Endometriosis and adverse pregnancy outcomes in primiparous women: a retrospective cohort study

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Methods Women with endometriosis were compared with primiparous controls without endometriosis. Primary outcomes were preterm birth and caesarean delivery; placenta previa was examined as a key secondary outcome. Multivariable logistic regression models adjusted for maternal age and mode of conception were used. Main Outcome Measures Preterm birth, caesarean delivery, placenta previa. Results Among 16,033 primiparous women, 118 had a diagnosis of endometriosis prior to pregnancy. After adjustment for maternal age and mode of conception, endometriosis was not independently associated with preterm birth (adjusted odds ratio 0.75; 95% confidence interval 0.44-1.28) or caesarean delivery (adjusted odds ratio, 1.17; 95% confidence interval, 0.81–1.71). In contrast, endometriosis was associated with placenta previa (adjusted odds ratio, 5.90; 95% confidence interval, 2.37–14.71). Conclusions In primiparous women, pre-existing endometriosis was independently associated with placenta previa, but not with preterm birth or caesarean delivery. These findings support abnormal early placentation as a potential mechanism linking endometriosis to adverse obstetric outcomes. Funding None. Medically Assisted reproduction (MAR) endometriosis placenta previa pregnancy outcomes primiparity Key message Whether endometriosis independently predisposes to placenta previa has been unclear. In this cohort of primiparous women, endometriosis was associated with a substantially increased risk independent of conception mode, though the relatively small number of events limits precision. These findings suggest that careful placental assessment may be warranted in women with endometriosis. Introduction Endometriosis is a chronic gynecological disease estimated to affect up to 10% of women of reproductive age and is commonly characterized by chronic pelvic pain and infertility. 1 Many affected women nevertheless conceive, and emerging evidence suggests that endometriosis is associated with an elevated risk of adverse obstetric outcomes, including preterm birth, placenta previa, and caesarean delivery. 2 – 6 However, interpretation of these associations is complicated by substantial heterogeneity across studies. In particular, much of the existing evidence is derived from large registry-based studies and meta-analyses that encompass heterogeneous populations, including multiparous women and rely on administrative endometriosis diagnoses ascertained during or after pregnancy, resulting in substantial variability in disease definition and timing across studies. 5 , 7 , 8 As a result, causal inference remains limited, and it is often unclear whether reported obstetric risks reflect the effect of endometriosis itself or downstream consequences of prior obstetric history. Furthermore, medical assisted reproduction (MAR) is disproportionately used among women with endometriosis and is independently associated with adverse pregnancy and delivery outcomes, including preterm birth, placenta previa, and caesarean delivery. 9 – 11 However, conception mode is inconsistently reported or accounted for in many observational studies. 5 , 7 Importantly, few studies have specifically examined whether obstetric risks associated with endometriosis are already present in the first pregnancy. 12 , 13 The aim of this study was to investigate the association between pre–existing endometriosis and adverse pregnancy and delivery outcomes, with a primary focus on preterm birth and caesarean delivery. In addition, we examined the risk of placenta previa as a key secondary outcome. To isolate the effect of endometriosis itself, analyses were restricted to primiparous women with histologically confirmed endometriosis diagnosed prior to conception. Material and Methods Study design and setting This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Ulm University Hospital, a certified endometriosis center and level I perinatal center. Women with endometriosis were identified through the hospital information system based on a documented surgical diagnosis and a subsequent delivery at our institution. All women in the endometriosis group had undergone laparoscopic surgery with histological confirmation of endometriosis prior to their first delivery. Only primiparous women were included, defined as women with no prior live or stillbirths before the index pregnancy. Multiple gestations were excluded. Deliveries in the endometriosis group occurred between April 2004 and June 2025, with prior surgical treatment for endometriosis performed between March 2000 and March 2024. The control group consisted of primiparous women without a diagnosis of endometriosis who delivered singleton pregnancies at the same institution between January 2014 and June 2025. Controls were identified from the institutional obstetric database and had no documented clinical or surgical diagnosis of endometriosis. The different inclusion periods reflect a transition in the hospital documentation system, which limited availability of complete obstetric data for controls prior to 2014. Exposure and covariates The exposure of interest was endometriosis, defined as laparoscopically and histologically confirmed disease diagnosed prior to the index pregnancy. In a small minority of women (n = 5), endometriosis was diagnosed intraoperatively at the time of caesarean delivery and was therefore presumed to have been present prior to pregnancy. Endometriosis phenotype was classified based on surgical reports as peritoneal endometriosis, ovarian endometrioma, and/or deep infiltrating endometriosis. Maternal age at delivery was included as a continuous variable in adjusted analyses. Body mass index (BMI) was incompletely documented and therefore not included in the primary multivariable models. Mode of conception was categorized as spontaneous conception or MAR. Outcome measures The primary outcomes were preterm birth and caesarean delivery. Preterm birth was defined as delivery before 37 + 0 weeks of gestation. Placenta previa was examined as a secondary outcome and was defined as placenta previa confirmed intraoperatively at the time of delivery. Gestational age at delivery was determined based on first–trimester ultrasound or last menstrual period. Statistical analysis Baseline characteristics were summarized using descriptive statistics. Categorical variables were compared using chi-square tests, and continuous variables using the Mann–Whitney U test. Continuous variables are presented as medians with interquartile ranges (IQR). Associations between endometriosis and obstetric outcomes were assessed using binary logistic regression