Seven Years of Vitrified Blastocyst Transfers: Comparison of 3 Preparation Protocols at a Single ART Center

Abstract

Introduction: Frozen-thawed embryo transfers (FET) have become a standard practice to increase cumulative pregnancy rates, however, the choice of the best preparation protocol remains a matter of debate. Design: Retrospective analysis of clinical pregnancy (CPR) and live birth rate (LBR) of FET in natural cycles (NC-FET), modified natural cycles with hCG-triggered ovulation (mNC-FET), and hormonal artificial replacement (AR-FET). Materials and Methods: For natural cycles, patients were monitored by ultrasound to evaluate the dominant follicle and by urinary LH kits (NC-FET). When the endometrial thickness reached at least 7 mm and the dominant follicle 16-20 mm, hCG was administered in absence of urinary LH surge (mNC-FET). Embryo thawing and transfer was planned 7 days after LH surge or hCG administration. For the AR-FET, oral estradiol valerate was administered from day 2 of menstrual cycle until endometrial thickness reached at least 7 mm and transfer was planned after 5 days of vaginal progesterone start. Only single vitrified blastocyst transfers were included. Results: In total 2,895 transfers were performed of which 561 (19.4%) carried out with NC-FET, 1,749 (60.4%) with mNC-FET and 585 (20.2%) with AR-FET. CPRs were 32.62, 43.05, and 37.26%, respectively. LBR were 24.06, 33.56, and 25.81%, respectively. A statistically significant (p < 0.001) higher LBR for mNC-FET vs. NC-FET (OR 0.49-0.78) and AR-FET (OR 0.47-0.74) was observed. A higher ectopic pregnancy rate (p = 0.002) was observed in NC-FET (3.28%) than in AR-FET (1.83%) and mNC-FET (0.40%). A higher abortion rate (p = 0.031) in pregnancies <12 weeks was observed in AR-FET (27.52%) than in NC-FET (19.67%) and in mNC-FET (19.39%). At Post hoc analysis only female age (OR 0.91-0.95), antimullerian hormone (AMH) (OR 1.01-1.07) and mNC-FET (OR 1.39-1.98) were statically significant prognostic factors for LBRs. Levi Setti et al. Preparation Protocols in Frozen Embryotransfer Conclusions: These results demonstrate a superior CPR and LBR following FET in hCG-triggered ovulation cycles compared to NC and AR-FET, a higher ectopic pregnancy rate in NC-FET and a higher abortion rate in pregnancies <12 weeks in AR-FET. However, these data need to be confirmed in randomized and prospective studies before definitive conclusions can be drawn.

Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles)

“…Previous studies have reported that the early pregnancy loss rate in FET was higher when using the AC protocol compared to NC or SC ( Veleva et al , 2008 ; Tomás et al , 2012 ; Cerrillo et al , 2017 ; Peigné et al , 2019 ; Liu et al , 2020 ; Levi Setti et al , 2020 ). A 7-year study of vitrified blastocyst transfers found that the risk of early pregnancy loss was higher using AC compared to NC or modified NC with ovulation triggering ( Levi Setti et al , 2020 ). Similarly, a retrospective study of 1846 normally ovulating patients also reported that the early pregnancy loss rate was significantly higher with AC than with NC ( Liu et al , 2020 ).…”

Treatment outcomes of blastocysts thaw cycles, comparing the presence and absence of a corpus luteum: a systematic review and meta-analysis

“…After screening by title and abstract, we reviewed 20 full-text and included an additional 4 articles from the reference lists of included articles and previous systematic reviews. We included nine studies in our final quantitative analysis 10 16 20–26. Two of which were RCTs22 23 both of which studied small sample sizes.…”

Effect of endometrial preparation protocols on the risk of ectopic pregnancy for frozen embryo transfer

“…Although many studies have investigated endometrial preparation protocols and pregnancy and live birth rates 27 – 29 , only a limited number of studies with conflicting results have investigated endometrial preparation protocols and the risk of EP 12 , 18 , 19 . Importantly, these studies did not specifically investigate endometrial preparation protocols and targeted other factors.…”

“…However, another Chinese study investigating the association between body mass index and EP using retrospective data (n = 16,378 pregnancies) demonstrated no significant associations between endometrial preparation protocols and the risk of EP for frozen cycles 18 . Furthermore, a retrospective analysis of clinical pregnancies in Italy following single blastocyst ETs with different endometrial preparation protocols demonstrated a significantly higher EP rate for natural cycles (6/561, 3.28%) than HRC (4/585, 1.83%) and modified natural cycles (3/1749, 0.4%) 19 . Our study, using the largest sample of subjects with single frozen-thawed ET cycles demonstrated that the risk of EP did not differ for HRC compared with natural cycles.…”

“…To date, only a few studies reported an association between endometrial preparation protocols on EP and results were conflicting 12 , 18 , 19 . In China, recent studies investigating the effect of endometrial thickness on EP in frozen-thawed ET cycles reported that the EP rate for HRC cycles was more than double the rate for natural cycles (4.7% vs. 2.1%, respectively) 12 .…”