male infertility by dr. preksha jain
DESCRIPTION
male infertility semen analysis icsi causes adam micro tese iui intra uterine insemination surgical & medical management of male infertilityTRANSCRIPT
MALE INFERTILITY
DR. PREKSHA JAINDR. BHAVANA KUMARE
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
Definitions
1. Prevalence 2. Spermatogenesis3. Hormonal regulation4. Aging & Fertility5. ADAM6. Causes7. Semen Analysis8. Evaluation9. Treatment
CONTENTS
It is sole cause in 20% of infertile couple Contributing factor in 20-40% couples Female infertility in 40-55%
PREVALENCE
74 days from spermatocyte stage Transport 12-21 days
SPERMATOGENESIS
200-300 million/day
LH
FSH
LEYDIG
SERTOLI
TESTOSTERONE
ABP
LH receptor
5-10mg/day
ESTRADIOL
BRAIN
HORMONE REGULATION
INHIBIN B
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
AGING & FERTILITY
PREGNANCY OUTCOMES: Point mutations Birth defects & congenital diseases Autosomal Dominant Schizophrenia & autism X-linked disease (grandfather effect) Spontaneous abortions
AGING & FERTILITY
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.
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
ADAM
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
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
CAUSES
3. SPERM TRANSPORT DISORDERS (10-20%)
• Epididymal obstruction or dysfunction• Hypospadias • CBAVD• Infections• Vasectomy, herniorraphy• Kartagener syndrome• Young syndrome• Ejaculatory dysfunction
CAUSES
Kallman syndromeGnRH deficiency +
HYPOTHALAMIC PITUITARY DISORDERS
Red-green blindnessAnosmia
Cleft palateNeurosensory hearing
loss
Synkinesis
Renal anomalies
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
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
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
PRIMARY GONADAL 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.
SPERM TRANSPORT DISORDERS
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
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
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
MALE INFERTILITY EVALUATION
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
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)
Normal Reference Values (WHO)
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
Alkaline & fructose CBAVD – acidic pH B/l ejaculatory duct block – acidic & neither
fructose or sperm Post ejaculatory urinalysis - Retrograde
ejaculation
Ejaculate volume & pH
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
Sperm Concentration & Total Sperm Count
% 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, Total motile count & Vitality
Viable non-motile sperm- Kartagener
syndrome
Vitality test- to differentiate viable non motile sperm from dead sperm for ICSI
Motility, Total motile count, Total motile count & Vitality
Teratospermia : > 70% abnormal morphology. Varicocele, primary & sec testicular failure
Necrospermia : dead sperm
Sperm Morphology
> 5million/ml round cells (round spermatid,
spermatocytes) Leucocytospermia > 1million leucocytes/ml.
Semen culture for Mycoplasma, ureaplasma, Chlamydia.
Rounds cells & leukocytospermia
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
Indications: • Abnormal semen analysis• Sexual dysfunction• Specific endocrinopathy
Tests :• Sr. FSH• Total testosterone• Sr. Free Testosterone• LH• PRL, TSH• Serum estradiol
Endocrine Evaluation
Disorder FSH LH Free Ts
Hypogonadotropic hypogonadism
low low low
Abnormal spermatogenesis N/high N N
Testicular Failure High High N/low
Physical examination TRUS (transrectal usg for duct obstruction) Transscrotal Usg Renal Scan Testis Biopsy in azoospermic men Vasogram
Urologic evaluation
Y chromosome deletions Chromosomal anomalies CFTR gene mutations (CABVD)
Genetic Evaluation
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) as1. hCG stimulate Leydig cells to produce testosterone2. hCG alone can stimulate spermatogenesis3. Annual costs lower than hMG (both FSH & LH)Sr. Ts every 1-2 mth for 1st 3-4 mth level 400-900 ng/dl
MEDICAL TREATMENT
• 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.
Eugonadotropin HypogonadismSevere oligospermiaLow Sr. testosteroneT/t by aromatase inhibitor (Testolactone 50-100 mg BD Anastrazole 1 mg OD)
Hypergonadotropic HypogonadismInsemination with donor sperm IVF with ICSI with preliminary genetic evaluation
Erectile dysfunctionSildenafil- 25-100mg 1hr before intercourse
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)
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 insemination2. With washed sperm concentrate delivers more no. of sperms3. IUI yields better results than cervical insemination.
ARTIFICIAL INSEMINATION
Types: 1. IUI2. Intracervical3. Pericervical & Vaginal4. DIPI (Direct intraperitoneal insemination)
ARTIFICIAL 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)
INTRAUTERINE INSEMINATION
INDICATIONS :1. Azoospermia2. Immunological factors not correctable3. Genetic disease in husband
Donor Sperm
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 cryptorchidism5. Vibratory stimulation & Electroejaculation
– In neurological dysfunctions
SURGICAL TREATMENT
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
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
Sperm may be cryopreserved for future use or,
if timed to coincide with oocyte retrieval, can be immediately used for ICSI.
1. Conventional TESE2. Fine Needle Aspiration/Testicular Mapping3. Microdissection TESE
Genetic Screening for TESE Candidates Y Microdeletion Testing Cytogenetic Analysis
Sperm Retrieval
Best Technique for Sperm Retrieval
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.
Micro-testicular Sperm Extraction
An area of the tunicaalbuginea is incised andmicrodissected
ICSI