models, with results presented as odds ratios and 95% confidence intervals. Primary multivariable models were adjusted for maternal age at delivery and MAR. Data completeness was assessed for all covariates prior to analysis. Body mass index (BMI) was incompletely documented and therefore not included in the primary multivariable models. Complete-case analyses were performed for all primary analyses. To determine whether the association between endometriosis and placenta previa differed by mode of conception, a two-way interaction term between endometriosis and MAR was included in the multivariable logistic regression model. As adenomyosis was present in a subset of the endometriosis cohort (n = 29; 24.6%) and may independently contribute to abnormal placentation, a prespecified sensitivity analysis was performed excluding women with documented adenomyosis to assess whether the observed association between endometriosis and placenta previa persisted in the absence of this comorbidity. No imputation methods were applied due to the retrospective nature of the study. All statistical analyses were performed using IBM SPSS Statistics for Mac (version 31.0.0.0; IBM Corp., Armonk, NY). A two-sided P value < 0.05 was considered statistically significant. Given the retrospective design, no core outcome set was applicable, and patients or the public were not involved in the design, conduct, or reporting of the research. Ethics approval This retrospective cohort study was approved by the Ethics Committee of Ulm University (approval number 197/25). Due to the retrospective nature of the study and the use of anonymized clinical data, the requirement for informed consent was waived. Strobe Statement This study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results Study population A total of 16,033 primiparous women with singleton pregnancies were included in the analysis, comprising 118 women with histologically confirmed endometriosis diagnosed prior to conception and 15,915 controls without endometriosis. All deliveries occurred at Ulm University Hospital. Women in the endometriosis group had undergone laparoscopic surgery for endometriosis before their first delivery. Multiple gestations were excluded. Baseline characteristics Baseline characteristics are shown in Table 1 . Women with endometriosis were significantly older at delivery compared with controls (median age, 32 vs 31 years; P < 0.001). Conception by MAR was substantially more common among women with endometriosis (41.5% vs 4.4%; P < 0.001). Documented pre–pregnancy BMI index did not differ significantly between groups (median (IQR), 24.0 (21.5–27.1) vs 23.4 (21.1–27.0); P = 0.443). Clinical characteristics of the endometriosis cohort are shown in Table 2 . Table 1 Baseline characteristics of primiparous women with and without endometriosis Characteristic Endometriosis (n = 118) Controls (n = 15,915) P-value Maternal age at delivery, years, median (IQR) 32 (30–36) 31 (27–34) < 0.001 Pre-pregnancy BMI, kg/m², median (IQR)* 24.0 (21.5–27.1) 23.4 (21.1–27.0) 0.443 Medically assisted reproduction, n (%) 49 (41.5) 694 (4.4) < 0.001 Data are presented as median (IQR) or n (%). P-values were calculated using the Mann–Whitney U test for continuous variables and chi-square test for categorical variables. *Body mass index was available for 97 women with endometriosis and 14,892 controls. BMI, body mass index; IQR, interquartile range. Table 2 Pregnancy and delivery outcomes in primiparous women with and without endometriosis Outcome Endometriosis (n = 118) Controls (n = 15,915) P-value Gestational age at delivery, days, median (IQR) 276 (267–283) 276 (268–283) 0.504 Preterm birth < 37 weeks, n (%) 16 (13.6) 2280 (14.3) 0.813 Caesarean delivery, n (%) 49 (41.5) 5198 (32.7) 0.041 Placenta previa, n (%) 6 (5.1) 83 (0.5) < 0.001 Placental abruption, n (%) 2 (1.7) 68 (0.4) 0.037 Fetal growth restriction, n (%) 13 (11.0) 823 (5.2) 0.004 Gestational hypertension, n (%) 5 (4.2) 129 (0.8) < 0.001 Pre-eclampsia, n (%) 9 (7.6) 815 (5.1) 0.219 Data are presented as median (IQR) or n (%). P-values were calculated using the Mann–Whitney U test for continuous variables and chi-square test or Fisher's exact test, as appropriate. IQR, interquartile range. Pregnancy and delivery outcomes Unadjusted pregnancy and delivery outcomes are summarized in Table 3 . Caesarean delivery rates were high in both groups (41.5% and 32.7%, Table S3), consistent with the tertiary referral setting. Caesarean delivery occurred more frequently among women with endometriosis than among controls (41.5% vs 32.7%; P = 0.041). In the endometriosis group, this corresponded to a total of 49 caesarean deliveries. Indications included placenta previa (n = 6), non–cephalic presentation (n = 5), and primary caesarean delivery for maternal indications (n = 3). The majority of procedures were secondary caesarean deliveries decided intrapartum (n = 31). Caesarean delivery on maternal request accounted for three cases. Rates of preterm birth before 37 weeks of gestation were similar between groups (13.6% vs 14.3%; P = 0.813). Placenta previa was significantly more common in the endometriosis group (5.1% vs 0.5%; P < 0.001). Table 3 Adjusted association between pre-existing endometriosis and obstetric outcomes Outcome Adjusted OR (95% CI) P-value Caesarean delivery 1.17 (0.81–1.71) 0.404 Preterm birth < 37 weeks 0.75 (0.44–1.28) 0.286 Placenta previa 5.90 (2.37–14.71) < 0.001 Binary logistic regression models adjusted for maternal age at delivery and medically assisted reproduction. Endometriosis was defined as laparoscopically and histologically confirmed disease diagnosed prior to conception. CI, confidence interval; OR, odds ratio. Multivariable analyses Results of adjusted logistic regression analyses are presented in Table 4 . After adjustment for maternal age at delivery and MAR, endometriosis was not independently associated with caesarean delivery (aOR 1.17; 95% CI, 0.81–1.71) or preterm birth (aOR 0.75; 95% CI, 0.44–1.28). In contrast, endometriosis was strongly associated with placenta previa, independent of maternal age and MAR (aOR 5.90; 95% CI, 2.37–14.71). Table 4 Interaction between endometriosis and mode of conception in relation to placenta previa Predictor Adjusted OR 95% CI P-value Endometriosis 6.00 1.44–24.99 0.014 MAR 2.59 1.33–5.04 0.005 Endometriosis × MAR 0.97 0.15–6.23 0.976 Maternal age at delivery 1.06 1.02–1.11 0.005 Binary logistic regression model including a two-way interaction term between endometriosis and medically assisted reproduction, adjusted for maternal age at delivery. CI, confidence interval; MAR, medically assisted reproduction; OR, odds ratio. Effect modification by mode of conception To determine whether mode of conception modified the association