The Effectiveness Of Different Down-regulating Protocols On In Vitro Fertilization-embryo Transfer In Endometriosis:a Meta-analysis

Background and ObjectiveEndometriosis(EMT)refers to the presence of active endometrial tissue(glands and stroma)outside the uterine body,which is more common in women of childbearing age.Although endometriosis is a benign hormone-dependent disease,it has malignant clinical behaviors such as invasion,implantation,metastasis and recurrence.Ectopic endometrium can invade any part of the body,and the main clinical manifestations are pain and infertility.At present,endometriosis-related infertility has become one of the important causes of infertility in women of childbearing age.With the continuous improvement of infertility treatment strategy,in vitro fertilization-embryo transfer(IVF-ET)has been gradually recommended by many scholars to improve the pregnancy outcome of infertility patients with endometriosis,but the impact of different down-regulation protocols on pregnancy outcome is still controversial.Therefore,this paper systematically evaluated the effectiveness of GnRH-a ultra-long protocol,GnRH-a long protocol and GnRH-a short protocol in the treatment of IVF-ET in infertile patients with endometriosis through the meta-analysis,and the aim was to screen out the optimal treatment option.MethodsWe performed literatures searched in PubMed,EMbase,Web of science,Cochrane Library,Elsevier Science Direct,OA Library,Google Scholar,CNKI,Wan-fang Database,VIP Chinese Science and Technology journal Database and Chinese Biomedical Literature Database by computer,and the literatures were a published randomized controlled trials(RCTs)and cohort studies(non-RCTs)on the efficacy of GnRH-a ultra-long protocol,GnRH-a long protocol and GnRH-a short protocol in IVF-ET treatment of infertile patients with endometriosis.The supplementary literatures were obtained by manual retrieval of relevant journals and reference backtracking,and the search time was from the establishment of the database to August 2019.All literatures obtained were screened strictly according to the inclusion and exclusion criteria.The bias risk assessment tool of the Cochrane Collaboration was used to assess the RCT studies,and the quality evaluation of non-RCT studies by NOS scale.Statistical analysis was performed using Review Manager 5.3 software.ResultsA total of 21 studies were included(seven randomized controlled trials and 14 cohort studies).The subgroup analysis was performed for RCTs and non-RCTs.1.In the RCT studies,compared with the GnRH-a long protocol group,the clinical pregnancy rate(RR?1.44,95%CI:1.21?1.72,P<0.0001)and implantation rate(RR=1.47,95%CI:1.13?1.90,P=0.004)in the ultra-long protocol group were significantly improved,but there were no significant differences between the two groups in the fertilization rate,basal FSH,stimulation duration,dose of gonadotropin and number of oocytes retrieved(P>0.05).2.In the non-RCT studies,the implantation rate(RR=1.18,95%CI:1.05?1.31,P=0.004),stimulation duration(SMD=0.53,95%CI:0.22?0.83,P=0.0007)and dose of gonadotropin(SMD=0.54,95%CI:0.32?0.76,P<0.00001)of the ultra-long protocol group were higher than those of the long protocol group,but there were no significant differences in the clinical pregnancy rate,fertilization rate,basic FSH and number of oocytes retrieved for these two groups(P>0.05).3.In the non-RCT studies,the clinical pregnancy rate(RR=1.78,95%CI:1.07?2.97,P=0.03),fertilization rate(RR=1.19,95%CI:1.01?1.40,P=0.04),stimulation duration(SMD=0.87,95%CI:0.29?1.44,P=0.003)and number of oocytes retrieved(SMD=0.50,95%CI:0.27?0.74,P<0.0001)of the ultra-long protocol group were higher than those of the short protocol group.However,the two groups in implantation rate,basic FSH and dose of gonadotropin were no statistical difference(P>0.05).4.In the RCT studies,the clinical pregnancy rate of patients with stage ?-?endometriosis in the ultra-long protocol group was higher than that of the long protocol group,and the difference between the two groups was statistically significant(RR=2.04,95%CI:1.37?3.04,P=0.0005).Conclusions1.Compared with the GnRH-a long protocol,the GnRH-a ultra-long protocol can significantly improve the pregnancy outcome of infertile patients with endometriosis,especially for patients in stage ?-?.2.For endometriosis patients at stage ?-? with infertility,the GnRH-a long protocol seems to be a more reasonable down-regulating protocol.