P-362 Pregnancy outcomes of frozen-thawed single euploid blastocyst transfers after endometrial preparation with natural cycle, letrozole use, or programmed cycle
Authors: Han S J , Park E A , Lee J H , Kim Y S , Kim H O , Lee H C , Kim M J , Yu E J , Hur Y J , Kim Y I , Yoon T K 
Published: June 2023

Study question

Is natural cycle the best protocol for endometrial preparation in frozen-thawed single euploid blastocyst transfers?

Summary answer

Clinical and ongoing pregnancy were comparable between endometrial preparation methods although programmed cycle was associated with a higher risk of miscarriage compared to natural cycle.

What is known already

Utilization of frozen-thawed single euploid embryo transfers based on PGT-A have been substantially increased recently, but there are still no firm conclusions on the optimal protocol in frozen-thawed embryo transfers (FETs). Even so, significant concerns have been raised about maternal and fetal safety associated with the programmed cycles and several favorable outcomes of natural cycles and letrozole use in FETs have been suggested in recent years. Pregnancy outcomes after endometrial preparation with natural cycle, letrozole use, programmed cycles have not been compared in euploid blastocyst FETs.

Study design, size, duration

This was a retrospective cohort study at a single center including FET cycles from January 2019 to October 2021.

Participants/materials, setting, methods

A total of 708 frozen-thawed single euploid blastocyst transfer cycles were analyzed. Endometrial preparation was performed using natural cycle with hCG trigger (n = 60), ovulation induction with letrozole (n = 32), or programmed cycle (n = 616) at the discretion of each attending physician. Pregnancy outcomes including clinical pregnancy, ongoing pregnancy, and miscarriage were calculated using multivariable logistic regression.

Main results and the role of chance

The three groups were similar for age, BMI, basal FSH, TSH, AMH levels, PGT-A indications, presence of ovulatory dysfunction, endometrial thickness on the starting day of progesterone supplementation, and the proportion of good quality embryo transferred. The crude clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate were not different among the groups (55.0% vs. 68.9% vs. 61.9%, p = 0.40; 51.7% vs. 59.4% vs. 50.0%, p = 0.58; 6.1% vs. 13.6% vs. 20.4%, p = 0.11, respectively). After adjusting for confounders, clinical pregnancy and ongoing pregnancy outcomes of natural cycle were similar to that of letrozole cycle and programmed cycle. However, programmed cycle was associated with significantly higher odds of miscarriage compared to natural cycle (aOR 4.33, 95% CI 1.01-18.58).

Limitations, reasons for caution

This was not an intention-to-treat study due to its retrospective design. Another limitation of this study includes a small sample size and risk of patient selection bias for indication of PGT-A.

Wider implications of the findings

Natural cycle and ovulation induction with letrozole may be safely and effectively carried out for endometrial preparation in patients undergoing single euploid FETs.

Trial registration number

not applicable