between endometriosis and placenta previa, we fitted an additional multivariable logistic regression model including a two-way interaction term between endometriosis and MAR (endometriosis × MAR), with adjustment for maternal age ( Table S1 ). The interaction term was not statistically significant (aOR for interaction 0.97; 95% CI, 0.15–6.23; P = 0.976), providing evidence that direction and strength of the endometriosis–placenta previa association did not differ between spontaneously conceived pregnancies and those conceived by MAR. In this model, endometriosis remained independently associated with placenta previa (aOR 6.00; 95% CI, 1.44–24.99; P = 0.014). Sensitivity analysis excluding women with adenomyosis To address the potential confounding effect of adenomyosis, we repeated the primary multivariable analysis after excluding the 29 women (24.6%) with documented adenomyosis. Among the remaining 89 women with endometriosis, 3 had placenta previa (3.4%). The association between endometriosis and placenta previa remained statistically significant (aOR 4.08; 95% CI 1.21–13.75; P = 0.023), indicating that the observed association was not solely attributable to coexisting adenomyosis ( Table S3 ). Discussion In this cohort of primiparous women with singleton pregnancies, pre–existing endometriosis was associated with a higher rate of placenta previa, whereas no independent associations were observed with preterm birth or caesarean delivery after adjustment for maternal age and mode of conception. Key strengths of this study include restriction to primiparous women, a well-defined exposure based on laparoscopic and histological confirmation of endometriosis prior to conception, and detailed clinical data from a single tertiary center. Together, these features minimize confounding by prior obstetric history and enhance internal validity. Limitations include the small number of placenta previa events (n = 6), resulting in wide confidence intervals and limited precision of effect estimates. The modest sample size precludes subgroup analyses by endometriosis phenotype and limits statistical power for secondary outcomes. Adenomyosis was present in approximately one-quarter of the endometriosis cohort and may independently contribute to abnormal placentation. However, a sensitivity analysis excluding women with adenomyosis yielded similar results, and the association between endometriosis and placenta previa remained directionally consistent after exclusion of this comorbidity. Mode of conception was categorized as spontaneous or MAR, without further distinction between IVF, ICSI, or ovulation induction, which may obscure heterogeneity within the MAR group. Finally, undiagnosed endometriosis among controls cannot be excluded, although any such misclassification would likely bias results toward the null. From a clinical perspective, these findings indicate that endometriosis represents an independent risk for placenta previa, irrespective of conception mode. Current international guidelines focus on established maternal risk factors for placenta previa, such as prior caesarean delivery, advanced maternal age, and MAR, but do not explicitly include endometriosis among guideline-defined risk determinants. 14,15 Nevertheless, the present findings support the hypothesis that endometriosis may constitute an additional uterine risk phenotype predisposing to low placental implantation. As placental location is routinely assessed at the mid–pregnancy anomaly scan, heightened attention to placental localization may be warranted for women with endometriosis. 15 If placenta previa is identified, management typically includes follow–up imaging with transvaginal ultrasound to reassess placental position and to guide individualized counselling, surveillance and delivery planning. 15 Beyond placenta–related considerations, the absence of independent associations with other obstetric outcomes suggests that routine obstetric management may not require modification solely on the basis of an endometriosis diagnosis. These observations are biologically plausible and consistent with well-described alterations in endometrial receptivity, decidualization, and uterine function associated with endometriosis. 9,16–19 As all women were primiparous, the strongest established risk factor for placenta previa—prior caesarean delivery—was absent, indicating that the observed association cannot be attributed to caesarean-related uterine scarring. Endometriosis is characterized by chronic inflammation, progesterone resistance, impaired decidualization, and abnormalities of the myometrial junctional zone, features that may disrupt normal implantation dynamics and trophoblast invasion. 9,16–19 Perturbed uterine peristalsis and altered implantation site selection have also been proposed as mechanisms linking endometriosis to abnormal placentation. 5,20 The present findings support the concept of a pre–existing uterine environment predisposing to abnormal placentation. Consistent with this interpretation, population-based cohort studies and meta-analyses have repeatedly reported an increased risk of placenta previa among women with endometriosis, although effect sizes vary. 7,21–23 Larger registry-based studies generally demonstrate moderate associations, whereas analyses accounting for conception mode or restricting to spontaneous conceptions tend to report stronger effects. 23,24 The magnitude observed in the present cohort aligns with estimates from studies minimizing exposure misclassification. 5 The systematic review and meta-analysis by Matsuzaki et al. demonstrated higher pooled effect estimates in adjusted analyses and in subgroups with histologically confirmed endometriosis, supporting the interpretation that reliance on registry-based diagnoses may attenuate observed associations due to dilution of the exposed population. 5 Several clinically detailed cohort studies with surgically and histologically confirmed endometriosis further contextualize these findings. Lin et al. reported a more than fourfold increased risk of placenta previa (adjusted OR 4.51; 95 % CI 1.23–16.50) among nulliparous women with spontaneous singleton pregnancies and preconception histological confirmation of endometriosis. 13 Compared with this cohort, the present study extends existing evidence by explicitly accounting for mode of conception. Vercellini et al. exclusively studied women achieving a first spontaneous pregnancy after surgery for endometriosis and reported that the risk of placenta previa varies by endometriosis phenotype and is highest in women with rectovaginal endometriosis (OR 5.81; 95% CI 1.53–22.03). 