Outcome of ovarian stimulation, pregnancy rates and multiple pregnancies

Controlled ovarian (hyper)stimulation (COH) intends to attain multifollicular development and therefore increase pregnancy rates in couples with unexplained or mild male subfertility. A meta-analysis has shown that clomiphene citrate significantly increases pregnancy rates in unexplained infertility, while multiple pregnancy rates remain under 10%. The absolute treatment effect is small, but clomiphene citrate is a safe and cheap first choice treatment, although combining it with intrauterine insemination further increases pregnancy rates. It does not seem that using gonadotrophins is more advantageous than clomiphene citrate for unexplained infertility. Also in male infertility cases COH probably increases the pregnancy rates, although no studies have been performed in the absence of IUI (when IUI is used, COH shows a clear advantage). COH using gonadotrophins substantially augments pregnancy rates, but also multiple pregnancy rates. Although it seems difficult to totally avoid multiple pregnancies, it is clear that cycle monitoring through ultrasound and estradiol measurements may help to set strict criteria to administer hCG or to cancel the cycle. These criteria should encompass the number of follicles (preferably no more than two), estradiol levels and maternal age, since these three factors seem to be predictive of the risk for multiple pregnancies. Health-economic studies are needed to determine which stimulation protocol would be most cost-efficient to treat unexplained and mild male infertility cases, prior to moving to or even in comparison to IVF.