{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:10:22Z","timestamp":1791461422096,"version":"4.3.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Does endometriosis prevalence differ in patients with obstructive M\u00fcllerian anomalies (OMA) versus those with nonobstructive M\u00fcllerian anomalies (NOMA), and in patients with NOMA versus those without M\u00fcllerian anomalies?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>The quantitative synthesis of published data demonstrates a substantially increased prevalence of endometriosis in patients with OMA compared with those with NOMA, and a similar prevalence in patients with NOMA and those without M\u00fcllerian anomalies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>The pathogenesis of endometriosis has not been definitively clarified yet. A higher prevalence of endometriosis in patients with OMA than in those with NOMA would support the retrograde menstruation (RM)\/implantation theory, whereas a higher prevalence of endometriosis in the NOMA group than in the group without M\u00fcllerian anomalies would support the embryonic remnants\/celomic metaplasia hypothesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>This systematic review with meta-analysis was restricted to full-length, English-language articles published in peer-reviewed journals between 1980 and 2023. The PubMed and EMBASE databases were searched using the keyword \u2018endometriosis\u2019 in combination with \u2018M\u00fcllerian anomalies\u2019, \u2018obstructive M\u00fcllerian anomalies\u2019, \u2018female genital malformations\u2019, \u2018retrograde menstruation\u2019, \u2018infertility\u2019, \u2018pelvic pain\u2019, and \u2018classification\u2019. References from relevant publications were screened, and PubMed\u2019s \u2018similar articles\u2019 and \u2018cited by\u2019 functions were used.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>Studies were selected if they reported the prevalence of surgically confirmed endometriosis in either individuals with OMA compared to those with NOMA, or patients with NOMA compared to those without M\u00fcllerian anomalies. Cohort and case-control studies and case series were deemed eligible for inclusion. Noncomparative studies, studies not reporting both the number of individuals with endometriosis and the total number of those with M\u00fcllerian anomalies or with other gynecological conditions, those including exclusively data on patients with absent or uncertain menstrual function (e.g. complete M\u00fcllerian agenesis category), or with imperforate hymen were excluded. Two reviewers independently abstracted data. The risk of bias was assessed with the Risk of Bias In Non-randomized Studies of Exposures tool. The overall certainty of the evidence was graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>Seven retrospective studies were included. The overall mean estimate of endometriosis prevalence was 47% (95% CI, 36\u201358%) in patients with OMA, and 19% (95% CI, 15\u201324%) in patients with NOMA, with a common odds ratio (OR) of 4.72 (95% CI, 2.54\u20138.77). The overall mean estimate of endometriosis prevalence in patients with NOMA was 23% (95% CI, 20\u201327%), and that in patients without M\u00fcllerian anomalies was 21% (95% CI, 20\u201322%), with a common OR of 0.95 (95% CI, 0.57\u20131.58). The overall certainty of the evidence according to GRADE guidelines was judged as low for both comparisons.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASON FOR CAUTION<\/jats:title>\n                  <jats:p>Some NOMA subtypes may create a partial obstacle to menstrual efflux and\/or generate dysfunctional myometrial contractions that favor transtubal reflux, thus increasing the risk of endometriosis and limiting the difference between OMA and NOMA. As infertility and pelvic pain are strongly associated with endometriosis, women with these symptoms are inappropriate controls. Confounding by indication could explain the lack of difference in endometriosis prevalence between patients with NOMA and those without M\u00fcllerian anomalies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>The results of this meta-analysis support the validity of the RM theory but do not definitively rule out alternative hypotheses. Thus, RM may be considered the initiator for the development of endometriotic lesions, while not excluding the contribution of both inheritable and tissue-specific genetic and epigenetic modifications as disease-promoting factors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>No funding was received for this review. P.Ve. is a member of the Editorial Board of Human Reproduction Open, the Journal of Obstetrics and Gynaecology Canada, and the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynecological practice. E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>REGISTRATION NUMBER<\/jats:title>\n                  <jats:p>N\/A.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humrep\/deae086","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T05:48:55Z","timestamp":1715406535000},"page":"1460-1470","source":"Crossref","is-referenced-by-count":38,"title":["M\u00fcllerian anomalies and endometriosis as potential explanatory models for the retrograde menstruation\/implantation and the embryonic remnants\/celomic metaplasia pathogenic theories: a systematic review and meta-analysis"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-0996","authenticated-orcid":false,"given":"Paolo","family":"Vercellini","sequence":"first","affiliation":[{"name":"Academic Center for Research on Adenomyosis and Endometriosis, 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Milano,","place":["Italy"]},{"name":"Department of Maternal, Infant, and Child Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5328-6696","authenticated-orcid":false,"given":"Martina","family":"Piccini","sequence":"additional","affiliation":[{"name":"Academic Center for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7917-1629","authenticated-orcid":false,"given":"Francesca","family":"Caprara","sequence":"additional","affiliation":[{"name":"Academic Center for Research on Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi , 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