25 However, the absence of a contemporaneous control group without endometriosis limited causal inference regarding endometriosis per se. Mannini and Sorbi et al. likewise observed higher rates of placenta previa in women with histologically confirmed endometriosis, but parity was mixed and nulliparity was treated as a covariate rather than a defining design feature. 26 Taken together, these studies support a biologically consistent association between endometriosis and abnormal placentation, while highlighting the importance of cohort definition, parity restriction, and conception-mode stratification. By restricting the population to primiparous women with a preconception, histologically confirmed diagnosis of endometriosis and explicitly accounting for MAR, the present study reduces key sources of confounding that have limited interpretability of earlier findings. From a clinical perspective, although infrequent at a population level, the absolute rate of placenta previa among women with endometriosis in the present cohort (5.1%) indicates that this placental phenotype is clinically meaningful and directly relevant to antenatal surveillance and delivery planning. Absolute rates among controls were consistent with population-based estimates, supporting the validity of the reference group. 21,22 Taken together, these findings suggest that previously reported associations between endometriosis and broader obstetric outcomes may be largely mediated through abnormal placentation, rather than reflecting a generalized obstetric risk attributable to endometriosis itself. 23,24 In this context, the absence of an independent association between endometriosis and preterm birth in the present analysis contrasts with several large population-based studies reporting modestly increased risks. 8,24 Ibiebele et al. reported a modest increase in preterm birth among women with endometriosis who conceived without ART compared with controls (adjusted risk ratio (aRR) 1.24; 99% CI 1.06–1.44). 24 Similarly, Velez et al. observed comparable estimates independent of mode of conception (aRR 1.26; 95% CI 1.20–1.33). 8 Notably, these studies included mixed-parity populations. Findings from clinical cohorts with histologically confirmed endometriosis are heterogeneous with respect to preterm birth. Lin et al. observed increased rates of preterm birth among nulliparous women with spontaneously conceived singleton pregnancies (adjusted OR 2.42; 95% CI 1.05–5.57). 13 Mannini and Sorbi et al. reported higher overall rates of preterm birth among women with surgically and histologically confirmed endometriosis (OR 0.32 for the non-event; 95% CI 0.20–0.52); however, estimates were not adjusted for mode of conception, and parity was mixed. 26 In our cohort, overall rates of preterm birth were high in both groups ( Table S3 ), which may have limited the ability to detect an additional effect attributable to endometriosis. Evidence from registry–based cohorts and meta-analyses suggests that preterm delivery in women with endometriosis is frequently associated with placental pathology, particularly placenta previa, rather than reflecting a primary tendency toward spontaneous preterm labor. 5,24 This interpretation is supported by lesion-specific analyses indicating that elevated preterm birth rates often co-occur with placental abnormalities or disease severity rather than representing a uniform effect of endometriosis across all pregnancies. 25,26 Similarly, although caesarean delivery was more frequent among women with endometriosis in unadjusted analyses, this association was no longer independent after adjustment. Comparable patterns have been reported in smaller clinically defined cohorts, where higher caesarean section rates were largely observed in conjunction with placental complications or disease severity. 12,13 These observations are consistent with population-based studies demonstrating attenuation after accounting for maternal age, infertility, mode of conception and placental pathology. 8,24 In the present cohort, all cases of placenta previa were delivered by caesarean section, underscoring that caesarean delivery represents a downstream consequence of abnormal placentation. 5 Conclusion In this analysis, endometriosis was associated with an increased risk of placenta previa, whereas no independent associations were observed with preterm birth or caesarean delivery after adjustment. These findings suggest that endometriosis may be linked to abnormal placentation rather than to a generalized obstetric risk profile. Together, the results underscore the importance of careful cohort definition and conception–mode stratification when evaluating pregnancy outcomes associated with endometriosis. Abbreviations BMI Body mass index CI Confidence interval IQR Interquartile range MAR Medically assisted reproduction OR Odds Ratio aOR Adjusted Odds Ratio Declarations Disclosure of Interests The authors report no conflict of interests. Acknowledgements The authors thank Prof. Dr. rer. nat. Thomas Friedl for their statistical advice. Contribution to Authorship JT, KH and KB conceived and designed the study. JT was responsible for data acquisition and statistical analysis. LZ and SA contributed to interpretation of the data and critically revised the manuscript. Funding This research received no external funding, and no funding body had any role in study design, data collection, analysis, interpretation, or manuscript preparation. References Parazzini F, Esposito G, Tozzi L, Noli S, Bianchi S. 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Arch Gynecol Obstet . 2017;295(1):141-151. doi:10.1007/s00404-016-4222-7 Additional Declarations No competing interests reported. Supplementary Files Supplementalmaterial260319.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 21 Apr, 2026 Reviews received at journal 21 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers invited by journal 03 Apr, 2026 Editor assigned by journal 27 Mar, 2026 Submission checks completed at journal 27 Mar, 2026 First submitted to journal 26 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9234842","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617123389,"identity":"92e1eede-e480-4382-b7fc-fe05e6ebdcdb","order_by":0,"name":"Julia Téoule","email":"data:image/png;base64,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","orcid":"","institution":"University of Ulm","correspondingAuthor":true,"prefix":"","firstName":"Julia","middleName":"","lastName":"Téoule","suffix":""},{"id":617123390,"identity":"5f01d70e-d269-4471-9a7f-1fb88fdcdfbd","order_by":1,"name":"Leonie Zikarsky","email":"","orcid":"","institution":"University of Ulm","correspondingAuthor":false,"prefix":"","firstName":"Leonie","middleName":"","lastName":"Zikarsky","suffix":""},{"id":617123391,"identity":"999e88d1-cee6-4fc6-a235-b2b4c9e19d74","order_by":2,"name":"Karin