Multiple pregnancy with complete hydatidiform mole and coexisting normal fetus: systematic review and meta‐analysis of clinical outcomes from non‐randomized studies

ABSTRACT Objective Complete hydatidiform mole and coexisting normal fetus (CHMCF) is a rare condition for which there is significant heterogeneity in diagnosis, counseling and management of complications. The objective of this study was to summarize the prevalence of clinical outcomes in reported cases of CHMCF. Methods A systematic literature search was conducted in PubMed, Embase and Scopus databases from inception until 1 October 2024. Case series and cohort studies including at least three cases of histologically confirmed CHMCF were included. A random‐effects model was used for meta‐analysis of proportions and heterogeneity was estimated using Higgins' I 2 index. The Newcastle–Ottawa scale and the Joanna Briggs Institute critical appraisal checklist were used to assess study quality, while certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The study was registered in the PROSPERO database (CRD42023431734). Results Quantitative synthesis included 19 studies and 417 cases of CHMCF. Diagnosis was made using ultrasound in 76.0% (95% CI, 58.5–90.6%) of cases and occurred in the first trimester in 52.7% (95% CI, 34.0–71.0%). Symptoms at diagnosis were present in 80.5% (95% CI, 66.1–92.3%) of cases, with vaginal bleeding being the most common symptom both at diagnosis and later in pregnancy. The pooled proportion of elective pregnancy termination was 48.8% (95% CI, 32.7–65.1%), with 6.2% (95% CI, 1.0–13.9%) due to maternal complications. The pooled proportion of live births was 46.5% (95% CI, 36.1–57.1%), with most being delivered by Cesarean section (71.2% (95% CI, 42.4–94.4%)). Preterm birth (< 37 weeks) occurred in 67.8% (95% CI, 44.7–88.1%) of cases, very preterm birth (< 32 weeks) in 12.4% (95% CI, 0.2–33.9%) and miscarriage (fetal death < 24 weeks) in 32.7% (95% CI, 26.1–39.6%). Pre‐eclampsia was present in 17.8% (95% CI, 5.9–32.7%) of cases and postpartum hemorrhage occurred in 42.7% (95% CI, 5.1–84.8%). A small‐for‐gestational‐age neonate (birth weight < 10 th percentile) was delivered in 40.6% (95% CI, 12.9–70.8%) of cases. Rates of neonatal and maternal mortality were negligible. The pooled proportion of gestational trophoblastic neoplasia was 33.8% (95% CI, 25.6–42.5%); among elective terminations, continued pregnancies and live births, the rates were 14.1% (95% CI, 5.4–24.9%), 20.3% (95% CI, 12.0–29.9%) and 5.9% (95% CI, 1.9–11.2%), respectively. The evidence level according to GRADE was low to very low. Conclusions Pregnancies with CHMCF present a high risk of maternal, obstetric and neonatal complications, including miscarriage, pre‐eclampsia, small‐for‐gestational age, postpartum hemorrhage and preterm birth. The risk of developing gestational trophoblastic neoplasia was not clearly mitigated by early pregnancy termination. Early diagnosis, referral to a maternal–fetal medicine unit with expertise in trophoblastic disorders and extensive implementation of screening protocols for preterm birth and pre‐eclampsia are recommended to facilitate timely intervention aimed at outcome improvement. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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