Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

Abstract

A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood.

Safety of Follitropin Alfa/Lutropin Alfa for Stimulation of Follicular Development

“…In most countries, r-hFSH/r-hLH is indicated for the stimulation of follicular development in adult women with severe LH and FSH deficiency [ 2 , 5 ]. It is also indicated for use in patients with sub-optimal response after controlled ovarian stimulation undergoing assisted reproductive technologies (ART) in Mexico, Russia, and Ukraine.…”

Luteinizing hormone supplementation in women with hypogonadotropic hypogonadism seeking fertility care: Insights from a narrative review

“…On the other hand, it is equally important not to exceed the proper daily dose to avoid the so called ‘ceiling effect’. Published data suggest that the ideal LH daily dose should be 75 IU ( 15 , 17 , 18 ). However, these recommendations cannot be applied to all patients and under all treatment circumstances.…”

“…Importantly, the group that received 225 IU rLH had a smaller number of growing follicles when compared with the group who received 75 IU rLH. This could suggest an LH ceiling effect, whereby some secondary follicles underwent atresia due to their high sensitivity to LH ( 17 ). Loumaye et al confirmed this effect showing that rLH when administered alone can trigger follicular growth arrest ( 18 ).…”

“…The few data about the safety profile of both rFSH/rLH combination and hMG are reassuring. Further comparative studies are warranted to investigate the tolerability, acceptability, and other adverse events, such as the risk of ovarian hyperstimulation syndrome of rFSH/rLH compared to the conventional hMG regimens to stimulate HH patients ( 17 ).…”

The Effect of Recombinant LH Addition to Recombinant FSH on Assisted Reproductive Technologies Outcomes in Overweight and Obese Patients without Polycystic Ovary Syndrome

“…Therefore LH plays a role in optimal follicular response and patients with low endogenous LH levels as in hypogonadotropic hypogonadism may benefit from rLH supplementation [16] [17].…”