A Prospective Randomized Controlled Study Of HCG Supplementation For Frozen And Thawed Embryo Transfer In HRT Cycles

Background:Assisted reproductive technology（ART）is currently the most effective treatment for infertility.With the maturation of embryo vitrification cryopreservation technology and clinical need,such as ovarian hyperstimulation syndrome（OHSS）,preimplantation genetic testing（PGT）and fertility preservation,frozen embryo transfer（FET）has become an important part of ART.How to improve the synchrony of embryo implantation competent and endometrium receptivity in FET cycle to raise embryo implantation rate and clinical pregnancy rate has become a hot topic in reproduction.In FET cycle,both hormone replacement therapy（HRT）and natural cycle（NC）therapy are regular endometrial preparation protocol.Due to the fewer number of returning patients and easy to control,HRT cycle is commonly used in clinical preparation of endometrium.Human chorionic gonadotropin（HCG）,benefit from its unique molecular structure,plays the role in luteal support and also the immune regulation of embryo implantation and maternal-fetal interaction.Previous views on the effectiveness of HCG addition on HRT-FET cycle are not uniform.This research aims to clarify whether HCG can improve the pregnancy outcome in HRT-FET cycle through a prospective randomized controlled study.Objectives of the Study:Whether adding HCG to the HRT-FET cycle for luteal support can improve pregnancy outcome.Study design:Prospective randomized controlled study.Materials and Methods:Patients who underwent FET in the reproductive center Northwest Women and Children’s Hospital from October 31,2019 to November 1,2018were included in the study.Inclusion criteria:1.Female age under 40 years-old;2.The first FET cycle.3.Preparation of endometrium by HRT（including GnRH-a+HRT cycle）.Exclusion criteria:1.Endometriosis;2.Uterine malformations;3.Endometrial thickness<8 mm on the transformation day;4.Patients that have been included in other studies.All enrolled patients were divided into a study group（group A）and control group（group B）according to the random numbers generated by the computer on the day of transformation and signed informed consent.The control group the routine luteal support therapy for luteal support.In the study group,2000 IU HCG was injected intramuscular on the third day of progesterone administration and then injected every 48h for consecutive 4 times.Results:300 patients that complete transplantation and follow up were included in this study.124 cases in group A and 121 cases in group B.1.Basic characteristics:There was no significant difference between the two groups in age、duration of infertility、cause of infertility、infertility type、AFC、BMI、bFSH（P>0.05）.2.Laboratory characteristics:There was no significant difference between the two groups in the fertilization type、E₂ level on HCG day、the number of oocytes retrieved、the available embryos rate and high quality embryos rate（P>0.05）.3.Clinical outcome in FET cycle:In FET cycle,the age and average number of embryos transferred in group A was significantly higher than group B,and there was a statistical difference between the two groups（P<0.05）.The percentage of blastocyst-stage embryo transfer in group A was significantly lower than that in group B（77.42%vs88.43%,P<0.05）.The embryo implantation rate in group A was lower than that in group B（58.97%vs 70.07%,P>0.05）,however,there was no statistical difference.The clinical pregnancy rate of group A was lower than group B（66.94%vs 74.38%,P>0.05）,without significant difference.The spontaneous abortion rate of group A was lower than group B（8.43%vs 8.89%,P>0.05）,no statistical difference.4.The clinical outcome of FET cycle in cleavage-stage embryo:The average number of transferred embryos in group A was more than that in group B,but the implantation rate（39.13%vs 55.00%,P>0.05）and clinical pregnancy rate（57.14%vs71.43%,P>0.05）in group A were lower than those in group B,there was no statistical difference in both items.The abortion rate of group A was higher than that in group B（18.75%vs 10.00%,P>0.05）,without statistical difference.5.The clinical outcome of FET cycle in blastocyst-stage embryo:The average number of blastocysts transferred in group A was more than that in group B,but the implantation rate（67.27%vs 72.65%,P>0.05）and clinical pregnancy rate（69.79%vs74.77%,P>0.05）in group A were both lower than those in group B,without statistical difference.The abortion rate of group A was lower than group B（5.97%vs 8.75%,P>0.05）without difference.6.Clinical outcome in HRT-FET cycle:In HRT-FET cycle,the average number of embryos transferred in group A was significantly higher than group B,and there was a statistical difference between the two groups（P<0.05）.The percentage of blastocyst-stage embryo transfer in group A was significantly lower than that in group B（77.17%vs90.48%,P<0.05）.The embryo implantation rate in group A was lower than that in group B（55.56%vs 68.13%,P>0.05）,however,there was no statistical difference.The clinical pregnancy rate of group A was lower than group B（65.22%vs 70.24%,P>0.05）,without significant difference.The spontaneous abortion rate of group A was lower than group B（10.00%vs 6.78%,P>0.05）,no statistical difference.7.Clinical outcome in GnRH-a+HRT-FET cycle:In GnRH-a+HRT-FET cycle,the average number of embryos transferred in group A was similar than group B,and there was no statistical difference between the two groups（P>0.05）.The percentage of blastocyst-stage embryo transfer in group A was lower than that in group B（78.13%vs83.78%,P>0.05）.The embryo implantation rate in group A was lower than that in group B（69.23%vs 73.91%,P>0.05）,however,there was no statistical difference.The clinical pregnancy rate of group A was lower than group B（71.88%vs 83.78%,P>0.05）,without significant difference.The spontaneous abortion rate of group A was lower than group B（4.35%vs 12.90%,P>0.05）,no statistical difference.8.Binary logistic regression analysis:A binary logistic regression model was constructed by forward method.The statistical value of Hosmer and Lemeshow test fitχ²of the model was 1.758（P=0.972）.The model could well fit the data（P>0.05）,excluding the average number of embryos transferred and the confounding factors of embryo types.The results showed that:The mean number of transferred embryos（OR=0.343,95%CI[0.140-0.840],P<0.05）and the type of transferred embryos（OR=2.391,95%CI[1.051-5.439],P<0.05）had significant effect on the clinical pregnancy rate.Conclusion:The use of HCG for luteal support could not improve the clinical outcome of HRT endometrial preparation protocol in FET cycle.