Does HCG and LH supplementation during ovarian stimulation improve clinical outcome? An evaluation of 30 years of clinical research

This review evaluates the effect of HCG and LH supplementation during ovarian stimulation. Controlled trials were divided into four groups comparing the treatment effect of recombinant FSH (r-FSH) with urinary FSH (u-FSH), with human menopausal gonadotrophin (HMG), with r-FSH + recombinant LH (r-LH) and with rFSH + recombinant HCG (r-HCG). First r-FSH seemed to be more potent than u-FSH in downregulated women, which translated into more follicles and oocytes. In line, numerous trials comparing HMG (containing u-FSH + u-HCG) with r-FSH demonstrated that HMG recruited fewer follicles, thus providing fewer oocytes but resulted in slightly higher pregnancy rates after a first fresh embryo transfer. The latter may be explained by the higher potency of r-FSH resulting in more and higher premature progesterone rises. Prospective trials addressing r-FSH + r-LH compared with r-FSH could not demonstrate any difference in pregnancy rates in normal or poor responders. A placebo-controlled trial of r-HCG added to a fixed daily r-FSH dose revealed that r-HCG inhibited the growth of intermediate follicles, resulting in fewer oocytes, fewer embryos and lower pregnancy rates. In conclusion, the beneficial effect of HCG and LH supplementation on clinical outcome has never been definitely proven for any of the combined gonadotrophin products.