Randomized, assessor-blinded trial comparing highly purified human menotropin and recombinant follicle-stimulating hormone in high responders undergoing intracytoplasmic sperm injection

We discuss how highly purified human menotropin provides comparable efficacy to recombinant follicle- stimulating hormone with fewer adverse events, including pregnancy loss; suggesting an optimized risk/benefit profile.

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VOLUME 114, ISSUE 2, P321-330

Authors:

Craig A. Witz, M.D., Gaurang S. Daftary, M.D., M.B.A., Kevin J. Doody, M.D., John K. Park, M.D., M.S., M.Sc., Yodit Seifu, Ph.D., Vladimir I. Yankov, M.D., Patrick W. Heiser, Ph.D., on behalf of the Menopur in GnRH Antagonist Cycles with Single Embryo Transfer – High Responder (MEGASET-HR) Trial Group

Abstract:

Objective

To evaluate the efficacy and safety of highly purified human menotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation in a population of patients predicted to be high responders.

Design

Randomized, open-label, assessor-blinded, parallel-group, noninferiority trial.

Setting

Fertility centers.

Patient(s)

A total of 620 women with serum antimüllerian hormone (AMH) ≥5 ng/mL.

Intervention(s)

Controlled ovarian stimulation with HP-hMG or rFSH in a GnRH antagonist assisted reproductive technology (ART) cycle. Fresh transfer of a single blastocyst was performed unless ovarian response was excessive, in which all embryos were cryopreserved. Subjects could undergo subsequent frozen blastocyst transfer within 6 months of randomization.

Main Outcome Measure(s)

Ongoing pregnancy rate (OPR) after fresh transfer (primary endpoint), as well as cumulative live birth, ovarian hyperstimulation syndrome (OHSS), and pregnancy loss rates.

Results

OPR/cycle start after fresh transfer was 35.5% with HP-hMG and 30.7% with rFSH (difference: 4.7%, 95% CI −2.7%, 12.1%); noninferiority was established. Compared to rFSH, HP-hMG was associated with significantly lower OHSS (21.4% vs. 9.7% respectively; difference: −11.7%, 95% CI −17.3%, −6.1%) and cumulative early pregnancy loss rates (25.5% vs. 14.5% respectively; difference: −11.0%, 95% CI −18.8%, −3.14%). Despite 43 more transfers in the rFSH group, cumulative live birth rates were similar with HP-hMG and rFSH at 50.6% and 51.5% respectively (difference: −0.8%, 95% CI −8.7%, 7.1%).

Conclusion(s)

In high responders, HP-hMG provided comparable efficacy to rFSH with fewer adverse events, including pregnancy loss, suggesting its optimized risk/benefit profile in this population.

Clinical Trial Registration Number

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. 

Comments

We have read with great interest the article by Witz et al. describing the results of the Menopur in GnRH Antagonist Cycles with Single Embryo Transfer – High Responder (MEGASET-HR) trial which compares highly purified human menotropin (HP-hMG) and recombinant human follicle-stimulating hormone (r-hFSH) in high responders undergoing intracytoplasmic sperm injection (Witz et al. 2020). With a standard starting dose of 150 IU for either r-hFSH or HP-hMG, Witz et al. report that HP-hMG was non inferior to r-hFSH in regards to ongoing pregnancy (primary endpoint) after fresh transfer (35.5% [HP-hMG] vs 30.7% [r-hFSH]; difference 4.7%, 95% CI, –2.7%, 12.1%).


We believe there are major methodological flaws in study design, statistical analysis, data collection and reporting, and interpretation of the results which raise serious questions regarding the validity of the authors’ conclusions.


Please read here the reasons and research for these findings.