Biosimilar recombinant human FSH (Follitropin alpha) for controlled ovarian stimulation in ovulatory women undergone IVF/ICSI cycles? A systematic review and meta-analysis

Abstract Study question Is biosimilar Follitropin alpha preparations for controlled ovarian stimulation in ovulatory women undergoing IVF, is effective as as compared to the originator Summary answer Biosimilar preparations of Follitropin alpha are probably associated with lower clinical pregnancy and ongoing pregnancy rates than the originator. What is known already As the patent expired for the originator, there was increasing interest in developing biosimilar follitropin alpha. Biosimilar medicinal product is a biological product developed to be highly similar to the already approved biological medicine (reference medicine) (EMA 2017). Biosimilar recombinant FSH preparations are manufactured in Chinese hamster ovary cells with a fully human glycosylation – which may differ slightly between products – and represent products with demonstrated similarity in physicochemical characteristics, efficacy, and safety to those of Gonal-F® (European Medicines Agency 2013; Weise et al 2011; Lammerich et al 2015 a, b; Wolzt et al., 2016; Abd-Elaziz et al., 2017). Study design, size, duration Systematic review and meta-analysis of randomized controlled trials (RCTs). Participants/materials, setting, methods Partticipants Infertile women undergoing in vitro fertilization (IVF). Setting Not applicable. Methods Five databases were searched through Jan.2022 for RCTs comparing the biosimilar Follitropin alpha to the originator for controlled ovarian stimulation and reporting clinical IVF outcomes, not restricted by language. We used the The Cochrane Risk of Bias 2 tool was used to assess the quality of the included studies. Main Outcome Measure clinical pregnancy rate and the number of retrieved oocytes. Main results and the role of chance The search retrieved 111 records. Six studies met the eligibility criteria and were included in the qualitative synthesis and the meta-analysis. Compared to the originator Follitropin alpha, biosimilars are probably associated with lower clinical pregnancy rates (RR 0.81, 95% CI 0.69 to 0.94, I2 = 0%, 6 RCTs, 1453 participants, moderate-quality evidence), but there was no evidence of a difference in the number of retrieved oocytes (MD 0.69, 95% CI -0.09 to 1.46, I2 = 0%, 6 RCTs, 1353 participants, moderate-quality evidence). We are uncertain of the effect of biosimilar preparations on live birth which may indicate no difference or serious harm (RR 0.86, 95% CI 0.71 to 1.05, I2 = 0%, 5 RCTs, 978 participants, low-quality evidence). Both preparations were similar in terms of OHSS (RR 1.25, 95% CI 0.89 to 1.76, 5 RCTs, 1353 participants, moderate-quality evidence) and adverse events (RR 1.09, 95% CI 0.92 to 1.30, 4RCTs, 981 participants, moderate-quality evidence). Limitations, reasons for caution Since it is based on a small number of RCTs and patients, therefore the findings in terms of pregnancy rates, number of oocytes and OHSS are derived from 6 RCTs . Thus, these low numbers limit the validity of the findings and indicate that more high-quality studies are needed. Wider implications of the findings Couples should be counseled for the possible inferiority of these preparations compared to the originator. More RCTs are required to confirm these results, and these RCTs should consider the cost-effectiveness outcomes in their designs and analyses. Trial registration number CRD42020124121