Sun Ling, Jiang Ling X, Chen Heng Z
Center of Reproductive Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of epidemiology, School of Public Health and Tropic Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Arch Gynecol Obstet. 2017 Mar;295(3):559-567. doi: 10.1007/s00404-017-4289-9. Epub 2017 Jan 17.
Due to the high number of multiple embryo transfers into the uterus performed in assisted reproductive technology treatment (ART), the incidences of twin pregnancy and of vanishing twin syndrome (VTS) are correspondingly high. A number of studies have described the obstetric outcomes of the remaining fetus produced after the other twin had vanished compared with a singleton at the start following ART, but the results are mixed and contradictory. We performed a systematic review of the existing studies to explore the actual obstetric outcome of VTS to allow physicians to adequately advise their patients.
A detailed search strategy was used to conduct electronic literature searches (spanning 1978-2015) on Medline, EMBASE, the Cochrane library and Web of Science. As randomized trials are not feasible in this aspect, we included observational (cohort and case-control) studies which compared the obstetric outcomes of the VTS group and singleton at the start control group after ART. The outcomes were evaluated by two aspects, the duration of pregnancy (gestational age, preterm delivery rate, extremely preterm delivery rate) and the birth weight of the fetus [mean birth weight, low birth weight rate, very low birth weight rate and small for gestational age (SGA)].
1271 publications were identified by the initial search. 499 studies were excluded following duplication checks. 760 were excluded after reviewing the abstracts. Of the remaining 12 articles, 7 were excluded after a detailed full-text review. Two case-control studies and three cohort studies were included in the final analysis. The pooled mean gestational age difference (95% confidence intervals) was -0.27 (-0.60, 0.06) and failed to demonstrate a difference between the two groups. A similar result was found in the preterm delivery rate, with a pooled risk ratio of 1.33 (0.91, 1.94). The prevalence of extremely preterm delivery rate was higher in the VTS group, with a pooled risk ratio of 3.5 (1.72, 7.12). The mean birth weight was lower in the VTS group, with a mean difference of -0.3 (-0.59, -0.01). No difference was found in low birth weight rate, very low birth weight rate and rate of small for gestational age, with risk ratio of 1.85 (0.88, 3.86), 4.86 (0.91, 25.91) and 1.29 (0.52, 3.18), correspondingly.
There is a slight adverse effect of VTS on the remaining fetus for birth weight and extremely preterm delivery rate, but sensitivity analysis shows these effects to be statistically unstable. It is too early to draw conclusions for adverse obstetric outcomes for VTS patients. It could reduce much of the anxiety of couples who experience early embryonic loss of one of their twins. More research with rigorously designed and standardized methodologies are required that include larger, better clinically defined populations. Studies that show no correlation should be published in the future to avoid any possible impact of publication bias. After that, patients can receive the most accurate information.
由于辅助生殖技术治疗（ART）中子宫内进行多胚胎移植的数量众多，双胎妊娠和消失双胎综合征（VTS）的发生率相应较高。许多研究描述了与ART开始时的单胎相比，另一双胎消失后剩余胎儿的产科结局，但结果不一且相互矛盾。我们对现有研究进行了系统评价，以探讨VTS的实际产科结局，以便医生能够充分地为患者提供建议。
采用详细的检索策略，在Medline、EMBASE、Cochrane图书馆和科学网进行电子文献检索（检索时间跨度为1978 - 2015年）。由于在这方面进行随机试验不可行，我们纳入了观察性（队列和病例对照）研究，这些研究比较了ART后VTS组与开始时的单胎对照组的产科结局。结局从两个方面进行评估，即妊娠持续时间（孕周、早产率、极早早产率）和胎儿出生体重[平均出生体重、低出生体重率、极低出生体重率和小于胎龄儿（SGA）率]。
初始检索共识别出1271篇出版物。经过重复检查后，排除了499项研究。在审阅摘要后，又排除了760项研究。在其余12篇文章中，经过详细的全文审阅后，排除了7篇。最终分析纳入了2项病例对照研究和3项队列研究。合并的平均孕周差异（95%置信区间）为 - ０.27（ - ０.60，0.06），未显示出两组之间存在差异。早产率方面也得到了类似的结果，合并风险比为1.33（0.91，1.94）。VTS组的极早早产率患病率较高，合并风险比为3.5（1.72，7.12）。VTS组的平均出生体重较低，平均差异为 - ０.3（ - ０.59， - ０.01）。低出生体重率、极低出生体重率和小于胎龄儿率方面未发现差异，相应的风险比分别为1.85（0.88，3.86）、4.86（0.91，25.91）和1.29（0.52，3.18）。
VTS对剩余胎儿的出生体重和极早早产率有轻微不良影响，但敏感性分析表明这些影响在统计学上不稳定。现在就得出VTS患者产科不良结局的结论还为时过早。这可以减轻经历双胞胎之一早期胚胎丢失的夫妇的许多焦虑。需要更多采用严格设计和标准化方法的研究，包括更大规模、临床定义更完善的人群。未来应发表无相关性的研究，以避免发表偏倚可能产生的任何影响。在此之后，患者才能获得最准确的信息。
