Economic evaluation of highly purified human menotropin or recombinant follicle-stimulating hormone for controlled ovarian stimulation in high-responder patients: analysis of the Menopur in Gonadotropin-releasing Hormone Antagonist Single Embryo Transfer-High Responder (MEGASET-HR) trial

Jared C Robins, Andrew F Khair, Eric A Widra, Michael M Alper, Winnie W Nelson, Eric D Foster, Anshul Sinha, Masakazu Ando, Patrick W Heiser, Gaurang S Daftary, Jared C Robins, Andrew F Khair, Eric A Widra, Michael M Alper, Winnie W Nelson, Eric D Foster, Anshul Sinha, Masakazu Ando, Patrick W Heiser, Gaurang S Daftary

Abstract

Objective: To determine the cost of achieving a live birth after first transfer using highly purified human menotropin (HP-hMG) or recombinant follicle-stimulating hormone (FSH) for controlled ovarian stimulation in predicted high-responder patients in the Menopur in Gonadotropin-releasing hormone Antagonist Single Embryo Transfer-High Responder (MEGASET-HR) trial.

Design: Cost minimization analysis of trial results.

Setting: Thirty-one fertility centers.

Patients: Six hundred and nineteen women with serum antimüllerian hormone ≥5 ng/mL.

Interventions: Controlled ovarian stimulation with HP-hMG or recombinant FSH in a gonadotropin-releasing hormone (GnRH) antagonist assisted reproduction cycle where fresh transfer of a single blastocyst was performed unless ovarian response was excessive whereupon all embryos were cryopreserved and patients could undergo subsequent frozen blastocyst transfer within 6 months of randomization.

Main outcome measures: Mean cost of achieving live birth after first transfer (fresh or frozen).

Results: First-transfer efficacy, defined as live birth after first fresh or frozen transfer, was 54.5% for HP-hMG and 48.0% for recombinant FSH (difference 6.5%). Average cost to achieve a live birth after first transfer (fresh or frozen) was lower with HP-hMG compared with recombinant FSH. For fresh transfers, the cost was lower with HP-hMG compared with recombinant FSH. The average cost to achieve a live birth after first frozen transfer was also lower in patients treated with HP-hMG compared with recombinant FSH.

Conclusions: Treatment of predicted high-responders with HP-hMG was associated with lower cost to achieve a live birth after first transfer compared with recombinant FSH.

Clinical trial registration number: NCT02554279.

Keywords: GnRH antagonist; Menopur; high responders; highly purified menotropin; recombinant FSH.

© 2020 The Authors.

Figures

Figure 1
Figure 1
Decision tree detailing possible outcomes from randomization to first transfer. Gray boxes indicate the path from randomization to first-transfer efficacy. hCG = human chorionic gonadotropin; HP-hMG = highly purified human menotropin; rFSH = recombinant follicle-stimulating hormone.

