| Summary: | <i>Background and objective</i>: Spontaneous heterotopic pregnancy (SHP) is a rare condition represented by the synchronous coexistence of an intrauterine and an ectopic pregnancy. It rarely occurs with natural conception and is usually a consequence of assisted reproductive techniques. Diagnosis of SHP can be a challenge for the clinician. The evolution of the intrauterine pregnancy is dependent on many factors, such as the location of the heterotopic pregnancy, gestational age at the time of diagnosis, the surgical procedure, the presence of other risk factors, early or delayed management. The aim of this systematic review of the literature was to extract existing evidence on spontaneous heterotopic pregnancy with otherwise unaffected intrauterine pregnancy. <i>Materials and Methods</i>: From a total of 1907 database entries identified in PubMed, EMBASE and Cochrane reviews, we selected 18 papers for narrative synthesis, for which we explored the diagnostic options, treatment, and outcome of these extremely rare epidemiologic occurrences. Manuscripts were assessed using the CARE guidelines for reporting case reports. <i>Results</i>: The main symptom was abdominal pain, and the preferred treatment approach was surgical, more precisely, using a laparoscopic approach. Most cases presented no risk factors, and the diagnosis was mostly made in the first semester. <i>Conclusions</i>: Normal follow-up and evolution of intrauterine pregnancy have been observed regardless of surgical approach (open or laparoscopic). Early diagnosis and treatment are advised, as they impact maternal and fetal outcomes. Evidence on this topic is scarce, predominantly comprised of case reports with variable degrees of adherence to dissemination guidelines. More studies on this topic are required to optimize care protocols for this type of pregnancy.
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