宫腔内人工授精妊娠结局相关影响因素:单中心十年26473个周期回顾性队列研究

Related influencing factors of intrauterine insemination pregnancy outcomes:a retrospective cohort study of 26473 cycles in single center for 10 years

目的探讨宫腔内人工授精(IUI)妊娠结局的相关影响因素。方法回顾性队列研究2007年1月至2017年6月期间在南京医科大学第一附属医院/江苏省人民医院生殖医学科就诊的12165对夫妇共26473个夫精人工授精(AIH)和供精人工授精(AID)周期的临床资料,数据来源于本中心临床辅助生殖技术管理系统(CCRM)数据库(15.2版本),研究女方年龄、男方年龄、周期次数、不孕年限、不孕类型、不孕原因、治疗方案和授精时机与妊娠结局的关系。结果①AIH中,女方年龄≥37岁者活产率(4.16%)显著低于<37岁者(9.58%,P<0.001),合并男方年龄≥45岁者无一例妊娠;3个AIH周期后累积妊娠率和活产率不再显著增加;女方年龄<37岁者,原发不孕和继发不孕患者不孕年限≥5年者的活产率(8.03%、5.75%)显著低于不孕年限<5年者(9.96%、10.91%,P=0.001、P<0.001);排卵障碍和性功能障碍组的活产率(13.24%、17.66%)显著高于男方轻度少弱精子症(7.04%)、输卵管因素(6.62%)、子宫内膜异位症(7.13%)和不明原因不孕(7.75%)(P均<0.001);克罗米芬(CC)/来曲唑(LE)联合促性腺激素(Gn)方案的活产率(12.20%、12.52%)显著高于自然周期(7.58%)、单独CC组(8.14%)、单独LE组(6.82%)、尿促性腺激素(hMG)组(7.82%)(P均<0.001);刺激周期排卵前授精的活产率(10.29%)显著高于排卵后授精(8.13%,P=0.034)。②AID中,不孕类型、治疗方案和授精时机均对妊娠结局没有显著影响(P>0.05);女方年龄≥37岁者流产率(37.5%)显著高于<37岁者(11.44%,P<0.001);4个AID周期后累积妊娠率和活产率不再显著增加;CC+Gn方案的活产率与LE+Gn方案类似(21.04%,20.12%),但LE+Gn方案患者的多胎活产率(4.80%)显著低于CC+Gn方案者(12.03%,P=0.012)。结论不论AIH还是AID,女方年龄均是妊娠结局的最主要影响因素,在AIH中,还必须考虑不孕年限、男方年龄和不孕原因对妊娠结局的影响。与CC+Gn相比,LE+Gn可在显著提高活产率的同时降低多胎妊娠的风险。

Objective To investigate the influencing factors the pregnancy outcomes of intrauterine insemination(IUI).Methods From January 2007 to June 2017,a total of 26473 artificial insemination by husband(AIH)and artificial insemination by donor(AID)cycles of 12165 couples in the Department of Reproductive Medicine,the First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital were retrospectively analyzed,and the data came from the Center’s Clinical Assisted Reproductive Technology Management(CCRM)system database version 15.2.The relationship of pregnancy outcomes to the female age,the male age,the number of cycles,the duration of infertility,infertility types,the cause of infertility,treatment regimens,the timing of insemination was studied.Results 1)In AIH,the live birth rate(LBR)(4.16%)of women aged≥37 years was significantly lower than those of<37 years old(9.58%,P<0.001),and there was no pregnancy when their husbands aged 45 years or older.After 3 AIH cycles,the cumulative live birth rate(CLBR)and clinical pregnancy rate(CCPR)were no longer significantly increased.If the woman was younger than 37 years old,no matter the primary or secondary infertility patients,the LBR was significantly lower in patients with more than 5 years of infertility(8.03%,5.75%)than those less than 5 years(9.96%,P<0.001;10.91%,P<0.001).The LBR of ovulatory disorder and sexual dysfunction group(13.24%,17.66%)was significantly higher than that of mild oligospermia and asthenospermia(7.04%),tubal factor(6.62%),endometriosis(7.13%)and unexplained infertility(7.75%)(all P<0.001).Clomiphene(CC)or letrozole(LE)combined with gonadotropin(Gn)could achieve higher LBR(12.20%,12.52%)than natural cycle(7.58%)or CC/LE/hMG used alone(8.14%,6.82%,7.82%,P<0.001).The LBR of pre-ovulation insemination in the stimulation cycle(10.29%)was higher than that of post-ovulation insemination(8.13%,P=0.034).2)In AID,infertility type,treatment regimen and the timing of insemination had no significantly effect on pregnancy outcome.The abortion rate of women aged≥37 years(37.5%)was significantly higher than that of<37 years old(11.44%,P<0.001).After 4 AID cycles,the CLBR was no longer significantly increased.The LBR of CC+Gn regimen was similar to that of LE+Gn regimen(21.04%,20.12%),but multiple LBR of LE+Gn regimen(4.80%)significantly reduced(12.03%,P=0.012).Conclusion No matter AIH or AID,the female age is the most important factor influencing the pregnancy outcome.Furthermore,the influence of infertility duration,the male age and the cause of infertility on the pregnancy outcome must be considered simultaneously in AIH.LE+Gn regimen can significantly increase the LBR and diminish the risk of multiple pregnancy compared with CC+Gn.