Infertility - Class Notes

Infertility Affects 1/6 couples at some point Subfertility (infertility) = inability to conceive within a year of regular unprotected intercourse Primary – neither person ever had children/pregnancy, Secondary – one or both has had children/pregnancy 80% of normal will conceive in a year, 92% by end of 2 years Fecundability = percentage of women exposed to risk of pregnancy, who will conceive in 1 cycle (15-28%) Normal fertility declines with age (as no of oocytes decreases). Steep decline over 40 yrs 22% of couples conceive whilst awaiting treatment Causes Idiopathic Male Anovulatory Tubal Endometriosis + Uterine Primary – 30% – 25% – 20% – 15% – 10% Secondary - 20% - 20% - 15% - 40% - 5% FEMALE - History & examinations Note age, duration of infertility & general history Height & weight (extreme of BMI affect fertility) Body hair distribution (hyperandrogenism, PCOS) Galactorrhoea (hyperprolactinaemia) Uterine structural problems or tenderness (endometriosis & PID) Offer chlamydia test, smear Advise should be on 0.4mg folic acid (5mg if prev NTD) Baseline Investigations Early follicular phase LH, FSH (esp if irreg cycle. High = low fetility) & oestrodiol Rubella (offer vaccination if not immune – not conceive for 1 month post vaccine) Mid-luteal progesterone level (ovulation if > 28nm) – day 21 of 28 day cycle (or 7 days before next cycle) Test of tube patency (laparoscopy, HyCoSy, hysterosalpingogram) Investigate earlier if >35yrs or predisposing factors Ovulation Ovarian failure - (50% of patients with primary amenorrhoea, 15% of secondary amenorrhoea). May be due to genetics (eg turners), iatrogenic (radio/chemo), or idiopathic menopause Weight related anovulation – if body fat < 22% of weight (athletes, anorexia, severe illness) cycles can stop due to loss of 24hr LHRH pattern à multifollicular ovaries (on USS). PCOS – 50% of primary anovulatory fertility will have PCOS Luteinized unruptured follicle syndrome – oocyte is retained following LH surge Hyperprolactinaemia – 10-15% of secondary amenorrhoea, 1/3 will have galactorrhoea, some have visual disturbance. ONLY test if ovulatory disorder, galactorrhoea or pituitary problems Tests of ovulation – 90% of women with regular cycle will ovulate, LH kits, mid-luteal progesterone (>28nm) Futher investigations pelvic USS serum testosterone - if evidence of hirsutism to exclude tumours 5 day progestogen challenge test - if amenorrhoea & normal FSH, withdrawl bleed shows patient has sufficient oestrogen Tubal Patency Phimosis - agglutination of fimbra Hydrosalpinx - complete agglutination – Rx salpingectomy & IVF Also possible to get intraluminal adhesions & tubal folds Diagnostic laparoscopy - gold standard. Use methylene blue dye injected into cervix to prove patency. Requires daycase & GA. Most expensive & invasive of investigations (so try others first) unless known risk factors (eg chlamydia) Hysterosalpingo contrast sonography (HyCoSy) – galactose containing US contrast medium. Will outline uterine polyps and fibroids + confirm tubal patency. Accuracy similar to HSG. 1st choice for no known risk factors as no radiation Hysterosalpingography (HSG) – create watertight seal aamd pass radioopaque dye into uterine cavity. Assess with series of X-rays. Can be performed as outpatient. If normal 97% reliable, if abnormal 66% false +ve à laparoscopy. USE if no known risk factors Salpingoscopy – only required if issue of tubal surgery is raised. Adhesions seen indicate damage Falloposcopy – very expensive & fragile, only used in research Treatment Anovulation if patient is oestrogenised Hyperprolactinaemia – treat with dopamine agonist (bromocriptine or cabergoline) Excess/Underweight – treat by diet PCOS, treat with anti-oestrogen eg clomiphene citrate (or tamoxifen. Clomiphene + metformin if BMI>25. Increases FSH by by blocking oestrogen feedback). à ovulation in 80% of cycles (preg rate of 81% after 12 months) although high miscarriage rate and increased risk of multiple births. Side effects of clomiphene include hot flushes (11%), pelvic discomfort (7%), nausea (2%), breast discomfort (2%). NB: US during first cycle to assess no of follicles and reduce risk of multiple birth If no success à exogenous gonadotrophins (subcutaneous / intramuscular). Can cause ovarian hyperstimulation. 