In about 20% of patients treated with anti-oestrogens, follicular growth is not followed by rupture because there is no LH surge. This can be seen by ultrasound scanning of the ovary. In such cases, an injection of hCG at the time of the oestrogen peak may trigger ovulation.
Human menopausal gonadotrophin - hMG or menotrophin- is an equal mixture of FSH and LH extracted from the urine of post menopausal women. Success rates are comparable to clomiphene but hMG may be associated with multiple pregnancies - about 25% of cases - and the ovarian hyperstimulation syndrome.
Pure FSH e.g urofollitrophin may be successful in PCOS since LH is often sufficient. It is associated with a high pregnancy rate - 60% - but also, a high incidence of multiple pregnancies - 30%.
GnRH analogues cause desensitisation of the pituitary within a few days of use. There is no response to GnRH, natural or the analogue, so the pituitary output of FSH and LH falls. The resultant quiescent ovary can then be stimulated by giving hMG or purified FSH.
Natural GnRH can be administered in pulses from a pump in order to induce pituitary release of FSH and LH. The ovulatory rate in patients who have not ovulated on clomiphene is about 50% and when combined with purified FSH, ovulation is induced in about half of those who fail with the pump and clomiphene. However, the pump must be worn continuously and is inconvenient.
NICE notes that women with PCOS who do not ovulate with clomiphene citrate (or tamoxifen) can be offered gonadotrophins (1):
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