{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T19:33:26Z","timestamp":1794339206683,"version":"4.9.0"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objective: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.<\/jats:p>","DOI":"10.3390\/medicina56120665","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T10:26:12Z","timestamp":1606731972000},"page":"665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Spontaneous Heterotopic Pregnancy with Unaffected Intrauterine Pregnancy: Systematic Review of Clinical Outcomes"],"prefix":"10.3390","volume":"56","author":[{"given":"Mihaela","family":"Oancea","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, \u2018Iuliu Hatieganu\u2019 University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razvan","family":"Ciortea","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, \u2018Iuliu Hatieganu\u2019 University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doru","family":"Diculescu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, \u2018Iuliu Hatieganu\u2019 University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra-Andreea","family":"Poienar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, \u2018Iuliu Hatieganu\u2019 University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6530-6874","authenticated-orcid":false,"given":"Mihaela","family":"Grigore","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, \u2018Grigore T Popa\u2019 University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana-Adelina","family":"Lupean","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, \u2018Iuliu Hatieganu\u2019 University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Nicula","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, \u2018Iuliu Hatieganu\u2019 University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Chira","sequence":"additional","affiliation":[{"name":"RoNeuro Institute for Neurological Research and Diagnostic, 400354 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-0223","authenticated-orcid":false,"given":"Stefan","family":"Strilciuc","sequence":"additional","affiliation":[{"name":"RoNeuro Institute for Neurological Research and Diagnostic, 400354 Cluj-Napoca, Romania"},{"name":"Department of Neurosciences, \u2018Iuliu Hatieganu\u2019 University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Mihu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, \u2018Iuliu Hatieganu\u2019 University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"ref_1","first-page":"851","article-title":"Grossesse h\u00e9t\u00e9rotopique: Int\u00e9r\u00eat de l\u2019\u00e9chographie sus pubienne (A propos d\u2019un cas) [Heterotopic pregnancy: Value of transabdominal sonography (a case report)]","volume":"82","author":"Ousehal","year":"2001","journal-title":"J. Radiol."},{"key":"ref_2","first-page":"76","article-title":"Grossesse heterotopique rompue avec naissance d\u2019un enfant vivant a terme au CHU de Youpougon","volume":"9","author":"Adjoussou","year":"2007","journal-title":"Rev. Int. Sci. M\u00e9dicales"},{"key":"ref_3","first-page":"866","article-title":"Heterotopic pregnancy in the absence of risk factors\u2014Diagnostics difficulties","volume":"82","author":"Marian","year":"2011","journal-title":"Ginekol. Pol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"355","DOI":"10.15557\/JoU.2018.0052","article-title":"Heterotopic pregnancy\u2014How easily you can go wrong in diagnosing? A case study","volume":"18","author":"Ciebiera","year":"2018","journal-title":"J. Ultrason."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stanley, R., Nair, A., and Fiallo, F. (2018). Spontaneous ovarian heterotopic pregnancy. BMJ Case Rep., 2018.","DOI":"10.1136\/bcr-2018-225619"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1093\/oxfordjournals.humrep.a136125","article-title":"Pregnancy: Heterotopic pregnancies after in-vitro fertilization and embryo transfer","volume":"10","author":"Marcus","year":"1995","journal-title":"Hum. Reprod."},{"key":"ref_7","unstructured":"(2019, November 26). Ectopic Pregnancy: MedlinePlus Medical Encyclopedia, Available online: https:\/\/medlineplus.gov\/ency\/article\/000895.htm."},{"key":"ref_8","first-page":"612","article-title":"Spontaneous Heterotopic Pregnancy with Live Infant: Report of Two Cases","volume":"85","author":"Dassah","year":"2008","journal-title":"East Afr. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1177\/1742271X17710965","article-title":"Management and outcome of heterotopic interstitial pregnancy: Case report and review of literature","volume":"25","author":"Dendas","year":"2017","journal-title":"Ultrasound"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"306","DOI":"10.11604\/pamj.2017.28.306.13696","article-title":"La grossesse h\u00e9t\u00e9rotopique spontan\u00e9e: \u00c0 propos de deux cas","volume":"28","author":"Guennoun","year":"2017","journal-title":"Pan Afr. Med. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.fertnstert.2006.06.037","article-title":"A comparison of heterotopic and intrauterine-only pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002","volume":"87","author":"Clayton","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_12","first-page":"131","article-title":"Grossesse h\u00e9t\u00e9rotopique: \u00c0 propos de 5 cas et revue de la litt\u00e9rature","volume":"29","author":"Diallo","year":"2009","journal-title":"J. Gynecol. Obstet. Biol. Reprod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/7232637","article-title":"Laparoendoscopic Single-Site Surgery for Management of Heterotopic Pregnancy: A Case Report and Review of Literature","volume":"2018","author":"Rezai","year":"2018","journal-title":"Case Rep. Obstet. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4103\/2321-4848.196190","article-title":"Histomorphology of fallopian tubes in ectopic pregnancy","volume":"4","author":"Ravindra","year":"2016","journal-title":"Arch. Med. Health Sci."},{"key":"ref_15","first-page":"768","article-title":"Management and pregnancy outcomes of heterotopic pregnancy","volume":"53","author":"Chen","year":"2018","journal-title":"Zhonghua Fu Chan Ke Za Zhi"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., and The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jclinepi.2017.04.026","article-title":"CARE guidelines for case reports: Explanation and elaboration document","volume":"89","author":"Riley","year":"2017","journal-title":"J. Clin. Epidemiol."