Interventions to prevent preterm birth following fetoscopic laser surgery for twin-to-twin transfusion syndrome: systematic review and meta-analysis

Abstract

Objective: To assess the impact of intervention with cervical cerclage, cervical pessary or vaginal progesterone on the risk of preterm birth (PTB) in monochorionic diamniotic (MCDA) twin pregnancies undergoing fetoscopic laser surgery (FLS) for twin-to-twin transfusion syndrome (TTTS). Methods: The MEDLINE, Embase and Cochrane databases were searched from inception to November 2023. The inclusion criteria were studies on MCDA twin pregnancies undergoing FLS for TTTS, comparing those receiving with those not receiving an intervention to prevent PTB, including vaginal progesterone, cervical cerclage and cervical pessary. The primary outcome was gestational age (GA) at birth. The secondary outcomes included the interval between FLS and birth, PTB prior to 34, 32, 28 and 24 weeks' gestation, delivery within 2 and 4 weeks after FLS, preterm prelabor rupture of membranes, chorioamnionitis, double survival, survival of at least one twin, no survival, overall fetal or perinatal loss, and overall fetal or perinatal survival. All outcomes were explored in the overall population of MCDA twin pregnancies undergoing FLS for TTTS according to different cut-offs of cervical length (CL) for intervention. Random-effects meta-analysis was used to directly compare the risk of each outcome. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of the retrieved evidence. Results: Ten studies (1159 MCDA pregnancies) were included in the systematic review, of which seven were included in the meta-analysis. There was no significant difference in mean gestational age at birth in MCDA twin pregnancies undergoing FLS for TTTS in women receiving vs not receiving cervical cerclage, with CL < 30, < 25, < 20 or < 15 mm. There was also no significant difference in the mean interval between FLS and delivery, and in the risk of fetal or perinatal loss between women receiving vs not receiving cervical cerclage. Similarly, intervention with cervical pessary was not associated with a higher gestational age at birth compared with no intervention. It was not possible to perform any comprehensive pooled data synthesis for women receiving progesterone. In women with CL < 30 mm, intervention with cervical pessary was not associated with a reduced risk of PTB < 32, < 28 or < 24 weeks' gestation, or with delivery within 2 or 4 weeks after FLS or perinatal loss. Finally, in women with CL < 25 mm, cervical pessary did not reduce the risk of PTB < 32 weeks or perinatal loss. On GRADE assessment, the quality of evidence was very low in showing that cervical cerclage and cervical pessary can affect gestational age at birth in MCDA twin pregnancies that underwent FLS for TTTS, irrespective of the degree of cervical shortening. Conclusions: There is currently no evidence that intervention with cervical cerclage or pessary leads to a greater gestational age at birth or reduces the risk of PTB in MCDA twin pregnancies complicated by TTTS and undergoing FLS in women with a short CL, while the level of evidence for intervention with vaginal progesterone is insufficient for evaluation. However, the small sample sizes of the included studies, lack of comparison in the original publications and lack of stratification of the observed outcomes according to Quintero stage, gestational age at FLS and CL cut-off highlight the need for appropriately powered studies.