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IVF- How it changed the perspective
of Male Infertility
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)
Clinical Director and Consultant: Reproductive Medicine, Genome Fertility
Centre, Kolkata
Managing Committee Member, BOGS, 2022-23
Executive Committee Member, ISAR Bengal, 2022-24
Clinical Examiner, MRCOG Part 3 Examination
Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London,
2019
IVF, 1978
1989-1992
We cannot treat
We bypass
Do we understand-
“Male Infertility?”
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)
Semen Report 1
Collection Method Masturbation Total Motility 41%
Abstinence 4 days Progressive
Motility
26%
Collection Complete Non
progressive
Motility
15%
Volume 2 ml Immotile 59%
Viscosity Normal Motile Sperm
Count
14.76 million
Liquefaction Time 45 minutes Normal
Morphology
5%
pH 7.6 Abnormal
Morphology
95%
Sperm
Concentration
18 million/ ml Vitality 62%
Sperm count 36 million/ ejaculate Round cells Nil
Semen Report 1
Collection Method Masturbation Total Motility 41%
Abstinence 4 days Progressive
Motility
26%
Collection Complete Non
progressive
Motility
15%
Volume 2 ml Immotile 59%
Viscosity Normal Motile Sperm
Count
14.76 million
Liquefaction Time 45 minutes Normal
Morphology
5%
pH 7.6 Abnormal
Morphology
95%
Sperm
Concentration
18 million/ ml Vitality 62%
Sperm count 36 million/ ejaculate Round cells Nil
Reference ranges
Limitations of WHO 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?
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)
Significance of SDF
• Live birth after IUI/ IVF/
ICSI- ?
• Oocytes can repair the
damaged DNA
• Lack of standardization
• Lack of definitive treatment
Is “Routine” Semen Analysis ENOUGH?
Points to note in semen report
Volume 1.4 ml
Colour Whitish
Viscosity Normal
Liquefaction Time 45 minutes
pH 7.6
Sperm Concentration 16 million/ ml
Sperm count 39 million/ ejaculate
Total Motility 42%
Progressive Motility 30%
Non progressive Motility 12%
Immotile 58%
Normal Morphology 4%
Vitality 54%
Round cells Nil
1
2
3
4
5
6
From which Laboratory?
Semen Report 2
Collection
Method
Masturbation Total Motility 35%
Abstinence 4 days Progressive
Motility
17%
Collection Complete Non progressive
Motility
18%
Volume 2 ml Immotile 65%
Viscosity Normal Motile Sperm
Count
8.4 million
Liquefaction
Time
45 minutes Normal
Morphology
3%
pH 7.6 Vitality 62%
Sperm
Concentration
12 million/ ml Round cells Nil
Semen Report 2
Collection
Method
Masturbation Total Motility 35%
Abstinence 4 days Progressive
Motility
17%
Collection Complete Non progressive
Motility
18%
Volume 2 ml Immotile 65%
Viscosity Normal Motile Sperm
Count
8.4 million
Liquefaction
Time
45 minutes Normal
Morphology
3%
pH 7.6 Vitality 62%
Sperm
Concentration
12 million/ ml Round cells Nil
Male Infertility- Mild or Severe?
• TMSC= Total Motile sperm count =
• Sperm concentration x total volume x total motility
(16 mil/ml x 1.4 ml x 42%)
• TMSC >5/ 10/ 20 million
Mild Male Factor
• Investigations- NOT
usually recommended
• 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)
When to repeat semen analysis?
• Mild problems- After 3 months
• Severe problems- ASAP
(NICE, 2013; EUA, 2018; ASRM, 2020)
I n f e r t i l i t y
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.
Semen Report 3
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 3
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
What next?
• Straightaway donor sperm IUI
• Antioxidants for 3 months and repeat test
• Investigate in details√
• History
• Physical Examination
• Hormone Assay
• Imaging
• Genetic Tests
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)
Sperm abnormality may be the first
symptom of testicular cancer
• 31 yrs
• Came for IUI (D)
• Malignant teratoma-
treated by orchidectomy
and chemotherapy
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.
Revisiting History
• Age
• Duration of subfertility
• Previous pregnancy- can have secondary male
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
Darren et al. Male infertility – The other side of the equation . 2017
Varicocele- always CLINICAL Diagnosis (EUA,
2018)
• 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
• Pain
• Abnormal semen parameters
• No other fertility factors in the couple
Do you recommend varicocelectomy here?
• 35 yr- Azoospermia
• Lt undescended testis
• 19 yr age- Lt orchidopexy
• 21 yr age- left testicular cancer
(mixed germ cell Tx)→
orchidectomy, f/b 3 cycles of
chemotherapy (BPC)
• 33 yr age-Papillary Ca Thyroid→
Total thyroidectomy and neck LN
dissection f/b Radio-iodine. Now
on Eltroxin 150
• FSH 27.14, LH 6.69, Testosterone
336 ng/dl, E2 26.0 pg/ml.