Bundschu","email":"","orcid":"","institution":"University of Ulm","correspondingAuthor":false,"prefix":"","firstName":"Karin","middleName":"","lastName":"Bundschu","suffix":""},{"id":617123392,"identity":"eddc19e5-60e7-45f9-979b-70956ac3b012","order_by":3,"name":"Sophia Andres","email":"","orcid":"","institution":"University of Ulm","correspondingAuthor":false,"prefix":"","firstName":"Sophia","middleName":"","lastName":"Andres","suffix":""},{"id":617123393,"identity":"f6f790c4-f94b-46a3-b0a5-9c7f9803f56b","order_by":4,"name":"Katharina Hancke","email":"","orcid":"","institution":"University of Ulm","correspondingAuthor":false,"prefix":"","firstName":"Katharina","middleName":"","lastName":"Hancke","suffix":""}],"badges":[],"createdAt":"2026-03-26 13:38:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9234842/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9234842/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106501562,"identity":"73f9fdde-be8e-41f2-b2db-6fbec8b1e56a","added_by":"auto","created_at":"2026-04-09 09:13:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":583287,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9234842/v1/ad14dc76-fda3-486c-b886-95e97532e765.pdf"},{"id":106501218,"identity":"22d2fc0b-b308-4890-8a02-771925236caa","added_by":"auto","created_at":"2026-04-09 09:12:49","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":20759,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementalmaterial260319.docx","url":"https://assets-eu.researchsquare.com/files/rs-9234842/v1/86a4c949728c4839901d2454.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Endometriosis and adverse pregnancy outcomes in primiparous women: a retrospective cohort study","fulltext":[{"header":"Key message","content":"\u003cp\u003eWhether endometriosis independently predisposes to placenta previa has been unclear. In this cohort of primiparous women, endometriosis was associated with a substantially increased risk independent of conception mode, though the relatively small number of events limits precision. These findings suggest that careful placental assessment may be warranted in women with endometriosis.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eEndometriosis is a chronic gynecological disease estimated to affect up to 10% of women of reproductive age and is commonly characterized by chronic pelvic pain and infertility.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Many affected women nevertheless conceive, and emerging evidence suggests that endometriosis is associated with an elevated risk of adverse obstetric outcomes, including preterm birth, placenta previa, and caesarean delivery.\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e However, interpretation of these associations is complicated by substantial heterogeneity across studies.\u003c/p\u003e \u003cp\u003eIn particular, much of the existing evidence is derived from large registry-based studies and meta-analyses that encompass heterogeneous populations, including multiparous women and rely on administrative endometriosis diagnoses ascertained during or after pregnancy, resulting in substantial variability in disease definition and timing across studies.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e As a result, causal inference remains limited, and it is often unclear whether reported obstetric risks reflect the effect of endometriosis itself or downstream consequences of prior obstetric history.\u003c/p\u003e \u003cp\u003eFurthermore, medical assisted reproduction (MAR) is disproportionately used among women with endometriosis and is independently associated with adverse pregnancy and delivery outcomes, including preterm birth, placenta previa, and caesarean delivery.\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e However, conception mode is inconsistently reported or accounted for in many observational studies.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Importantly, few studies have specifically examined whether obstetric risks associated with endometriosis are already present in the first pregnancy.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe aim of this study was to investigate the association between pre\u0026ndash;existing endometriosis and adverse pregnancy and delivery outcomes, with a primary focus on preterm birth and caesarean delivery. In addition, we examined the risk of placenta previa as a key secondary outcome. To isolate the effect of endometriosis itself, analyses were restricted to primiparous women with histologically confirmed endometriosis diagnosed prior to conception.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003eStudy design and setting\u003c/p\u003e \u003cp\u003eThis retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Ulm University Hospital, a certified endometriosis center and level I perinatal center. Women with endometriosis were identified through the hospital information system based on a documented surgical diagnosis and a subsequent delivery at our institution. All women in the endometriosis group had undergone laparoscopic surgery with histological confirmation of endometriosis prior to their first delivery. Only primiparous women were included, defined as women with no prior live or stillbirths before the index pregnancy. Multiple gestations were excluded. Deliveries in the endometriosis group occurred between April 2004 and June 2025, with prior surgical treatment for endometriosis performed between March 2000 and March 2024. The control group consisted of primiparous women without a diagnosis of endometriosis who delivered singleton pregnancies at the same institution between January 2014 and June 2025. Controls were identified from the institutional obstetric database and had no documented clinical or surgical diagnosis of endometriosis. The different inclusion periods reflect a transition in the hospital documentation system, which limited availability of complete obstetric data for controls prior to 2014.\u003c/p\u003e \u003cp\u003eExposure and covariates\u003c/p\u003e \u003cp\u003eThe exposure of interest was endometriosis, defined as laparoscopically and histologically confirmed disease diagnosed prior to the index pregnancy. In a small minority of women (n\u0026thinsp;=\u0026thinsp;5), endometriosis was diagnosed intraoperatively at the time of caesarean delivery and was therefore presumed to have been present prior to pregnancy. Endometriosis phenotype was classified based on surgical reports as peritoneal endometriosis, ovarian endometrioma, and/or deep infiltrating endometriosis. Maternal age at delivery was included as a continuous variable in adjusted analyses. Body mass index (BMI) was incompletely documented and therefore not included in the primary multivariable models. Mode of conception was categorized as spontaneous conception or MAR.