Double embryo transfer may increase the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer
Authors: Wang Yufeng , Wan Qin , Lu Xiaohui , Li Lingjun , Wang Huihui , Chen Li , Dai Xiuliang 
Published: June 2024

STUDY QUESTION: Does double embryo transfer (DET) increases the risk of clinical pregnancy loss (CPL) in singleton pregnancies (excluding vanishing twin) following frozen-thawed embryo transfer (FET)?
SUMMARY ANSWER: Double may be associated with increased clinical pregnancy loss in the setting of singleton pregnancies following FET, particularly for transferring two top blastocysts.
WHAT IS KNOWN ALREADY?:Previous studies have showed adverse outcomes in singleton births following DET compared to SET. However, it remains unclear whether DET increases the risk of clinical pregnancy loss (CPL) in singleton pregnancies.
STUDY DESIGN, SIZE, DURATION:This is a retrospective study including data from a total of 2448 confirmed singleton pregnancies via frozen-thawed single or double embryo transfer in our reproductive center from January 2017 to September 2022.
PARTICIPANTS/MATERIALS, SETTING, METHODS: According to embryo stage and number of embryos transfer, all the FET cycles were divided into 4 groups: SET or DET with day 3 cleavage embryo (SETc or DETc) , SET or DET with blastocyst (SETb or DETb) . In addition, data from SET or DET with top blastocyst (day 5 and morphologically good blastocysts, SETtb or DETtb) were extracted for analysis. Binary logistic regression analysis was used to evaluate the influence of DET on the occurrence of CPL in three populations, including couples with day3 cleavage embryo transfer, with blastocyst transfer and with top blastocyst transfer.
MAIN RESULTS AND THE ROLE OF CHANCE: After adjusting for confounding factors, compared to SET, DET showed a slightly higher rate of CPL for the transfer of day 3 cleavage embryos [OR (95% CL): 1.124 (0.70-1.80), p=0.63]; a moderate higher rate of CPL for the transfer of blastocysts [1.350 (0.97-1.88), p=0.08]; a significant higher rate of CPL for the transfer of top blastocysts [1.54 (1.01-2.37), p=0.05].
LIMITATIONS, REASONS FOR CAUTION: Due to the retrospective nature of the present study, there remains the possibility that important confounding factors were not fully taken into account. Since our study was based on data from FET cycles, the applicability of our conclusions to fresh embryo transfer cycles warrants further investigation.
WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight that transfer of two top blastocysts increases the risk of CPL compared to SET. In addition our data show that as the developmental potential of the embryo transferred increases, the impact of DET on the CPL gradually strengthened. We proposed a situation in which the late death of an embryo with a large cell mass may trigger excess intrauterine inflammation, thereby elevating the risk of CPL of another surviving embryo with full potential. The embryo with a higher developmental potential means a higher chance to have a large cell mass before death, explaining the result form different groups. Due to the inevitable occurrence of abovementioned situation by the strategy of DET, therefore, our study indicates that DET even for double cleavage embryos may increase the risk of CPL. Our study provides a novel and compelling evidence to support the strategy of SET.
STUDY FUNDING/COMPETTING INTEREST(S): This study was supported by the Top Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project, the Key Project funded by Changzhou Clinical Medical Center, and the China Reproductive Public Welfare Fund “Pilotage Plan”(Y. Wang). All authors report no conflict of interest.
TRIAL REGISTRATION NUMBER: N/A.