Objective: To report a case of heterotopic interstitial pregnancy after in vitro fertilization-embryo transfer (IVF-ET), presenting with a second trimester uterine rupture. To review the clinical presentations, risk factors, treatment options, and outcome of heterotopic interstitial pregnancies., Methods: We describe the clinical presentation, management, and outcome of a patient with a heterotopic interstitial pregnancy, diagnosed following second trimester rupture of the interstitial pregnancy. We reviewed all published cases of heterotopic interstitial pregnancies., Results: A 35-year-old pregnant woman with a past history of right adnexectomy and 16 weeks pregnant with dichorionic diamniotic twins following IVF-ET, was admitted to our department with unexplained recurrent abdominal pain and anemia. Further investigation showed a hemoperitoneum and because of hypovolemic shock an emergency laparotomy was performed, with diagnosis of a ruptured heterotopic interstitial pregnancy. The uterine defect was sutured using simple interrupted sutures. The intrauterine pregnancy progressed uneventful afterwards.We found 86 cases in the published literature, reporting on heterotopic interstitial pregnancies. 80.2% (69/86) occurred after IVF-ET. History of uni- or bilateral salpingectomy is a major risk factor, present in 39.5% (34/86). 37.2% (32/86) presented with cornual rupture. Surgery was performed in 53.5% (46/86) of cases. Medical management was possible in case of unruptured, early diagnosed heterotopic interstitial pregnancy (32.6% (28/86)). Watchful waiting was only possible when the interstitial pregnancy miscarried (5.8% (5/86)). The live birth rate of the intrauterine pregnancy, when viable at presentation, was 70.0% (56/80). The live birth rate of the interstitial pregnancy was only 4.7% (4/86)., Conclusions: The majority of cases are diagnosed by detailed ultrasound in the setting of early follow-up after IVF-ET and are asymptomatic at diagnosis. Yet, a substantial number of patients present with cornual rupture. Risk factors are IVF-ET and a history of salpingectomy. Depending on clinical presentation, treatment options include watchful waiting, medical treatment, or surgery. Unfortunately, the interstitial pregnancy is generally lost, and only has a chance of survival in case of presentation at a viable gestational age. The outcome of the coexisting intrauterine pregnancy is generally good.