This document provides guidelines for evaluating and treating male infertility. It discusses when to evaluate couples for infertility, how to perform semen analysis according to WHO guidelines, and how to differentiate between obstructive and non-obstructive azoospermia. It provides recommendations on treating varicoceles, lifestyle factors, oxidative stress, and infections. For non-obstructive azoospermia, it discusses evaluating genetic causes and techniques for sperm retrieval like microdissection testicular sperm extraction. Medical therapies for infertility including hormones, antioxidants, and supplements are discussed along with their effectiveness. The document concludes by discussing fertility preservation and future areas of research like gene therapy.

1. Male Infertility
SEVERE OAT –management
- Dr Arun Kumar

2. Whom to evaluate
● Infertility-
primary=secondary
● RPL

3. When to evaluate
● Even after a year of marital life
● In less than 1 year if- 1) male infertility risk factors such as a history
of bilateral cryptorchidism are known to be present; 2) female
infertility risk factors, including advanced female age (over 35 years),
are suspected; or 3) the couple questions the male partner's fertility
potential (AUA guidelines)
● Testicular abnormalities
● Hormonal abnormalites

4. ● At least two Semen Analysis, ideally obtained at least one month
apart, are important to obtain, especially if the first SA has abnormal
parameters.
● 3 day abstinence
SEMEN ANALYSIS

5. WHO 2021

6. Evidence Based Practise

7. Lifestyle Factors and Relationships Between
Infertility and General Health
● Health risks associated with abnormal
sperm production.
(Grade B – ASRM 2020)
● Clinicians should advise couples with advanced
paternal age (40 years) that there is an increased
risk of adverse health outcomes for their offspring.
(Expert Opinion)

8. Concept of Oxidative Stress

9. Mechanism of sperm damage

10. Cancer Risks !
● Men with abnormal semen parameters have higher rates of
testicular cancer (6–9) and men with azoospermia have higher rates
of cancer in general than fertile men
● Eisenberg, et al. Increased risk of cancer among azoospermic men.
Fertil Steril 2013;100:681.

12. Infertile men with impaired libido, erectile dysfunction,
oligozoospermia, 10million or azoospermia
● Should obtain hormonal evaluation including follicle-stimulating
hormone (FSH) and Total testosterone
● Luteinizing hormone is indicated for men with low serum
testosterone
● Prolactin for decreased libido

13. Azoospermic men
● Semen volume,
● Physical exam,
● FSH levels
● To differentiate OA and NOA.
● Testis length >4.6 cm, FSH <7.6 and/or semen volume <0.5 or 1.0 mL
most likely have obstructive azoospermia, especially if the proximal
epididymis is enlarged on physical examination or the vasa
deferentia are absent on exam.

14. NOA & SOAT
● Karyotype and Y-chromosome microdeletion
analysis should be recommended

15. Factors that influence choice of therapy in
OATS
● 1. Age of the couple and duration of infertility: A young couple
with a short trying time -option of medical therapy in order to buy
time to achieve a natural pregnancy. Older- ART
● 2. Severity of OATS and realistic chances of improvement expected
a patient with severe OATS (less than 5 million/ml with very poor
progressive motility) with no obvious reversible factors is more likely
to benefit from ART.
● 3. Past illness causing irreversible damage: For example, a patient
who had post-mumps orchitis and testicular atrophy, or who was
operated for undescended testes- medical therapy not useful
● 4. Reversible, correctable gonadotoxic factors- occupational
exposure (heat, chemical fumes), heavy smoking, recent febrile
illness, accessory gland infections, etc., then such patients can be
given supportive medical therapy to buy time

16. Factors that influence choice of therapy in
OATS
● 5.Treatment history: there should be no repetition. If various drugs
have already proved ineffective there is no point in giving further
medical therapy.
● 6. Socioeconomic status of the couple should also be considered
when deciding medication since many empirical drugs are rather
expensive.
● 7. Psycho-social pressures on the couple play an important role in
decision making. In a couple who is socially hard-pressed for a baby,
less time should be spent on medical therapy.