\u003c/p\u003e \u003cp\u003eOutcome measures\u003c/p\u003e \u003cp\u003eThe primary outcomes were preterm birth and caesarean delivery. Preterm birth was defined as delivery before 37\u0026thinsp;+\u0026thinsp;0 weeks of gestation. Placenta previa was examined as a secondary outcome and was defined as placenta previa confirmed intraoperatively at the time of delivery. Gestational age at delivery was determined based on first\u0026ndash;trimester ultrasound or last menstrual period.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eBaseline characteristics were summarized using descriptive statistics. Categorical variables were compared using chi-square tests, and continuous variables using the Mann\u0026ndash;Whitney U test. Continuous variables are presented as medians with interquartile ranges (IQR). Associations between endometriosis and obstetric outcomes were assessed using binary logistic regression models, with results presented as odds ratios and 95% confidence intervals. Primary multivariable models were adjusted for maternal age at delivery and MAR. Data completeness was assessed for all covariates prior to analysis. Body mass index (BMI) was incompletely documented and therefore not included in the primary multivariable models. Complete-case analyses were performed for all primary analyses.\u003c/p\u003e \u003cp\u003eTo determine whether the association between endometriosis and placenta previa differed by mode of conception, a two-way interaction term between endometriosis and MAR was included in the multivariable logistic regression model.\u003c/p\u003e \u003cp\u003eAs adenomyosis was present in a subset of the endometriosis cohort (n\u0026thinsp;=\u0026thinsp;29; 24.6%) and may independently contribute to abnormal placentation, a prespecified sensitivity analysis was performed excluding women with documented adenomyosis to assess whether the observed association between endometriosis and placenta previa persisted in the absence of this comorbidity. No imputation methods were applied due to the retrospective nature of the study. All statistical analyses were performed using IBM SPSS Statistics for Mac (version 31.0.0.0; IBM Corp., Armonk, NY). A two-sided P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003eGiven the retrospective design, no core outcome set was applicable, and patients or the public were not involved in the design, conduct, or reporting of the research.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthics approval\u003c/h3\u003e\n\u003cp\u003e This retrospective cohort study was approved by the Ethics Committee of Ulm University (approval number 197/25). Due to the retrospective nature of the study and the use of anonymized clinical data, the requirement for informed consent was waived.\u003c/p\u003e \u003cp\u003eStrobe Statement\u003c/p\u003e \u003cp\u003e This study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eStudy population\u003c/p\u003e \u003cp\u003eA total of 16,033 primiparous women with singleton pregnancies were included in the analysis, comprising 118 women with histologically confirmed endometriosis diagnosed prior to conception and 15,915 controls without endometriosis. All deliveries occurred at Ulm University Hospital. Women in the endometriosis group had undergone laparoscopic surgery for endometriosis before their first delivery. Multiple gestations were excluded.\u003c/p\u003e\n\u003ch3\u003eBaseline characteristics\u003c/h3\u003e\n\u003cp\u003eBaseline characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Women with endometriosis were significantly older at delivery compared with controls (median age, 32 vs 31 years; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Conception by MAR was substantially more common among women with endometriosis (41.5% vs 4.4%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Documented pre\u0026ndash;pregnancy BMI index did not differ significantly between groups (median (IQR), 24.0 (21.5\u0026ndash;27.1) vs 23.4 (21.1\u0026ndash;27.0); P\u0026thinsp;=\u0026thinsp;0.443). Clinical characteristics of the endometriosis cohort are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of primiparous women with and without endometriosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEndometriosis (n\u0026thinsp;=\u0026thinsp;118)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControls (n\u0026thinsp;=\u0026thinsp;15,915)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age at delivery, years, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (30\u0026ndash;36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (27\u0026ndash;34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pregnancy BMI, kg/m\u0026sup2;, median (IQR)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.0 (21.5\u0026ndash;27.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.4 (21.1\u0026ndash;27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.443\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedically assisted reproduction, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e694 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as median (IQR) or n (%). P-values were calculated using the Mann\u0026ndash;Whitney U test for continuous variables and chi-square test for categorical variables. *Body mass index was available for 97 women with endometriosis and 14,892 controls. BMI, body mass index; IQR, interquartile range.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePregnancy and delivery outcomes in primiparous women with and without endometriosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEndometriosis (n\u0026thinsp;=\u0026thinsp;118)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControls (n\u0026thinsp;=\u0026thinsp;15,915)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at delivery, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e276 (267\u0026ndash;283)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e276 (268\u0026ndash;283)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.504\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2280 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean delivery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5198 (32.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlacenta previa, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlacental abruption, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal growth restriction, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e823 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational hypertension, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-eclampsia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e815 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as median (IQR) or n (%). P-values were calculated using the Mann\u0026ndash;Whitney U test for continuous variables and chi-square test or Fisher's exact test, as appropriate. IQR, interquartile range.