• Female age 35
In couples seeking fertility with ART, varicocele repair
• may offer improvement in semen parameters
• may decrease level of ART needed
• 14 studies (980 individuals) in the systematic review.
• Contradictory findings were reported in sperm
concentration, morphology, and motility, as well as
DNA fragmentation.
• Most included studies also raised methodological
concerns.
• Therefore, definitive conclusions about the efficacy of
antioxidant supplementation in this setting cannot be
drawn
Antioxidants in Varicocele
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
Cryptorchidism- bilateral in adults?
• 31 yr
• Azoospermia
• USG- Rt testis in lower abdomen, Lt testis in inguinal canal
• FSH 13.40. LH 6.87. Testo 6.89. E2 <10.
B/L cryoptorchidism in ADULTS!!!
Other congenital anomalies
Transverse testicular ectopia (TTE), or
crossed testicular ectopia (CTE)
Subcoronal Hypospadias
Testicular size-
Prader’s Orchidometer
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)
History can save us
• 33 yr
• Secondary anejaculation
and ED
• B/L abdominal testes
• 3 yr age- attempted Rt
orchidopexy but failed
• 13 yr age- Left sided
orchidopexy attempted
but partial success.
• 32 yr age- B/L
orchidectomy after failed
orchidopexy attempt
Can we do SSR here?
• Left cryptorchidism (abdominal testis)
• Lt orchidectomy at 12 yr
• Testicular prosthesis
• Azoospermia
• Opted for AID
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)
Epididymal cysts
•NOT associated with infertility
•Surgery may cause obstruction
Weatherly D, et al. Epididymal Cysts: Are They Associated With Infertility? Am J
Mens Health. 2018
Testicular microlithiasis
• Sertoli cell only
• No sperms obtained
• Biopsy sent
• Opted for AID
• Mumps orchitis
• Initially azoopsermia
• Next- 1-2 sperms/ hpf
• Conceived by ICSI
Hormone Evaluation
Sperm concentration <10 million/ml
Sexual dysfunction
Clinically suspected endocrinopathy
FSH, LH, testosterone, HbA1C
FSH, LH low
Testosterone low
Hypogonadotropic hypodonadism
Pituitary imaging
FSH high LH high
Testosterone low
Global testicular failure
LH normal
Testosterone normal
Spermatogenesis defect
LH high
Testosterone normal
Sublinical hypogonadism
PRL, TSH If clinically suspected
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
• 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
•Azoospermia persists
•Started hCG f/b hMG by endocrinologist
•Sperm conc 1-2/ hpf
•Advised to continue hMG
“Empty Sella Syndrome”
• 30 yr, azoospermia
• 17 yr age, sudden testicular atrophy, started testo 250 mg IM monthly
injection from 23 yr age
• B/L testes 6 cc each
• FSH 1.11, LH 0.26, Testo 194
• ACTH, cortisol, PRL- all normal
• Started hCG
Non-targeted investigations ?
• Delayed puberty
• Testo 100.86. FSH 28.33. LH 13.65. E2 27.83
• Testosterone injection started at puberty - sec sex charac, voice, genital size
improved
• MRI pitutary microadenoma
• GH, TSH, Cortisol, PRL, - all normal
Targeted female investigations
• If no risk factors for
tubal block- 3 cycles of
IUI, then tubal patency
test
• If risk factors- tubal
patency first
•Ovaries
•Tubes- IUI or IVF/ICSI?
Role Of Medical Therapy
(EUA, 2018, ASRM, 2020)
Hypogonadotropic
hypodonadism
•hCG 2000-5000 IU 3 times a week
•If hCG alone cannot restore spermatogenesis, FSH is
added 75-150 IU 3 times a week
•Serum testosterone and semen analysis every 1–2 months
•Usual time to recover 6 – 12 months (may take 24
months)
•Natural conception vs ART?
Idiopathic Male
infertility
CC
Tamoxifen
Letrozole
hCG
All empirical
Evidences?
Testosterone
supplementation
Strongly CONTRAINDICATED
Feedback inhibition on FSH, LH→ secondary
hypogonadism
Aromatase
inhibitors (Letrozole,
Anastrozole)
If T:E2 ratio <10 (T- ng/dl, E2- pg/ml)
Antioxidants in severe male
factor?
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.
• In some studies, AS was found to be beneficial in
reversing OS-related sperm dysfunction and improving
pregnancy rates.
