Vanishing Twin Syndrome After In Vitro Fertilization and Embryo Transfer: Mechanisms, Perinatal Consequences, Diagnostic Pitfalls, and Prevention

Bereczki, Kristóf Gergő and Bukva, Mátyás and Reuter, Krisztina and Bereczki, Csaba and Kolcsár, Bálint (2026) Vanishing Twin Syndrome After In Vitro Fertilization and Embryo Transfer: Mechanisms, Perinatal Consequences, Diagnostic Pitfalls, and Prevention. BIOMEDICINES, 14 (9). No. 2036. ISSN 2227-9059

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Abstract

Vanishing twin syndrome (VTS) denotes the spontaneous loss of one conceptus from an initially recognized multiple pregnancy, most often during the first trimester. Its clinical relevance has increased with in vitro fertilization and embryo transfer (IVF-ET), as multiple embryo transfer creates the substrate for dizygotic VTS, while blastocyst transfer may be followed by monozygotic splitting and serial early ultrasonography increases detection. However, the literature remains heterogeneous, with empty gestational sacs, losses after fetal cardiac activity, and later single fetal demise often grouped together despite different biological and prognostic implications. New evidence published in recent years on frozen embryo transfer outcomes, cell-free DNA screening, and early childhood development warrants an updated synthesis of vanishing twin syndrome to inform individualized risk assessment, counselling, and standardized research reporting. Overall, the surviving singleton appears to have a lower risk than an ongoing twin pregnancy but a higher risk than a primary singleton, particularly for preterm birth, low birthweight, and small-for-gestational-age birth, with risk increasing when loss occurs after fetal cardiac activity or later in gestation. Nevertheless, evidence is not unanimous, as several well-characterized cohorts and earlier meta-analyses reported no measurable perinatal disadvantage. Two reports from a single tertiary center, based on substantially overlapping recruitment periods, further suggest that VTS may be proportionally less frequent among established twin pregnancies after IVF/ICSI than after spontaneous conception, while IVF-associated VTS has been linked to placental abnormalities, diabetes, and fetal growth restriction; this observation requires independent confirmation. Contemporary frozen embryo transfer cohorts indicate that VTS remains relevant in modern practice, whereas limited long-term data have not demonstrated impaired early childhood growth or development. Management should document the initial number of gestational sacs, embryonic structures, cardiac activity, chorionicity, and timing of loss, while adapting aneuploidy screening to residual trophoblastic DNA and individualizing fetal-growth surveillance. Elective single-embryo transfer remains the most effective preventive strategy, although it cannot eliminate monozygotic twinning. Standardized definitions and long-term offspring follow-up are needed.

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