factors for male infertility

2. 
INTRODUCTION
 INFERTILITY - one year of unprotected intercourse
without conception
 SUBFERTILITY- couples who conceive after 12
months of attempted impregnation.
 FECUNDABILITY - probability of achieving
pregnancy within a single menstrual cycle
 FECUNDITY - probability of achieving a live birth
within a single cycle.

3. 
 It is sole cause in 20% of infertile couple
 Contributing factor in 20-40% couples
 Female infertility in 40-55%
PREVALENCE

4. 
SPERMATOGENESIS
• During embryogenesis, there are approximately
300 thousand spermatogonia in each gonad.
• Each undergoes mitotic division, and by
puberty 600 million in each testis.
4

5. 
Sperm production takes place in seminiferous tubules
within testis.
Spermatogenesis takes about 75 days
Adult males produce 100-200 million sperm each day.
Under the effect of LH, Leydig cells produce
testosterone (which along with FSH, stimulates
spermatogenesis).
Maturation of sperms takes place in epididymis.
Transport of sperms – vas deferens 5

6. 
Physiology of Semen after
Ejaculation
1. Liquefaction
2. Capacitation
3. Acrosome reaction
4. Cortical reaction
6

7. 7

8. 1. IDIOPATHIC (40-50%)
2. HYPOTHALAMIC & PITUITARY DISORDERS (1-2%)
• Idiopathic isolated gonadotropin deficiency(M/C)
• Kallmann syndrome
• Single gene mutations
• Hypothalamic and pituitary tumours
• Infilterative diseases
• Hyperprolactinemia
• Drugs
• Critical illness
• Chronic systemic illness
• Infections
• Obesity
CAUSES OF MALE
INFERTILITY

9. 
2. PRIMARY GONADAL DISORDERS (30-40%)
• Klinefelter syndrome
• Y chromosome deletions
• Single gene mutations
• Cryptorchidism
• Varicoceles
• Infections
• Drugs
• Radiation
• Environmental Gonadotoxins
• Chronic illness
CAUSES

10. 
3. SPERM TRANSPORT DISORDERS (10-20%)
• Epididymal obstruction or dysfunction
• CBAVD
• Infections
• Vasectomy, herniorraphy
• Kartagener syndrome
• Young syndrome
• Ejaculatory dysfunction
CAUSES

11. 
Kallman syndrome
GnRH deficiency +
HYPOTHALAMIC PITUITARY
DISORDERS
Red-green blindness
Anosmia
Cleft palate
Neurosensory
hearing loss
Synkinesis
Renal anomalies

12. 
 Klinefelter syndrome:
47XXY and other forms & no. of CAG repeats
• Small firm testes
• FSH & LH and Testosterone
• Cryptorchidism
• Long arms & legs
• Psychosocial abnormalities
• Pulmonary diseases
• Mediastinal germ cell tumors, breast cancer
PRIMARY GONADAL DISORDERS

13. 
 Y chromosome deletions: 20% men with infertility
• Severe oligospermia & azoospermia
• Genetic counselling offered before ICSI, as these
deletions are transmitted to sons.
 Single gene mutations & polymorphism:
No. of CAG repeats inversely proportional to sperm
concentration & fertility
PRIMARY GONADAL DISORDERS

14.  Cryptorchidism: Failure of testicular descent.
An androgen dependent process.
FSH levels raised. LH normal
Risk of tumors
 Varicoceles: Dilatation of pampiniform plexus of spermatic veins.
More common on left side.
No causal relationship with infertility
 Radiation: 0.015 Gy (15 rads) supress spermatogenesis
> 6 Gy permanent azoospermia
PRIMARY GONADAL DISORDERS

15. 
 Epididymal dysfunction: Intrauterine exposure to
DES. Causes isolated asthenospermia
 CBAVD: Congenital bilateral absence of the vas
deferens related to CFTR gene mutations. 1-2% of
infertile men
 Kartagener syndrome: Recurrent sinus infection,
bronchiectasis, situs inversus, male infertility.
SPERM TRANSPORT DISORDERS

17. 
 Goals are to Identify-
• Specific cause & correct it
• Individuals who can be offered IUI & ART
• Individuals with genetic abnormality that may affect
offspring conceived by ART
• Adoption & donor sperm options for those who are
not candidate for ART
• Underlying Medical condition
MALE INFERTILITY EVALUATION

