (H) was planned
Mrs BD cancelled that cycle, came
next cycle for IUI again

28. On the day of IUI
• Husband- Mr PS collected semen
• Previous semen analysis- Normozoospermia
• Today- 1-2 motile sperms/hpf
 Explanation?
 Remedy?

29. Possible reasons of sudden abnormal
semen parameters
• Significant intra-individual variability (10.3-26.8%
(Alvarez et al., 2003).
• Laboratories not adhering to WHO standards (Penn et al.,
2010; Keel et al., 2002, Dasgupta, 2019)
• Testicular heat exposure 3 months back (e.g., fever)
(WHO, 2010)
• Inadequate sexual stimulation can affect semen
quality (van Roijen et al., 1993)

31. Double Ejaculate often produces
better quality of sperms

33. Case Scenario 2
• Mrs AC, 33-yr-old
woman having regular
cycles
• Trying for pregnancy for
3 years
• c/o severe and
progressively increasing
dysmenorrhoea and
dysparaeunia
• TVS-

34. Line of management?
• Laparoscopy
• IVF, embryo freezing
and then consider
laparoscopy
• IVF only
• Hormonal therapy for 3
months, then reevaluate
 Cystectomy/ Drainage?
 Counselling before
surgery?
 Dienogest
 GnRH agonists

35. Factors to decide the mode of
treatment?
• Ovarian reserve- Age,
AMH, AFC
• Semen parameters
• Tubal patency
• Severity of symptoms
• Past surgery
• Previous fertility
treatment
• Patient’s wishes
Mrs AC
 Age 33, AMH- 2.5 ng/ml,
AFC- 8+10
 Normozoospermia
 Tubes not yet checked
 Pain not responded to
NSAID
 No previous surgery
 Received 6 cycles of
letrozole for OI
 Relief of pain and wants to
conceive

36. Endometriosis and Subfertility
Hormonal Suppression
• Clinicians should NOT
prescribe ovarian
suppression treatment to
improve fertility
• Most of the hormone
therapies will prevent
pregnancy
• Ovarian suppression does
NOT improve subsequent
ovarian response (ESHRE,
2022)
Surgery
• Still controversial if
cumulative pregnancy rate is
more after surgery but time
to achieve pregnancy was
significantly shorter (ESHRE,
2022)

37. Surgery for Endometriosis-
Subfertility
rASRM stage I/II
endometriosis
Operative laparoscopy could be offered
Improves the rate of ongoing pregnancy.
Endometrioma Operative laparoscopy may increase their
chance of natural pregnancy
No data from comparative studies exist
Cystectomy >> Drainage/coagulation
Possible decline in ovarian reserve
Deep
endometriosis
No compelling evidence exists
Operative laparoscopy may represent a treatment
option in symptomatic patients wishing to conceive
(RCOG, 2017; NICE, 2017; ESHRE, 2022)

38. Mrs AC underwent laparoscopy
• Right Ovarian 5 cm
chocolate cyst
removed
• Severe adhesion in
POD- complete
adhesiolysis was
done
• Dye test B/L positive

39. After laparoscopy- Attempt of
natural conception or IVF?
• Women should be counselled
of their chances of becoming
pregnant after surgery.
• To identify patients that may
benefit from ART after
surgery, the Endometriosis
Fertility Index (EFI) should
be used as it is validated,
reproducible and cost-
effective.
• The results of other fertility
investigations such as their
partner’s sperm analysis
should be taken into account
(ESHRE, 2022)

41. Adamson and Pasta. Fertil Steril. 2010

42. What should be the post-operative
treatment plan?
• Counselling?
• Ovarian suppression
after surgery?
 Chance of recurrence
 Better not to delay
pregnancy
 Women seeking pregnancy
should NOT be prescribed
postoperative hormone
suppression with the sole
purpose to enhance future
pregnancy rates (ESHRE, 2022)

43. Mrs AC is now pain-free
• Visited 4 doctors over the period of next 2
years.
• Received different brands of letrozole for
ovulation induction- total 12 cycles
• She wants to do IUI

44. ESHRE, 2022
rASRM stage I/II
endometriosis
•May perform IUI with ovarian
stimulation, instead of expectant
management or IUI alone
•IUI+OS increases pregnancy rates.
rASRM stage III/IV
endometriosis
•The value of IUI in women with tubal
patency is uncertain
•IUI +OS could be considered
Can IUI be done in endometriosis?

