Clomiphene citrate—end of an era? a mini-review

The purpose of this review is to examine whether the time has come to replace clomiphene citrate (CC) as the first line therapy for WHO group II (eu-oestrogenic) infertility, the majority of which is associated with polycystic ovary syndrome. CC has been the first line therapy for these cases for the last 40 years. It is a simple, cheap treatment, almost devoid of side effects which yields a single live birth rate of approximately 25% of starters. Non-response to CC and the gap between ovulation and pregnancy rates have variously been attributed to its anti-estrogen effects, and high LH and androgen concentrations. Three possible contenders for the replacement of CC as first-line treatment are scrutinized: metformin, aromatase inhibitors and low-dose FSH. Each has their advantages and disadvantages, but none of them, while showing much potential promise, has been proven, as yet, to be a feasible replacement for CC in this role. For CC, it may not yet be the end of an era but it may be the beginning of the end.