Effect Of Different Luteal Support Program On The Pregnancy Outcome Of Frozen Embryo Transfer

Background:Appropriate endometrial receptivity is the key to embryo implantation and development.Progesterone plays significant roles in endometrial implantation preparation and also trophoblast invasion and migration regulation.However.it could be badly influenced in the luteal phase due to the implicated treatments during the in vitro assisted pregnancy such as controlled ovarian stimulation(COS).negative pressure puncture and egg retrieval,resulting in insufficient secretion of estrogen and progesterone,and showing adverse effects on the implantation of embryos and maintenance of early pregnancy.As a result,corpus luteum support is essential for obtaining and maintaining pregnancy for patients undergoing assisted pregnancy’treatment.In most reproductive centers,progesterone combined with dydrogesterone is currently the most common protocol of luteal support after embryo transfer and is continuously administered until 10-12 weeks of pregnancy.However,there is currently no uniform standard for the use and dosage of luteal support.Most of the optimal time and dosage of luteal support are empirical,which may adversely affect embryo implantation and decidual formation.Objective:To determine whether the program of different luteal support drugs under different methods of endometrial preparations has an effect on pregnancy outcome.Study design:We analyzed all data from women who underwent in vitro fertilization(IVF)/intracytoplasmic sperm Injection(ICSI)-frozen embryo transfer(FET)and oral/vaginal progesterone support luteal stage from January 2017 to May 2020 in our hospital.A total of 8659 cycles were included in this study and divided into three groups(natural cycle(A),ovulation cycle(B),and hormone replacement therapy with or without GnRHa downregulation(C))based on the different endometrial preparation methods,each of which was then divided into differe.nt subgroups according to different luteal support program(natural cycle A1,natural cycleA2;ovulation cycle B1,ovulation cycle B2).In this context,the cycles treated with simple hormone replacement or hormone replacement combined with down-regulation were grouped together since their luteal support programs were consistent.The basic clinical characteristics(age,body mass index(BMI),)and pregnancy follow-up records were collected and compared in the different luteal phase support groups.Biochemical pregnancy rate,clinical pregnancy rate and early abortion rate were taken as main Outcome Measures.Logistic regression analysis was performed to correct the factors with statistically significant differences in baseline data characteristics of patients within each group(P<0.05)to eliminate the confounding influence of baseline data on pregnancy outcomes.Results:In this paper we analyzed the influence of luteal support programs on the pregnancy outcome to provide guidance for clinical medication programs.The results indicated that different progesterone drugs widely used for luteal support showed similar effects.For patients undergoing natural cycle and ovulation stimulation cycle,no significant difference of pregnancy outcome was observed when treated with different dosage of Duphaston or Yimaxin.the biochemical pregnancy rate,clinical pregnancy rate and early abortion rate were 68.95 ± 1.36%(P=0.528),61.25 ± 1.06%(P=0.713)and 11.78±1.56%(P=0.224);69.13±3.51%(P=0.613),58.48± 3.99%(P=0.569),11.45 ± 4.04%(P=0.620).Additionally,when patients were treated with combined medication of Duphaston and Utrogestan with different Utrogestan fractions,the efficacy still kept consistent,the biochemical pregnancy rate,clinical pregnancy rate and early abortion rate were 70.22± 1.79%(P=0.511),61.77±0.57%(P=0.952)and 12.30±3.05%(P=0.141);66.87 ± 8.65%(P=0.150),57.67±10.87%(P=0.069).17.33±7.94%(P=0.105).Indicating that the change of the medication in either single drug treatment program or combination treatment program made little difference to the pregnancy outcome.For patients undergoing hormone replacement therapy cycle with or without GnRH-a down-regulation,the combined medication of the Duphaston and Utrogestan or Duphaston and Crinone presented with higher clinical pregnancy rate((60.8%.55.8%,47.9%;P=0.002)than the single medication of Duphaston.Conclusions:1.This retrospective analysis shows that clinically commonly used progesterone drugs and medication programs have equivalent effects in the process of luteal support.Lower dosages of progesterone can achieve pregnancy outcomes similar to high dosages of progesterone.2.For patients with natural cycle and Ovulation stimulation cycle,a single low-dose progesterone drug can be used for luteal support.It is recommended to combine at least two progesterone drugs for better pregnancy outcome in patients undergoing artificial endometrial preparation.