References

    1. Wu A.K., Elliott P., Katz P.P., Smith J.F. Time costs of fertility care: the hidden hardship of building a family. Fertil Steril. 2013;99:2025–2030.
    1. Chambers G.M., Adamson G.D., Eijkemans M.J. Acceptable cost for the patient and society. Fertil Steril. 2013;100:319–327.
    1. Chambers G.M., Hoang V.P., Sullivan E.A., Chapman M.G., Ishihara O., Zegers-Hochschild F. The impact of consumer affordability on access to assisted reproductive technologies and embryo transfer practices: an international analysis. Fertil Steril. 2014;101:191–198.e4.
    1. Dyer S.J., Vinoos L., Ataguba J.E. Poor recovery of households from out-of-pocket payment for assisted reproductive technology. Hum Reprod. 2017;32:2431–2436.
    1. Gonen L.D., Bokek-Cohen Y. Valuing the invaluable: do emotional experience during fertility treatments affect the willingness to pay for them? Eur Rev Appl Physiol. 2018;68:45–60.
    1. Witz C.A., Daftary G.S., Doody K.J., Park J.K., Seifu Y., Yankov V.I. Randomized, assessor-blinded trial comparing highly purified human menotropin and recombinant follicle-stimulating hormone in high responders undergoing intracytoplasmic sperm injection. Fertil Steril. 2020;114:P321–P330.
    1. European and Israeli Study Group on Highly Purified Menotropin versus Recombinant Follicle-Stimulating Hormone Efficacy and safety of highly purified menotropin versus recombinant follicle-stimulating hormone in in vitro fertilization/intracytoplasmic sperm injection cycles: a randomized, comparative trial. Fertil Steril. 2002;78:520–528.
    1. Kilani Z., Dakkak A., Ghunaim S., Cognigni G.E., Tabarelli C., Parmegiani L. A prospective, randomized, controlled trial comparing highly purified hMG with recombinant FSH in women undergoing ICSI: ovarian response and clinical outcomes. Hum Reprod. 2003;18:1194–1199.
    1. Andersen A.N., Devroey P., Arce J.C. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Hum Reprod. 2006;21:3217–3227.
    1. Devroey P., Pellicer A., Nyboe Andersen A., Arce J.C., Group MEGASET A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Fertil Steril. 2012;97:561–571.
    1. Bosch E., Vidal C., Labarta E., Simon C., Remohi J., Pellicer A. Highly purified hMG versus recombinant FSH in ovarian hyperstimulation with GnRH antagonists—a randomized study. Hum Reprod. 2008;23:2346–2351.
    1. Hompes P.G., Broekmans F.J., Hoozemans D.A., Schats R., Group F. Effectiveness of highly purified human menopausal gonadotropin vs. recombinant follicle-stimulating hormone in first-cycle in vitro fertilization–intracytoplasmic sperm injection patients. Fertil Steril. 2008;89:1685–1693.
    1. Ye H., Huang G., Pei L., Zeng P., Luo X. Outcome of in vitro fertilization following stimulation with highly purified hMG or recombinant FSH in downregulated women of advanced reproductive age: a prospective, randomized and controlled trial. Gynecol Endocrinol. 2012;28:540–544.
    1. Broer S.L., Dólleman M., Opmeer B.C., Fauser B.C., Mol B.W., Broekmans F.J. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Update. 2011;17:46–54.
    1. Romero J.M.S., Ortega Sanchez I., Garcia-Velasco J. The high responder: optimizing the stimulation without complication. In: Arora S., editor. Infertility management series: handbook of ovarian stimulation. J.P. Medical; London: 2018. pp. 65–77.
    1. Arce J.C., Andersen A.N., Fernández-Sánchez M., Visnova H., Bosch E., García-Velasco J.A. Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimüllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2014;102:1633–1640.e5.
    1. Arce J.C., La Marca A., Mirner Klein B., Nyboe Andersen A., Fleming R. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good-prognosis patients. Fertil Steril. 2013;99:1644–1653.
    1. Chen Z.J., Legro R.S. Fresh versus frozen embryos in polycystic ovary syndrome. N Engl J Med. 2016;375:e42.
    1. Mascarenhas M., Balen A.H. The high responder: a review of pathophysiology and outcomes during IVF treatment. Hum Fertil (Camb) 2017;20:155–167.
    1. Husereau D., Drummond M., Petrou S., Carswell C., Moher D., Greenberg D. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMJ. 2013;346:f1049.
    1. Fertility Drug Calculator . ViralMD; TX: 2019. Farmers Branch. Available at:
    1. Rai M., Goyal R. Pharmacoeconomics in Healthcare. In: Vohora D., Singh G., editors. Pharmaceutical medicine and translational clinical research. Academic Press; San Diego, CA: 2018. pp. 465–472.
    1. Lloyd A., Kennedy R., Hutchinson J., Sawyer W. Economic evaluation of highly purified menotropin compared with recombinant follicle-stimulating hormone in assisted reproduction. Fertil Steril. 2003;80:1108–1113.
    1. Connolly M., De Vrieze K., Ombelet W., Schneider D., Currie C. A cost per live birth comparison of HMG and rFSH randomized trials. Reprod Biomed Online. 2008;17:756–763.
    1. Wechowski J., Connolly M., Schneider D., McEwan P., Kennedy R. Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha. Fertil Steril. 2009;91:1067–1076.
    1. Wex-Wechowski J., Abou-Setta A., Nielsen S., Kennedy R. HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation. Reprod BioMed Online. 2010;21:166–178.
    1. Barriere P., Porcu-Buisson G., Hamamah S. Cost-effectiveness analysis of the gonadotropin treatments HP-hMG and rFSH for assisted reproductive technology in France: a Markov model analysis. Appl Health Econ Health Policy. 2018;16:65–77.
    1. Munne S., Kaplan B., Frattarelli J.L., Child T., Nakhuda G., Shamma F.N. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019;112:1071–1079.e7.
    1. Murugappan G., Ohno M.S., Lathi R.B. Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss. Fertil Steril. 2015;103:1215–1220.
    1. Neal S.A., Morin S.J., Franasiak J.M., Goodman L.R., Juneau C.R., Forman E.J. Preimplantation genetic testing for aneuploidy is cost-effective, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage. Fertil Steril. 2018;110:896–904.
    1. Huang L., Bogale B., Tang Y., Lu S., Xie X.S., Racowsky C. Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy. Proc Natl Acad Sci USA. 2019;116:14105–14112.
    1. Boulet S.L., Crawford S., Zhang Y., Sunderam S., Cohen B., Bernson D. Embryo transfer practices and perinatal outcomes by insurance mandate status. Fertil Steril. 2015;104:403–409.e1.
    1. Csokmay J.M., Yauger B.J., Henne M.B., Armstrong A.Y., Queenan J.T., Segars J.H. Cost analysis model of outpatient management of ovarian hyperstimulation syndrome with paracentesis: “tap early and often” versus hospitalization. Fertil Steril. 2010;93:167–173.

Source: PubMed

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