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePregnancy and delivery outcomes\u003c/p\u003e \u003cp\u003eUnadjusted pregnancy and delivery outcomes are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Caesarean delivery rates were high in both groups (41.5% and 32.7%, Table S3), consistent with the tertiary referral setting. Caesarean delivery occurred more frequently among women with endometriosis than among controls (41.5% vs 32.7%; P\u0026thinsp;=\u0026thinsp;0.041). In the endometriosis group, this corresponded to a total of 49 caesarean deliveries. Indications included placenta previa (n\u0026thinsp;=\u0026thinsp;6), non\u0026ndash;cephalic presentation (n\u0026thinsp;=\u0026thinsp;5), and primary caesarean delivery for maternal indications (n\u0026thinsp;=\u0026thinsp;3). The majority of procedures were secondary caesarean deliveries decided intrapartum (n\u0026thinsp;=\u0026thinsp;31). Caesarean delivery on maternal request accounted for three cases. Rates of preterm birth before 37 weeks of gestation were similar between groups (13.6% vs 14.3%; P\u0026thinsp;=\u0026thinsp;0.813). Placenta previa was significantly more common in the endometriosis group (5.1% vs 0.5%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdjusted association between pre-existing endometriosis and obstetric outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.17 (0.81\u0026ndash;1.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.404\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.75 (0.44\u0026ndash;1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.286\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlacenta previa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.90 (2.37\u0026ndash;14.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eBinary logistic regression models adjusted for maternal age at delivery and medically assisted reproduction. Endometriosis was defined as laparoscopically and histologically confirmed disease diagnosed prior to conception. CI, confidence interval; OR, odds ratio.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMultivariable analyses\u003c/p\u003e \u003cp\u003eResults of adjusted logistic regression analyses are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. After adjustment for maternal age at delivery and MAR, endometriosis was not independently associated with caesarean delivery (aOR 1.17; 95% CI, 0.81\u0026ndash;1.71) or preterm birth (aOR 0.75; 95% CI, 0.44\u0026ndash;1.28). In contrast, endometriosis was strongly associated with placenta previa, independent of maternal age and MAR (aOR 5.90; 95% CI, 2.37\u0026ndash;14.71).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInteraction between endometriosis and mode of conception in relation to placenta previa\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredictor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometriosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.44\u0026ndash;24.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMAR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.33\u0026ndash;5.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometriosis \u0026times; MAR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.15\u0026ndash;6.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age at delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.02\u0026ndash;1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBinary logistic regression model including a two-way interaction term between endometriosis and medically assisted reproduction, adjusted for maternal age at delivery. CI, confidence interval; MAR, medically assisted reproduction; OR, odds ratio.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eEffect modification by mode of conception\u003c/h3\u003e\n\u003cp\u003eTo determine whether mode of conception modified the association between endometriosis and placenta previa, we fitted an additional multivariable logistic regression model including a two-way interaction term between endometriosis and MAR (endometriosis \u0026times; MAR), with adjustment for maternal age (\u003cb\u003eTable \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e). The interaction term was not statistically significant (aOR for interaction 0.97; 95% CI, 0.15\u0026ndash;6.23; P\u0026thinsp;=\u0026thinsp;0.976), providing evidence that direction and strength of the endometriosis\u0026ndash;placenta previa association did not differ between spontaneously conceived pregnancies and those conceived by MAR. In this model, endometriosis remained independently associated with placenta previa (aOR 6.00; 95% CI, 1.44\u0026ndash;24.99; P\u0026thinsp;=\u0026thinsp;0.014).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analysis excluding women with adenomyosis\u003c/h2\u003e \u003cp\u003eTo address the potential confounding effect of adenomyosis, we repeated the primary multivariable analysis after excluding the 29 women (24.6%) with documented adenomyosis. Among the remaining 89 women with endometriosis, 3 had placenta previa (3.4%). The association between endometriosis and placenta previa remained statistically significant (aOR 4.08; 95% CI 1.21\u0026ndash;13.75; P\u0026thinsp;=\u0026thinsp;0.023), indicating that the observed association was not solely attributable to coexisting adenomyosis (\u003cb\u003eTable S3\u003c/b\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this cohort of primiparous women with singleton pregnancies, pre–existing endometriosis was associated with a higher rate of placenta previa, whereas no independent associations were observed with preterm birth or caesarean delivery after adjustment for maternal age and mode of conception.\u003c/p\u003e\n\u003cp\u003eKey strengths of this study include restriction to primiparous women, a well-defined exposure based on laparoscopic and histological confirmation of endometriosis prior to conception, and detailed clinical data from a single tertiary center. Together, these features minimize confounding by prior obstetric history and enhance internal validity. Limitations include the small number of placenta previa events (n = 6), resulting in wide confidence intervals and limited precision of effect estimates. The modest sample size precludes subgroup analyses by endometriosis phenotype and limits statistical power for secondary outcomes. Adenomyosis was present in approximately one-quarter of the endometriosis cohort and may independently contribute to abnormal placentation. However, a sensitivity analysis excluding women with adenomyosis yielded similar results, and the association between endometriosis and placenta previa remained directionally consistent after exclusion of this comorbidity. Mode of conception was categorized as spontaneous or MAR, without further distinction between IVF, ICSI, or ovulation induction, which may obscure heterogeneity within the MAR group. Finally, undiagnosed endometriosis among controls cannot be excluded, although any such misclassification would likely bias results toward the null.