{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:05:25Z","timestamp":1777100725433,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Objective: This study aimed to assess whether oocyte donation in triplet pregnancies is associated with increased risk of placental abnormalities and pregnancy complications compared to triplet pregnancies conceived through assisted reproductive technology (ART) without oocyte donation. Methods: This single-center, retrospective, case\u2013control study analyzed triplet pregnancies conceived via ART. The case group included pregnancies resulting from oocyte donation, while the control group comprised triplet pregnancies conceived by ART without oocyte donation. Maternal, obstetric, fetal, and neonatal outcomes were assessed. Gross and histopathological placental findings were evaluated using standardized criteria. Univariate and multivariate statistical analyses were performed. Results: A total of 77 triplet pregnancies (231 fetuses) were included: 29 in the oocyte donation group (87 fetuses) and 48 in the non-oocyte donation group (144 fetuses). Multivariate analysis revealed significantly higher rates of pregnancy-induced hypertension (p = 0.03), preeclampsia (p = 0.03), fetal growth restriction (p = 0.04), and fetal death (p = 0.01) in the oocyte donation group. Placental evaluation showed a higher frequency of infarcts (p = 0.04) and chronic inflammatory lesions\u2014chronic villitis (p = 0.02) and chronic deciduitis (p = 0.03)\u2014as well as signs of fetal vascular malperfusion, including avascular villi (p = 0.02) and stromal\u2013vascular karyorrhexis (p = 0.01). Intervillous fibrin deposition was also more common in this group (p = 0.02). Conclusions: Oocyte donation in triplet pregnancies is associated with increased rates of placental abnormalities and adverse maternal and fetal outcomes when compared with ART without oocyte donation. Placental examination may provide valuable insights into the mechanisms involved. Further research is warranted to clarify the underlying immunological and vascular pathways. Synopsis: In our cohort of 77 triplet pregnancies, those conceived via oocyte donation showed significantly higher rates of preeclampsia, fetal growth restriction, and fetal death. Placental examination revealed more chronic villitis, deciduitis, intervillous fibrin, avascular villi, and stromal\u2013vascular karyorrhexis, suggesting immune and vascular dysfunction in oocyte donation pregnancies.<\/jats:p>","DOI":"10.3390\/diagnostics15212681","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T01:35:11Z","timestamp":1761269711000},"page":"2681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Placental Pathological Findings and Clinical Outcomes in Triplet Pregnancies Conceived via Oocyte Donation and Non-Oocyte Donation: A Case\u2013Control Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Eva Manuela","family":"Pena-Burgos","sequence":"first","affiliation":[{"name":"Pathology Department, Gregorio Mara\u00f1\u00f3n General University Hospital, 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-3699","authenticated-orcid":false,"given":"Maria","family":"De la Calle","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Juan","family":"Pozo-Kreilinger","sequence":"additional","affiliation":[{"name":"Pathology Department, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Garc\u00eda-D\u00edaz","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department, Gregorio Mara\u00f1\u00f3n General University Hospital, 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita Mar\u00eda","family":"Regojo-Zapata","sequence":"additional","affiliation":[{"name":"Pathology Department, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.siny.2014.03.001","article-title":"Multiple pregnancies following assisted reproductive technologies\u2014A happy consequence or double trouble?","volume":"19","author":"Murray","year":"2014","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103419","DOI":"10.1016\/j.rbmo.2023.103419","article-title":"Comparison of maternal, fetal, obstetric and neonatal outcomes for 234 triplet pregnancies conceived in vivo versus IVF and ICSI conceptions","volume":"48","year":"2024","journal-title":"Reprod. Biomed. Online"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/j.1471-0528.2005.00627.x","article-title":"Prenatal diagnosis and obstetric outcomes in triplet pregnancies in relation to chorionicity","volume":"112","author":"Geipel","year":"2005","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0301-2115(02)00270-1","article-title":"Neonatal outcome of triplet versus twin and singleton pregnancies: A matched case control study","volume":"107","author":"Ballabh","year":"2003","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ajog.2003.12.003","article-title":"Maternal morbidity and obstetric complications in triplet pregnancies and quadruplet and higher-order multiple pregnancies","volume":"191","author":"Wen","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1093\/humrep\/deu175","article-title":"Assisted reproductive technology in Europe, 2010: Results generated from European registers by ESHRE\u2020","volume":"29","author":"Kupka","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_7","unstructured":"Martin, J.A., Hamilton, B.E., and Osterman, M.J.K. (2012). Three decades of twin births in the United States, 1980\u20132009. NCHS Data Brief., 1\u20138."