ABSTRACT BACKGROUND

背景

ART is associated with higher rates of twin pregnancies than singleton pregnancies. Whether twin pregnancies conceived following ART have additional maternal and neonatal complications compared with non-ART twin pregnancies is not known.

相比于单胎妊娠，辅助生殖技术（ART）与高风险的双胎妊娠相联系。目前尚不清楚与非ART双胞胎妊娠相比，ART妊娠所带来的母婴并发症是否更多。

OBJECTIVE AND RATIONALE

目标和理由

The objective was to quantify the risk of adverse maternal and perinatal outcomes among twin pregnancies conceived following ART compared with non-ART and natural conception. Existing reviews vary in the reported outcomes, with many studies including triplet pregnancies in the study population. Therefore, we aimed to perform an up-to-date review with an in-depth analysis of maternal and perinatal outcomes limited to twin pregnancies.

本研究的目标是量化ART所孕育的双胎妊娠与非ART和自然受孕的双胎相比，不良孕产妇和围产儿结局的风险。现有的研究中，报告的结局各不相同，许多研究将三胎妊娠纳入研究人群中。因此，我们的目的是进行一个最新的综述，深入分析限于双胎妊娠的孕产妇和围产期的结果。

SEARCH METHODS

搜索方法

We searched electronic databases MEDLINE and EMBASE from January 1990 to May 2023 without language restrictions. All cohort studies reporting maternal and perinatal outcomes following ART compared with non-ART twin pregnancies and natural conception were included. Case–control studies, case reports, case series, animal studies, and in vitro studies were excluded. The Newcastle–Ottawa Scale was used to assess the methodological quality of the studies. Using random-effects meta-analysis, the estimates were pooled and the findings were reported as odds ratios (OR) with 95% CI.

我们检索了从1990年1月到2023年五月的电子数据库MEDLINE和EMBASE，未设语言限制。所有的队列研究报道了ART与非ART双胎妊娠和自然受孕下的孕产妇和围产期结局。我们排除了病例对照研究、病例报告、病例系列、动物研究和体外研究。将Newcastle-Ottawa量表用于评估研究的方法学质量。使用随机效应荟萃分析，将估计值汇总，并将结果报告为比值比（OR）和95% CI。

OUTCOMES

结果

We included 111 studies (802 462 pregnancies). Twin pregnancies conceived following ART were at higher risk of preterm birth at <34 weeks (OR 1.33, 95% CI 1.14–1.56, 29 studies, I² = 73%), <37 weeks (OR 1.26, 95% CI 1.19–1.33, 70 studies, I² = 76%), hypertensive disorders in pregnancy (OR 1.29, 95% CI 1.14–1.46, 59 studies, I² = 87%), gestational diabetes mellitus (OR 1.61, 95% CI 1.48–1.75, 51 studies, I² = 65%), and caesarean delivery (OR 1.80, 95% CI 1.65–1.97, 70 studies, I² = 89%) compared with non-ART twins. The risks for the above maternal outcomes were also increased in the ART group compared with natural conception. Of the perinatal outcomes, ART twins were at significantly increased risk of congenital malformations (OR 1.17, 95% CI 1.05–1.30, 39 studies, I² = 59%), birthweight discordance (>25% (OR 1.31, 95% CI 1.05–1.63, 7 studies, I² = 0%)), respiratory distress syndrome (OR 1.32, 95% CI 1.09–1.60, 16 studies, I² = 61%), and neonatal intensive care unit admission (OR 1.24, 95% CI 1.14–1.35, 32 studies, I² = 87%) compared with non-ART twins. When comparing ART with natural conception, the risk of respiratory distress syndrome, intensive care admissions, and birthweight discordance >25% was higher among the ART group. Perinatal complications, such as stillbirth (OR 0.83, 95% CI 0.70–0.99, 33 studies, I² = 49%), small for gestational age <10th centile (OR 0.90, 95% CI 0.85–0.95, 26 studies, I² = 36%), and twin–twin transfusion syndrome (OR 0.45, 95% CI 0.25–0.82, 9 studies, I² = 25%), were reduced in twin pregnancies conceived with ART versus those without ART. The above perinatal complications were also fewer amongst the ART group than natural conception.

我们纳入了111项研究（802462例妊娠）。ART后受孕的双胎在<34周时早产的风险更高（OR 1.33，95% CI 1.14-1.56，29项研究，I² = 73%），<37周（OR 1.26，95% CI 1.19-1.33，70项研究，I² = 76%），妊娠期高血压疾病（OR 1.29，95% CI 1.14-1.46，59项研究，I² = 87%），妊娠期糖尿病（OR 1.61，95% CI 1.48-1.75，51项研究，I² = 65%）和剖宫产（OR 1.80，95% CI 1.65-1.97，70项研究，I² = 89%）。与自然受孕相比，ART组上述孕产妇结局的风险也增加。在围产期结局中，ART双胎先天畸形的风险显著增加（OR 1.17，95% CI 1.05-1.30，39项研究，I² = 59%），出生体重不一致（>25%（OR 1.31，95% CI 1.05-1.63，7项研究，I² = 0%）），呼吸窘迫综合征（OR 1.32，95% CI 1.09- 1.63，7项研究，I²= 0%）。60，16项研究，I² = 61%），新生儿重症监护病房入院（OR 1.24，95% CI 1.14-1.35，32项研究，I² = 87%）与非ART双胞胎相比。当比较ART与自然受孕时，ART组的呼吸窘迫综合征、重症监护入院和出生体重不一致>25%的风险更高。围产期并发症，如死胎（OR 0.83，95% CI 0.70-0.99，33项研究，I² = 49%），小于胎龄儿<第10百分位数（OR 0.90，95% CI 0.85-0.95，26项研究，I² = 36%）和双胎输血综合征（OR 0.45，95%CI 0.25-0.82，9项研究，I² = 25%），减少了双胎妊娠的ART与那些没有ART。上述围产期并发症也较少ART组比自然受孕。

WIDER IMPLICATIONS

更广泛的影响

ART twin pregnancies are associated with higher maternal complications than non-ART pregnancies and natural conception, with varied perinatal outcomes. Women seeking ART should be counselled about the increased risks of ART twin pregnancies and should be closely monitored in pregnancy for complications. We recommend exercising caution when interpreting the study findings owing to the study’s limitations.

与ART和自然受孕相比，ART双胎妊娠与更高的母体并发症以及多样化的围产期结果相关。寻求ART的女性应该接受有关ART双胎妊娠风险增加的咨询，并在妊娠期密切监测并发症。鉴于该研究的局限性，我们建议在解读研究结果时要谨慎。

参考文献：

Shemoon Marleen, Wasana Kodithuwakku, Ruvini Nandasena, Shezoon Mohideen, John Allotey, Silvia Fernández-García, Andrea Gaetano-Gil, Gabriel Ruiz-Calvo, Joseph Aquilina, Asma Khalil, Priya Bhide, Javier Zamora, Shakila Thangaratinam, Maternal and perinatal outcomes in twin pregnancies following assisted reproduction: a systematic review and meta-analysis involving 802 462 pregnancies, Human Reproduction Update, Volume 30, Issue 3, May-June 2024, Pages 309–322, https://doi.org/10.1093/humupd/dmae002