Subfertility Flashcards
What is subfertility?
The unwanted delay of 2 years in achieving conception despite regular unprotected sexual intercourse. Affects 15% of the population in the UK and as women embark on conceiving pregnancies later in life, the incidence of subfertility is increasing.
What is the impact of age on conception?
Advancing female age negatively effects the changes of both natural and assisted conception. Most cases have relative subfertility which can be attributed to one or more factors in one or both partners whilst a small number have absolute infertility i.e. impossible to conceive.
What hormones can cause irregular/absent periods?
- GnRH pulses (hypothalamus): not measure routinely in clinical practice
- FSH/LH (pituitary): low - hypothalamic/pituitary pathology; normal - disrupted folliculogenesis, but oocytes present (seen in PCOS); high - low number/absence of oocytes
- Oestradiol (ovary): produced by granulosa cells
- MH (Anti-Mullerian hormone) (ovary): produced by pre-antral and small antral follicles. Regarded as best measure of oocyte reserve (can be measured at any time of cycle)
What are the causes of ovulatory dysfunction?
- Hypothalamic: FSH and LH low, oestradiol low, GnRH deficiency, weight loss etc
- Pituitary: FSH + LH low, oestradiol low, hyperprolactinaemia, other pituitary dysfunction etc.
- Ovarian: (PCOD - FSH normal, LH raised, oestradiol normal) (premature ovarian failure - FSH and LH high, oestradiol low)
How do you test ovarian reserve?
- AMH: can be measured anytime in the cycle, little inter-cycle variability, best marker
- FSH: baseline day 2-5 (when oestradiol levels are low), normal: 4-7iu/l, >9 = reduced reserve
- AFC: antral follicle count, small follicles 2-5mm, measured at any time in cycle, estimates remaining egg reserve
What is the Tanner Scale?
A scale of physical development in children, adolescents and adults. The scale defines physical measurements of development based on external primary and secondary sex characteristics, such as the size of the breasts, genitals, testicular volume and development of pubic hair.
What do you want to know in a history of infertility?
- Initial consultation should include full history from both partners as well as clinical examination. Regular coital frequency of 2-3x weekly is usually recommended.
- Ovulation: is the woman ovulating? If anovulation, why?
- Ovarian reserve: good, satisfactory, poor diminished
- Tubes and transport: problem with the tubes?
- Sperm: are sperms present in ejaculate? If not present or reduced number, why?
What factors affect fertility?
- Female age
- Female BMI (<20 or >30)
- Uterine function - endometrial problems, fibroids, polyps
- Duration of trying: couples who have a short duration of infertility are more likely to conceive both with/without treatment
- Lifestyle: obesity, smoking, excessive alcohol intake, drugs
- Medical history: ensure patient’s medical conditions optimised for pregnancy e.g. diabetic control
- Previous pregnancy
- Infertility consultation is important for pre-conception counselling
What investigations for infertility do you do for females with a regular cycle?
- FSH, LH and oestradiol: assessment of ovarian reserve (early follicular phase - day 1-5 of cycle)
- Progesterone: confirm ovulation, although a regular cycle is a very good indicator even without confirmation from progesterone measurements - mid-luteal phase (adjust to cycle length - 7 days prior to expected menses)
What investigations for infertility do you do for females with an irregular cycle or amenorrhoea?
- FSH, LH: assess pituitary function and possible indicator of PCOD (early follicular phase or any time in very prolonged cycles)
- Oestrogen: assess associated ovarian function (anytime)
- Prolactin, free testosterone: explore causes of oligo/amenorrhoea (anytime)
What initial investigations do you do for infertility in all females?
- Rubella serology: check/offer immunisation
- AMH: good indicator of ovarian reserve
- Cervical smear: ensure no cervical pathology before pregnancy
- Transvaginal USS: assess uterus and ovaries
What initial investigations do you do for infertility in all males?
Semen analysis x2 (abstinence 2-5 days) - if 1st sample abnormal, 2nd sample after 3 months, assess spermatogenesis
What factors influence spermatogenesis?
- Body-building drugs
- Alcohol
- Male obesity
- Smoking
What do progesterone levels mean?
- <16nmol/l - repeat, if consistently low, refer to specialist
- 16-30 nmol/l - repeat
- > 30nmol/l - indicates ovulation
What is PCOS/D?
- Elevated LH
- Insulin resistance
- These lead to: ovarian growth, ovarian cyst formation, androgen production
What are the features of PCOS?
- Signs of androgen excess: hirsutism (excess hair e.g. facial hair), acne
- Obesity
- Irregular menses/amenorrhoea - infertility
What are the investigations for PCOS?
- Increased serum testosterone (ovaries make more testosterone)
- Increased LH, decreased FSH (ratio can be as high as 3:1)
- Other tests include prolactin and TSH
- Pelvic USS: visualise enlarged follicles in ovaries (usually >10 follicles per ovary, normal ovaries 2-10mm, in PCOS >10mm)
What is the criteria for PCOS?
Must have at least 2/3:
- Irregular menses - oligo/anovulation
- Evidence of androgen excess - hyperandrogenism (hirsutism/male pattern alopecia, acne, raised testosterone)
- Polycystic ovaries (>10 follicles per ovary)
What is the treatment for PCOS?
- If not wanting to get pregnancy, then can give OCP which suppresses androgens - decreases testosterone and LH levels
- Weight loss
- If women wants to get pregnant: metformin (increases insulin sensitivity), or clomiphene (binds to hypothalamic oestrogen receptors which stops oestradiol binding - prevents negative feedback inhibition of FSH secretion (infertility drug)
- If <3 periods a year then risk of endometrial cancer
What is the main side effect of clomiphene?
Ovarian Hyperstimulation Syndrome (OHSS) - ovaries enlarge, severe GI symptoms, abdo swelling, dyspnoea, pleural effusions, decreased urination (OHSS typically caused by drugs used to treat infertility). Up to 1/3 of women doing IVF may get mild form of OHSS.