45. Hughes, 1997 Meta-analysis- IUI success is halved in stage I/II
endometriosis
Gandhi et al., 2014 No difference between expectant management and IUI
Dmowski et al., 2002 First-cycle chance of pregnancy with IVF is
significantly higher than the cumulative pregnancy rate
after 6 IUI cycles
Van der Houwen et al., 2014;
D’Hooghe et al., 2006
The risk of endometriosis recurrence appears to be
increased by IUI (more than IVF)
IVF, but not IUI, can be expected to overcome the
detrimental effects of a pelvic inflammatory milieu.
Limitations of IUI in endometriosis

47. Finally Mrs AC (now 35) did 3 cycles
of IUI and now visited the 5th doctor
What to assess?
Severity of pain
Serum AMH
Scan finding-
Pain-free
0.5 ng/ml
B/L endometrioma
(6 cm in right side, 4 cm
left side)
AFC 4+3
Follicles seem accessible

48. Options
1. Egg donation-IVF because of low AMH
2. Give DHEA, reassess AMH after 3 months,
consider letrozole for OI
3. IVF with self egg directly
4. Laparoscopy again

49. Low AMH- what does it mean?
• Conclusions: Serum AMH
levels have poor predictive
value for natural
pregnancy. The predictive
value of AMH was poor in
the younger and older
subgroups.

50. Role of DHEA
• Dehydroepiandrosterone supplementation may
improve in vitro fertilization outcomes and ovarian
response in patients with poor ovarian response.
However, a few questions still loom over the
effectiveness of dehydroepiandrosterone.

52. IVF or Laparoscopy in
Endometriosis?
In infertile women with
endometrioma > 3 cm only
consider cystectomy prior to
ART to improve
1. endometriosis-associated
pain or
2. the accessibility of
follicles (ESHRE, 2022)
Concern about
endometrioma puncture
during OPU?
• In women with
endometrioma, clinicians
may use antibiotic
prophylaxis at the time of
oocyte retrieval, although
the risk of ovarian abscess
following follicle
aspiration is low (0-1.9%)
(ESHRE, 2022, RCOG 2017)

53. RCOG Scientific Impact Paper (2017)
Directly ART
• Asymptomatic women,
• women of advanced
reproductive age,
• those with reduced
ovarian reserve,
• B/L endometriomas,
• a history of prior ovarian
surgery
Surgery before IVF
• Highly symptomatic
women,
• with an intact ovarian
reserve,
• unilateral and large cysts,
• cysts with suspicious
radiological and clinical
features.
53

55. Case Scenario 3
• Mrs BG, 28-yr old
• Trying for pregnancy for only 5 months
• Already received letrozole and dydrogesterone
for 4 months (no follicular monitoring)
• AMH, HSG- all investigations done and all are
normal
• Semen analysis done subsequently

56. Is this semen analysis “Abnormal”?
Volume 2 ml
Colour Whitish
Viscosity Normal
Liquefaction Time 45 minutes
pH 7.6
Sperm Concentration 18 million/ ml
Total Motility 42%
Progressive Motility 17%
Non progressive Motility 25%
Immotile 58%
Normal Morphology 5%
Abnormal Morphology 95%
Vitality 62%
Round cells Nil

57. WHO guideline on semen
analysis

58. Can this be labeled as “Unexplained
Subfertility”?
• Unexplained subfertility
is usually diagnosed if a
couple fails to conceive
after 1 year of regular
unprotected sexual
intercourse even though
investigations for
ovulation, tubal patency
and semen analysis are
normal