20% risk of multiple pregnancy (important to start low & titrate dose up). Monitor development by US. Use HCG to stimulate ovulation If still no success à laparoscopic ovarian diathermy (pierce holes in ovary with diarthermy à stimulates ovaries Anovulation if oestrogen deficient If low FSH, normal prolactin & low oestrodiol or negative progestogen withdrawl test à require exogenous gonadotrophins or if hypothalamus disorder try pulsatile LHRH. Tubal disease – surgery (only if damage is minor – 10x increase of ectopic risk) or IVF Endometriosis – no evidence that treating improves conception (can create anovulation for 6 months!) MALE - History & examination General – weight, smoking, alcohol, cannabis (low motility), anabolic steroids (reversible testicular failure) Lifestyle – hot baths, sat down all day, tight underwear, cyclists, trauma/torsion History – childhood problems, mumps, STIs, Scrotum (varicocele) Volume of testes (small testes assoc with oligospermia) Position of testes (undecended?) Prostate (chronic infection) Baseline investigations Semen analysis x 2 Assess using Kruger criteria - volume (>2ml), pH (>7.2), number (>20 x 106), motility (> 50% forward, > 25% rapid linear progress), morphology (> 15% normal), survival (> 75%), WBC (<1 x 106/ml), liquefaction time (within 60 mins) Any problems may be linked to absence/blockage of tubes, impotence, premature ejaculation etc Produce sample by masturbation / intercourse into non-lubricated condom after 3-5 days abstinence Repeat sample after 3 months if abnormal (approx 3 months for spermatogenesis) Further investigations Sperm function tests (if baseline is abnormal) – tests of sperms ability to penetrate cervical mucus Mixed agglutination reaction (MAR) – for antisperm antibodies FSH, LH & testosterone – if low sperm count. High FSH if testicular failure, low if CNS cause Transrectal US for suspected abnormality of seminal vesicles & prostate Treatment Idiopathic oligospermia – most common diagnosis. Use IVF or ICSI Azoospermia & raised FSH = spermatogenic failure (confirm by testicular biopsy). If islands of spermatogenesis seen sperm can be extracted and used for intracytoplasmic sperm injection (part of IVF). Most cases require sperm donor (screened for infection & family history of disease), inserted into cervix / uterus. 18% success in first cycle, then 6% per cycle for 12 months Azoospermia with normal FSH – block of vas deferens of epididymis (most commonly due to vasectomy), Can be reanastomosed (vasovasostomy) or attached to epididymis (vasoepididymostomy). Better prognosis if sperm found distal to surgery or short time elapsed from initial surgery. If surgery not possible can try epididymal aspiration, IVF & intracytoplasmic sperm injection (ICSI). If congenital blockage found is likely to be CF related so careful councilling required. Hypogonadotrophic Hypogonadism – exogenous gonadotrophins, FSH & HCG or LHRH infusion pump Varicocele – surgery CANT improve low sperm count Assisted Conception Eligibilty Trying for at least 1 year Neither partner has child/pregnancy BMI <30 Exclusions – under 23, over 40, overweight, baby) Clomiphene (6 cycles on NHS) Even if women is ovulating – can stimulate ovulation (most women ovulate on 95% cycles) Intrauterine Insemination (IUI) (3 cycles on NHS) Sperm is prepared in culture medium à sample of pure, highly motile sperm à placed into uterus by fine catheter. Limited to cases where intercourse is not feasible (due to sexual dysfunction) Usually used with superovulation (usually clomiphene) In Vitro Fertilisation (IVF) (1 cycle on NHS) Used for male factor infertility, severe endometriosis, failed ovulation induction, long history of unexplained fertility, pre-implantation genetics, surrogacy & egg donation Exogenous FSH given to recruit follicles. Oocytes collected with needle by US guidance. Sperm collected by masturbation & sperm added to egg. If after 16 hrs fertilation has occurred the embryo à incubator for 24-48 hrs. 2 embryos planted back into mother. Luteal support required until embryo implants & HCG produced Live birth rate dep on maternal age 29-39yrs with 3yr infertility or identified cause should be offered 3 cycles (after which effectiveness decreases) Gamete intrafallopian tube transfer (GIFT) Oocytes collected & best chosen. Replaced into fallopian tube by laparoscopy with sperm sample to allow in vivo fertilisation (only used if IVF unacceptable for religious grounds) Intracytoplasmic sperm injection (ICIS) As seen on tv – sperm is injected into oocyte. Used if sperm only available from testicular biopsy Egg donation – only treatment for primary ovarian failure. Also used for maternal genetic disease Pre-implantation genetric diagnosis (PGD) If repeated child/fetus with genetic disease. IVF used & cells taken at day 3 for sampling Side effects of assisted conception Multiple pregnancy – 28% (24% twin, 4% triplet) Ovarian hyperstimulation – over response to gonadotrophins. >30 follicles develop à high conc of oestrogen & progesterone à nausea. Can à shifts in fluid à hypovolaemia Fetal Abnormality – almost identical to population risk