Abstract

Abstract Study question Does strict embryo-endometrium synchronization relate to pregnancy during vitrified-warmed embryo transfer (ET) with hormone replacement (HRT) cycles? Summary answer A 12-hour delay in the embryo-endometrial synchrony was acceptable, and this delay was not an independent predictor of pregnancy during vitrified-warmed ET with HRT cycles. What is known already Embryo-endometrium synchrony is considered to be necessary for successful pregnancy in both fresh and frozen-thawed cycles. Until now, the date of ET has been determined by the synchronization of the embryo developmental stage and the endometrium on a daily basis. To date, with the advent of the time-lapse incubator, it is possible to observe the embryo development from fertilization over time and to calculate the exact time from fertilization of the transferred embryo. However, there are very few studies on the extent to which increases the accuracy of synchronization between embryo and endometrium contributes to a successful pregnancy. Study design, size, duration This retrospective cohort study included 319 consecutive cycles during vitrified-warmed ET with HRT between August 2016 and August 2018. This study was conducted in an academically affiliated private practice. Participants/materials, setting, methods We analyzed 319 vitrified-warmed single-blastocyst transfer cycles. All frozen expanded blastocysts were inseminated by intracytoplasmic sperm injection (ICSI) and cultured in a time-lapse incubator. We calculated time for the in vitro culture of the embryo after ICSI (t1) and time for progesterone-priming (t2) up to ET. The difference between t1 and t2 (delta-t) was used as an indicator of embryo-endometrium synchrony. We examined the relationship between delta-t and treatment outcomes using multivariate logistic analysis. Main results and the role of chance The mean patient’s age at oocyte retrieval was 35.7 (SD 4.3). The number of pregnant cycles was 157 in all treatment cycles (pregnancy rate, 49.2%). The mean value of delta-t was 9.9 h (SD 2.6) in all cycles. There was no significant difference of delta-t in pregnant (mean, SD: 10.0 h, 2.8 h) and non-pregnant cycles (mean, SD: 10.0 h, 2.3 h). Treatment cycles were classified according to the quartile of delta-t, and we examined the percentages of pregnant cycles in each group. There were no significant differences in pregnancy rates among the groups (p = 0.75). On multivariate logistic analysis, patient’s age (adjusted odds ratio [aOR]: 0.94, 95% confidence interval [CI]: 0.89–0.99), previous treatment cycles (aOR: 0.74, 95% CI: 0.56–0.99), endometrial thickness at ET (aOR: 1.19, 1.04–1.36), and good quality blastocysts (>3BB according to Gardner’s classification) at vitrification (aOR: 2.49, 95% CI: 1.23–5.05) were independent predictive factors for pregnancy. On the other hand, delta-t did not contribute to pregnancy (aOR: 1.00, 95% CI: 0.99–1.00). Limitations, reasons for caution We did not examine the effects of embryo-endometrium synchrony during vitrified-warmed ET in a natural cycle. Therefore, careful interpretation of the significance of embryo-endometrium synchrony during the vitrified-warmed ET should be taken. Wider implications of the findings: We showed the embryo-endometrium synchrony did not contribute to the pregnancy during vitrified-warmed ET with HRT cycles. These results cast doubt on the existence of an optimal implantation window by changing the timing of ET with the results of gene expression testing of the endometrium. Trial registration number Not applicable

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