59. Mrs BG is very anxious to conceive
What’s the next step?
• Continue further cycles of OI with letrozole
• Change OI regime- CC/ Gonadotropin
• Advise IUI
• Counsel for IVF
• Explain facts and figures and ask to try naturally for few
cycles (NICE, 2013)
Age (years) Pregnant after 1 year (12 cycles) % Pregnant after 2 years (24 cycles) %
19–26 92 98
27–29 87 95
30-34 86 94
35-39 82 90

60. Mrs BG changed the doctor
• She came back after 3
years
• Meanwhile she tried
multiple cycles of OI with
letrozole, CC and
gonadotropins
• What’s next step?
 Laparoscopy?
 IUI?
Rationale?
 IVF?
“Only treatment”?

61. • Meta-Analysis
• Success rate of IVF - ∼25% (NNT- 4)
*European IVF-Monitoring Consortium (EIM) for ESHRE, 2016
Jacobson et al., 2010 Duffy et al., 2014
OR for ongoing pregnancy (95% CI) 1.64 (1.05– 2.57) 1.94 (1.20–3.16)
The number of infertile women that
should undergo destruction of
superficial peritoneal endometriosis
12 8
The prevalence of grade I/ II
endometriosis among women with
unexplained infertility
≤50%
NNT 24 16
Laparoscopy in Unexplained
Infertility

62. Canadian Fertility and Andrology
Society , 2019

63. NICE, 2013- “IVF is the ONLY treatment for
Unexplained Subfertility after 2 years”
• Based on a single RCT (Bhattacharya et al., 2008)
• Increases “unnecessary” IVF (Woodward et al., 2016)
• NICE recommendation - proper utilization of NHS funding is
important to get the maximum benefits for fertility treatment
(Chambers et al., 2012).
• No such funding in India
• Many trusts in the UK- provide OS with IUI with reasonable
good success rate (Nandi and Homburg, 2016).
• A recent large retrospective study- IUI is more cost-effective
than IVF in improving the live birth rate (Bahadur et al., 2020).

64. Other side of the Atlantic
• The treatment of unexplained infertility is by necessity
empiric.
• For young women, the best initial therapy is a course
(typically 3 or 4 cycles) of ovarian stimulation with oral
medications and OS-IUI followed by IVF

65. IUI in unexplained subfertility
• Bypasses cervical factors
• Deposits good number of motile spermatozoa near
the tubes
• Overcomes “improper” coital techniques
• “Superovulation” leads to release of >1 egg and
improves the follicular development

66. Treatment as per age and duration
of infertility
(Nandi and Homburg, 2016)

67. Mrs BG wants to do IUI
• Satisfactory stimulation-
response
• hCG triggered
• On the day of IUI
Husband failed to
produce semen
 How to tackle this
situation?
 Can this situation be
avoided?

68. Semen collection problem is NOT
uncommon
• 8.3% of the men experienced ejaculation-
failure on the day of operation for ART (Li et al.,
2016).
• Only 59% of the men attending the fertility
clinic felt comfortable in masturbation and
48% required external stimulation to collect
semen (Pottinger et al., 2016).

69. Issues in Semen Collection
• Privacy
• Relaxation
• Bed
• Partner
• Washing facility
• Elective Freezing of sperms
• Counselling
• Sildenafil
• Vibroejaculator
• Coitus interruptus
• Nontoxic condom
• Home Collection
• Urine (In Retrograde
ejaculation)
• Prostatic Massage
• Electroejaculation
• Surgical Sperm retrieval f/b
ICSI

71. Case 4
• Mrs PM, 20 years, trying for pregnancy for 1
year
• Husband works in Dubai, comes twice a year,
stays for 1 month each time
• Cycles regular, no dysmenorrhoea
• AMH 2.9 ng/ml
• Semen- normozoospermia

72. HSG was done

73. Precautions before interpreting HSG
• Spasm of the smooth muscles of the tube → “false”
impression of “fallopian tube block” (Suresh and Narvekar,
2014)
• In 40-60% cases of B/L proximal block diagnosed in
HSG, at least one tube may be found open on further
investigations (repeat HSG, SSG, laparoscopy)
(Hajishafiha et al., 2009; Verhoeve et al., 2010; Foroozanfard and Sadat, 2013)