18. PYOSPERMIA
● Men with increased round cells on SA (>1million/mL) should be evaluated further to
differentiate white blood cells (pyospermia) from germ cells. (Expert Opinion)
● Semen cultures??
● Common organisms responsible are Streptococcus fecalis and Escherichia coli,
Chlamydia trachomatis and Ureaplasma urealyticum. Because of the difficulty of
culturing chlamydia or ureaplasma - Doxycycline 200 mg/day on an empirical basis for 15
days and then start antibiotics as per culture reports.
● Commonly used are: Fluoroquinolones 0.5 to 1 g/day, Cotrimoxazole (Sulfamethoxazole
800 mg, Trimethoprim 160 mg) or Erythromycin 1.5 to 2 5 g/day. These drugs are
administered for 2 to 3 weeks

19. Should we do ASA? In Initial Evaluation
● Antisperm antibody (ASA) testing should not be done in the initial
evaluation of male infertility. (Expert Opinion)
● Thus, treatment of antisperm antibodies using corticosteroids should not
be prescribed routinely,
● It can be considered if earlier failed fertilization during IVF or ICSI.
● Some use the following low-dose regimen in men with proven high titres,
or OATS with clinical evidence of chronic epididymitis: tablet
prednisolone 5 mg, thrice-a-day for 10 days, then twicea-day for 10 days,
then once-a-day for 10 days.

20. RPL
For couples with RPL, men should be evaluated with
● karyotype (Expert Opinion)
● sperm DNA fragmentation. (Moderate Recommendation; Evidence
Level: Grade C)
● Sperm chromosome aneuploidy by FISH (expert opinion)

22. Diagnostic testicular biopsy
● Should not routinely be performed to
differentiate between obstructive
azoospermia and non-obstructive
azoospermia (NOA). (Expert Opinion)
● Can be done along with sperm retrieval

24. NOA- Genetic causes
● Klinefelter syndrome (the presence of extra X chromosomes). There
may be rare foci of spermatogenesis found upon microdissection-
testicular sperm extraction in at least 50%-60% of 47, XXY men
● Y chromosome microdeletions are the second most common known
genetic cause
● Testicular sperm extraction IS SUCCESSFUL in at least 50% of men
with an AZFc deletion
● Sperm have not been retrieved in men with complete AZFa and/or
AZFb microdeletions, so surgical intervention is not indicated.

25. ● Scrotal ultrasound should not be routinely performed in the
initial evaluation of the infertile male
● Recommend TRUS in men with SA suggestive of ejaculatory
duct obstruction (i.e., acidic, azoospermic, semen volume
<1.5mL, with normal serum T, palpable vas deferens). (Expert
Opinion)
● Renal ultrasonography for patients with vasal agenesis to
evaluate for renal abnormalities. (Expert Opinion)

27. SOAT MEDICAL THERAPY
● Non-specific treatments include
● A. Hormonal agents: Androgens, Antiestrogens, Aromatase
inhibitors, Gonadotropins.
● B. Antioxidants : Glutathione, Lycopene, Vitamin –E
● C. Sperm vitalisers : L -carnitine, Co-enzyme Q 10
● D. Nutritional supplements : Folic acid, Zinc, Multivitamins, Trace
elements
● E. Miscellaneous: Indomethacin, Kallikrien, Low dose
corticosteroids.
● F. Elimination of gonadotoxic factors

28. ANTI-OXIDANTS in SOAT

29. Hormone therapy
● Antiestrogens : • Rationale: Antiestrogens inhibit the negative
feedback effect of estrogen by blocking estrogen receptors in the
hypothalamus, which in turn increases endogenous gonadotropin
secretion. In turn, FSH and LH stimulate Sertoli and Leydig cells with
a possible improvement in spermatogenesis
● • Drugs used and dose : i. Clomiphene citrate : 25mg daily, or on
alternate days ii. Tamoxifen citrate : 10 to 20 mg daily
● • Aromatase Inhibitors : • Rationale: Estrogen has a potent negative
feedback effect on gonadotropin secretion. Obese men have
excessive aromatization, in their fat cells, of Testosterone to
Estrogen resulting in excess estrogen and an altered Testosterone
to Estrogen ratios (T/E). Aromatase inhibitors correct this by
inhibiting the peripheral conversion of Testosterone and may
thereby enhance spermatogenesis.
● • Drugs used and dose : i. Letrozole 2.5mg daily orally
●

30. Hormone therapy
● • Gonadotropins : • Rationale: Some patients with idiopathic
infertility may have a subclinical endocrinopathy which 13 results in
abnormalities in the bio-activity, half-life or pulsatility of
gonadotropin secretion . Such men may benefit from exogenous
gonadotropins despite normal levels on immunoassay.
● • Drugs used: Human chorionic gonadotropin (HCG) (1500 IU i.m 3
times per week), Human menopausal gonadotropin (HMG) ( 37.5-75
IU i.m 3 times per week)