18.  Time to start evaluation : When pregnancy fails to occur after 1 yr of
regular unprotected intercourse.
 Earlier evaluation for men with any obvious infertility factor.
 HISTORY:
• Duration of infertility & previous fertility
• Coital frequency & sexual dysfunction
• h/o previous evaluation & t/t
• Childhood illness
• Previous surgical & medical illness
• Past episodes of STI
• Exposure to gonadotoxins & heat
• Medications & allergies
• Occupation & addictions
MALE INFERTILITY EVALUATION

19. 
 PHYSICAL EXAMINATION:
• Examination of penis, location of urethral meatus
• Palpation of testes & size
• Presence & consistency of vas & epididymis
• Secondary sexual characteristics, habitus, hair &
breast development
• Digital rectal examination
MALE INFERTILITY EVALUATION

20. 
 Collection method: After a defined period of
abstinence of 2-3 days.
 Semen may be collected in a clean container by
masturbation or via intercourse using silastic
condom that does not contain spermicidal agents.
 Sample should be examined within an hour of
collection.
 If abnormal, repeat it after 4 weeks.
SEMEN ANALYSIS

22. 
 Volume 1.5-5 ml
 pH >7.2
 Viscosity < 3 (scale 0-4)
 Sperm concentration >20 million/ml
 Total sperm number >40million/ejaculate
 Percent motility > 50%
 Forward progression >2 (scale 0-4)
 Normal morphology >14%
 Round cells < 5 million/ml
 Sperm agglutination <2 (scale 0-3)
Normal Reference Values (WHO)

23. 
 Volume 1.5 ml (1.4 – 1.7)
 Sperm concentration 15 million/ml (12 - 16)
 Total sperm number 39 million/ejac (33-46)
 Total motility 40% (38 - 42)
 Progressive motility 32% (31 - 34)
 Normal morphology 4% (3 - 4)
 Vitality 58% (55 - 63)
To assess prognosis for achieving pregnancies with their
partner
Lower Reference Limits

24. 
 The lower limit is 1.5 ml
 pH : 7.2 or higher (Alkaline)
 CBAVD or Bliateral Ejaculatory duct block – acidic
pH
 High volumes >5ml
Indicate inflammation of accessory glands
Ejaculate volume & pH

25.  Azoospermia : Complete absence of sperm on microscopic
examination in ejaculate.
• 1-3% male population, 10-15% male infertility
• To confirm diagnosis semen is centrifuged & pellet examined
1. OBSTRUCTIVE: blockage in ductal system ( CBAVD, scrotal or
inguinal surgery)
2. NON OBSTRUCTIVE: primary testicular failure,
endocrinopathies that suppress spermatogenesis.
 Oligospermia : sperm density < 15 million/ml. Severe when < 5
million/ml
Sperm Concentration & Total Sperm
Count

26. 
 % of total sperm exhibiting any motion
 Total motile sperm count = total sperm count & % of
progressively motile sperm
 Asthenospermia : Poor sperm motility. Suggests
anti sperm antibodies, genital tract infections, partial
obstruction of ejaculatory duct, varicoceles,
vasectomy reversal, prolonged abstinence
Motility, Total motile count, Vitality

27. 
 Viable non-motile sperm- Kartagener syndrome
 Vitality test- to differentiate viable non motile sperm
from dead sperm for ICSI
Motility, Total motile count & Vitality

28. 
 Teratospermia : > 70% abnormal morphology.
Varicocele, primary & secondary testicular failure
 Necrospermia : dead sperm
Sperm Morphology

29. 
 > 5million/ml round cells (round spermatid,
spermatocytes)
 Leucocytospermia > 1million leucocytes/ml. Semen
culture for Mycoplasma, ureaplasma, Chlamydia.
Round cells & leukocytospermia

30. 
 To evaluate attachment to zona pellucida, penetration of
the oocyte, release of acrosomal enzymes.
 Sperm autoantibodies (PCT)
 Sperm penetration assay
 Human Zona Binding Assay
 Computer Assisted Sperm Analysis
 Acrosome reaction
 Biochemical test
 Sperm Chromatin Structure & DNA
SPECIALIZED TEST

31.  Indications:
• Abnormal semen analysis
• Sexual dysfunction
• Specific endocrinopathy
 Tests :
• Serum FSH
• Total testosterone
• Serum Free Testosterone
• LH
• PRL, TSH
• Serum estradiol
Endocrine Evaluation

32. 
Disorder FSH LH Free Ts
Hypogonadotropic
hypogonadism
low low low
Abnormal spermatogenesis N/high N N
Testicular Failure High High N/low

