Efficacy Analysis Of Antagonist Protocol Compared With Modified Ultra-long Protocol For Fresh Cycle In Patients With High Ovarian Response

After decades of development,assisted reproductive technology(ART)has gradually become the main way to solve fertility problems in infertile patients.In the ART cycle,patients with high ovarian response account for about 3% to 8%,because the high number of retrieved oocytes in Controlled Ovarian Hyperstimulation(COH)is accompanied by an increase in the incidence of ovarian hyperstimulation(OHSS),and at the same time,high steroid hormone levels will also have adverse effects on endometrial receptivity.Therefore,it is particularly important to choose a suitable COH protocol to achieve good pregnancy outcomes while avoiding the occurrence of OHSS as far as possible.Therefore,in recent years,it has become one of the most important issues in the process of superovulation.In recent years,more and more antagonist protocol have been used in patients with high ovarian response.However,it is still controversial whether the antagonist protocol can achieve better clinical outcomes while reducing Gn dosage and the incidence of moderate to severe OHSS in patients with high ovarian response.Studies have shown that GnRH-a modified super-long protocol(modified super-long protocol)combined with human menopausal gonadotropin(HMG)can significantly improve endometrial receptivity in patients with high ovarian response(e.g.PCOS patients),thereby improving embryo implantation rate and pregnancy rate.Therefore,the purpose of this study is to clarify the effects of antagonist protocol and modified super-long protocol on pregnancy outcomes and endometrial receptivity in patients with high ovarian response,and to explore the application value of two COH protocol in ovarian hyperresponsiveness patients.Part I.Comparison of the clinical efficacy of antagonist protocol and modified super-long protocol in IVF/ICSI-ET with high ovarian responseObjective: To compare the value of gonadotropin-releasing hormone antagonist(GnRH-ant)protocol and modified ultra-long protocol in patients with high ovarian response.Methods: To retrospectively analyze patients with high ovarian response with IVF/ICSI(number of retrieved oocytes >15)A total of 853 cycles.According to the ovulation induction protocol,they are divided into two groups.Among them,the GnRH-ant group had a total of 186 cycles,and the modified super-long group had a total of 667 cycles.The general condition and clinical outcome of the patients were compared.Results: The total Gn used dosage and duration were significantly lower in the antagonist group as compared to the modified super-long group(P<0.05).The number of retrieved oocytes and the level of serum E2 in HCG day were statistically significantly higher in the antagonist group(P<0.05).The P/E2 value of HCG day was statistically significantly lower in the antagonist group(P<0.05).The implantation rate,clinical pregnancy rate and live birth rate were significantly lower in the antagonist group as compared to the modified super-long group(P<0.05).The incidence of moderate and severe OHSS and cancellation rate of transplantation were statistically significantly lower in the antagonist group(P<0.05).Conclusions: The clinical outcome of the antagonist protocol in patients with high ovarian response is significantly lower than that of the modified ultra-long protocol,which may be related to the reduction of endometrial receptivity,so it should be considered whole embryo cryopreservation and thawing transplantation to reduce the risk of OHSS at the same time there is a good pregnancy outcome.Part II.Comparison of the effects of antagonist protocol and modified super-long protocol on endometrial receptivity with high ovarian response during implantation.Objective: To investigate the effects of antagonist protocol and modified super-long protocol on endometrial receptivity in patients with high ovarian response during implantation.Methods: Endometrial tissues of patients with high ovarian response,antagonist protocol and modified super-long protocol were selected as specimens.HE staining was used for histological classification;SEM was used to observe the changes of endometrial ultrastructure-pinopodes process expression;IHC,q PCR and Western-Blot were used to detect the expression of LIF factor and HOXA10 protein in endometrium of patients with different cycles.Results: Compared with the modified super-long group,the number of pinocytes in the antagonist group decreased and the development of pinopodes was incomplete.The expression of LIF and HOXA10 in the antagonist group decreased significantly.The results were further confirmed by Western-Blot and density analysis.Conclusions: In the population with high ovarian response,compared with the modified ultra-long protocol,the antagonist protocol reduced the endometrial receptivity of patients with high ovarian response by down-regulating the expression levels of pinocytosis,HOXA10 and LIF on the uterine membrane during implantation.