This document summarizes male and female infertility treatments. It discusses common causes of infertility like hormonal imbalances, anatomical abnormalities, genetic factors, etc. It provides details on initial lifestyle modifications and treatments for specific etiologies. Treatments mentioned include counseling, surgery, medication, assisted reproduction techniques like IUI, IVF, ICSI, and donor gametes. The document is intended as an educational guide for residents on evaluating and managing infertility cases.
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Basic infertility rx 17.02.2016
1. Maneenuch Sripha, 1st year resident
Chayanis Tinsopharat, 2nd year resident
Adviser : Assist. Prof. Matchuporn Sukprasert
2. Objectives
• Recall etiologies of male and female infertility
• Approach to infertility management by etiology
• Treatment of common causes of male & female
factors
• Assisted reproductive technologies : basic
pharmacology & procedures
3. Etiology
Berek & Novak's Gynecology, 15th edition
Male
factor
Female factor
Both
Unexplained
10-40%
10-20%
40-55%
20-30%
4. Initial : Lifestyle modifications
Smoking cessation
Reducing excessive caffeine and alcohol consumption
Appropriate frequency of coitus (every one to two days
around the expected time of ovulation)
9. Sperm transport
• 70 days: complete
spermatocyte stage
• 12-21 days : testisepididymis
ejaculatory duct
Ejaculated semen
• mature spermatozoa,
fluid from the prostate gland,
seminal vesicles and
bulbourethral gland
Capacitation
• remove of inhibitory mediator
10. Fertilization Acrosome reaction
• hydrolytic enzyme Sperm binds to and penetrates
zona pellucida
Cortical reaction
• oocyte release cortical granules Stop binding
to new sperm and inhibit penetration of previously bound sperm
17. Treatment of Male factor
1. Lifestyle modification in all cases
2. Treat underlying/identificable causes
Varicocele repair
Post-vasectomy reversal
3. Assisted reproductive technologies
Sperm collection : autologous sperm from surgical
sperm recovery (MESA, PESA, TESE, TESA) , donor sperm
Fertilization : Artificial insemination, ICSI
18. • 15% in male population. 40% in infertile
• Improve semen parameter BUT not clear to
improve fertility
• Consider in
• Palpable varicocele
• Abnormal semen
analysis
Varicocele repair
20. Vasectomy reversal
• Microsurgical vasovasostomy
or vasoepididymostomy
• 100%patency
• 80%subsequent pregnancy
rate
• Rate of patency and
pregnancy inverse variation
from time that vasectomy
(esp. 15yr or more)
• Azoospermia 6mo after
reversal considered failure =>
sperm aspiration with ICSI
21. • repeat sperm retrievals,
minimum interval between is 3-6mo for adequate healing.
Surgical sperm recovery for ICSI
22. • Placement of whole semen or processed sperm
into female reproductive tract
• Treat – unexplained infertility and male factor
infertility
• Technique: IUI (intrauterine insemination)
Intracervical insemination
Insemination processing
Artificial insemination
23. • Pregnancy rate
-10.5%/cycle
-38% after 4-6 cycles
• Single IUI
a single cycle
IUI(intrauterine insemination)
• 0.3-0.5 ml washed, processed, and concentrated
sperm
• Intrauterine placement through transcervical
catheterization
24. • injection of a live sperm into the oocyte
• Bypassing limitation of
-sperm motility
-defect in capacitation
-acrosome reaction
-sperm binding to zona pellucida
ICSI : Intracytoplasmic Sperm Injection
Offer for
< 2 million motile sperm
< 5% motility
Or surgically recovered sperm used
25. ICSI
Risk of ICSI
• Oocyte degeneration 30-50%
• Higher congenital anomaly risk (4.2% compared
with IVF 2-3%)
• Higher risk of sex chromosome abnormality &
translocation
Counsel for infertility/ abnormality risk in offspring
• Y chromosome deletion
• abnormal karyotype
• cystic fibrosis mutation
• congenital absence of vas deferens
26. Donor insemination
• Donor sperm screening
• Screen for HIV infection, HBV, HCV, syphilis,
gonorrhea, chlamydia, CMV infection
• Cryopreserved sample guarantee for 6mo, donor
replace for HIV before clinical use of specimen
36. Gonadotropin
• Fail to ovulate or conceive with oral agents
• hMG (Repronex, Menopur)
• FSH (Follistim, Gonal-F, Bravelle)
• LH (Luveris)
• Dose : 37.5-75 IU/day
• Monitor : Estradiol or TVS follicle
• Increase dose by 50% next cycle
37. “hCG ovulation triggering”
• Induce final follicular maturation & ovulation
• After clomiphene citrate cycle
If dominant follicle develops, but no LH surge
• After gonadotropin cycle
When 1-2 follicles are 16-18 mm
& E2 level 150-300 pg/ml/dominant follicle
• Ovulation within 40 hr later
• SI within 24-48 hr
• IUI at 24-36 hr
Deficiency of GnRH or gonadotropins infertility
-Kallmann The most common congenital cause
isolated gonadotropin deficiency due to absent or defective GnRH secretion (resulting in sexual infantilism).
extragonadal abnormalities: anosmia, red-green color blindness, midline facial defects (e.g., cleft palate), neurosensory hearing loss, synkinesis (mirror movements), or renal anomalies
Hypothalamic and pituitary tumors
(e.g., craniopharyngioma, macroadenoma)
Infiltrative diseases (sarcoidosis, histiocytosis, transfusion siderosis, hemochromotosis)
Obesity : aromatase activityestrogen
Klinefelter Syndrome
primary testicular failure,1 in 1,000
extra X chromosome (47,XXY)-common form
translocation of the testis-determining gene (SRY) to an X chromosome
CAG repeats on the androgen receptor gene
:taller stature, lower BMD, gynecomastia, and decreased penile length, small, firm testes, resulting from damage to both seminiferous tubules and Leydig cells.
