Unexplained third-trimester intrauterine fetal demise after vanishing twin syndrome in a large for gestational age fetus: Possible association of subclinical and multifactorial hypercoagulability factors

Introduction: Diagnosing late intrauterine fetal demise (IUFD) can be challenging, especially with an otherwise uncomplicated pregnancy course. Identifying maternal risk factors and multifactorial thrombophilia patterns can be helpful to further understand its etiology and provide medical guidance for future pregnancies. Case Report: A 31-year-old primigravida with a history of polycystic ovary syndrome (PCOS), obesity, and anemia conceived dichorionic-diamniotic twins with clomiphene. The patient had spontaneous early loss of Twin A at about eight weeks’ gestation, which was confirmed by ultrasound as vanishing twin syndrome. The surviving fetus (Twin B) demonstrated appropriate developmental growth and was large-for-gestational-age (LGA) through 33 weeks. At 34+4 weeks, the patient presented with decreased fetal movement, and IUFD was confirmed. Placental pathology and fetal karyotype were unremarkable, despite grossly abnormal placental architecture upon delivery. Two months postpartum, thrombophilia testing revealed a methylenetetrahydrofolate reductase (MTHFR) mutation, low protein S activity, and low PT/INR, highlighting the possibility of a subclinical thrombotic or microvascular process leading up to the fatal event. Conclusion: This case demonstrates the potential significance of subclinical hypercoagulable or microvascular factors in an otherwise unexplained late IUFD, especially in patients with comorbid conditions such as PCOS, obesity, and vanishing twin syndrome. Consideration of earlier detection and individualized thrombophilia screening may be helpful in developing preventative approaches in similar high-risk pregnancies.