Required amount of rFSH, HP-hMG and HP-FSH to reach a live birth: a systematic review and meta-analysis.

STUDY QUESTION: In women undergoing IVF or ICSI cycles, do recombinant gonadotrophins differ from urinary-derived highly purified human menopausal gonadotropin (HP-hMG) or highly purified follicle-stimulating hormone (HP-FSH) in the total amount of gonadotrophins required to reach a live birth?

SUMMARY ANSWER: The difference between recombinant and urinary-derived HP-hMG or HP-FSH in the required amount to reach a live birth in IVF/ICSI cycles appears small.

WHAT IS KNOWN ALREADY: At present, gynecologists can choose between recombinant FSH (rFSH), urinary-derived HP-hMG and HP-FSH. These products are equally effective and safe, but it is unknown how these gonadotrophins compare in terms of IU required to reach a live birth.

STUDY DESIGN SIZE AND DURATION: We conducted a search in Medline, Embase and CINAHL up to July 2018. We included randomized controlled trials (RCTs) that compared rFSH with HP-hMG or HP-FSH for ovarian stimulation in couples scheduled for IVF or ICSI treatment. From each randomized trial, we extracted the outcome data and information on participants, methods, interventions and funding.

PARTICIPANTS/MATERIALS SETTING AND METHODS: Women undergoing ovarian stimulation with rFSH, HP-hMG or HP-FSH were included. We extracted data for the mean amount of gonadotrophins with SD, clinical pregnancy rate, live birth rate and cumulative live birth rate per woman from the included RCTs. We summarized these outcomes by calculating the individual and pooled mean difference (MD) or relative risk (RR) with 95% CI. We used the Review Manager software to perform the meta-analyses. We applied a random effect model to pool the data. We estimated the total amount of gonadotrophins used per extra live birth by STATA 14.2 and R software.

MAIN RESULTS AND THE ROLE OF CHANCE: A total of 28 studies with 7553 women were included in this review, of which 24 studies provided information on the total amount of gonadotrophins per woman who started an IVF/ICSI cycle. The total amount of gonadotrophins varied significantly between studies. The MDs in total amount were -37 IU (seven studies; N  = 3220; 95% CI, -115 to 41; I 2  = 68%) for rFSH versus HP-hMG and -31 IU (17 studies; N  = 3629; 95% CI, -290 to 228; I 2  = 97%) for rFSH versus HP-FSH. For rFSH versus HP-hMG, the RR for clinical pregnancy, live birth and cumulative live birth were 0.90 (95% CI, 0.81-1.00), 0.88 (95% CI, 0.78-0.99) and 0.91 (95% CI, 0.80-1.04), respectively. For rFSH versus HP-FSH, the RR for clinical pregnancy and live birth were 1.03 (95% CI, 0.94-1.13) and 1.03 (95% CI, 0.90-1.18), respectively; the data on cumulative live birth rate were lacking. The estimated difference in mean gonadotrophin amount per extra live birth was 789 IU (95% CI, -9.5 to 1570) for rFSH versus HP-hMG and -365 IU (95% CI, -2675 to 1945) for rFSH versus HP-FSH.

LIMITATIONS REASONS FOR CAUTION: There was severe heterogeneity in the total amount of gonadotrophins between studies. A small fraction of women did not start gonadotrophin treatment; this was usually not accounted for in the provided mean amount of gonadotrophins per study and might have affected the averaged total amount of gonadotrophins but is unlikely to have affected the differences in the amount between rFSH and HP-hMG or HP-FSH.

WIDER IMPLICATIONS OF THE FINDINGS: The differences in the required amount to reach a live birth between rFSH, HP-hMG and HP-FSH appear to be small. Decision-making should be based on convenience, availability, actual costs and patient preferences.

STUDY FUNDING/COMPETING INTERESTS: The authors declare no conflict of interest. No external funding was either sought or obtained for this study.

REGISTRATION NUMBER: Prospero CRD42016038238.