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.

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.

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

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: NCT02554279 (clinicaltrials.gov).

Economic evaluation of alternative assisted reproduction techniques in management of infertility in Greece.

BACKGROUND: The purpose of this study was to compare Gonal-F(®), a recombinant follicle-stimulating hormone, with Menopur(®), a highly purified human menopausal gonadotrophin (hpHMG) in assisted reproduction in Greece. METHODS: A decision tree in combination with a Markov model was used to assess the clinical and economical impact of comparators for up to three consecutive cycles. Transition probabilities were derived from the literature and validated by clinical experts. Cost components were derived from the electronic databases of selected private and public clinics. A probabilistic sensitivity analysis was performed to deal with uncertainty and to construct a cost-effectiveness acceptability curve. RESULTS: There was a statistically significant difference in favor of the recombinant follicle-stimulating hormone arm compared with hpHMG, which was associated with 52 more births (95% uncertainty interval 26-78, P = 0.001) per 1000 patients. The cost per birth was estimated at €16,906 and €17,286 in the recombinant follicle-stimulating hormone and hpHMG arms, respectively. The cost per in vitro fertilization was estimated at €4365 in the recombinant follicle-stimulating hormone arm and €3815 in the hpHMG arm, indicating a difference of €550. The incremental cost per birth for recombinant follicle-stimulating hormone versus hpHMG was estimated at €14,540, while the incremental cost per life-year was estimated at €175.41. CONCLUSION: Recombinant follicle-stimulating hormone may represent a cost-effective choice compared with hpHMG when used for ovarian stimulation for a pharmacoeconomic point of view in the Greek public health care setting. However, it must be noted that in clinical practice both agents may be used together to increase the number of follicles, oocytes, embryos, and/or pregnancies in treated patients, an approach which has not been evaluated in Greece or reported in the literature due to obvious limitations.