Fertility 2 Flashcards
What is the 1st line treatment for ovulation in PCOS?
Clomifene
usually limited to 6 months’ use, but results in ovulation and live birth rates of 70% and 40%
it is an anti-oestrogen, so blocks oestrogen receptors in the hypothalamus and pituitary causing an increase in FSH & LH release
given at days 2-6, so initiates the process of follicular maturation
response should be monitored for ovarian response (1st month) and endometrial thickness
if no follicles develop then dose is increase and if >3 develop then dose is stopped to prevent multiple pregnancies
can cause endometrium thinning affecting live birth rate, but high ovulation rate
What is the alternative 1st line treatment for ovulation in PCOS?
taken every day through the cycle in multiple doses, but GI side effects are common
more efficacious than clomifene in women with a BMI <30
increases effectiveness of clomifene in women who are clomifene-resistant women, so can be used jointly as 2nd line
treats hirsutism and if continued through pregnancy reduces the risk of early miscarriage and gestational diabetes
What are the other medications used for ovulation in PCOS?
o Oral aromatase inhibitors (letrozole)
can be used to induce ovulation, resulting in higher live birth rate than clomifene
may be due to reduced negative effects on the endometrium
not licensed for fertility treatment and not yet widely used
What is laparoscopic ovarian diathermy?
2nd line, but is as effective as gonadotrophins with lower multiple pregnancy rate
each ovary is monopolar diathermied at a few points for a few seconds
tubal patency can be tested at the same time and any endometriosis or adhesion treated
if successful then regular ovulation can continue for years
risks include periovarian adhesion formation and ovarian failure (rare)
What is gonadotrophin induction?
Used when 1st line have failed or in hypothalamic hypogonadism
recombinant or purified urinary FSH ± LH act as a substitute for normal pituitary production by being given daily subcutaneous infections to stimulate follicle growth, with often more than one follicle maturing
for PCOS patients, a ‘low-dose step-up’ regimen is used with small increment increased every 5-7 days until the ovaries begin to respond
follicular development is monitored with USS
once a follicle is of adequate size for ovulation (17mm), the process can be artificially started by injection of hCG or recombinant LH
What are the side effects of ovulation induction?
o Multiple pregnancy- more likely with clomifene, letrozole and gonadotrophins as more than one follicle may mature, multiple pregnancies increased perinatal complications rate
Ovarian hyperstimulation syndrome
o Ovarian and breast carcinoma- evidence is conflicting, but generally reassuring
What is ovarian hyperstimulation syndrome?
gonadotrophins overstimulate the follicles, which can get very large and painful
more common during IVF than standard ovulation induction
Risk factors:
gonadotrophin stimulation, <35yrs, previous OHSS and PCO
Prevention is by lowest effective dose
USS monitoing of follicular growth and withdrawal of gonadotrophins if seen
in severe cases hypovolaemia, electrolyte disturbance, ascites, thromboembolism and pulmonary oedema can occur
What is the physiology of sperm production?
• Spermatogenesis in the testis is dependent on pituitary LH & FSH
LH largely acting via testosterone production in the Leydig cells of testis
• FSH and testosterone control Sertoli cells, which are involved in synthesis and transport of sperm
• Testosterone and other steroids inhibit the release of LH- completing a –ve feedback loop with the HPA
• It takes about 70 days for sperm to develop fully
How is a semen sample collected?
• Sample collected by masturbation
last ejaculation having occur 2-7 days previously
must be analysed within 1-2hrs of production
• Abnormal result must be repeated after 12 weeks (no delay is azoospermia)
What is a normal semen analysis?
o Volume- >1.5ml
o Sperm count- >15 million/ml
o Progressive motility- >32%
What are the definitions of sperm problems?
o Azoospermia- no sperm present
o Oligospermia- <15 million/ml
o Severe oligospermia- <5 million/ml
o Asthenospermia- absent or low motility
What are the causes of abnormal/absent sperm release?
• Idiopathic oligospermia & asthenozoospermia
• Drug exposure- alcohol, smoking, drugs (sulfasalazine or anabolic steroids) and exposure to industrial chemicals (solvents)
• Varicocoele- varicosities of the pampiniform plexus normally occurring on the left side, present in 25% of infertile men (15% of all men)- not fully understood how it impairs fertility, but surgical treatment does not improve conception
• Anti-sperm antibodies- present in 5% of infertile men, common after vasectomy reversal- poor motility
and ‘clumping’ together
What are the other causes of poor sperm production?
o Infection- eg. Epididymitis o Mumps orchitis o Testicular abnormalities- eg. Klinefelter’s syndomre o Obstruction to delivery- eg. CF o Hypothalamic problems o Kallamnn’s syndrome- hypogonadotrophic hypogonadism o Hyperprolactinaemia o Retrograde ejaculation- into bladder
What are the investigations for poor sperm production?
• Azoospermia- blood test for FSH, LH, testosterone, prolactin and TSH
o Hypogonadotropic hypogonadism- very low FSH, LH & testosterone
o Hyperprolactinaemia- high prolactin
o Thyroid dysfunction- abnormal TSH
o Primary testicular failure- high FSH & LH and low testosterone, may be due to cryptorchidism, surgery or radiochemotherapy
• Serum karyotype- used to demonstrate genetic causes, including Klinefelter’s syndrome (XXY) or
chromosomal translocation
• Absent vas deferens- should have a blood test for cystic fibrosis
What is the management for male factor sub fertility?
- General advice- lifestyle changes and drug exposure addressed, wear loose clothing to keep testicles below body temperature
- Specific measures- treat hypogonadotrophic hypogonadism may be treated with x3 weekly subcutaneous FSH & LH injections (± hCG) for 6-12 months
