Heterotopic Triplet Pregnancy After Assisted Reproductive Techniques: A Systematic Review

Heterotopic pregnancy is defined as the simultaneous presence of an intrauterine and an extrauterine pregnancy and is considered a rare condition. As a part of this entity, heterotopic triplet pregnancy, defined as the presence of three embryos, with at least one being ectopic, is exceedingly rare. In recent years, the broad use of assisted reproductive techniques to help infertile couples has contributed to the constant rise of non-spontaneous heterotopic triplets. An analysis of all the cases reported in the English literature could provide useful messages to clinicians. This literature review had the aim to provide an analytic overview of all the cases of heterotopic triplet pregnancy after ovulation induction and assisted reproductive techniques published in the English literature by searching the National Library of Medicine (PubMed), Scopus, and Google Scholar until December 2023. We identified 57 articles of heterotopic triplets after assisted reproductive techniques and recorded the year, maternal age, gravida/para, medical history, medication used and mode of conception, number of embryos and stage of cells transferred, number of embryos in utero and ectopic embryos, time of diagnosis after ovulation induction or embryo transfer, symptoms, rupture of the ectopic pregnancy with hemoperitoneum, complications in pregnancy, obstetric outcome, weeks of delivery, birth-weight status and sex of the infants. Although this situation could be life-threatening and should alert the medical community, misdiagnosis or delayed diagnosis is still present. The commonest site of ectopic is in the salpinx. Currently, there is no consensus on the treatment strategy for heterotopic triplets, and all the data is derived from case reports. It is important to highlight the current recommendation of transferring one, or at most two, fertilized embryos during a single ovarian-controlled cycle to minimize the risk of multiple gestations and associated complications. Clinicians must remain vigilant, as pregnancies following in vitro fertilization (IVF) are considered "high-risk." Complications, such as multiple pregnancies, preterm delivery, or maternal-fetal health issues, may arise. Early diagnosis, appropriate surgical or conservative interventions, and rigorous follow-up are essential to ensure optimal maternal and fetal outcomes.