Controlled Ovarian Stimulation with recombinant-FSH plus recombinant-LH vs. human Menopausal Gonadotropin based on the number of retrieved oocytes: results from a routine clinical practice in a real-life population

Abstract

BackgroundThe association of recombinant FSH (rFSH) plus recombinant LH (rLH) is currently used for Controlled Ovarian Stimulation (COS) in human IVF, but its efficacy has, to date, not yet been compared to that of human Menopausal Gonadotropin (hMG), the FSH + LH activity-containing urinary drug.MethodsEight hundred forty-eight (848) IVF patients classified as expected “poor” or “normal” responders according to antral follicle count (AFC) and basal (day 3) FSH were treated with rFSH + rLH (2:1 ratio, n = 398, Group A) or hMG (n = 450, Group B). Data were collected under real-life practice circumstances and the pregnancy rate with fresh embryos was calculated by stratifying patients according to the number of retrieved oocytes (1–2, 3–4, 5–6, 7–8, >8).ResultsOverall, the pregnancy rate in both groups progressively improved according to the number of oocytes retrieved. When comparing patients within the same subgroup of oocyte yield, Group A and B showed a comparable outcome up to the reported highest yield (>8). When more than 8 oocytes were available, Group A had a significantly better pregnancy rate outcome. Patients’ characteristics did not significantly differ between the two groups and the better outcome in the best responding patients in Group A was confirmed by a multivariable logistic regression analysis, that showed that both the use of rFSH + rLH and the total number of retrieved oocytes increased the probability of pregnancy with odd ratio (OR) of 1.628 and 1.083, respectively.ConclusionsWhen comparing patients with the same number of retrieved oocytes under real-life circumstances, the association of rFSH + rLH results in a significantly higher pregnancy rate than hMG when more than 8 oocytes are retrieved. The reason(s) for this are unknown, but a more favorable effect on oocyte quality and/or endometrial receptivity could be involved.

HMG versus recombinant FSH plus recombinant LH in ovarian stimulation for IVF: does the source of LH preparation matter?

“…The search yielded 11 articles, of which three were prospective trials (Pacchiarotti et al, 2010;Requena et al, 2014;Tehraninejad et al, 2017): two were randomized controlled trials (Pacchiarotti et al, 2010;Tehraninejad et al, 2017) and one was a prospective observational study, in which patients were assigned to each treatment group based on a quasi-experimental design comprising consecutive opportunity sampling (Requena et al, 2014). Eight retrospective studies were found (Buhler and Fischer, 2012;Fábregues et al, 2013;Dahan et al, 2014;Revelli et al, 2015;Schwarze et al, 2016;Bleau et al, 2017;Renzini et al, 2017;Xia et al, 2019). The characteristics of all the studies are presented in TABLE 1.…”

“…The studies used different ovarian stimulation protocols (TABLE 1): long GnRH-agonist (Pacchiarotti et al, 2010;Buhler and Fischer, 2012;Fábregues et al, 2013;Requena et al, 2014;Bleau et al, 2017;Renzini et al, 2017;Tehraninejad et al, 2017;Xia et al, 2019), GnRH-antagonist (Schwarze et al, 2016), both (Revelli et al, 2015), or long GnRH-agonist and microdose flair GnRH-agonist (Dahan et al, 2014). Considering the type and source of gonadotrophin preparations, eight used HMG (Pacchiarotti et al, 2010;Buhler and Fischer, 2012;Dahan et al, 2014;Revelli et al, 2015., Schwarze et al, 2016Bleau et al, 2017;Tehraninejad et al, 2017;Xia et al, 2019) and three used HP-HMG (Fábregues et al, 2013;Requena et al, 2014;Renzini et al, 2017).…”

“…The studies used different ovarian stimulation protocols (TABLE 1): long GnRH-agonist (Pacchiarotti et al, 2010;Buhler and Fischer, 2012;Fábregues et al, 2013;Requena et al, 2014;Bleau et al, 2017;Renzini et al, 2017;Tehraninejad et al, 2017;Xia et al, 2019), GnRH-antagonist (Schwarze et al, 2016), both (Revelli et al, 2015), or long GnRH-agonist and microdose flair GnRH-agonist (Dahan et al, 2014). Considering the type and source of gonadotrophin preparations, eight used HMG (Pacchiarotti et al, 2010;Buhler and Fischer, 2012;Dahan et al, 2014;Revelli et al, 2015., Schwarze et al, 2016Bleau et al, 2017;Tehraninejad et al, 2017;Xia et al, 2019) and three used HP-HMG (Fábregues et al, 2013;Requena et al, 2014;Renzini et al, 2017). Moreover, nine used LH preparation during the stimulation period (Pacchiarotti et al, 2010;Buhler and Fischer, 2012;Fábregues et al, 2013;Dahan et al, 2014;Requena et al, 2014;Revelli et al, 2015;Schwarze et al, 2016;Renzini et al, 2017;Xia et al, 2019), whereas two studies (Bleau et al, 2017;Tehraninejad et al, 2017) added the LH preparation only after 5 and 6 days of FSH treatment, respectively.…”

“…Considering the type and source of gonadotrophin preparations, eight used HMG (Pacchiarotti et al, 2010;Buhler and Fischer, 2012;Dahan et al, 2014;Revelli et al, 2015., Schwarze et al, 2016Bleau et al, 2017;Tehraninejad et al, 2017;Xia et al, 2019) and three used HP-HMG (Fábregues et al, 2013;Requena et al, 2014;Renzini et al, 2017). Moreover, nine used LH preparation during the stimulation period (Pacchiarotti et al, 2010;Buhler and Fischer, 2012;Fábregues et al, 2013;Dahan et al, 2014;Requena et al, 2014;Revelli et al, 2015;Schwarze et al, 2016;Renzini et al, 2017;Xia et al, 2019), whereas two studies (Bleau et al, 2017;Tehraninejad et al, 2017) added the LH preparation only after 5 and 6 days of FSH treatment, respectively. The daily dose of the LH-activity in the HMG preparations was reported in eight studies and ranged between 75 and 300 IU, whereas, in recombinant LH, it was 75-300 IU (TABLE 1).…”

“…Of the retrospective studies, Revelli et al (2015) evaluated the IVF performance of 848 IVF patients classified as expected 'poor' or 'normal' responders who underwent ovarian stimulation for IVF with either recombinant FSH plus recombinant LH (2:1 ratio) or HMG. Data were collected under real-life practice circumstances and the clinical and ongoing pregnancy rates with fresh embryos were calculated by stratifying patients according to the number of oocytes retrieved.…”