• The most commonly used preparations, either as
monotherapy or in combination as multi-AS, were: vitamin
E (400 mg), carnitines (500–1000 mg), vitamin C (500–
1000 mg), CoQ10 (100–300 mg), NAC (600 mg), zinc (25–
400 mg), folic acid (0.5 mg), selenium (200 mg), and
lycopene (6–8 mg).
• Still debatable due to the heterogeneity in study designs
and the multifactorial genesis of infertility.
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
Male factor- IUI, IVF or ICSI?
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
Semen Report 4
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 4
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
What next?
• Straightaway donor sperm IUI
• Testicular FNAC
Problems with indiscriminate FNAC
• Repeat test showed SC 3-4 sperms/ hpf
• Repeat semen analysis- 58 mil/ml, TM 48%
Problems with indiscriminate FNAC
• 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
Problems with indiscriminate FNAC
• LH 30.10, FSH 43.70, E2 38.48, Testo 432
Problems with indiscriminate FNAC
• 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
Problems with indiscriminate FNAC
• 37 yr
• Inguinal hernia operated
Rt sided- 2 yr ago and
Lt sided15 yr ago
• B/L testes- 18 cc each
• FSH 5.96. LH 4.74.
Testo 212. Estradiol
14.22.
• FNAC- SCO
FNAC- role?
• Isolated foci of
spermatogenesis
ASRM, 2020
• Consider TESA in
indeterminate cases- NOT
NECESSARY
FSH >7.6 <7.6
Testicular long axis (cm) <4.6 >4.6
89% chance of NOA 96% chance of OA
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%
Surgical Sperm Retrieval (SSR) in
Azoospermia (OA>NOA)
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 NOA
• The ONLY negative prognostic
factor is the presence of AZFa
and AZFb microdeletions.
Genetic testing
• Sperm
concentration <5
million/ml
• Azoospermia
• Testicular atrophy
• Elevated FSH
• Karyotyping
• Y chromosome
Microdeletion (YCM)
In presence of genetic defect
• Sperm Aneuploidy testing by FISH
• PGT-SR (previously- PGD)
• Prenatal invasive testing (EUA, 2018; ASRM,
2020)
Klinefelter Syndrome
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
Robertsonian Translocation
45, XY rob (14, 21), (q10, q10) Sperm FISH after TESE
Reciprocal translocation
• 35 yr
• Severe OAT
• ICSI done
• Awaiting PGT(SR)
46,XY,t(3;6)(p21;p23)
Alternative- Prenatal testing
46,XY22ps+
• Oligospermia →Azoospermia
• YCM normal
• Spermes obtained by TESA
Amniocentesis
• Normal Karyo & CMA
• Live born by 34/40
Other Translocations
46,XY,t(15:17) (q10;q10)
• Azoospermia
• FNAC- B/L SCO
• YCM normal
46,XY;t(2:22)(q37;q11.21)
• Azospermia
• TESE- no sperms available
• YCM normal
Other chromosomal aberrations
46,X,del(Y)(q11.23) 46,X,del(Y)(q11.2) 46,X,+mar
Familial Azoospermia
46,XY, dup(9)(q11-q12)
• Duplication of long arm of
chromosome 9- partial
trisomy
• FSH 4.65, LH 2.94, testo
294. Estradiol 40.
• FNAC B/L Late maturation
arrest
• Family History of
Azoospermia in
a) Own brother
b) 2 maternal uncles
c) 2 Cousin brothers (of
same maternal aunt)
Genetic abnormality ≠ Advanced interventions
46,XYqh-
Severe OAT
46,XY,16qh+
Azoospermia
Keep Geneticist on board
46,XY,15ps+
46,X,Y,q+
46,X,inv(Y)(p11.q11)
46,X,inv(Y)(p11.2q11.2)
Look for type of YCMD
Y chromosome Microdeletion (AZF)
• 39 yr
• FSH 25.4, LH 12.6, Estradiol 14, Testo 61.
Sometimes nothing can be done
46,XX SRY+ sex reversal
Medical Therapy in Idiopathic
Azoospermia
• To improve the chance
of sperm retrieval
(Alkandari and Zini, 2021; Kumar,
2021; Holtermann et al., 2022).
• Sometimes, can lead to
appearance of sperms in
the ejaculate (Alkandari and
Zini, 2021; Kumar, 2021).
• hCG
• FSH
• CC
• Tamoxifen
• Letrozole
• Antioxidants??
