Abstract Study question Do couples with two blastocysts opting for DET have a better outcome than those with SET, freezing of the second and eventually subsequent second SET? Summary answer More children are born after 2x SET with the overwhelming majority (96.3%) of these children being singletons, whereas after 1x DET 49.5% are multiples What is known already According to the most recent publication of the European IVF Monitoring Consortium, in 33 European countries reporting data on these topics SET is performed in 55.4% of fresh transfers whereas in the other cycles, two, three and even 4 or more embryos are transferred, often resulting in twin or higher order multiple pregnancies, but there is no information on the duration of culture and number of embryos available in these cycles. The German IVF-Registry (D·I·R) has collected more than 2.4 million datasets from German ART clinics since 1997 and has access to these data and other relevant patient characteristics. Study design, size, duration Retrospective real-world data analysis from 140 German IVF-centers collected by the German IVF-Registry (D·I·R) between 2017 and 2021. Data were collected prospectively, controlled for plausibility, and evaluated anonymously. Treatment cycles from four years between January 1st, 2017 and December 31st, 2020 were evaluated. Pregnancy outcome was monitored until end of 2021. All couples having at least 2 blastocysts available for fresh transfer in their 1st treatment cycle were identified and included in the analysis. Participants/materials, setting, methods 19,702 women with similar characteristics (i.e. first cycle of IVF or ICSI, fresh embryo transfer, two blastocysts available on the day of fresh ET, signed consent to freeze supernumerous 2PN or embryos) were stratified into two groups. Therapy results after 1x DET (fresh) vs. 1x SET (fresh) plus 1x SET (frozen-thawed) were evaluated for clinical pregnancy rates, life birth rates, number and order of multiple pregnancies, multiple deliveries, and total number of children born. Main results and the role of chance From 19,702 women meeting the inclusion criteria, 9,643 (48.9%) had a DET and 10,059 (51.1%) had a SET. The age of patients in both groups was not significantly different (DET: 34.1y vs. SET: 33.7y). As expected, ongoing pregnancy rate (OPR) and life birth rate (LBR) after DET were higher compared to SET (OPR: 49.4% vs. 42.3%; LBR 38.5% vs. 33.1%). Those opting for SET however had the chance of a second SET with the frozen-thawed blastocyst and so far, from 7,207 women who started the frozen embryo transfer cycle (FET), 6,431 had the second blastocyst transferred with a CPR of 29.5% and LBR of 19.4% per started FET. After DET, only 67.4% of deliveries were singletons. Of the 32.6% multiples, 97.4% were twins, 2.5% triplets and 0.1% quadruplets. After fresh (or frozen) SET, 98.4% (97.6%) of deliveries were singletons, the remaining were solely twins (1.6% (2.4%)) and no higher order multiples. Per 1,000 women having a DET, 514 children were born and 49.5% of those were either twins, triplets or quadruplets. Per 1,000 women after 2x SET, more children were born (536), and only 3.7% of those were twins, no triplets or quadruplets. Limitations, reasons for caution In this retrospective analysis, the reasons of the couples for the decision of having SET or DET is not known. One potential bias caused by the additional costs for freezing/thawing (not reimbursable in Germany) can be excluded (only those having opted to freeze supernumerous 2PN or embryos were evaluated). Wider implications of the findings Couples undergoing IVF understandably want to maximize their chances of success, sometimes opting for a DET, underestimating the number of multiples and neglecting the risks. We clearly show that after DET every second child is a twin, triplet or quadruplet, and even more children are born after two successive SETs. Trial registration number not applicable
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