Abstract
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) act on the same receptor, activating different signal transduction pathways. The role of LH or hCG addition to follicle-stimulating hormone (FSH) as well as menopausal gonadotropins (human menopausal gonadotropin; hMG) in controlled ovarian stimulation (COS) is debated. To compare FSH + LH, or FSH + hCG or hMG vs. FSH alone on COS outcomes. A meta-analysis according to PRISMA statement and Cochrane Collaboration was performed, including prospective, controlled clinical trials published until July 2016, enrolling women treated with FSH alone or combined with other gonadotropins. Trials enrolling women with polycystic ovarian syndrome were excluded (PROSPERO registration no. CRD42016048404). Considering 70 studies, the administration of FSH alone resulted in higher number of oocytes retrieved than FSH + LH or hMG. The MII oocytes number did not change when FSH alone was compared to FSH + LH, FSH + hCG, or hMG. Embryo number and implantation rate were higher when hMG was used instead of FSH alone. Pregnancy rate was significantly higher in FSH + LH-treated group vs. others. Only 12 studies reported live birth rate, not providing protocol-dependent differences. Patients' stratification by GnRH agonist/antagonist identified patient subgroups benefiting from specific drug combinations. In COS, FSH alone results in higher oocyte number. HMG improves the collection of mature oocytes, embryos, and increases implantation rate. On the other hand, LH addition leads to higher pregnancy rate. This study supports the concept of a different clinical action of gonadotropins in COS, reflecting previous in vitro data.
Highlights
Luteinizing hormone (LH) and human chorionic gonadotropin are heterodimeric glycoprotein hormones, acting on the same receptor (LHCGR) [1]
An insufficient number of studies were available on the comparison between follicle-stimulating hormone (FSH) alone vs. FSH + Human chorionic gonadotropin (hCG) and between FSH + LH vs. FSH + hCG, limiting the possibility to subgroup studies
Considering the whole group of studies included in the meta-analysis, the ART approaches chosen after controlled ovarian stimulation (COS) were different, ranging from intrauterine insemination (IUI) to intracytoplasmatic sperm injection (ICSI)
Summary
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are heterodimeric glycoprotein hormones, acting on the same receptor (LHCGR) [1]. Follicle-stimulating hormone (FSH) and LH act in concert to stimulate folliculogenesis and ovulation These gonadotropins are used in the controlled ovarian stimulation (COS) in order to produce relatively high oocyte number to be used fresh or after cryopreservation [5] to obtain pregnancies. The pregnancy hormone hCG is generally used to obtain LH-like activity and support of multi-follicle growth since decades [9] With this in mind, human menopausal gonadotropin (hMG) is commonly used as preparation with LH-like activity, due to the presence of LH and/or hCG molecules. Human menopausal gonadotropin (hMG) is commonly used as preparation with LH-like activity, due to the presence of LH and/or hCG molecules. hMG alone and hCG/LH + FSH were repeatedly proposed [10, 11] but some unfavorable results, in particular in terms of number of oocytes retrieved [12, 13], provided concerns about the usefulness of addition of “LH activity.”
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