(Agarwal A, Majzoub A, 2017)
Ethical dilemma in NOA
Trial TESA
• Avoids Unnecessary ovarian
stimulation
• May need repeat TESA
TESA during OPU
• What to do if sperms are not
obtained
OPTIONS
1. Donor sperm
2. Discard eggs
3. Freeze eggs
Semen Report 5
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 5
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
Assess
• Abstinence period
• Completeness of collection
• Usual amount of ejaculate
• Exclude retrograde ejaculation
• 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< 2020)
• Partner testing
• Indian prevalence- 1:10,000- 1:40,000 (Kapoor et al., 2006;
Prasad et al., 2010)
CBAVD, TRUS, CFTR mutation
• TRUS-
• B/L agenesis of seminal vesicles
• Male partner- CFTR carrier
• Female partner- CFTR carrier
CBAVD is NOT uncommon
• CFTR negative • CFTR carrier
• Wife- normal
• CFTR refused
• CFTR carrier
• Wife- normal
• CFTR negative
Semen Report 6
Collection Method Masturbation Total Motility 0%
Abstinence 4 days Progressive
Motility
0%
Collection Complete Non progressive
Motility
0%
Volume 2 ml Immotile 100%
Viscosity Normal Motile Sperm
Count
Nil
Liquefaction Time 45 minutes Normal
Morphology
2%
pH 7.6 Vitality 12%
Sperm
Concentration
18 million/ ml Round cells Nil
Semen Report 6
Collection Method Masturbation Total Motility 0%
Abstinence 4 days Progressive
Motility
0%
Collection Complete Non progressive
Motility
0%
Volume 2 ml Immotile 100%
Viscosity Normal Motile Sperm
Count
Nil
Liquefaction Time 45 minutes Normal
Morphology
2%
pH 7.6 Vitality 12%
Sperm
Concentration
18 million/ ml Round cells Nil
Steps
• Abstinence, frequency of discharge
• Place of collection
• Look for vitality- HOS, Supravital
staining
• Repeat after proper abstinence
• Can be associated with smoking, varicocele,
Immotile Cilia Syndrome
• Antioxidants ?
ICSI with Ejaculate vs Testicular sperms
Case of total asthenospermia
• 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 12/40.
Semen Report 7
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
Semen Report 7
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
Isolated teratozoospermia
• Isolated abnormal morphology is not the
indication for ART
Penn HA, Windsperger A, Smith Z, et al. Fertil Steril. 2011; 95(7):2320–3.
Semen Report 8
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
5%
pH 7.6 Vitality 32%
Sperm
Concentration
36 million/ ml Pus cells 10-12/hpf
Semen Report 8
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
5%
pH 7.6 Vitality 32%
Sperm
Concentration
36 million/ ml Pus cells 10-12/hpf
MAGI (Male Accessory Gland Infection)
EUA, 2018; ASRM, 2020; Vignera et al., J Med Microbiology, 2014
• The clinical significance is controversial.
• Special Tests- Round cells vs Pus cells
• Method of collection
• Hand washing before collection
• Culture of semen
• Antibiotics- only when documented infections
• Routine antibiotics- can harm
• Consider prostatic fluid culture
A story of “Pus cells”
• 36-yr
• Apparently
unexplained infertility
• Persistent Pus cells in
semen
• Culture negative
• Pain during
intercourse
• Paraphimosis
• No pus cells after
circumcision
• Conceived after OI,
delivered
Symptomatic “pus cells”
• 26 yr
• Concentration 14
million/ml, motility 35%,
pus cells 10-15/ hpf
• Occasional Rt scrotal pain
• After antibiotics- symptoms
subsided, semen became
normal
• Conceived spontaneously
“Pus Cells” and ART outcome
Semen collection- Is it so easy?
(Inhorn 2007; Saleh et al., 2003; Gerris, 1999; Bahyah et al., 2010;
Pottinger et al., 2016)
• Privacy- Locked room
• Relaxation
• Bed
• Partner
• Erotic materials
• Washing facility
Problems in Semen collection
(Meng et al., 2013; Fahmy et al., 1999; Ibrahim et al., 2016; Sønksen et al., 2002)
• Ask- Why
Difficulty
• Erection issue
• Vibroejaculator
• Coitus interruptus
• Nontoxic condom
• Home Collection
• Urine (In RE)
• Prostatic Massage
• Electroejaculation
• Surgical sperm
retrieval (for ICSI
only)
All cases may not have “Subfertility”
• Female factors normal (AMH,
HSG)
• Male- 32
• Could not collect semen
• Disclosed- never had
consummation
• ED and anejaculation
• Hormonal profile, sugar-
normal
• Genitals- NAD
• Requested AID without
woman’s consent
• Lost to follow up
Disclaimer
• Written consent from all the patients
1. Meticulous semen analysis in a standard laboratory
2. Physical examination and rational investigations
3. Avoid non-evidence based drugs for long time
4. Antioxidants- May be useful in mild problem
5. Antioxidants- Not reliable in severe problem
6. Donor sperm is NOT the only solution
7. IUI or IVF/ICSI- depends on the overall assessment
Take Home Messages
Treatment burden for MALE
infertility falls on FEMALE

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IVF Changed Male Infertility Perspective

  • 1. IVF- How it changed the perspective of Male Infertility 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) Clinical Director and Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata Managing Committee Member, BOGS, 2022-23 Executive Committee Member, ISAR Bengal, 2022-24 Clinical Examiner, MRCOG Part 3 Examination Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019
  • 5. Do we understand- “Male Infertility?”
