| Background: According to a survey released by the China Population Association,the number of infertile couples in my country is increasing rapidly in China.They suffer from psychological problems due to the negative influence from their families and the social opinion,and even become less enthusiastic about life and appear world-weary.However,assisted reproductive technology has brought good news to infertile couples.The freeze-thaw embryo transfer(FET)cycles offer certain advantages to patients including higher cumulative pregnancy rates and less complications.Under the conditions of cryopreservation with an uncontrollable quality of the embryos,the quality of the endometrium directly affects the success of the FET technology.Various methods of endometrium preparation have been widely used in clinical practice.However,due to a lack of research based on molecular mechanisms,there has been controversy as to the endometrial preparation program for a maximum of the pregnancy rate and live birth rate.Objective: A combination of clinical and basic researche is adopted to study the clinical efficacy and mechanism of Gn RH-a in the FET cycles and explore the optimal programme of endometrial preparation for patients in FET cycles.Methods: The current study retrospectively analyzed 1,589 patients in FET cycles in our hospital in recent years were given a retrospective analysis.Subjects were assigned to 6 groups as follows: group HT received oestradiol(E2)and progesterone(P4)(n=338);group HT+ 1 Gn RH-a received 1 cycle of Gn RH-a,E2,and P4(n=323);HT+ 2 Gn RH-a received 2 cycles of Gn RH-a,E2,and P4(n=329);group HT+ 3 Gn RH-a received 3 cycles of Gn RH-a,E2,and P4(n=323);group HT+ 4 Gn RH-a received 4 cycles of Gn RH-a,E2,and P4(n=316);group HT+ 5 Gn RH-a received 5 cycles of Gn RH-a,E2,and P4(n=313).The data of clinical pregnancy outcome and subendometrial blood flow parameters on the embryo transfer day in each group were collected and analyzed.At the same time,part of the endometrial tissues at the luteal phase or on the day of embryo transfer were collected to assess the endometrial receptivity.Finally,an in vitro cell model was used to study the effect and mechanism of Gn RH-a pretreatment on the proliferation,receptivity and decidualization of human endometrial cells.Results: 1.The HT+3 Gn RH-a group has better clinical pregnancy outcomes and endometrial receptivity,mainly manifested in: 1)higher embryo implantation rate,clinical pregnancy rate and live birth rate;2)better subendometrial blood perfusion on the day of embryo transfer;3)a higher expression level of the receptivity marker molecules like LIF,integrin b3,OPN,and Hoxa10 etc.in the endometrial tissue on the day of transplantation are higher;4)mi RNAs such as mi R-125b-5p,mi R-223-3p,mi R-27a-3p to restrain the endometrial receptivity in both the endometrial tissue and the serum on the day of transplantation have lower expression.2.Despite the endometrial cell apoptosis induced by Gn RH-a through the mitochondrial pathway,Little influence on the proliferation of endometrial cells is exerted by Gn RH-a when estrogen and progesterone are combined.3.Gn RH-a pretreatment can promote the expression of receptivity marker molecules in endometrial cells,especially glandular epithelial cells.4.Gn RH-a can promote the decidualization of human endometrial stromal cells in a time-dependent manner,and it is ERK1/2 dependent.Conclusion: The above studies indicate that the three-cycle Gn RH-a down-regulation for endometrial preparation in the freeze-thaw embryo transfer cycle may be the best choice,but the randomized controlled trials and molecular regulation mechanisms for this subject need to be studied in depth.In summary,this article provides a clinical reference and theoretical support for the choice of endometrial preparation methods in the freeze-thaw embryo transfer cycle,and lays a solid foundation for further improving the clinical pregnancy rate,alleviating the pressure from infertility,and promoting harmony in families and society. |
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