74. Options for Mrs PM?
• Laparoscopy?
• IVF?
• Noninvasive options?
 Lap dye test alone?
 Additional procedure?
 Implication of ART bill?
 Repeat HSG
 Sonosalpingography
(SSG)
 Hysterosalpingo-Contrast-
Sonography (HyCoSy)

75. She is 20. Is she eligible for IVF?

76. Noninvasive options
Repeat
HSG
• After premedication with antispasmodics
• 60% cases initially “blocked” tubes were found open
(Dessole et al., 2000)
• Increased risk of radiation exposure and hypothyroidism
(Hart et al., 2009)
SSG • Relatively simple procedure, no radiation exposure (Suresh
and Naverkar, 2014, Maheux-Lacroix, 2014)
• Assesses uterine cavity, myometrium and the ovaries
• In 70-80% at least one tube is found open by SSG
(Hajishafiha, 2009; Lanzani, 2009)
• Can avoid both laparoscopy and IVF
HyCoSy • Delineates exact site of block (Luciano, 2011)
• Expensive, not easily available
• Meta-analysis-HyCoSy NOT superior to SSG (Maheux-
Lacroix, 2014)

77. Decisive factors for IVF vs
laparoscopy?
• Age of the woman
• Ovarian reserve
• Sperm parameters
• Number of children desired
• Site and extent of the tubal disease
• Risk of ectopic pregnancy
• Risk of OHSS
• Success rates of IVF programme
• Cost- Financial burden- “two
consecutive medical procedures to
achieve parenthood”
• Expertise of the surgeon
• Patient’s preferences
(Suresh and Narvekar, 2014; ASRM, 2015)
SSG of Mrs PM - no spill in POD

78. Hysteroscopic Tubal Cannulation
Type of study Authors Successful
cannulation
Concepti
on rates
Ectopic
pregnancy
Case series Ikechebelu et
al., 2018
90.2% per tube and
88.9% per patient
33.3% Nil
Case series Chung et al.,
2018
67.0% per tube and
71.4% per woman
55%
Cohort study Mekaru et al.,
2011
25.9% per tube and
37.1% per patient
30.77% 7.69%
Meta-analysis Honore et al.,
1999
85% per tube tube 48.9% 9.2%
• Proximal tubal obstruction
• Young women
• No other significant infertility factors (NICE, 2013; ASRM, 2015)

79. Husband of Mrs PM
• Meanwhile had mumps orchitis
• Requests repeating semen analysis

80. Collection Method Masturbation
Abstinence 4 days
Collection Complete
Volume 2 ml
Colour Whitish
Viscosity Normal
Liquefaction Time 45 minutes
pH 7.6
Sperm Concentration 1.2 million/ ml
Total Motility 20%
Progressive Motility 6%
Non progressive Motility 14%
Immotile 70%
Motile Sperm Count 0.48 million
Normal Morphology 1%
Vitality 34%
Round cells Nil

81. Options?
1. Donor sperms
2. Antioxidants for 6 months, then review
3. IVF-ICSI

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

83. • 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.

85. 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.

86. 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?

88. Case 5
• Mr RC, 32 yr came with a report of
Azoospermia
• Did not bring his wife
• Requests, “Her all reports are OK. You just
treat my condition”

89. Female partner evaluation is
important
• Female age- most important predictor for
fertility (Shallo, 2020)
• Ovarian reserve
• Tubal patency- IUI/ IVF

90. Options
1. Donor sperm IUI
2. FNAC of testicles
3. Detailed evaluation

91. FNAC- role?
• May not be necessary
• 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

92. 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%

93. Clinical Examination or ultrasound?
• 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.
• Testicular size
• Bilateral absent vasa
• Undescended testicles
• Varicocele

94. 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
Hormonal Investigations

95. 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)

96. 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.

97. Genetic testing
• Karyotyping
• Y chromosome Microdeletion (YCM)
• CFTR testing- for CBAVD

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