  • 6. 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)
  • 7. Semen Report 1 Collection Method Masturbation Total Motility 41% Abstinence 4 days Progressive Motility 26% Collection Complete Non progressive Motility 15% Volume 2 ml Immotile 59% Viscosity Normal Motile Sperm Count 14.76 million Liquefaction Time 45 minutes Normal Morphology 5% pH 7.6 Abnormal Morphology 95% Sperm Concentration 18 million/ ml Vitality 62% Sperm count 36 million/ ejaculate Round cells Nil
  • 8. Semen Report 1 Collection Method Masturbation Total Motility 41% Abstinence 4 days Progressive Motility 26% Collection Complete Non progressive Motility 15% Volume 2 ml Immotile 59% Viscosity Normal Motile Sperm Count 14.76 million Liquefaction Time 45 minutes Normal Morphology 5% pH 7.6 Abnormal Morphology 95% Sperm Concentration 18 million/ ml Vitality 62% Sperm count 36 million/ ejaculate Round cells Nil
  • 10. Limitations of WHO 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?
  • 11. 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) Significance of SDF • Live birth after IUI/ IVF/ ICSI- ? • Oocytes can repair the damaged DNA • Lack of standardization • Lack of definitive treatment Is “Routine” Semen Analysis ENOUGH?
  • 12. Points to note in semen report Volume 1.4 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 16 million/ ml Sperm count 39 million/ ejaculate Total Motility 42% Progressive Motility 30% Non progressive Motility 12% Immotile 58% Normal Morphology 4% Vitality 54% Round cells Nil 1 2 3 4 5 6
  • 14.
  • 15. Semen Report 2 Collection Method Masturbation Total Motility 35% Abstinence 4 days Progressive Motility 17% Collection Complete Non progressive Motility 18% Volume 2 ml Immotile 65% Viscosity Normal Motile Sperm Count 8.4 million Liquefaction Time 45 minutes Normal Morphology 3% pH 7.6 Vitality 62% Sperm Concentration 12 million/ ml Round cells Nil
  • 16. Semen Report 2 Collection Method Masturbation Total Motility 35% Abstinence 4 days Progressive Motility 17% Collection Complete Non progressive Motility 18% Volume 2 ml Immotile 65% Viscosity Normal Motile Sperm Count 8.4 million Liquefaction Time 45 minutes Normal Morphology 3% pH 7.6 Vitality 62% Sperm Concentration 12 million/ ml Round cells Nil
  • 17. Male Infertility- Mild or Severe? • TMSC= Total Motile sperm count = • Sperm concentration x total volume x total motility (16 mil/ml x 1.4 ml x 42%) • TMSC >5/ 10/ 20 million
  • 18. Mild Male Factor • Investigations- NOT usually recommended • 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)
  • 19. When to repeat semen analysis? • Mild problems- After 3 months • Severe problems- ASAP (NICE, 2013; EUA, 2018; ASRM, 2020)
  • 20. I n f e r t i l i t y
  • 21. 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.
  • 22.
  • 23. Semen Report 3 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
  • 24. Semen Report 3 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
  • 25. What next? • Straightaway donor sperm IUI • Antioxidants for 3 months and repeat test • Investigate in details√ • History • Physical Examination • Hormone Assay • Imaging • Genetic Tests
  • 26. 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)
  • 27. Sperm abnormality may be the first symptom of testicular cancer • 31 yrs • Came for IUI (D) • Malignant teratoma- treated by orchidectomy and chemotherapy
  • 28. 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.
