目的:量化早产(PTB)风险,并检查体外受精/胞浆内精子注射(IVF/ICSI)单胎妊娠与自然受孕相比的假定病因。
方法:全面搜索PubMed/MEDLINE,Embase,截至12月31日,Scopus和Cochrane图书馆数据库2023年。
方法:系统评价和荟萃分析比较IVF/ICSI和自然受孕单胎妊娠的PTB风险。关于病因的现有信息,表型,启动PTB和相关调节因子用于亚分析.
方法:随机效应荟萃分析模型用于汇集效应测量。估计值以比值比(OR)和95%置信区间(CI)表示。使用校正的覆盖区域评估来测量原始研究中的重叠程度。使用AMSTAR2工具评估了所包含评论的质量。采用等级方法对证据确定性进行评级。该协议在PROSPERO(CRD42023411418)上注册。
结果:纳入了12项meta分析(16,522,917例妊娠;433,330IVF/ICSI)。与自然受孕相比,IVF/ICSI单身患者的PTB风险明显更高(PTB治疗37周:OR:1.72,95CI:1.57-1.89;PTB<32周:OR:2.19,95CI:1.82-2.64)。影响分析加强了这种关联的强度。调查假定病因的亚组分析显示,自发性PTB的风险大小相当(OR1.79,95CI:1.56-2.04),医源性PTB的风险更大(OR:2.28,95CI:1.72-3.02)。PTB风险在常规IVF亚组中一致(OR:1.95,95CI:1.76-2.15),在仅新鲜的亚组中更高(OR:1.79,95CI:1.55-2.07)与冻融胚胎移植(OR:1.39,95CI:1.34-1.43)。有最小的研究重叠(13%)。证据的确定性低至非常低。
结论:与自然受孕相比,通过IVF/ICSI受孕的单胎患PTB的风险增加了两倍,尽管证据的确定性很低。关于PTB病因的可用数据很少,表型,或启动。在新鲜胚胎移植中观察到更大的风险增加,涉及医源性PTB和PTB后32周,可能归因于胎盘病因。未来的研究应该收集有关PTB病因的数据,表型,和开始。IVF/ICSI妊娠应进行特殊护理,并进行胎盘疾病的早期筛查。宫颈长度,和生长异常,允许适当的及时随访,预防措施,和治疗干预策略。
BACKGROUND: The rate of preterm birth of singletons conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is increased, being as high as 15% to 16% across Europe and the United States. However, the underlying etiology, phenotype, and mechanisms initiating preterm birth (PTB) are poorly understood.
OBJECTIVE: To quantify the PTB risk and examine supposed etiology in IVF/ICSI singleton pregnancies compared to naturally conceived.
METHODS: Overview of reviews including all available systematic reviews with meta-analysis comparing PTB risk in IVF/ICSI and naturally conceived singletons. A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases was performed up to December 31, 2023. Information available on etiology, phenotype, initiation of PTB, and relevant moderators was retrieved and employed for subgroup analyses. Random-effects meta-analysis models were used for pooling effect measures. Estimates were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The extent of overlap in the original studies was measured using the corrected covered area assessment. The quality of the included reviews was evaluated with the AMSTAR 2 tool. The Grading of Recommendations Assessment, Development and Evaluation approach was applied to rate evidence certainty. The protocol was registered on PROspective Register of Systematic Reviews (CRD42023411418).
RESULTS: Twelve meta-analyses (16,522,917 pregnancies; ˃433,330 IVF/ICSI) were included. IVF/ICSI singletons showed a significantly higher PTB risk compared to natural conception (PTB ˂37 weeks: OR: 1.72, 95% CI: 1.57-1.89; PTB<32 weeks: OR: 2.19, 95% CI: 1.82-2.64). Influential analysis reinforced the strength of this association. Subgroup analyses investigating supposed etiology revealed a comparable risk magnitude for spontaneous PTB (OR: 1.79, 95% CI: 1.56-2.04) and a greater risk for iatrogenic PTB (OR: 2.28, 95% CI: 1.72-3.02). PTB risk was consistent in the subgroup of conventional IVF (OR: 1.95, 95% CI: 1.76-2.15) and higher in the subgroup of fresh only (OR: 1.79, 95% CI: 1.55-2.07) vs frozen-thawed embryo transfers (OR: 1.39, 95% CI: 1.34-1.43). There was minimal study overlap (13%). The certainty of the evidence was graded as low to very low.
CONCLUSIONS: Singletons conceived through IVF/ICSI have a 2-fold increased risk of PTB compared to natural conception, despite the low certainty of the evidence. There is paucity of available data on PTB etiology, phenotype, or initiation. The greater risk increase is observed in fresh embryo transfers and involves iatrogenic PTB and PTB ˂32 weeks, likely attributable to placental etiology. Future studies should collect data on PTB etiology, phenotype, and initiation. IVF/ICSI pregnancies should undertake specialistic care with early screening for placental disorders, cervical length, and growth abnormalities, allowing appropriate timely follow-up, preventive measures, and therapeutic interventions strategies.