31. ● Benefits of supplements (e.g., antioxidants, vitamins) are of
questionable clinical utility in treating male infertility.
● For Idiopathic infertility, Follicle-Stimulating Hormone (FSH) analogue
with the aim of improving sperm concentration, pregnancy rate, and
live birth rate. (Grade B)
Medical & Nutraceutical Interventions
for Fertility

32. Medical & Nutraceutical Interventions
for Fertility
Low serum testosterone , T/E is low ( <10)(Grade C)
( T- 300-800ng/dl), e2 - <40)
1. Aromatase inhibitors (AIs) 1mg,
2. HCG
3. SERMs- CC 25mg /Tamoxifen , or a
combination
Idiopathic infertility / Pre treatment to Sperm Retrieval in NOA
● SERMs has limited benefits relative to results of
ART. (Expert Opinion)
● Inj HCG monotherapy optional

33. NOA and Medical Rx
● limited data supporting pharmacologic manipulation with SERMs, AIs, and
gonadotropins prior to surgical intervention. Grade C
● Clinicians should inform the man with idiopathic infertility that the use of SERMs
has limited benefits relative to results of ART. (Expert Opinion)
● For men with idiopathic infertility, a clinician may consider treatment using an FSH
analogue with the aim of improving sperm concentration, pregnancy rate, and live
birth rate. (Conditional Recommendation; Evidence Level: Grade B)

34. HH – medical Rx
● hCG injections are typically initiated with a response of serum
testosterone monitored. After normalization of testosterone, FSH or
FSH analogues may be added to optimize sperm production

35. Exogenous testosterone administration – NO
● provides negative feedback to the hypothalamus and pituitary gland
that can result in inhibition of gonadotropin secretion. Depending on
the degree of testosterone-induced suppression, spermatogenesis
may decrease or cease altogether, resulting in azoospermia

36. Varicocele Repair / Varicocelectomy.
Surgical varicocelectomy should be considered
palpable varicocele(s), infertility, and
abnormal semen parameters,
except for azoospermic men.
(Grade B)
Clinicians should not recommend varicocelectomy in
Nonpalpable varicoceles detected solely by imaging. (Grade C)

37. Clinical varicocele and non-obstructive
azoospermia (NOA)

38. Sperm Retrieval
● For men with NOA undergoing sperm retrieval,
microdissection testicular sperm extraction (TESE)
should be performed. (Moderate Recommendation; Evidence
Level: Grade C)
● In men undergoing surgical sperm retrieval, either
fresh or cryopreserved sperm may be used for
ICSI. (Moderate Recommendation; Evidence Level:
Grade C)
● In men with azoospermia due to obstruction
undergoing surgical sperm retrieval, sperm may be
extracted from either the testis or the epididymis.
(Moderate Recommendation; Evidence Level: Grade C)

39. Micro TESE

40. Microsurgical sperm extraction
● Azoospermia- NOA 60%
● MESA
● TESA-15-50%
● TESE- 20-50%
● PESA- IN obstructive azoospermia- 70 to 80%
● TEFNA
● TESTICULAR MAPPING

41. Micro TESE
● Medications –clomiphene,
aromatase inhibitor,HCG
● 12 weeks treatment
● Correction of clinical
varicocele in NOA-increases
retrieval -40% acc. To meta-
analysis
● Lab handling, mechanical
mincing, air quality control

44. ● Men to bank sperm, preferably multiple specimens when
possible, prior to commencement of gonadotoxic therapy.
● Based on the known mutagenic effects of gonadotoxic
therapies it is recommended to use contraception for a
period of at least 12 months after completion of therapy
● Testicular tissue should be considered during orchiectomy or
excisional biopsy of the testicular lesion
Fertility Preservation in Males

45. ● RPLND is a cornerstone in the management of some patients with
testis cancer. After nerve sparing RPLND by an experienced testis
cancer surgeon, it is rare to have permanent sympathetic nerve
damage and long-term failure to ejaculate (RE or failure of emission).
However, in the post-chemo RPLND patient the likelihood of
ejaculatory dysfunction higher

46. FUTURE - Gene Therapy in Male fertility
Azoospermia Conditions
● Stem Cell Therapy
● Genomic editing – Safe/ Ethical / Use Crisper /cas9 gene editing –
Limited to monogenic disorders – HGE 2020
● TEX11 GENE identified in some men with Azoospermia

48. Laser assisted selection of immotile spermatozoa

49. LAISS- FOR ICSI

50. MICRO TESE

51. Thank you!
A4 Fertility Centre
Address:
87, Arcot Rd, Udhayam Colony, AVM Avenue,
Virugambakkam, Chennai, Tamil Nadu 600092
Find us on:
www.a4hospital.com
/a4hospital
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in Families