  • 29. Revisiting History • Age • Duration of subfertility • Previous pregnancy- can have secondary male 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
  • 30. Darren et al. Male infertility – The other side of the equation . 2017
  • 31. Varicocele- always CLINICAL Diagnosis (EUA, 2018) • 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
  • 32. Surgery for Varicocele (EUA, 2018) • Grade 3 varicocele • Ipsilateral testicular atrophy • Pain • Abnormal semen parameters • No other fertility factors in the couple
  • 33. Do you recommend varicocelectomy here? • 35 yr- Azoospermia • Lt undescended testis • 19 yr age- Lt orchidopexy • 21 yr age- left testicular cancer (mixed germ cell Tx)→ orchidectomy, f/b 3 cycles of chemotherapy (BPC) • 33 yr age-Papillary Ca Thyroid→ Total thyroidectomy and neck LN dissection f/b Radio-iodine. Now on Eltroxin 150 • FSH 27.14, LH 6.69, Testosterone 336 ng/dl, E2 26.0 pg/ml. • Female age 35
  • 34. In couples seeking fertility with ART, varicocele repair • may offer improvement in semen parameters • may decrease level of ART needed
  • 35. • 14 studies (980 individuals) in the systematic review. • Contradictory findings were reported in sperm concentration, morphology, and motility, as well as DNA fragmentation. • Most included studies also raised methodological concerns. • Therefore, definitive conclusions about the efficacy of antioxidant supplementation in this setting cannot be drawn Antioxidants in Varicocele
  • 36. 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
  • 37. Cryptorchidism- bilateral in adults? • 31 yr • Azoospermia • USG- Rt testis in lower abdomen, Lt testis in inguinal canal • FSH 13.40. LH 6.87. Testo 6.89. E2 <10.
  • 39. Other congenital anomalies Transverse testicular ectopia (TTE), or crossed testicular ectopia (CTE) Subcoronal Hypospadias
  • 41. 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)
  • 42. History can save us • 33 yr • Secondary anejaculation and ED • B/L abdominal testes • 3 yr age- attempted Rt orchidopexy but failed • 13 yr age- Left sided orchidopexy attempted but partial success. • 32 yr age- B/L orchidectomy after failed orchidopexy attempt
  • 43. Can we do SSR here? • Left cryptorchidism (abdominal testis) • Lt orchidectomy at 12 yr • Testicular prosthesis • Azoospermia • Opted for AID
  • 44. 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)
  • 45. Epididymal cysts •NOT associated with infertility •Surgery may cause obstruction Weatherly D, et al. Epididymal Cysts: Are They Associated With Infertility? Am J Mens Health. 2018
  • 46. Testicular microlithiasis • Sertoli cell only • No sperms obtained • Biopsy sent • Opted for AID • Mumps orchitis • Initially azoopsermia • Next- 1-2 sperms/ hpf • Conceived by ICSI
  • 47. Hormone Evaluation Sperm concentration <10 million/ml Sexual dysfunction Clinically suspected endocrinopathy FSH, LH, testosterone, HbA1C FSH, LH low Testosterone low Hypogonadotropic hypodonadism Pituitary imaging FSH high LH high Testosterone low Global testicular failure LH normal Testosterone normal Spermatogenesis defect LH high Testosterone normal Sublinical hypogonadism PRL, TSH If clinically suspected
  • 48. 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 • 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 •Azoospermia persists •Started hCG f/b hMG by endocrinologist •Sperm conc 1-2/ hpf •Advised to continue hMG
  • 49. “Empty Sella Syndrome” • 30 yr, azoospermia • 17 yr age, sudden testicular atrophy, started testo 250 mg IM monthly injection from 23 yr age • B/L testes 6 cc each • FSH 1.11, LH 0.26, Testo 194 • ACTH, cortisol, PRL- all normal • Started hCG
  • 50. Non-targeted investigations ? • Delayed puberty • Testo 100.86. FSH 28.33. LH 13.65. E2 27.83 • Testosterone injection started at puberty - sec sex charac, voice, genital size improved • MRI pitutary microadenoma • GH, TSH, Cortisol, PRL, - all normal
  • 51. Targeted female investigations • If no risk factors for tubal block- 3 cycles of IUI, then tubal patency test • If risk factors- tubal patency first •Ovaries •Tubes- IUI or IVF/ICSI?
  • 52. Role Of Medical Therapy (EUA, 2018, ASRM, 2020) Hypogonadotropic hypodonadism •hCG 2000-5000 IU 3 times a week •If hCG alone cannot restore spermatogenesis, FSH is added 75-150 IU 3 times a week •Serum testosterone and semen analysis every 1–2 months •Usual time to recover 6 – 12 months (may take 24 months) •Natural conception vs ART? Idiopathic Male infertility CC Tamoxifen Letrozole hCG All empirical Evidences? Testosterone supplementation Strongly CONTRAINDICATED Feedback inhibition on FSH, LH→ secondary hypogonadism Aromatase inhibitors (Letrozole, Anastrozole) If T:E2 ratio <10 (T- ng/dl, E2- pg/ml)
  • 53. Antioxidants in severe male factor?
  • 54.
  • 55. 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.
  • 56. • In some studies, AS was found to be beneficial in reversing OS-related sperm dysfunction and improving pregnancy rates. • The most commonly used preparations, either as monotherapy or in combination as multi-AS, were: vitamin E (400 mg), carnitines (500–1000 mg), vitamin C (500– 1000 mg), CoQ10 (100–300 mg), NAC (600 mg), zinc (25– 400 mg), folic acid (0.5 mg), selenium (200 mg), and lycopene (6–8 mg). • Still debatable due to the heterogeneity in study designs and the multifactorial genesis of infertility.
