Pregnancy and neonatal outcomes in fresh and frozen cycles using blastocysts derived from ovarian stimulation with follitropin delta

Jon Havelock, Anna-Karina Aaris Henningsen, Bernadette Mannaerts, Joan-Carles Arce, ESTHER-1 and ESTHER-2 Trial Groups, Jon Havelock, Anna-Karina Aaris Henningsen, Bernadette Mannaerts, Joan-Carles Arce, ESTHER-1 and ESTHER-2 Trial Groups

Abstract

Purpose: To describe the pregnancy and neonatal outcomes using fresh and vitrified/warmed blastocysts obtained from ovarian stimulation with follitropin delta in controlled trials versus follitropin alfa.

Methods: This investigation evaluated the outcome from 2719 fresh and frozen cycles performed in 1326 IVF/ICSI patients who could start up to three ovarian stimulations in the ESTHER-1 (NCT01956110) and ESTHER-2 (NCT01956123) trials, covering 1012 fresh cycles and 341 frozen cycles with follitropin delta and 1015 fresh cycles and 351 frozen cycles with follitropin alfa. Of the 1326 first cycle patients, 513 continued to cycle 2 and 188 to cycle 3, and 441 patients started frozen cycles after the fresh cycles. Pregnancy follow-up was continued until 4 weeks after birth.

Results: The overall cumulative take-home baby rate after up to three stimulation cycles was 60.3% with follitropin delta and 60.7% with follitropin alfa (-0.2% [95% CI: -5.4%; 5.0%]), of which the relative contribution was 72.8% from fresh cycles and 27.2% from frozen cycles in each treatment group. Across the fresh cycles, the ongoing implantation rate was 32.1% for follitropin delta and 32.1% for follitropin alfa, while it was 27.6% and 27.8%, respectively, for the frozen cycles. Major congenital anomalies among the live-born neonates up until 4 weeks were reported at an incidence of 1.6% with follitropin delta and 1.8% with follitropin alfa (-0.2% [95% CI: -1.9%; 1.5%]).

Conclusions: Based on comparative trials, the pregnancy and neonatal outcomes from fresh and frozen cycles provide reassuring data on the efficacy and safety of follitropin delta.

Trial registration: ClinicalTrials.gov Identifier: NCT01956110 registered on 8 October 2013; NCT01956123 registered on 8 October 2013.

Keywords: Follitropin delta; Fresh cycle; Frozen cycle; Neonatal outcome; Ovarian stimulation; Take-home baby rate.

Conflict of interest statement

AKAH has received a consulting fee from Ferring Pharmaceuticals for review of all cases of congenital anomalies in the ESTHER-1 and ESTHER-2 trials. BM and J-CA are employees of Ferring Pharmaceuticals. J-CA has patent applications on follitropin delta granted and pending. The authors report no other relevant financial or non-financial conflicts of interests related to the trials.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Schematic overview of ESTHER-1 and ESTHER-2 trial designs. The flow of patients is provided for fresh and frozen cycles using day 5 blastocysts obtained after ovarian stimulation with follitropin delta and follitropin alfa. Frozen cycles (optional) were started within 1 year after start of stimulation of the last fresh cycle in either of the trials. ESTHEREvidence-based Stimulation Trial with Human rFSH in Europe and Rest of World.
Fig. 2
Fig. 2
Cumulative take-home baby rate in fresh and frozen cycles. The cumulative take-home baby rate is shown by fresh and frozen cycles with follitropin delta and follitropin alfa. N total number of women.

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