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1093\/humupd\/dmw012","article-title":"Maternal and fetal outcomes in oocyte donation pregnancies","volume":"22","author":"Savasi","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1093\/humrep\/deaa108","article-title":"Increased risk of severe maternal morbidity in women with twin pregnancies resulting from oocyte donation","volume":"35","author":"Korb","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1093\/humupd\/dmq017","article-title":"Clinical and immunologic aspects of egg donation pregnancies: A systematic review","volume":"16","author":"Lashley","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1093\/humrep\/der469","article-title":"Association between oocyte donation and maternal and perinatal outcomes in women aged 43 years or older","volume":"27","author":"Scherier","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ajog.2015.11.020","article-title":"Oocyte donation pregnancies and the risk of preeclampsia or gestational hypertension: A systematic review and metaanalysis","volume":"214","author":"Masoudian","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/1471-0528.14257","article-title":"Obstetric and neonatal complications in pregnancies conceived after oocyte donation: A systematic review and meta-analysis","volume":"124","author":"Storgaard","year":"2017","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/ppe.12857","article-title":"Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF","volume":"36","author":"Modest","year":"2022","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.fertnstert.2014.01.055","article-title":"Effect of oocyte donation on pregnancy outcomes in in vitro fertilization twin gestations","volume":"101","author":"Sekhon","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejogrb.2017.09.015","article-title":"Higher risk of preterm birth and low birth weight following oocyte donation: A systematic review and meta-analysis","volume":"218","author":"Mascarenhas","year":"2017","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1080\/14767058.2018.1533944","article-title":"Impact of oocyte donation on obstetric and perinatal complications in twin pregnancies","volume":"33","author":"Boria","year":"2020","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1067\/S0002-9378(03)00577-5","article-title":"Placental villitis of unclear etiology during ovum donor in vitro fertilization pregnancy","volume":"189","author":"Styer","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1515\/JPM.2005.004","article-title":"Placental pathology and pregnancy outcomes in donor and non-donor oocyte in vitro fertilization pregnancies","volume":"33","author":"Perni","year":"2005","journal-title":"J. Perinat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejogrb.2019.05.006","article-title":"Structural, immunohistochemical and molecular features of placentas and placental sites after in vitro fertilization with donor eggs (surrogate motherhood)","volume":"238","author":"Kogan","year":"2019","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.placenta.2020.09.011","article-title":"Abnormal placental pathological findings and adverse clinical outcomes of oocyte donation","volume":"101","author":"Esteves","year":"2020","journal-title":"Placenta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e32347","DOI":"10.1371\/journal.pone.0032347","article-title":"Pregnancy Close to the Edge: An Immunosuppressive Infiltrate in the Chorionic Plate of Placentas from Uncomplicated Egg Cell Donation","volume":"7","author":"Schonkeren","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.fertnstert.2008.12.144","article-title":"Placental pathology in egg donor pregnancies","volume":"93","author":"Gundogan","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s10024-002-0014-0","article-title":"Triplet Placentas: Reference Values for Weights","volume":"5","author":"Pinar","year":"2002","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"698","DOI":"10.5858\/arpa.2015-0225-CC","article-title":"Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement","volume":"140","author":"Khong","year":"2016","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/s41379-021-00747-4","article-title":"Four major patterns of placental injury: A stepwise guide for understanding and implementing the 2016 Amsterdam consensus","volume":"34","author":"Redline","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"938","DOI":"10.3109\/14767058.2015.1024649","article-title":"Obstetrical and neonatal outcomes of triplet births\u2014Spontaneous versus assisted reproductive technology conception","volume":"29","author":"Morency","year":"2016","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1055\/s-0038-1660457","article-title":"The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations","volume":"35","author":"Shah","year":"2018","journal-title":"Am. J. Perinatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ajog.2022.08.010","article-title":"Placental pathology is necessary to understand common pregnancy complications and achieve an improved taxonomy of obstetrical disease","volume":"228","author":"Redline","year":"2023","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.1055\/s-0037-1599124","article-title":"Perinatal and Neonatal Outcomes of Triplet Gestations Based on Chorionicity","volume":"7","author":"Downing","year":"2017","journal-title":"AJP Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/uog.21987","article-title":"Effect of monochorionicity on perinatal outcome and growth discordance in triplet pregnancy: Collaborative multicenter study in England, 2000\u20132013","volume":"57","author":"Glinianaia","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Claverol, M.B., Moreno, I.A., Minaya, M.R., Mu\u00f1oz, M.F., Angullo, Z.R.R., Navarro, P.G., Garc\u00eda-Honduvilla, N., Ortega, M.A., Tiz\u00f3n, S.G., and Pintado-Recarte, M.P. (2024). Maternal, Perinatal and Neonatal Outcomes of Triplet Pregnancies According to Chorionicity: Our 15-Year Experience in a Tertiary-Level