Serum concentrations of FSH and LH are elevated and testosterone levels are decreased.
Y Chromosome Deletions
Microdeletions of the long arm of the Y chromosome .
severe oligospermia and azoospermia
affecting up to 20% of men with infertility – TRANSMIT TO SON IF CONCIEVE
Cryptorchidism
a failure of testicular descent,which is an androgen-dependent process. (Kallmann syndrome, androgen resistance)
impaired spermatogenesis and an increased risk for developing testicular tumors.
↑FSH /↔LH
The severity of the semen abnormality relates to the duration of time the testes have been outside of the scrotum
Varicoceles
dilation of the panpiniform plexus
up to 30% infertile,more common on left than right
increased testicular temperature, delayed removal of local toxins, hypoxia, and stasis
Drug alkylating agents-cyclophosphamide, alcohol, anti-androgenspinorolactone, cimetidine
Radiation - 15 rads – suppress spermatogenesis
- 6 Gy – permanent azoospermia
Epididymis: obstruction and dysfunction--asthenoazoospermia
Kartagener syndrome : primary ciliary dyskinesia/ Cilia structure and function in vas and epi/ bronchiectasis, pulm infection
Young synd : inspissate secretion in Vas and epi
Infections: causing obstruction of the vas deferens (e.g., gonorrhea, chlamydia, tuberculosis
CBAVD : Congenital bilateral absence of the vas deferens –CFTR gene mutation
Varicocele- abnormal dilation of the vein within spermatic cord
Pathophysiology: Temp testis ที่สูงขึ้น, reflux metabolite fr. L adrenal or renal v, high reactive o2 species
Varicocele- abnormal dilation of the vein within spermatic cord
Pathophysiology: Temp testis ที่สูงขึ้น, reflux mebabolite fr. L adreanal or renal v, high reactive o2 species
Washing specimen- remove seminal factor and isolate pure sperm
Centifugation
Sperm migration protocol
Differential adherence procedure
Phosphodiesterase inhibitor – enhance sperm motility,
fertilization capacity, and acromase reactivity
Total motile sperm should be 5 million or 10 million
A single sperm to The mature metaphase II egg
Higher pregnancy rates with fresh and ejaculated sperm
Success rate affect by age of female partner & Oocyte quality
Ovulation induction
Weight reduction
Clomiphene citrate/MFM/Letrozole
Preovulatory monitoring
SI q 2-3 d after last CC
Midluteal serum progesterone d 7
Urinary LH d 5-12 or when
hCG
If no spontaneous LH surge
Ovulation within 40 hr
IUI
24 hr after LH surge
36 hr after hCG
Sperm preparation
CC :SERMs = Estrogen antagonist activity in CNS
Intact hypothalamic-pituitary-ovarian axis
Dose : CC 50 mg/day within day 5 (x5days)
➡ block ER in hypothalamus
➡ decrease negative feedback loop
➡ Rapid, low amplitude GnRH pulse
➡ increase FSH, LH
➡ Follicular growth & ovulation
Increase 50 mg/day each next cycle
Metformin: Biguanide
Inhibit gluconeogenesis, increase peripheral glucose uptake
PCOS ↔ Insulin resistance
Metformin
Biguanide
Increase spontaneous ovulation in PCOS (3-6 mo)
Dose : 500 mg tid, 850 mg bid, 1000 mg bid
Warning :
Induced withdrawal bleeding
Beware risk of endometrial hyperplasia
Administration at midcycle does not improve conception chance in patient using CC but useful in patient with known ovarian dysfunction
Contraindication to gonadotropins for infertility treatment :
Primary ovarian failure with elevated FSH levels
Uncontrolled thyroid & adrenal dysfunction
Organic intracranial lesion; pituitary tumor
Undiagnosed abnormal uterine bleeding
Ovarian cysts or enlargement not caused by PCOS
Prior hypersensitivity to gonadotropin
Sex hormone-dependent tumors of reproductive tract
Pregnancy
For CC-resistant pt.
Ex : ov. Wedge resection ไม่นิยมทำ
Now : ovarian drilling ลด ovarian androgen-producing tissue, กระตุ้น ovulation
ข้อดี low risk to multiple pregnancy
Drilling 3-15 puncture/ovary
via laparoscopy using electrocautery/laser or vaginal hydro-laparoscopy
Failed catheterization Diagnostic laparoscopy เห็น proximal blockage site repair
Or ถ้า repair ไม่ได้ หรือ severe adhesion หรือมี distal blockage ด้วย shift to ART (IVF)