| Chapter ⅠThe impact of dual trigger(GnRH agonist and hCG)and hCG trigger on embryonic development and pregnancy outcomeBackground:Triggering the final maturation of oocytes and ovulating are the very important steps during the assisted reproductive technology(ART),so human chorionic gonadotropin(hCG)has been used as a classic trigger instead of endogenous luteinizing hormone(LH)for a long time.However,due to the long half-life of hCG,the LH activity it induced can lead to ovarian hyperstimulation syndrome(OHSS),which brings serious adverse consequences to healthy women who are receiving infertility treatment.Since studies have reported that the use of gonadotropin releasing hormone agonist(GnRHa)can reduce the risk of OHSS,GnRHa trigger has become more widely used.Nevertheless,compared with hCG triggers,the implantation rate,pregnancy rate and persistent pregnancy rate of GnRHa trigger are lower.How to improve the outcome of assisted reproduction without increasing the risk of OHSS is an urgent problem for clinicians.This chapter mainly compares the effect of different doses of hCG combined with GnRHa or not on patients’ pregnancy outcome.Methods:The data of 3888 infertile patients who received assisted reproductive technology at the Reproductive Hospital of Shandong University from January 2015 to January 2019 and applied antagonist protocol to stimulate ovarian were selected for retrospective analysis.The data was divided into 4 groups according to the different doses of hCG,group A:2000～4000IU hCG,group B:5000～6000IU hCG,group C:7000～8000IU hCG and group D:10000～12000IU hCG.Each group was futher divided into hCG alone trigger(hCG subgroup)and dual trigger with a combination of GnRH agonist and hCG(GnRHa+hCG subgroup),and subgroup analysis was carried out.Results:1.In all groups,there were no statistical significances in biochemical pregnancy rate,clinical pregnancy rate,live birth rate,cumulative live birth rate,abortion rate and ectopic pregnancy rate between hCG subgroups and GnRHa+hCG subgroups(P>0.05).2.In the group of hCG at the dosages of 5000～6000IU and 7000～8000IU,the number of oocytes retrieved,the number of double-pronuclear and Day-3(D3)high-quality embryos in hCG subgroups were lower significantly than those in GnRHa+hCG subgroups(P<0.05).3.There was no statistical significance in the proportion of the cancellation of fresh embryo transfer due to various reasons between the two trigger schemes(P>0.05).After group comparison,the main reason for cancellation of fresh embryo transfer in the group of hCG at the dosages of 2000～4000IU and 5000～6000IU was the prevention of OHSS,while for the dosages of 7000～8000IU and 10000～12000IU,the main reason was the embryo factor.Conclusion:There is no difference in patients’ pregnancy outcome of fresh embryo transfer and cumulative live birth rate between hCG trigger and dual trigger,but for patients given 5000～8000IU hCG on trigger day,dual trigger can improve the number of oocytes retrieved,promote the production of double-pronuclear and improve the quality of embryos.Chapter ⅡThe impact of trigger day with or without GnRH antagonist on embryonic development and pregnancy outcomeBackground:In recent years,the application of gonadotropin releasing hormone antagonist(GnRHant)protocols in controlled ovarian stimulation in assisted reproductive shows a growing trend.GnRH antagonist can immediately block the luteinizing hormone secretion in pituitary cell.Compared with GnRH agonist,GnRH antagonist has no "flare-up" effect,short treatment time,flexible adding time and low incidence of ovarian hyperstimulation syndrome.Clinical experience has proved that it is safe and well tolerated.GnRH antagonist is usually used on trigger day to prevent early ovulation.However,there is no clear conclusion as to whether the antagonist will continue to be used on trigger day,whether the extra dose of GnRH antagonist will reduce the rate of early ovulation,whether it will affect the function of follicular granulosa cells,reduce the response to human chorionic gonadotropin,and then affect the quality of oocyte and pregnancy outcome.In order to answer the above questions,this study will compare the GnRH antagonist protocol with and without GnRH antagonist on trigger day,and analyze its effects on embryonic development and pregnancy outcome in patients with different ovarian reserve.Methods:According to the inclusion and exclusion criteria,a total of 2394 infertile patients who underwent assisted reproductive technologies cycles in Reproductive Hospital of Shandong University from January 2015 to January 2019 were included in this retrospective cohort study.According to the condition of ovarian reserve,the patients were divided into two groups:decreased ovarian reserve group(group A,663 cycles)and non-decreased ovarian reserve group(group B,1731 cycles).According to whether or not to use GnRH antagonist on trigger day,each group was further divided into two subgroups:GnRHant subgroup and non-GnRHant subgroup.According to the Bologna Criteria,we define the decrease ovarian reserve as:the basal antral follicle count<7 or anti-Mullerian hormone<1.1 ng/mL.Results:1.For patients with decreased ovarian reserves,the number of oocytes retrieved,the number of double-pronuclear and D3 high-quality embryos in GnRHant subgroup were significantly lower than those in non-GnRHant subgroup after adjusting the age factors(P<0.05).There were no statistical significances in biochemical pregnancy rate,clinical pregnancy rate,live birth rate,cumulative live birth rate,abortion rate and ectopic pregnancy rate between two subgroups(P>0.05).2.For patients with non-decreased ovarian reserves,there were no statistical significances in embryo logical and pregnancy outcomes above mentioned between two subgroups after adjusting the age factors(P>0.05).3.There was no statistical significance in the proportion of the cancellation of fresh embryo transfer due to various reasons between two subgroups.After group comparison,the main reason for cancellation of fresh embryo transfer in the decreased ovarian reserve group were the early ovulation and embryo factor,while for non-decreased ovarian reserve group,the main reason were the prevention of OHSS and embryo factor.Conclusion:The results indicate that the use of GnRH antagonist on trigger day neither significantly reduce the patients’ early ovulation rate nor change the pregnancy outcome of fresh embryo transfer and cumulative live birth rate.But for patients with decreased ovarian reserve,the use of GnRH antagonist on trigger day can reduce the number of oocytes retrieved,effect fertilization and the quality of embryos. |
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