},{"key":"ref_18","first-page":"2145937","article-title":"Spontaneous Heterotopic Pregnancy: Dual Case Report and Review of Literature","volume":"2016","author":"Chadee","year":"2016","journal-title":"Case Rep. Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4103\/1117-1936.186302","article-title":"A successfully managed spontaneous heterotopic pregnancy diagnosed in the second trimester of pregnancy","volume":"23","author":"Okunowo","year":"2016","journal-title":"Niger. Postgrad. Med. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1447-0756.2012.01920.x","article-title":"Heterotopic simultaneous splenic and intrauterine pregnancy after spontaneous conception and review of literature","volume":"39","author":"Julania","year":"2013","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1093\/humrep\/12.5.1098","article-title":"Spontaneous heterotopic pregnancy presenting with tubal rupture","volume":"12","author":"Jibodu","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"162","DOI":"10.5811\/cpcem.2019.1.41312","article-title":"Early Diagnosis of Heterotopic Pregnancy in a Primigravid Without Risk Factors in the Emergency Department","volume":"3","author":"Siacunco","year":"2019","journal-title":"Clin. Pract. Cases Emerg. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4103\/1596-3519.108251","article-title":"Heterotopic pregnancy with live infant","volume":"12","author":"Ikechukwu","year":"2013","journal-title":"Ann. Afr. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jemermed.2015.02.050","article-title":"Spontaneous Heterotopic Pregnancy Presenting with Hemoperitoneum","volume":"50","author":"Mihmanli","year":"2016","journal-title":"J. Emerg. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/j.1447-0756.2010.01180.x","article-title":"Successful treatment of a heterotopic tubal pregnancy by gasless laparoscopic surgery","volume":"36","author":"Phupong","year":"2010","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lialios, G.A., Kallitsaris, A., Kabisios, T., and Messinis, I.E. (2008). Ruptured heterotopic interstitial pregnancy: Rare case of acute abdomen in a Jehovah\u2019s Witness patient. Fertil. Steril., 90.","DOI":"10.1016\/j.fertnstert.2007.11.070"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8153","DOI":"10.4076\/1752-1947-3-8153","article-title":"Spontaneous heterotopic pregnancy with tubal rupture: A case report and review of the literature","volume":"3","author":"Tandon","year":"2009","journal-title":"J. Med. Case Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"375","DOI":"10.7863\/jum.2013.32.2.375","article-title":"Spontaneous heterotopic cervical pregnancy and successful pregnancy outcome","volume":"32","author":"Uysal","year":"2013","journal-title":"J. Ultrasound Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.jogoh.2017.05.008","article-title":"Spontaneous heterotopic triplets\u2014A review of literature","volume":"46","author":"Bataille","year":"2017","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.4103\/0366-6999.241820","article-title":"Successful Laparoscopic Management of Heterotopic Pregnancy at 12+2 Weeks of Gestation","volume":"131","author":"Xie","year":"2018","journal-title":"Chin. Med. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1055\/s-0039-1683910","article-title":"Spontaneous Heterotopic Triplet Pregnancy with a Two Viable Intrauterine Embryos and an Ectopic One with Right Tubal Rupture","volume":"41","author":"Reis","year":"2019","journal-title":"Rev. Bras. Ginecol. Obs."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e00144","DOI":"10.1016\/j.crwh.2019.e00144","article-title":"Live birth after treatment of a spontaneous ovarian heterotopic pregnancy: A case report","volume":"24","author":"Ramalho","year":"2019","journal-title":"Case Rep. Womens Health"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1055\/a-1079-6260","article-title":"Spontaneous Heterotopic Pregnancy as an Uncommon Clinical Problem","volume":"224","author":"Stanic","year":"2020","journal-title":"Z. Geburtshilfe Neonatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"\u010cerniauskait\u0117, M., Vaigauskait\u0117, B., Rama\u0161auskait\u0117, D., and \u0160ilk\u016bnas, M. (2020). Spontaneous Heterotopic Pregnancy: Case Report and Literature Review. Medicina, 56.","DOI":"10.3390\/medicina56080365"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"178","DOI":"10.5811\/cpcem.2020.2.45933","article-title":"Heterotopic Pregnancy Diagnosed with Point-of-care Ultrasound in the Emergency Department: A Case Report","volume":"4","author":"Holley","year":"2020","journal-title":"Clin. Pract. Cases Emerg. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/8892273","article-title":"Vaginal Delivery at Term in a Woman with a Spontaneous Heterotopic Pregnancy Treated with Laparoscopic Salpingectomy","volume":"2020","author":"Diakosavvas","year":"2020","journal-title":"Case Rep. Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1080\/01443615.2019.1607269","article-title":"Successful hysteroscopic treatment of a cervical heterotopic pregnancy: Case report and literature review","volume":"40","author":"Rubattu","year":"2020","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e03373","DOI":"10.1016\/j.heliyon.2020.e03373","article-title":"A case of spontaneous heterotopic pregnancy in natural conception complicated with hemoperitoneum","volume":"6","author":"Aziz","year":"2020","journal-title":"Heliyon"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0002-9378(83)90755-X","article-title":"Combined intrauterine and extrauterine gestations: A review","volume":"146","author":"Reece","year":"1983","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"672","DOI":"10.4103\/njcp.njcp_67_16","article-title":"Ruptured ectopic in heterotopic pregnancy: Management and spontaneous vertex delivery of a live baby at term","volume":"21","author":"Onoh","year":"2018","journal-title":"Niger. J. Clin. Pract."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/12\/665\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:39:43Z","timestamp":1760179183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/12\/665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["medicina56120665"],"URL":"https:\/\/doi.org\/10.3390\/medicina56120665","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]}}}