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
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
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
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.
19.
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.
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
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
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
48.
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
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
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
Sperms r formed in seminiferous tubule from germinal cells spermatogonium
Spermatogenesis depend on the hth ant pit testicular functn. …ABP bind testosterone & dihydrotest to maintain high local conc for spermatogenesis & maturation & testosterone for systemic functions as well.
Fsh induces appearance of lh receptors o Leydig cells.
Testosterone exerts its negative feedback effects on lh directly & indirectly via conversion to estradiol in brain.
Not sperm conc.
May be caused by cellular or physiological changes in male reproductive tract adversly affecting sperm prod & semen. Another mechanism are age related changes that occur in hypoth pituitary testicular axis.
Birth defects like cardiac limb neural tube. Autosomal dominant mutations like achondroplasia Alpert Marfan.
Carrier daughter to affected grandsons
Andropause include symptoms of androgen deficiency i.e. dcreased libido, stamina, irritability, sleeplessness, depression, cognitive disturbances.physical changes like osteopenia porosis decrs muscle mass, testicular atrophy,gynecomastia can be present .
Morning levels are evaluated to minimize influence pulsatile & circadian rythms
Hth & pit tumors like craniopharyngioma & macroadenoma. Infilterative dis like sarcoidosis, histiocytosis hemochromatosis. Drugs like gnrh analogs for prostate cancer, androgen, opiates estrogen
Obesity caause increase aromatase activity leading to conversion into estrogen
Infections like orchitis leprosy tb
Drugs like antiandrogens cimetidine
Gonadotoxins smoking pesticides
Chrnic illness like cancer renal insufficiency
Infections like gonorrhea chlamydia tb
Ejaculatory dysfunction like spinal cord diseases autonomic dysfunction
As left spermatic vein is longer & joins left renal vein at right angle. Hypoxia stasis delayed removal of toxins increaseed temp likely responsible
normal semen production. Mechanical blockage. Post infection, vasectomy, congenital
Abnml sperm analysis i.e sperm conc <10mill/ml, decrs libido
Sr estradiol in pt wid severe oligo
Testes small in testicular failure, epididymal fullness in obstruction, CBAVD , spermatic cord palpation for varicocele
Renal scan to detect renal agenesis in men wid vasal agenesis
Cong hypog hypogonadism t/t can induce sec sex charact but not initiate or support normal spermatogenesis
Cycle fecundity is probability of pregnancy per cycle
Success declines with increasing maternal age.>35, family ho early menopause, chemo/radiation With poor ovarian reserve reduced success with Ivf & poor chance with IUI
Risk of multiple ovulation, hyperstimulation higher, costs poor quality sperm with exogenous gonadotropin
Neurological dysfunctions due to diabetes spinal cord injuries demyelinating diseases
Art encompasses all procedures that involve manipulation of gametes & embryos outside the body