male infertility semen analysis icsi causes adam micro tese iui intra uterine insemination surgical & medical management of male infertility

1. DR. PREKSHA JAIN
DR. BHAVANA KUMARE

2. Definitions

 INFERTILITY: Failure to conceive within one or
more years of regular unprotected coitus.
 PRIMARY INFERTILITY: Patients who have never
conceived
 SECONDARY INFERTILITY : Previous pregnancies
but failure to conceive subsequently

3. CONTENTS

1. Prevalence
2. Spermatogenesis
3. Hormonal regulation
4. Aging & Fertility
5. ADAM
6. Causes
7. Semen Analysis
8. Evaluation
9. Treatment

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

5. SPERMATOGENESIS

 74 days from spermatocyte stage
 Transport 12-21 days
200-300 million/day

6. HORMONE REGULATION
LH
FSH
LEYDIG
SERTOLI
TESTOSTERONE
ABP
LH receptor
5-10mg/day
ESTRADIOL
BRAIN
INHIBIN B

7. AGING & FERTILITY

 Semen volume 0.03ml/yr
 Total Motility -0.7%/yr
 Morphologically normal sperm proportion
decreases.
 Pregnancy rates >50yrs are 23-38%
 Causes
 Male factors contribute less to age related decline in
fertility

8. AGING & FERTILITY

PREGNANCY OUTCOMES:
 Point mutations
 Birth defects & congenital diseases
 Autosomal Dominant
 Schizophrenia & autism
 X-linked disease (grandfather effect)
 Spontaneous abortions

9. ADAM

 Androgen deficiency in aging male
 Serum Total & free testosterone levels
 Decrease in SHBG so Free levels decrease more than Total
 Hypogonadal men : Total Ts <300-325 ng/dl
Free Ts <5ng/dl
 Andropause
 Evaluation by morning levels of Total serum ts, Free ts
index (FTI= total/SHBG) for amount of bioavailable ts.
 Secondary hypogonadism : When LH normal or low
levels. MRI & PRL done to rule out Hth or Pituitary mass.

10. ADAM

 TREATMENT:
• When Total Testosterone levels < 200ng/dL
• Side effect- fluid retention, gynecomastia, sleep
apnea, malignant prostatic disease, cvd.
• Parenteral (75 gm/wk)
• Pellets (225 mg every 4-6 mth)
• Gel (5 g/d)
• Patches

11. CAUSES

1. IDIOPATHIC (40-50%)
2. HYPOTHALAMIC & PITUITARY DISORDERS (1-2%)
• Idiopathic isolated gonadotropin deficiency(M/C)
• Kallmann syndrome
• Single gene mutations
• Hth & pit tumors
• Infilterative diseases
• Hyperprolactinemia
• Drugs
• Critical illness
• Chronic systemic illness
• Infections
• Obesity

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

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

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

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

16. PRIMARY GONADAL DISORDERS

 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

17. PRIMARY GONADAL DISORDERS

 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

18. SPERM TRANSPORT DISORDERS

 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.

20. MALE INFERTILITY EVALUATION

 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

21. MALE INFERTILITY EVALUATION

 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

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

23. SEMEN ANALYSIS

 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.

25. Normal Reference Values (WHO)

 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 >50%, >30%, >14%
 Round cells < 5 million/ml
 Sperm agglutination <2 (scale 0-3)

26. Lower Reference Limits

 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

27. Ejaculate volume & pH

 Alkaline & fructose
 CBAVD – acidic pH
 B/l ejaculatory duct block – acidic & neither fructose
or sperm
 Post ejaculatory urinalysis - Retrograde ejaculation

28. Sperm Concentration & Total Sperm
Count

 Azoospermia : Complete absence of sperm on std
microscopic examination in ejaculate.
• 1-3% male population, 10-15% male infertility
• To confirm diagnosis semen is centrifuged & pellet
examined
• Obstructive
• Non Obstructive- Primary & secondary testicular failure.
Candidate for IVF (TESE)
 Oligospermia : sperm density < 20 million/ml. Severe
when < 5 million/ml
 Total sperm count – semen volume* sperm conc

29. Motility, Total motile count, Total motile
count & Vitality

 % 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

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

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

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

33. SPECIALIZED TEST

 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

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

35. 
Disorder FSH LH Free Ts
Hypogonadotropic
hypogonadism
low low low
Abnormal spermatogenesis N/high N N
Testicular Failure High High N/low

36. Urologic evaluation

 Physical examination
 TRUS (transrectal usg for duct obstruction)
 Transscrotal Usg
 Renal Scan
 Testis Biopsy in azoospermic men
 Vasogram

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

39. MEDICAL TREATMENT

 Hypogonadotropic Hypogonadism:
• Hyperprolactinoma- Dopamine agonists
• Cong 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)
Sr. Ts every 1-2 mth for 1st 3-4 mth level 400-900 ng/dl

40. 
• 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.

41. 
 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

42. 
 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)

43. ARTIFICIAL INSEMINATION

 Indications :
• Oligospermia,
• Asthenospermia,
• Premature or retrograde ejaculation,
• Sperm autoantibodies & cervical factors,
• Unexplained infertility
• Sex selection in genetic & chromosomal anomalies
• 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.

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

45. INTRAUTERINE INSEMINATION

 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)

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

47. SURGICAL TREATMENT

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

49. 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

50. Sperm Retrieval Techniques

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

52. Sperm Retrieval

 Sperm may be cryopreserved for future use or, if timed to
coincide with oocyte retrieval, can be immediately used
for ICSI.
1. Conventional TESE
2. Fine Needle Aspiration/Testicular Mapping
3. Microdissection TESE
 Genetic Screening for TESE Candidates
 Y Microdeletion Testing
 Cytogenetic Analysis

53. Best Technique for Sperm Retrieval


54. Micro-testicular Sperm Extraction

 Non obstructive azoospermia (NOA) defines men with
testicular failure who have severely deficient sperm
production with no sperm in the ejaculate.
 10% of infertile men
 On testicular biopsy, hypospermatogenesis, maturation
arrest, or Sertoli cell-only pattern (germinal cell aplasia).
Genetic causes- Klinefelter syndrome (KS) and XX-male
syndrome.
 Acquired- Testicular failure secondary to
cryptorchidism or systemic chemotherapy.

55. An area of the tunica
albuginea is incised and
microdissected

56. ICSI
