年龄≤35岁女性供精人工授精不同助孕方案的妊娠结局及围产结局比较

Comparison of pregnancy outcomes and perinatal outcomes of different protocols for artificial insemination by donor cycles in female patients aged≤35 years

目的探讨年龄≤35岁女性供精人工授精(artificial insemination by donor,AID)周期中不同助孕方案的临床结局及围产结局是否存在差异。方法本研究为回顾性队列研究,分析2016年1月1日至2021年1月31日期间于郑州大学第三附属医院生殖医学中心行AID助孕患者的临床资料,根据是否进行促排卵治疗分为自然周期(natrual cycle,NC)组、来曲唑(letrozole,LE)/克罗米芬(clomiphene,CC)组、促性腺激素(gonadotropin,Gn)组和LE/CC+Gn组。分别比较各组间患者的临床结局、并发症发生以及子代健康情况,并利用logistic回归分析探究不同助孕方案对AID临床结局和围产结局的影响。结果 NC组、LE/CC组、Gn组和LE/CC+Gn组间周期取消率[0.5%(11/2 147)、1.1%(12/1 045)、1.6%(9/549)、3.2%(9/315),P<0.001]、临床妊娠率[31.5%(673/2 136)、35.8%(370/1 033)、42.8%(231/540)、38.2%(117/306),P<0.001]、多胎妊娠率[0.7%(5/673)、3.2%(12/370)、3.5%(8/231)、6.8%(8/117),P<0.001]、流产率[12.8%(86/673)、9.2%(34/370)、5.2%(12/231)、8.5%(10/117),P=0.008]以及活产率[27.2%(581/2 136)、31.4%(324/1 033)、40.0%(216/540)、34.3%(105/306),P<0.001]差异均存在统计学意义,而异位妊娠率、早产率以及过期产率组间差异均无统计学意义(均P>0.05);对混杂因素进行调整后,除LE/CC+Gn组流产率高于NC组(aOR=2.141,95%CI:1.12~4.09;P=0.021),其余各指标与NC组差异均无统计学意义(均P>0.05)。对于一直使用同一种方案的患者,仅NC组和LE/CC组累积妊娠率和累积活产率随助孕周期的增加而提高,差异均有统计学意义(均P<0.001)。无论是否调整混杂因素,各组间新生儿死亡率、低体质量发生率、正常体质量率、巨大儿发生率、男婴占比差异均无统计学意义(均P>0.05)。结论在女方年龄≤35岁的AID患者群体中,刺激周期临床妊娠结局与自然周期相似,不会增加AID周期中多胎妊娠和新生儿不良结局的风险,选择LE/CC刺激方案能够提高卵泡发育或排卵功能异常患者的累积妊娠率。

Objective To investigate whether there are differences in clinical pregnancy and perinatal outcomes among different protocols for artificial insemination by donor(AID)in female patients aged≤35 years.Methods This retrospective cohort study analyzed clinical data of patients who underwent AID at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 1,2016 to January 31,2021.Based on ovulation induction therapy,patients were divided into 4 groups:natural cycle(NC)group,letrozole(LE)/clomiphene(CC)group,gonadotropin(Gn)group and LE/CC combined with Gn(LE/CC+Gn)group.The clinical outcomes,incidence of complications,and offspring health were compared among these groups,and logistic regression analysis was employed to investigate the effects of different protocols on the clinical and perinatal outcomes of AID cycles.Results In NC group,LE/CC group,Gn group and LE/CC+Gn group,the cycle cancellation rate[0.5%(11/2147),1.1%(12/1045),1.6%(9/549),3.2%(9/315),P<0.001],the clinical pregnancy rate[31.5%(673/2136),35.8%(370/1033),42.8%(231/540),38.2%(117/306),P<0.001],the multiple pregnancy rate[0.7%(5/673),3.2%(12/370),3.5%(8/231),6.8%(8/117),P<0.001],the abortion rate[12.8%(86/673),9.2%(34/370),5.2%(12/231),8.5%(10/117),P=0.008]and the live birth rate[27.2%(581/2136),31.4%(324/1033),40.0%(216/540),34.3%(105/306),P<0.001]were statistically significant,while the differences among the four groups in the ectopic pregnancy rate,the preterm birth rate,and the overdue birth rate were not statistically significant(all P>0.05).After adjusting for confounding factors,the differences were not statistically significant in all indicators compared with the NC group(all P>0.05),except for the miscarriage rate in the LE/CC+Gn group,which was significantly higher than that in the NC group(aOR=2.141,95%CI:1.12-4.09;P=0.021).For patients who have been using the same treatment protocol,the cumulative pregnancy rate and the cumulative live birth rate in the NC group and the LE/CC group increased with the increase of assisted reproductive cycles,and the difference was statistically significant(all P<0.001).Regardless of whether confounding factors were adjusted,there were no statistically significant differences in neonatal mortality rate,low birth weight rate,normal birth weight rate,macrosomia rate,and male-to-female ratio among the groups(all P>0.05).Conclusion In AID cycles with female patients aged≤35 years,stimulated cycles had similar pregnancy outcomes to natural cycles and did not increase the risk of adverse neonatal outcomes or multiple pregnancies.Choosing the LE/CC stimulation protocol can improve the cumulative pregnancy rate of patients with abnormal ovarian follicle development or ovulation function.