Influence of human chorionic gonadotrophin during ovarian stimulation: an overview

Abstract

It is widely known that luteinising hormone (LH) and human chorionic gonadotrophin (hCG) are integral in the female reproductive lifecycle. Due to the common binding site and similarity in molecular structure, they were previously thought to have overlapping roles. However, with the development of both purified urinary-derived and recombinant gonadotrophins, the individual characteristics of these molecules have begun to be defined. There is evidence to suggest that LH and hCG preferentially activate different signalling cascades and display different receptor-binding kinetics. The data generated on the two molecules have led to an improved understanding of their distinct physiological functions, resulting in a debate among clinicians regarding the most beneficial use of LH-and hCG-containing products for ovarian stimulation (OS) in assisted reproductive technologies (ARTs). Over the past few decades, a number of trials have generated data supporting the use of hCG for OS in ART. Indeed, the data indicated that hCG plays an important role in folliculogenesis, leads to improved endometrial receptivity and is associated with a higher quality of embryos, while presenting a favourable safety profile. These observations support the increased use of hCG as a method to provide LH bioactivity during OS. This review summarises the molecular and functional differences between hCG and LH, and provides an overview of the clinical trial data surrounding the use of products for OS that contain LH bioactivity, examining their individual effect on outcomes such as endometrial receptivity, oocyte yield and embryo quality, as well as key pregnancy outcomes.

Recombinant follicular stimulating hormone plus recombinant luteinizing hormone versus human menopausal gonadotropins- does the source of LH bioactivity affect ovarian stimulation outcome?

“…The distinct molecular structure of the beta-LH and beta-hCG subunits results in different conformational changes of the LH/CGR, leading to activation of different intracellular cascades [5]. The post receptor, intra-cellular reactions, include an activation of adenylate cyclase, which increases the intracellular pool of cAMP and results in steroidogenesis, and an extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and AKT, with putative roles in cell proliferation, differentiation and survival [7]. In vitro studies found that hCG is five times more potent than LH with respect of cAMP production and steroidogenesis pathway, while LH strongly activates ERK1/2 and AKT pathways, thus induces proliferation and anti-apoptotic effect [6,15].…”

“…Nonetheless, in vitro studies revealed specific bioactivity effects of LH and hCG, which differ by triggering separate intracellular signaling cascades. LH binding to the LH/CG receptor results in a more potent activation of the proliferative and anti-apoptotic pathways, whereas hCG has a higher potency for activation of the steroidogenic pathways [5][6][7].…”

Recombinant Follicular Stimulating Hormone Plus Recombinant Luteinizing Hormone Versus Human Menopausal Gonadotropins- Does the Source of LH Bioactivity Affect Ovarian Stimulation Outcome?

“…The distinct molecular structure of the beta-LH and beta-hCG subunits results in different conformational changes of the LH/CGR, leading to activation of different intracellular cascades (5). The post receptor, intra-cellular reaction, includes an activation of adenylate cyclase, which increases the intracellular pool of cAMP and results in steroidogenesis, and an extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and AKT, with putative roles in cell proliferation, differentiation and survival (7). In vitro studies found that hCG is ve times more potent than LH with respect of cAMP production and steroidogenesis pathway, while LH strongly activates ERK1/2 and AKT pathways, thus induces proliferation and anti-apoptotic effect (6, 15).…”

“…Nonetheless, in vitro studies revealed speci c bioactivity effects of LH and hCG, which differ by triggering separate intracellular signaling cascades. LH binding to the LH/CG receptor results in a more potent activation of the proliferative and anti-apoptotic pathways, whereas hCG has a higher potency for activation of the steroidogenic pathways (5)(6)(7).…”

Tie1 contributes to the development of ovarian hyperstimulation syndrome under the regulation of EGR1 in granulosa cells

“…In the first week of pregnancy, cells surrounding the newly fertilized egg produce human chorionic gonadotropin (hCG), the so-called “pregnancy hormone”, which subsequently stimulates the production of progesterone to maintain pregnancy and establish the placenta. In infertile women undergoing controlled ovarian stimulation, hCG is administered at extremely high doses to stimulate the release of eggs from mature follicles 1 . However, these women are at an increased risk of developing ovarian hyperstimulation syndrome (OHSS), with approximately 3–8% of women experiencing moderate-to-severe symptoms within weeks of hCG injection 2 , 3 .…”