Recombinant LH(San Carlo Public Hospital, Potenza, Italy)

Gonadotropins and anti-Müllerian hormone (AMH) regulate reproductive development and ovarian function. While AMH plays a well-established role in early folliculogenesis by counteracting gonadotropins, luteinizing hormone (LH) becomes more active later, during the antral phase, when granulosa and theca cells express their respective receptors. There are hints suggesting the existence of an interplay between these hormones regulating granulosa cell functions at late stages of the folliculogenesis., but the mechanisms remain unclear. In this context, we explored whether gonadotropin LH can modulate AMH action in cells of ovarian origin.

Primary human granulosa lutein cells isolated from in vitro fertilization (IVF) patients were pretreated with recombinant LH, followed by stimulation with recombinant AMH. AMH receptor type II (AMHR2) expression, AMH signaling activation, and the expression of AMH-responsive genes were assessed through RT-PCR, ELISA, and Western blotting. The involvement of the LH receptor was confirmed using siRNA-mediated knockdown.

Our findings showed that LH treatment downregulates AMHR2 transcripts and protein, impairing AMH-induced phosphorylation of small mothers against decapentaplegic (SMAD) 1, 5, and preventing osterix ( OSX ) and matrix metalloprotease 2 ( MMP2 ) gene expression.

These data are consistent with the possible interplay between gonadotropins and AMH in cells from antral/luteal stages and provide the molecular basis for further studies evaluating the impact of LH in modulating AMH signaling and follicular responsiveness during the antral stage.

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.