33. 
 Physical examination
 TRUS (trans rectal ultrasound for duct obstruction)
 Trans scrotal Ultrasound
 Renal Scan
 Testis Biopsy in azoospermic men
 Vasogram
Urologic evaluation

34. 
 Y chromosome deletions
 Chromosomal anomalies
 CFTR gene mutations (CABVD)
Genetic Evaluation

35.  Hypogonadotropic Hypogonadism:
• Hyperprolactinoma- Dopamine agonists
• Congenital hypogonadotropic hypogonadism- hCG or
exogenous testosterone
• Adult onset hypogonadotropin hypogonadism- hCG 2000-5000
IU 3 times per week.
Start alone with hCG (as LH) as
1. hCG stimulate Leydig cells to produce testosterone
2. hCG alone can stimulate spermatogenesis
3. Annual costs lower than hMG (both FSH & LH)
MEDICAL TREATMENT

36. 
• Non-responders - hCG & hMG or pure FSH (75-100
IU 3 times weekly)
• Hypogonadotropin hypogonadism unrelated to
cause- Portable programmable pulsatile infusion
pump s/c.

37. 
 Eugonadotropin Hypogonadism
Severe oligospermia
Low Sr. testosterone
T/t by aromatase inhibitor (Testolactone 50-100 mg BD
Anastrazole 1 mg OD)
 Hypergonadotropic Hypogonadism
Insemination with donor sperm
IVF with ICSI with preliminary genetic evaluation
 Erectile dysfunction
Sildenafil- 25-100mg 1hr before intercourse

38.  Retrograde Ejaculation-
• Sympathomimetics, pseudoephidrine, ephedrine
• IVF & IUI & ICSI
 Leucocytospermia-
• Antibiotics (doxycycline, erythromycin, cotrimoxazole)
 Idiopathic Male Infertility-
• Androgen therapy
• Exogenous FSH
• Clomiphene citrate (25 mg)/Tamoxifen (20 mg)

39.  Indications :
• Oligospermia,
• Asthenospermia,
• Premature or retrograde ejaculation,
• Sperm autoantibodies & cervical factors,
• Unexplained infertility
• Hypospadias
• HIV positive
 Advantages :
1. Overcome limitation of decreased sperm density or motility. Better than
Cervical insemination
2. With washed sperm concentrate delivers more no. of sperms
3. IUI yields better results than cervical insemination.
ARTIFICIAL INSEMINATION

40. 
 Types:
1. IUI
2. Intracervical
3. Pericervical & Vaginal
4. DIPI (Direct intraperitoneal insemination)
ARTIFICIAL INSEMINATION

41. 
 Cycle fecundity 3-10% infertile partner sperm
9-30% donor sperm
 Processed motile sperm count at least 1 million
 Best results when no. of TOTAL MOTILE SPERMS > 10 million
 Success rates
• Highest > 14% sperm have normal morphology
• Intermediate 4-14%
• Poor <4% (advised IVF & ICSI)
INTRAUTERINE INSEMINATION

42.  INDICATIONS :
1. Azoospermia
2. Immunological factors not correctable
3. Genetic disease in husband
Donor Sperm

43. 
1. Vasovasostomy & vasoepididymostomy- In
vasectomized men
2. Transurethral resection of the ejaculatory ducts- in
men with Ejaculatory duct obstruction (1-5% of
infertile men)
3. Varicocele repair- In men with varicoceles (20-45%
of infertile men)
4. Orchipexy – In cryptorchidism
5. Vibratory stimulation & Electroejaculation – In
neurological dysfunctions
SURGICAL TREATMENT

44. 
Assisted Reproductive Techniques
 IVF-ET – In vitro fertilization & embryo transfer
 GIFT – Gamete intra fallopian transfer
 ZIFT – Zygote intra fallopian transfer
 POST – Peritoneal oocyte & sperm transfer
 TET – Tubal embryo transfer zone
 SUZI – Subzonal insemination
 ICSI – Intracytoplasmic sperm injection
 AH – Assisted Hatching
 IVM – In vitro maturation of oocyte
 PGD – Preimplantation genetic diagnosis

45. 
1. NON OBSTRUCTIVE AZOOSPERMIA:
 TESE – Testicular sperm extraction
 Micro-TESE – Microdissection testicular sperm extraction
2. OBSTRUCTIVE AZOOSPERMIA :
 MESA – Microsurgical Epididymal Sperm Aspiration
 PESA – Percutaneous epididymal sperm aspiration
Sperm Retrieval Techniques