Center. J. Clin. Med., 13.","DOI":"10.3390\/jcm13061793"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.placenta.2009.12.024","article-title":"Placental markers of twin-to-twin transfusion syndrome in diamniotic\u2013monochorionic twins: A morphometric analysis of deep artery-to-vein anastomoses","volume":"31","author":"Shapiro","year":"2010","journal-title":"Placenta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1053\/j.semperi.2014.10.005","article-title":"Examination of the twin placenta","volume":"39","author":"Paepe","year":"2015","journal-title":"Semin. Perinatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Eliner, O., Koren, R.R., Ram, H.S., Levi, M., Herzberger, E.H., Wiser, A., and Miller, N. (2024). Perinatal Outcomes of Singleton, Twin and Triplet Gestations after Oocyte Donation: A Retrospective, Population-Based Cohort Analysis. Children, 11.","DOI":"10.3390\/children11080962"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1007\/s00404-020-05562-x","article-title":"Is advanced maternal age associated with placental vascular malperfusion? A prospective study from a single tertiary center","volume":"301","author":"Miremerg","year":"2020","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.5858\/arpa.2019-0481-OA","article-title":"Placentas From Women of Advanced Maternal Age","volume":"144","author":"Torous","year":"2020","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"E01","DOI":"10.3810\/pgm.2008.09.1920","article-title":"Maternal obesity and pregnancy","volume":"120","author":"Satpathy","year":"2008","journal-title":"Postgrad. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.fertnstert.2023.01.029","article-title":"Diminished ovarian reserve is a risk factor for preeclampsia and placental malperfusion lesions","volume":"119","author":"Herman","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1177\/1093526618775958","article-title":"Classification of Preterm Birth With Placental Correlates","volume":"21","author":"Chisholm","year":"2018","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2350\/13-05-1337-OA.1","article-title":"Peripheral Insertion of Umbilical Cord","volume":"16","author":"Luo","year":"2013","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1080\/14767058.2019.1636371","article-title":"Placental weight and size in relation to fetal growth restriction: A case-control study","volume":"34","author":"Liu","year":"2021","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1515\/jpm-2020-0141","article-title":"Assisted reproductive technologies (ART) and placental abnormalities","volume":"48","author":"Cochrane","year":"2020","journal-title":"J. Perinat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1067\/mob.2002.121653","article-title":"Clinical implications of velamentous cord insertion in triplet gestations","volume":"186","author":"Feldman","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/jso.24183","article-title":"Prognostic factors in alveolar soft part sarcoma: A SEER analysis: Alveolar Soft Part Sarcoma","volume":"113","author":"Wang","year":"2016","journal-title":"J. Surg. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/apm.12849","article-title":"Fetal vascular malperfusion, an update","volume":"126","author":"Redline","year":"2018","journal-title":"APMIS"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"588","DOI":"10.5858\/arpa.2015-0160-OA","article-title":"Chorangiosis of Chorionic Villi: What Does It Really Mean?","volume":"140","author":"Stanek","year":"2016","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_48","first-page":"163","article-title":"Chorioangioma\u2014New insights into a well-known problem I. Results of a clinical and morphological study of 136 cases","volume":"31","author":"Guschmann","year":"2003","journal-title":"J. Perinat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1517\/14656566.2015.1066335","article-title":"Aspirin and heparin in pregnancy","volume":"16","author":"Grandone","year":"2015","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.fertnstert.2021.12.017","article-title":"Placental pathology of term singleton live births conceived with fresh embryo transfer compared with those conceived without assisted reproductive technology","volume":"117","author":"Sacha","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3724\/zdxbyxb-2022-0510","article-title":"Comparison of perinatal outcomes and pregnancy complications between fresh embryo transfer and frozen embryo transfer in singleton pregnant women","volume":"52","author":"Wang","year":"2023","journal-title":"J. Zhejiang Univ. (Med. Sci.)"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1007\/s10815-020-01741-6","article-title":"Placental histopathology in IVF pregnancies resulting from the transfer of frozen-thawed embryos compared with fresh embryos","volume":"37","author":"Mizrachi","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ejogrb.2013.05.008","article-title":"Triplet pregnancies\u2014A three-decade perspective: Do we fare better?","volume":"170","author":"Weissman","year":"2013","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_54","first-page":"102735","article-title":"How Have the Baseline Characteristics and Outcomes of Triplet Pregnancies Changed over the Last Two Decades?","volume":"47","year":"2024","journal-title":"J. Obstet. Gynaecol. Can."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2681\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T01:56:29Z","timestamp":1761270989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":54,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["diagnostics15212681"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15212681","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}