Abstract

Abstract Study question Should a national embryo transfer (ET) policy designed in the era of cleavage stage transfers be adapted for blastocyst transfers to avoid twin pregnancies? Summary answer Double embryo transfer policy results in unacceptable high twin rates at all ages and treatment ranks which is significantly more pronounced after double blastocyst transfer. What is known already In 2003, authorities in Belgium implemented a law to reduce multiple pregnancies after ART by tailoring ET policies based on age, embryo quality, and cycle rank. A choice between SET or Double Embryo Transfer (DET) depending on embryo quality is allowed in the second cycle for patients under 36y with SET being mandatory with top quality embryos. DET is allowed as of the first cycle for patients aged 36y or more regardless of embryo quality. Blastocyst transfer results in significantly higher live birth rates, implying an increased risk of multiple pregnancies after multiple blastocyst transfers. Study design, size, duration A analysis of 35,523 double embryo fresh transfer cycles over a period of 10 years from 2012 to 2021 from the Belgian national BELRAP (Belgian Registry on Assisted Procreation) registry was performed. The study included 26,930 double cleavage stage transfers (DET-CL) and 8,593 double blastocyst transfers (DET-BL). Participants/materials, setting, methods The primary outcomes were delivery rate (DR) per transfer and twin delivery rate (TDR). DR includes all deliveries with a least one live birth per transfer; the TDR includes all twin deliveries as a proportion of all deliveries. For analysis, the data were categorized into the following age groups: 18-25 years, 26-29 years, 30-35 years, 36-39 years and 40-45 years. Cycle ranks were categorized as follows: rank 1, rank 2 and cycle 3- ≥ 6. Main results and the role of chance For all age groups and cycle ranks, delivery rate per transfer and twin delivery rate per delivery were significantly higher after DET-Bl compared to DET-Cl (26.0% versus 19.9%; p < 0.0001 and 28.0% versus 20.6%; p < 0.0001, respectively). In the age groups 26-29 years, 30-35 years and 36-39 years, a significantly higher TDR was observed in DET-Bl compared to DET-Cl, respectively (34.4% versus 24.2%, p = 0.0005; 33.5% versus 24.9%, p < 0.0001 and 24.3% versus 17.3%, p = 0.0002). TDR after DET-Bl was significantly lower in women aged 40-45 years compared to all other age groups, 18-25 years, 26-29 years, 30-35 years and 36-39 years, respectively (11.3% versus 32.8%, p < 0.0001; 11.3% versus 34.4%; p < 0.0001; 11.3% versus 33.5%; p < 0.0001 and 11.3% versus 24.3%; p < 0.0001), respectively). DR was significantly lower in cycle rank 1 compared to cycle rank 2 (22.5% versus 25.5%; p < 0.0001) and compared to cycle rank 3 - > 6 rank 1 and (22.5% versus 27.1%; p < 0.0001). After DET-Bl, a significantly lower TDR was observed in cycle rank 1 compared to cycle rank 2 (15.6% versus 30.0%; p < 0.0001) and compared to cycle rank 3 - > 6 (15.6% versus 29.7%; p < 0.0001). Limitations, reasons for caution The retrospective design is a limitation. Outcomes might be influenced by clinical and laboratory improvements over the years. The registry does not collect embryo quality data making it impossible to assess the effect of embryo quality on the ET policy and outcome. Wider implications of the findings This data indicates that a double blastocyst transfer should only be considered from the age of 40 onwards. In the first cycle, regardless of age, we observe a significantly lower twin delivery rate, suggesting that a double ET is performed when only poor-quality blastocysts are available. Trial registration number Not applicable

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