Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders

Abstract

STUDY QUESTIONHow does the efficacy and safety of a fixed-ratio combination of recombinant human FSH plus recombinant human LH (follitropin alfa plus lutropin alfa; r-hFSH/r-hLH) compare with that of r-hFSH monotherapy for controlled ovarian stimulation (COS) in patients with poor ovarian response (POR)?SUMMARY ANSWERThe primary and secondary efficacy endpoints were comparable between treatment groups and the safety profile of both treatment regimens was favourable.WHAT IS KNOWN ALREADYAlthough meta-analyses of clinical trials have suggested some beneficial effect on reproductive outcomes with r-hLH supplementation in patients with POR, the definitions of POR were heterogeneous and limit the comparability across studies.STUDY DESIGN, SIZE, DURATIONPhase III, single-blind, active-comparator, randomized, parallel-group clinical trial. Patients were followed for a single ART cycle. A total of 939 women were randomized (1:1) to receive either r-hFSH/r-hLH or r-hFSH. Randomization, stratified by study site and participant age, was conducted via an interactive voice response system.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen classified as having POR, based on criteria incorporating the ESHRE Bologna criteria, were down-regulated with a long GnRH agonist protocol and following successful down-regulation were randomized (1:1) to COS with r-hFSH/r-hLH or r-hFSH alone. The primary efficacy endpoint was the number of oocytes retrieved following COS. Safety endpoints included the incidence of adverse events, including ovarian hyperstimulation syndrome (OHSS). Post hoc analyses investigated safety outcomes and correlations between live birth and baseline characteristics (age and number of oocytes retrieved in previous ART treatment cycles or serum anti-Müllerian hormone (AMH)). The significance of the treatment effect was tested by generalized linear models (Poisson regression for counts and logistic regression for binary endpoints) adjusting for age and country.MAIN RESULTS AND THE ROLE OF CHANCEOf 949 subjects achieving down-regulation, 939 were randomized to r-hFSH/r-hLH (n = 477) or r-hFSH (n = 462) and received treatment.Efficacy assessment: In the intention-to-treat (ITT) population, the mean (SD) number of oocytes retrieved (primary endpoint) was 3.3 (2.71) in the r-hFSH/r-hLH group compared with 3.6 (2.82) in the r-hFSH group (between-group difference not statistically significant). The observed difference between treatment groups (r-hFSH/r-hLH and r-hFSH, respectively) for efficacy outcomes decreased over the course of pregnancy (biochemical pregnancy rate: 17.3% versus 23.9%; clinical pregnancy rate: 14.1% versus 16.8%; ongoing pregnancy rate: 11.0% versus 12.4%; and live birth rate: 10.6% versus 11.7%). An interaction (identified post hoc) between baseline characteristics related to POR and treatment effect was noted for live birth, with r-hFSH/r-hLH associated with a higher live birth rate for patients with moderate or severe POR, whereas r-hFSH was associated with a higher live birth rate for those with...

Does freeze‐all policy affect IVF outcome in poor ovarian responders?

“…Nowadays, there is evidence of increasing prevalence of POR with a poor IVF prognosis. In the present study, IRs were lower than 10%, both in the fresh ET and freeze‐all groups, in accordance with previous studies published on POR,. Previously, Çelik et al .…”

“…Poor ovarian responders (POR) represent 9–24% of patients undergoing IVF treatment; these individuals have very low pregnancy rates ranging from 3–14%. Although several strategies have been proposed to optimize the ovarian response and the number of retrieved oocytes, there is no consensus regarding the treatments that are beneficial to POR.…”

Management Strategies for POSEIDON Group 2

“…Additionally, it comprises of several subpopulations with varied baseline characteristics (9). Furthermore, the Bologna criteria encompasses a very poor prognosis group that is associated with very low live birth rates (10,11) raising the interrogation if any interventions could enhance clinical outcomes for these women with very poor prognosis (12,13).…”

Commentary: The Development of Gonadotropins for Clinical Use in the Treatment of Infertility

“…It remains, nonetheless, important to emphasize that the ESPART trial was a superiority study that failed to meet its primary endpoint. All ensuing post-hoc analyses were therefore put in this context (4,5).…”