GnRH Antagonist Protocol Compared To The Standard Long Protocol Of GnRH Agonist For IVF-ET:A Systematic Review And Meta-analysis

BackgroundControlled ovarian stimulation(COS)is a crucial step in IVF-ET,during which GnRH antagonist protocol and the standard long protocol of GnRH agonist(GnRHa)are most commonly used to prevent premature LH surges and to retrieve more oocytes.In contrast to the long protocol,antagonist protocol needs shorter duration of stimulation,less dose,less cost along with fewer side effects.Since the emergence and development of antagonist protocol,the choice of these two protocols is always controversial.In the recent five years several reports showed that antagonist protocol does not reduce the effectiveness of IVF-ET.Nowadays antagonist protocol has become a common choice in many reproductive centers abroad,while in our country the long protocol remains the routine choice.ObjectivesThis study aims to evaluate the effectiveness and safety of GnRH antagonist protocol compared with the standard long protocol of GnRH agonist for IVF-ET through systematic review and meta-analysis.Methods1.Infertile couples undergoing IVF/ICSI treatment were selected as participants.The RCTs which compared GnRH antagonist protocol with the long protocol of GnRH agonist were included.The primary outcomes were measured by live birth rate and OHSS rate,and the secondary outcomes were compared using ongoing pregnancy rate,clinical pregnancy rate and miscarrige rate.Subgroup analyses were performed according to women's ovarian response.2.Cochrane Central Register of Controlled Trials(CENTRAL),MEDLINE,EMBASE,PubMed were searched updated to January 22,2018.Articles of relevant publications and abstracts of major scientific meetings were manually searched.3.After initial and full-text screening among the literatures retrieved with inclusion and exclusion criteria,the quality of studies was assessed.Then the extracted data was meta-analyzed with RevMan 5.3.Results54 RCTs,10362 participants were included,and the meta-analysis showed that:1.Twelve trials reported live birth rates in 3454 women.There was no evidence of a difference between GnRH antagonist protocol and the long protocol(RR 1.02,95%CI 0.91~1.14,I~2=21%).Three trials(634 women)in the high responder group and two(180 women)in low,in which neither comparison was statistically significant.2.Twenty-nine studies reported OHSS rates in 6572 women.GnRH antagonist protocol was associated with lower OHSS rate than the long protocol(RR 0.58,95%CI 0.49~0.70,I~2=6%).A subgroup analysis showed that in the high responder group(9 studies,1221 women),antagonist protocol significantly reduced the risk of OHSS(RR 0.34,95%CI 0.22~0.53,I~2=39%),whereas in the normal responder group(2studies,326 women)the difference was not statistically significant.3.There was no evidence of a difference between the two protocols in ongoing pregnancy rate,clinical pregnancy rate and miscarrige rate.Conclusions1.The effectiveness of GnRH antagonist protocol is comparable with the standard long protocol of GnRH agonist.2.Compared with the long protocol,GnRH antagonist protocol can significantly reduce the risk of OHSS and improve the safety of IVF-ET eventually.The conclusions supported wider use of GnRH antagonist protocol.In order to provide more economical and convenient treatment,improving COS protocols should be the goals for clinicians.In addition,a more convincing arguement to widen the use of antagonist protocol in our country needs more high-qualitied RCTs,which requires larger samples and higher quality RCTs,to provide theoretical evidence for COS protocol choosing,and to guide the ongoing improvement for clinical work.