不同年龄段人群三种促排卵方案胚胎发育及临床结局比较

Comparative Study of the Embryo Development and Clinical Outcomes of 3 Ovarian Stimulation Protocols in Different Age Groups

目的 比较不同年龄段人群使用促性腺激素释放激素(gonadotropin releasing hormone, GnRH)拮抗剂方案、GnRH激动剂长方案与早卵泡期长方案进行体外受精(IVF)过程中的胚胎发育及临床结局情况。方法 回顾性纳入2021年1月–2023年2月期间收治的患者。(1)在总人群中,对三种促排方案[拮抗剂方案组(4 173例),激动剂长方案组(2 410例)与早卵泡长方案组(341例)]患者的基本情况、胚胎发育情况及临床结局进行比较;(2)将总人群划分为三个年龄段[<30岁(2 576例),30~35岁(3 249例),>35岁(1 099例)],并在此基础上,进一步对三种促排方案进行比较。分别比较<30岁、30~35岁、>35岁人群中使用三种促排方案的胚胎发育情况及临床结局。结果 在总人群中,激动剂长方案组的获卵数高于拮抗剂方案组[(13.85±7.162)个vs.(13.36±7.862)个,P=0.022 4]与早卵泡长方案组[(13.85±7.162)个vs.(11.86±6.802)个,P<0.000 1];拮抗剂方案组的促性腺激素(gonadotropin, Gn)启动量、Gn使用天数均低于其余两组(P<0.05);拮抗剂方案组的囊胚形成率高于激动剂长方案组(64.91%vs. 62.35%,P<0.000 1),同时也高于早卵泡长方案组(64.91%vs. 61.18%,P=0.000 1),而三种促排方案临床妊娠率、活产率差异无统计学意义(P>0.05);(2)在<30岁人群中,拮抗剂方案组的囊胚形成率高于激动剂长方案组(66.12%vs. 63.33%,P<0.000 1)与早卵泡长方案组(66.12%vs. 62.13%,P=0.009 4);在30~35岁人群中,拮抗剂方案组的囊胚形成率高于激动剂长方案组(64.88%vs. 62.93%,P=0.000 9)与早卵泡长方案组(64.88%vs.60.39%,P=0.001 1);在>35岁人群中,拮抗剂方案组的囊胚形成率高于激动剂长方案组(59.83%vs. 56.51%,P=0.009 3),而与早卵泡长方案组差异无统计学意义(P>0.05)。在三个年龄段人群中,三种促排方案的临床妊娠率、活产率、胎儿体质量及评分差异均无统计学意义(P>0.05)。结论 拮抗剂方案能减少促排时间、促排卵Gn剂量,增强患者就医依从性。高龄患者使用拮抗剂方案能提高囊胚形成率,但三种方案的活产率并没有明显差异。

Objective The main purpose of this study is to compare the embryo development and clinical outcomes of women in different age groups undergoing in vitro fertilization(IVF)processes using gonadotrophin-releasing hormone(GnRH)antagonist protocol,GnRH agonist long protocol,and early follicular phase protocol.We aim to provide reliable reference for future clinical treatments.Methods We conducted a detailed analysis of patients who underwent treatment between January 2021 and February 2023.1)In the overall patient population,we comprehensively compared the basic characteristics,the embryo development,and the clinical outcomes of patients treated with three different ovarian stimulation protocols,including the GnRH antagonist protocol group(n=4173),the agonist long protocol group(n=2410),and the early follicular phase long protocol group(n=341).2)We divided the overall population into three age groups,one group for patients under 30 years old(n=2576),one for patients aged 30-35(n=3249),and one for patients older than 35 years old(n=1099).Then,we compared the three stimulation protocols based on the group division.We separately compared the embryo development and clinical outcomes of patients using the three stimulation protocols in the under 30 years old,the 30-35 years old,and the over 35 years old age groups.With this analysis,we aimed to explore the response of different age groups to different stimulation protocols and their impact on the success rate of IVF.Results 1)In the overall population,we found that the average number of oocytes retrieved in the GnRH agonist long protocol group was significantly higher than that in the GnRH antagonist protocol group([13.85±7.162]vs.[13.36±7.862],P=0.0224),as well as the early follicular phase long protocol group([13.85±7.162]vs.[11.86±6.802],P<0.0001).Patients in the GnRH antagonist protocol group not only had a significantly lower starting dose of gonadotrophin(Gn)compared to the other two groups(P<0.05)but also had a significantly lower number of days of Gn use(P<0.05).The blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups,significantly higher compared to the GnRH agonist long protocol group(64.91%vs.62.35%,P<0.0001)and the early follicular phase long protocol group(64.91%vs.61.18%,P=0.0001).However,there were no significant differences in the clinical pregnancy rates or the live birth rates among the three groups treated with different ovarian stimulation protocols(P>0.05).2)In the<30 age group,the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups,significantly higher compared to the GnRH agonist long protocol group(66.12%vs.63.33%,P<0.0001)and the early follicular phase long protocol group(66.12%vs.62.13%,P=0.0094).In the 30-35 age group,the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups,significantly higher compared to the GnRH agonist long protocol group(64.88%vs.62.93%,P=0.0009)and the early follicular phase long protocol group(64.88%vs.60.39%,P=0.0011).In the>35 age group,the blastocyst formation rate in the GnRH antagonist protocol group was significantly higher than that in the GnRH agonist long protocol group(59.83%vs.56.51%,P=0.0093),while there was no significant difference compared to that of the early follicular phase long protocol group(P>0.05).In the three age groups,we found that there were no significant differences in clinical pregnancy rate,live birth rate,and neonatal outcome indicators(fetal weight and Apgar score)among the three stimulation protocols(antagonist protocol,GnRH agonist long protocol,and early follicular phase long protocol)(P>0.05).The findings showed no significant differences between clinical and neonatal outcomes in patients of all ages,regardless of the ovarian stimulation protocol,suggesting that the three ovarian stimulation protocols have similar therapeutic effects in patients of different ages.The results of this study have important implications for the selection of an appropriate ovarian stimulation protocol and the prediction of treatment outcomes.Conclusion In the younger than 30 and 30-35 age groups,the GnRH antagonist protocol showed a more significant advantage over the GnRH agonist long protocol and the early follicular phase long protocol.This suggests that for younger and middle-aged patients,the antagonist protocol may lead to better outcomes during ovarian stimulation.In the older than 35 age group,while the antagonist protocol still outperformed the GnRH agonist long protocol,there was no significant difference compared to the early follicular phase long protocol.This may imply that with increasing age,the early follicular phase long protocol may have effects similar to the antagonist protocol to some extent.The advantages of the antagonist protocol lie in its ability to reduce stimulation duration and the dosage of GnRH,while enhancing patient compliance with treatment.This means that patients may find it easier to accept and adhere to this treatment protocol,thereby improving treatment success rates.Particularly for older patients,the use of the antagonist protocol may significantly increase the blastocyst formation rate,which is crucial for improving the success rates.Although there were no significant differences in the clinical outcomes of patients treated with the three protocols in each age group,further research is still needed to validate these findings.Future multicenter studies and increased sample sizes may help comprehensively assess the efficacy of different stimulation protocols.Additionally,prospective studies are needed to further validate these findings and determine the optimal treatment strategies.