Perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia: a systematic review of observational studies and meta-analysis.

Objective: To assess perinatal outcomes of first pregnancy after remission from gestational trophoblastic neoplasia and the impact of the time between the end of chemotherapy and the subsequent pregnancy.

Data Sources: The Medical Subject Headings related to perinatal outcomes, chemotherapy, and gestational trophoblastic neoplasia were used alone or in combination to retrieve relevant articles. We searched all references registered until April, 2019 in Embase, LILACS, MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science.

Study Eligibility Criteria: We included any observational or interventional studies that evaluated perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia. Animal studies, narrative reviews, expert opinions, and previous treatments with potential risks for future perinatal outcomes which may introduce confounding bias were excluded.

Study Appraisal And Synthesis Methods: Two reviewers independently screened all identified references for eligibility and data extraction. Methodological quality and bias of included studies were assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Institutes of Health. For the meta-analysis, the measures of association were calculated using bivariate random-effects models. Statistical heterogeneity was evaluated with I statistics and explored through sensitivity analysis. Publication bias was assessed by visual inspection of the funnel plot or Egger's test, according to the number of articles included. For all analyses, a P value of <.05 indicated statistical significance. This study was registered on PROSPERO (CRD42018116513).

Results: A total of 763 studies were identified after literature search and 23 original studies were included in the systematic review and in the meta-analysis. The combined data from the subgroup meta-analysis (outcome vs time after chemotherapy) showed an incidence of spontaneous abortion of 15.28% (95% confidence interval, 12.37-18.74; I=73%), 3.30% of malformation (95% confidence interval, 2.27-4.79; I=31%), 6.19% of prematurity (95% confidence interval, 5.03-7.59; I=0), and 1.73% of stillbirth (95% confidence interval, 1.17-2.55; I=0%). These results were not influenced by the time between the end of chemotherapy and the subsequent pregnancy in most of the studied outcomes, including malformation (P=.14, I=31%), prematurity (P=.46, I=0), and stillbirth (P=.66, I=0). However, there was a higher occurrence of spontaneous abortion (P<.01, I=73%) in pregnancies that occurred ≤6 months after chemotherapy.

Conclusion: Chemotherapy for gestational trophoblastic neoplasia does not appear to increase the chance of unfavorable perinatal outcomes, except for the higher occurrence of spontaneous abortion in pregnancies occurring ≤6 months after chemotherapy.