  • 57. 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 Male factor- IUI, IVF or ICSI?
  • 58. 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
  • 59. Semen Report 4 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
  • 60. Semen Report 4 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
  • 61. What next? • Straightaway donor sperm IUI • Testicular FNAC
  • 62. Problems with indiscriminate FNAC • Repeat test showed SC 3-4 sperms/ hpf • Repeat semen analysis- 58 mil/ml, TM 48%
  • 63. Problems with indiscriminate FNAC • 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
  • 64. Problems with indiscriminate FNAC • LH 30.10, FSH 43.70, E2 38.48, Testo 432
  • 65. Problems with indiscriminate FNAC • 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
  • 66. Problems with indiscriminate FNAC • 37 yr • Inguinal hernia operated Rt sided- 2 yr ago and Lt sided15 yr ago • B/L testes- 18 cc each • FSH 5.96. LH 4.74. Testo 212. Estradiol 14.22. • FNAC- SCO
  • 67. FNAC- role? • Isolated foci of spermatogenesis ASRM, 2020 • Consider TESA in indeterminate cases- NOT NECESSARY FSH >7.6 <7.6 Testicular long axis (cm) <4.6 >4.6 89% chance of NOA 96% chance of OA
  • 68. 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%
  • 69. Surgical Sperm Retrieval (SSR) in Azoospermia (OA>NOA)
  • 70. 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 NOA • The ONLY negative prognostic factor is the presence of AZFa and AZFb microdeletions.
  • 71. Genetic testing • Sperm concentration <5 million/ml • Azoospermia • Testicular atrophy • Elevated FSH • Karyotyping • Y chromosome Microdeletion (YCM)
  • 72. In presence of genetic defect • Sperm Aneuploidy testing by FISH • PGT-SR (previously- PGD) • Prenatal invasive testing (EUA, 2018; ASRM, 2020)
  • 74. 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
  • 75. Robertsonian Translocation 45, XY rob (14, 21), (q10, q10) Sperm FISH after TESE
  • 76. Reciprocal translocation • 35 yr • Severe OAT • ICSI done • Awaiting PGT(SR) 46,XY,t(3;6)(p21;p23)
  • 77. Alternative- Prenatal testing 46,XY22ps+ • Oligospermia →Azoospermia • YCM normal • Spermes obtained by TESA Amniocentesis • Normal Karyo & CMA • Live born by 34/40
  • 78. Other Translocations 46,XY,t(15:17) (q10;q10) • Azoospermia • FNAC- B/L SCO • YCM normal 46,XY;t(2:22)(q37;q11.21) • Azospermia • TESE- no sperms available • YCM normal
  • 80. Familial Azoospermia 46,XY, dup(9)(q11-q12) • Duplication of long arm of chromosome 9- partial trisomy • FSH 4.65, LH 2.94, testo 294. Estradiol 40. • FNAC B/L Late maturation arrest • Family History of Azoospermia in a) Own brother b) 2 maternal uncles c) 2 Cousin brothers (of same maternal aunt)
  • 81. Genetic abnormality ≠ Advanced interventions 46,XYqh- Severe OAT 46,XY,16qh+ Azoospermia
  • 82. Keep Geneticist on board 46,XY,15ps+ 46,X,Y,q+ 46,X,inv(Y)(p11.q11) 46,X,inv(Y)(p11.2q11.2)
  • 83. Look for type of YCMD
  • 85. • 39 yr • FSH 25.4, LH 12.6, Estradiol 14, Testo 61. Sometimes nothing can be done
  • 86. 46,XX SRY+ sex reversal
  • 87. Medical Therapy in Idiopathic Azoospermia • To improve the chance of sperm retrieval (Alkandari and Zini, 2021; Kumar, 2021; Holtermann et al., 2022). • Sometimes, can lead to appearance of sperms in the ejaculate (Alkandari and Zini, 2021; Kumar, 2021). • hCG • FSH • CC • Tamoxifen • Letrozole • Antioxidants?? (Agarwal A, Majzoub A, 2017)
  • 88. Ethical dilemma in NOA Trial TESA • Avoids Unnecessary ovarian stimulation • May need repeat TESA TESA during OPU • What to do if sperms are not obtained OPTIONS 1. Donor sperm 2. Discard eggs 3. Freeze eggs
  • 89. Semen Report 5 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
  • 90. Semen Report 5 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
  • 91. Assess • Abstinence period • Completeness of collection • Usual amount of ejaculate • Exclude retrograde ejaculation • Suspect obstructive pathology- TRUS
  • 92. 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< 2020) • Partner testing • Indian prevalence- 1:10,000- 1:40,000 (Kapoor et al., 2006; Prasad et al., 2010)
