Corifollitropin alfa 150micrograms/0.5ml solution for injection pre-filled syringes

BackgroundCorifollitropin alfa, a fusion protein lacking LH activity, has a longer elimination half-life and extended time to peak levels than recombinant FSH (rFSH). A single injection of corifollitropin alfa may replace seven daily gonadotrophin injections during the first week of ovarian stimulation.MethodsIn this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 microg corifollitropin alfa during the first week of stimulation and compared with daily injections of 200 IU rFSH using a standard GnRH antagonist protocol.ResultsThe study population comprised 1506 treated patients with mean age of 31.5 years and body weight of 68.6 kg. Ongoing pregnancy rates of 38.9% for the corifollitropin alfa group and 38.1% for rFSH were achieved, with an estimated non-significant difference of 0.9% [95% confidence interval (CI): -3.9; 5.7] in favor of corifollitropin alfa. Stratified analyses of pregnancy rates confirmed robustness of this primary outcome by showing similar results regardless of IVF or ICSI, or number of embryos transferred. A slightly higher follicular response with corifollitropin alfa resulted in a higher number of cumulus-oocyte-complexes compared with rFSH [estimated difference 1.2 (95% CI: 0.5; 1.9)], whereas median duration of stimulation was equal (9 days) and incidence of (moderate/severe) ovarian hyperstimulation syndrome was the same (4.1 and 2.7%, respectively P = 0.15).ConclusionCorifollitropin alfa is a novel and effective treatment option for potential normal responder patients undergoing ovarian stimulation with GnRH antagonist co-treatment for IVF resulting in a high ongoing pregnancy rate, equal to that achieved with daily rFSH. The trial was registered under ClinicalTrials.gov identifier NTC00696800.

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ImportanceThe clinical management of women with diminished ovarian reserve (DOR) is a challenge in the field of medically assisted reproduction. Several therapeutic strategies have been proposed, but with mixed results, mainly because the definition of DOR used was inconsistent among trials.ObjectiveTo investigate adjuvant treatments and protocols involving only women with DOR according to POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria.Data sourcesWe conducted a systematic search using the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases to identify relevant studies published up to June 2024.The review protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number: CRD42022346117).Study selection and synthesisAfter duplication removal, the titles and abstracts of 4,806 articles were scrutinized, and 124 full-text articles were assessed for eligibility. In total, 38 randomized controlled trials were included in the qualitative/quantitative analysis. The following interventions were evaluated: dehydroepiandrosterone (n = 1,336); testosterone (n = 418); high- vs. low-dose gonadotropin (n = 957); delayed-start protocol with gonadotropin hormone-releasing hormone antagonist (n = 398); letrozole (n = 612); clomiphene citrate (1,113); growth hormone (311); luteal phase stimulation (n = 57); dual triggering (n = 139); dual stimulation (168); luteinizing hormone (979); oestradiol pretreatment (n = 552); and corifollitropin alfa (n = 561).Main outcomesThe primary outcome was live birth rate or ongoing pregnancy if data on live birth were unavailable. Secondary outcomes were number of oocytes retrieved, number of metaphase II oocytes, clinical pregnancy rate and miscarriage rate.ResultsTestosterone supplementation is associated with higher live birth rates compared with nonsupplemented women among all interventions evaluated (odds ratio: 2.19, 95% confidence interval [CI]: 1.11-4.32, four studies, 368 patients). Testosterone (weighted mean difference [WMD] 0.88, 95% CI: 0.03-1.72; 4 studies, n = 368 patients), dehydroepiandrosterone (WMD 0.60, 95% CI: 0.07-1.13; 4 studies, n = 418 patients), and delayed started protocol (WMD 1.32, 95% CI: 0.74 to 1.89; 3 studies, n = 398 patients) significantly improved the total number of eggs collected. Lower number of oocytes retrieved is achieved in women undergoing low dose gonadotropin regimen vs high dose (WMD: -1.57, 95% CI: -2.12 to -1.17; 2 studies, n = 905 patients), The other interventions did not produce significant improvements.Conclusion and relevanceSpecific interventions such as testosterone seem to correlate with a better live birth rate in women with DOR; these findings should be further explored in randomized trials.

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Background : Corifollitropin alfa (CFA) is a long-acting recombinant follicle-stimulating hormone (rFSH) used for controlled ovarian stimulation (COS). Several studies analyzing the clinical efficacy and safety of CFA compared to daily rFSH during COS have been carried out. The present study offers a meta-analysis of the randomized controlled trials (RCTs) on this topic. Methods : A computerized search of the published literature was carried out using PubMed, MEDLINE, Science direct and Google Scholar databases. The comparison between CFA and daily rFSH treatments during COS were investigated only in RCTs. The primary endpoint of the study is represented by the number of total oocytes retrieved at ovum pick-up. The studies included in the analysis were pooled together in order to estimate the log odds ratio (OR) or the mean difference (MD) along with the corresponding 95% confidence intervals (CI) by using a random effects model. The heterogeneity between the studies was evaluated with the Higgins and Chi-square tests. Results : The study examined a total of twelve RCTs published from 2004 to date and included a total of 4980 patients, with 2664 receiving CFA and 2316 patients receiving daily rFSH for COS. Women treated with CFA had higher number of total oocytes retrieved at ovum pick-up (MD 0.91, 95% CI [0.34, 1.49], p = 0.001), and higher number of metaphase II (MII) oocytes (MD 1.00, 95% CI [0.37, 1.62], p = 0.002) compared to those receiving daily rFSH. There were no significant differences between the two study groups regarding the other outcomes analyzed. The subgroup analysis performed comparing “normal” versus “poor” responders revealed that normal responders receiving CFA showed an higher cancellation rate, with respect to those receiving rFSH. Conclusions : This study shows that COS with CFA results in a higher number of oocytes retrieved at ovum pick-up in comparison with daily rFSH.

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