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Meta-Analysis
. 2021 Apr 2;19(1):51.
doi: 10.1186/s12958-021-00727-y.

Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment: a systematic review and meta-analysis

Su Jen Chua  1 , Ben W Mol  2 , Salvatore Longobardi  3 , Raoul Orvieto  4   5 , Christos A Venetis  6   7 , Monica Lispi  8   9 , Ashleigh Storr  10   11 , Thomas D'Hooghe  9   12   13
Affiliations
Meta-Analysis

Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment: a systematic review and meta-analysis

Su Jen Chua et al. Reprod Biol Endocrinol. .

Erratum in

Abstract

Background: Live birth has increasingly been identified as the standard clinical approach to measure the success of medically assisted reproduction (MAR). However, previous analyses comparing biosimilar preparations of follitropin alfa versus the reference product (GONAL-f®, Merck KGaA, Darmstadt, Germany or GONAL-f® RFF; EMD Serono, Inc., Rockland, MA), have had insufficient power to detect differences in clinically meaningful outcomes such as live birth.

Methods: Medline, Embase, the Cochrane Library, Web of Science and clinical trial registries were searched for randomised controlled trials (RCTs) and conference abstracts comparing biosimilar follitropin alfa versus the reference product in controlled ovarian stimulation (COS) cycles published before 31 October 2020. Only studies in humans and publications in English were included. Retrieved studies were screened independently by two authors based on titles and abstracts, and then by full text.

Inclusion criteria: RCTs comparing follitropin alfa biosimilar preparations with the reference product in infertile patients of any age, with any type of infertility for any duration, undergoing COS for the purposes of MAR treatment (including frozen cycles). The primary outcome was live birth. Combined data for biosimilar preparations were analysed using a fixed-effects model.

Results: From 292 unique records identified, 17 studies were included in the systematic review, representing five unique RCTs that were included in the meta-analysis. Rates of live birth (RR = 0.83, 95% CI 0.71, 0.97; 4 RCTs, n = 1881, I2 = 0%), clinical pregnancy (RR = 0.82, 95% CI 0.72, 0.94; 4 RCTs, n = 2222, I2 = 0%) and ongoing pregnancy (RR = 0.81, 95% CI 0.68, 0.96; 4 RCTs, n = 1232, I2 = 0%) were significantly lower with biosimilar preparations versus the reference product. Rates of cumulative live birth and cumulative clinical pregnancy were also significantly lower with biosimilars versus the reference product. There was high risk of publication bias.

Conclusions: This meta-analysis included data from RCTs evaluating the efficacy and safety of the biosimilar follitropin alfa preparations and demonstrated lower probability of live birth and pregnancy (ongoing and clinical) in couples treated with biosimilar preparations compared with the reference product. This study provides more insight into the differences between biosimilar r-hFSH preparations and the reference product than previously reported.

Trial registration: Registration number: CRD42019121992 .

Keywords: Biosimilar; Follitropin alfa; IVF; Ovarian stimulation; r-hFSH.

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Conflict of interest statement

BWM has received investigator grant from NHMRC, personal fees from ObsEva, personal fees and research support from Merck KGaA, Darmstadt, Germany, personal fees from Merck KGaA, Darmstadt, Germany, personal fees and research support from Guerbet and personal fees from iGenomix. CAV has received personal fees from Merck KGaA, Darmstadt, Germany, personal fees, grant, and non-financial support from Merck KGaA, Darmstadt, Germany, personal fees and non-financial support from Merck Sharp & Dohme, grant and non-financial support from Ferring, personal fees from Besins, personal fees and non-financial support from Gedeon-Richter, and research funding and non-financial support from Abbott. SL is employee of Merck Serono S.p.A., Rome, Italy, an affiliate of Merck KGaA, Darmstadt, Germany. TDH and ML are employees of Merck KGaA, Darmstadt, Germany. SJ, AS and RO have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Relative risk for live birth rate with biosimilar preparations of follitropin alfa versus the reference product
Fig. 2
Fig. 2
Relative risk for clinical pregnancy rate (a), ongoing pregnancy rate (b) and ovarian hyperstimulation syndrome (c) with biosimilar preparations of follitropin alfa versus the reference product
Fig. 3
Fig. 3
Mean difference in total dose of gonadotrophins (a), number of oocytes retrieved (b) and duration of ovarian stimulation (c) with biosimilar preparations of follitropin alfa versus the reference product
Fig. 4
Fig. 4
Relative risk for cumulative live birth rate* (a), cumulative clinical pregnancy rate (b) and cumulative ongoing pregnancy rate (c) with biosimilar preparations of follitropin alfa versus the reference product. *For the cumulative live birth, only data from the first cycle could be used for the RCT investigating Ovaleap® as all participants crossed over to the exclusive use of Ovaleap® in subsequent cycles
See this image and copyright information in PMC

References

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