Does the addition of luteal function support drug benefit pregnancy and perinatal outcome in modified natural cycle frozen thawed embryo transfer in women under the age of 35- year-old?

Abstract Background:In the freeze-thaw embryo transfer, the use of best luteal phase support protocols is continuously being discussed, especially in the natural cycles. Previous comparisons of luteal phase support protocols in natural cycles focused on pregnancy outcome, with less attention to perinatal outcome. Thus, convincing conclusion about which protocol is more appropriate could not be drawn. At the same time, with increasing luteal support drugs, the benefit of using these drugs also needs evidence. Methods: The clinical data of 3658 mNC-FET cycles in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 with the participants’ age of less than or equal to 35 years old，were retrospectively analyzed. The cycles were divided into three groups based on luteal phase support protocols used. The patients received a combination of progesterone soft capsule and dydrogesterone in the group A (882 cycles), the patients received dydrogesterone in the group B (627cycles), and the patients received a combination of progesterone vaginal sustained-release gel and dydrogesterone in the group C (2149 cycles). Pregnancy and perinatal outcomes in the group A, group B, and group C were compared. Results: HCG positive rate, clinical pregnancy rate, and implantation rate were higher in the group B than in the groups A and C （67.30% vs. 57.37% and 61.05%; 64.43% vs. 55.67 % and 57.88 %; 54.83 % vs 42.70 % and 45.92 %）. The 12-week pregnancy rate and live birth rate in the group B were higher than those in the group A （56.30% vs. 49.55%；53.26% vs. 46.83%）. There were no significant differences in newborn weight, premature delivery rate, pregnancy complications rate, and incidence of birth defects among the three groups. Logistic regression analyses showed that three different luteal phase support regimens were not associated with live birth rate （0R 95% CI B VS. A=1.23，P=0.056；0R 95%CI B VS. A=1.07，P=0.374）. Conclusions: In the mNC-FET cycle, patients younger than or equal to 35 years of age, who chose dydrogesterone alone as luteal support drug, had no difference in live birth rate and perinatal outcome between progesterone soft capsules or progesterone vaginal sustained-release gel combined with dydrogesterone, but the outcome still needs to be confirmed by large sample prospective studies.