P–586 Clinical outcome in frozen cycles using cryopreserved blastocysts derived from ovarian stimulation with follitropin delta
Authors: Havelock J , Arce J C , ESTHER-. an. ESTHER X 
Published: August 2021

Study question

To compare the live birth rate using frozen-thawed blastocysts obtained from ovarian stimulation with individualised follitropin delta dosing to conventional follitropin alfa dosing.

Summary answer

The live birth rate in cryo cycles conducted within 1 year after ovarian stimulation was comparable for individualised follitropin delta and conventional follitropin alfa treatment.

What is known already

It has been demonstrated that the follitropin delta (Rekovelle, Ferring Pharmaceuticals) in an individualised dosing regimen based on anti-Müllerian hormone (AMH) level and body weight is non-inferior to conventional follitropin alfa (Gonal-f, Merck Serono) dosing with respect to ongoing pregnancy and ongoing implantation rates in fresh cycles. The individualised approach also reduced the risk of ovarian hyperstimulation syndrome (OHSS) versus the conventional approach. Furthermore, treatment with follitropin delta and follitropin alfa gave comparable pregnancy rates in repeated fresh cycles.

Study design, size, duration

Analysis of frozen cycles using blastocysts obtained from a randomised trial comparing follitropin delta versus follitropin alfa in 1,326 IVF/ICSI patients (18–40 years) and a subsequent trial of up to two additional ovarian stimulation cycles. The clinical outcome includes women with cryopreserved blastocysts following ovarian stimulation and who underwent frozen cycles within 1 year after starting stimulation in their last cycle.

Participants/materials, setting, methods

A total of 917 women had at least one Day 5 blastocyst which was vitrified and stored following up to three ovarian stimulation cycles. A started cryo cycle was defined as warming of a blastocyst. After warming, 1–2 blastocysts were transferred in cryo cycles, using natural cycle or programmed regimens. Treatment differences and 95% confidence intervals (CI) were calculated with adjustment for age strata and accounting for repeated cycles within patient.

Main results and the role of chance

The proportion of women with frozen blastocysts was similar in the two treatment groups, with 69.5% in the follitropin delta group and 68.8% in the follitropin alfa group. Similar postwarming blastocyst survival rates were observed for the two groups, with 87.4% of the warmed blastocysts proceeding to transfer in the follitropin delta group and 88.8% in the follitropin alfa group. About half of the women (48.1% in each treatment group) with frozen blastocysts underwent at least one frozen cycle with transfer within the 1-year period, with an average of 1.5 cycles per woman in the follitropin delta group and 1.6 cycles per woman in the follitropin alfa group. The ongoing implantation rate was 27.6% in the follitropin delta group and 27.8% in the follitropin alfa group (adjusted difference 0.5% [95% CI: –7.1%; 8.2%]). The live birth rate per started cryo cycle was 32.0% in the follitropin delta group and 31.3% in the follitropin alfa group (adjusted difference 1.2% [95% CI: –6.8%; 9.3%]), while the live birth rate per cryo cycle with transfer was 33.2% and 31.9% (adjusted difference 1.9% [95% CI: –6.2%; 10.0%]), respectively.

Limitations, reasons for caution

The number of blastocysts to be transferred in the frozen cycles as well as the protocol for endometrial preparation was based on local centre practices.

Wider implications of the findings: These findings suggest that the follitropin delta and follitropin alfa dosing regimens are equally effective in terms of live birth rate in frozen replacement cycles and add reassuring information to the clinical performance of cryopreserved blastocysts derived from ovarian stimulation with follitropin delta.

Trial registration number

NCT01956110, NCT01956123.