  • 93. CBAVD, TRUS, CFTR mutation • TRUS- • B/L agenesis of seminal vesicles • Male partner- CFTR carrier • Female partner- CFTR carrier
  • 94. CBAVD is NOT uncommon • CFTR negative • CFTR carrier • Wife- normal • CFTR refused • CFTR carrier • Wife- normal • CFTR negative
  • 95. Semen Report 6 Collection Method Masturbation Total Motility 0% Abstinence 4 days Progressive Motility 0% Collection Complete Non progressive Motility 0% Volume 2 ml Immotile 100% Viscosity Normal Motile Sperm Count Nil Liquefaction Time 45 minutes Normal Morphology 2% pH 7.6 Vitality 12% Sperm Concentration 18 million/ ml Round cells Nil
  • 96. Semen Report 6 Collection Method Masturbation Total Motility 0% Abstinence 4 days Progressive Motility 0% Collection Complete Non progressive Motility 0% Volume 2 ml Immotile 100% Viscosity Normal Motile Sperm Count Nil Liquefaction Time 45 minutes Normal Morphology 2% pH 7.6 Vitality 12% Sperm Concentration 18 million/ ml Round cells Nil
  • 97. Steps • Abstinence, frequency of discharge • Place of collection • Look for vitality- HOS, Supravital staining • Repeat after proper abstinence • Can be associated with smoking, varicocele, Immotile Cilia Syndrome • Antioxidants ?
  • 98. ICSI with Ejaculate vs Testicular sperms
  • 99. Case of total asthenospermia • 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 12/40.
  • 100. Semen Report 7 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
  • 101. Semen Report 7 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
  • 102. Isolated teratozoospermia • Isolated abnormal morphology is not the indication for ART Penn HA, Windsperger A, Smith Z, et al. Fertil Steril. 2011; 95(7):2320–3.
  • 103. Semen Report 8 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 5% pH 7.6 Vitality 32% Sperm Concentration 36 million/ ml Pus cells 10-12/hpf
  • 104. Semen Report 8 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 5% pH 7.6 Vitality 32% Sperm Concentration 36 million/ ml Pus cells 10-12/hpf
  • 105. MAGI (Male Accessory Gland Infection) EUA, 2018; ASRM, 2020; Vignera et al., J Med Microbiology, 2014 • The clinical significance is controversial. • Special Tests- Round cells vs Pus cells • Method of collection • Hand washing before collection • Culture of semen • Antibiotics- only when documented infections • Routine antibiotics- can harm • Consider prostatic fluid culture
  • 106. A story of “Pus cells” • 36-yr • Apparently unexplained infertility • Persistent Pus cells in semen • Culture negative • Pain during intercourse • Paraphimosis • No pus cells after circumcision • Conceived after OI, delivered
  • 107. Symptomatic “pus cells” • 26 yr • Concentration 14 million/ml, motility 35%, pus cells 10-15/ hpf • Occasional Rt scrotal pain • After antibiotics- symptoms subsided, semen became normal • Conceived spontaneously
  • 109. Semen collection- Is it so easy? (Inhorn 2007; Saleh et al., 2003; Gerris, 1999; Bahyah et al., 2010; Pottinger et al., 2016) • Privacy- Locked room • Relaxation • Bed • Partner • Erotic materials • Washing facility
  • 110. Problems in Semen collection (Meng et al., 2013; Fahmy et al., 1999; Ibrahim et al., 2016; Sønksen et al., 2002) • Ask- Why Difficulty • Erection issue • Vibroejaculator • Coitus interruptus • Nontoxic condom • Home Collection • Urine (In RE) • Prostatic Massage • Electroejaculation • Surgical sperm retrieval (for ICSI only)
  • 111. All cases may not have “Subfertility” • Female factors normal (AMH, HSG) • Male- 32 • Could not collect semen • Disclosed- never had consummation • ED and anejaculation • Hormonal profile, sugar- normal • Genitals- NAD • Requested AID without woman’s consent • Lost to follow up
  • 112. Disclaimer • Written consent from all the patients
  • 113. 1. Meticulous semen analysis in a standard laboratory 2. Physical examination and rational investigations 3. Avoid non-evidence based drugs for long time 4. Antioxidants- May be useful in mild problem 5. Antioxidants- Not reliable in severe problem 6. Donor sperm is NOT the only solution 7. IUI or IVF/ICSI- depends on the overall assessment Take Home Messages
  • 114. Treatment burden for MALE infertility falls on FEMALE