Pregnancy Outcomes After Different Cycle Regimens for Frozen-Thawed Embryo Transfer: A Retrospective Study Using Propensity Score Matching

Background: Nowadays, the choice of frozen embryo transfer (FET) regimens is mainly guided by personal convenience. Clinicians prefer the predictability and reliability of artificial cycle (AC) FET and have extended its usage to general in vitro fertilization population. More recent primary studies are beginning to challenge the comparability of AC-FET and suggest reduced clinical pregnancy rate and live birth rate (LBR) compared with those in modified natural cycle (mNC) FET (ovulation triggered by human chorionic gonadotrophin) and stimulated cycle (SC) FET. Objective: To assess the pregnancy outcomes within matched mNC-FET, SC-FET, and AC-FET cycles by using propensity score matching (PSM) in a larger cohort. Methods: A total of 16,946 women who underwent their first autologous FET cycle between July 2014 and July 2017 were evaluated. PSM, using the nearest neighbor matching, were established to adjust the baseline features within the three protocols in proportion of 1:1 (mNC-FET vs. SC-FET, mNC-FET vs. AC-FET, SC-FET vs. AC-FET). Furthermore, there were 3,567, 2,917, and 3,964 cycles compared between matched mNC-FET and SC-FET, mNC-FET and AC-FET, and SC-FET and AC-FET after the PSM, respectively. Results: LBR was significant lower in the AC-FET group than that in the mNC-FET (40.0 vs. 43.3%) and SC-FET groups (40.9 vs. 46.5%). The adjusted odds ratios (95% CIs) were 1.11 (1.00, 1.24) for mNC/AC (P = 0.044) and 0.84 (0.76, 0.92) for AC/SC (P < 0.001), which indicated that the AC-FET group was associated with lowest LBR. The LBR was comparable between matched mNC-FET and SC-FET after adjusting for endometrial thickness. Moreover, a lower clinical pregnancy rate and a higher risk of early pregnancy loss were discovered in AC-FET cycles compared with those in SC-FET. Conclusion: In view of our data, AC used for scheduling FET was associated with lower LBR compared with SC and modified natural cycle. This interpretation requires future verification from well-designed prospective multicenter randomized clinical trials, although the comparisons in our study were conducted in the homogenous population after the PSM.