\u003c/p\u003e\n\u003cp\u003eFrom a clinical perspective, these findings indicate that endometriosis represents an independent risk for placenta previa, irrespective of conception mode. Current international guidelines focus on established maternal risk factors for placenta previa, such as prior caesarean delivery, advanced maternal age, and MAR, but do not explicitly include endometriosis among guideline-defined risk determinants. \u003csup\u003e14,15\u003c/sup\u003e Nevertheless, the present findings support the hypothesis that endometriosis may constitute an additional uterine risk phenotype predisposing to low placental implantation. As placental location is routinely assessed at the mid–pregnancy anomaly scan, heightened attention to placental localization may be warranted for women with endometriosis.\u003csup\u003e15\u003c/sup\u003e If placenta previa is identified, management typically includes follow–up imaging with transvaginal ultrasound to reassess placental position and to guide individualized counselling, surveillance and delivery planning.\u003csup\u003e15\u003c/sup\u003e Beyond placenta–related considerations, the absence of independent associations with other obstetric outcomes suggests that routine obstetric management may not require modification solely on the basis of an endometriosis diagnosis.\u003c/p\u003e\n\u003cp\u003eThese observations are biologically plausible and consistent with well-described alterations in endometrial receptivity, decidualization, and uterine function associated with endometriosis.\u003csup\u003e9,16–19\u003c/sup\u003e As all women were primiparous, the strongest established risk factor for placenta previa—prior caesarean delivery—was absent, indicating that the observed association cannot be attributed to caesarean-related uterine scarring. Endometriosis is characterized by chronic inflammation, progesterone resistance, impaired decidualization, and abnormalities of the myometrial junctional zone, features that may disrupt normal implantation dynamics and trophoblast invasion.\u003csup\u003e9,16–19\u003c/sup\u003e Perturbed uterine peristalsis and altered implantation site selection have also been proposed as mechanisms linking endometriosis to abnormal placentation.\u003csup\u003e5,20\u003c/sup\u003e The present findings support the concept of a pre–existing uterine environment predisposing to abnormal placentation.\u003c/p\u003e\n\u003cp\u003eConsistent with this interpretation, population-based cohort studies and meta-analyses have repeatedly reported an increased risk of placenta previa among women with endometriosis, although effect sizes vary.\u003csup\u003e7,21–23\u003c/sup\u003e Larger registry-based studies generally demonstrate moderate associations, whereas analyses accounting for conception mode or restricting to spontaneous conceptions tend to report stronger effects.\u003csup\u003e23,24\u003c/sup\u003e The magnitude observed in the present cohort aligns with estimates from studies minimizing exposure misclassification.\u003csup\u003e5\u003c/sup\u003e The systematic review and meta-analysis by Matsuzaki et al. demonstrated higher pooled effect estimates in adjusted analyses and in subgroups with histologically confirmed endometriosis, supporting the interpretation that reliance on registry-based diagnoses may attenuate observed associations due to dilution of the exposed population.\u003csup\u003e5\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeveral clinically detailed cohort studies with surgically and histologically confirmed endometriosis further contextualize these findings. Lin et al. reported a more than fourfold increased risk of placenta previa (adjusted OR 4.51; 95 % CI 1.23–16.50) among nulliparous women with spontaneous singleton pregnancies and preconception histological confirmation of endometriosis.\u003csup\u003e13\u003c/sup\u003e Compared with this cohort, the present study extends existing evidence by explicitly accounting for mode of conception. Vercellini et al. exclusively studied women achieving a first spontaneous pregnancy after surgery for endometriosis and reported that the risk of placenta previa varies by endometriosis phenotype and is highest in women with rectovaginal endometriosis (OR 5.81; 95% CI 1.53–22.03).\u003csup\u003e25\u003c/sup\u003e However, the absence of a contemporaneous control group without endometriosis limited causal inference regarding endometriosis per se.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMannini and Sorbi et al. likewise observed higher rates of placenta previa in women with histologically confirmed endometriosis, but parity was mixed and nulliparity was treated as a covariate rather than a defining design feature.\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eTaken together, these studies support a biologically consistent association between endometriosis and abnormal placentation, while highlighting the importance of cohort definition, parity restriction, and conception-mode stratification. By restricting the population to primiparous women with a preconception, histologically confirmed diagnosis of endometriosis and explicitly accounting for MAR, the present study reduces key sources of confounding that have limited interpretability of earlier findings.\u003c/p\u003e\n\u003cp\u003eFrom a clinical perspective, although infrequent at a population level, the absolute rate of placenta previa among women with endometriosis in the present cohort (5.1%) indicates that this placental phenotype is clinically meaningful and directly relevant to antenatal surveillance and delivery planning. Absolute rates among controls were consistent with population-based estimates, supporting the validity of the reference group.\u003csup\u003e21,22\u003c/sup\u003e Taken together, these findings suggest that previously reported associations between endometriosis and broader obstetric outcomes may be largely mediated through abnormal placentation, rather than reflecting a generalized obstetric risk attributable to endometriosis itself.\u003csup\u003e23,24\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn this context, the absence of an independent association between endometriosis and preterm birth in the present analysis contrasts with several large population-based studies reporting modestly increased risks.\u003csup\u003e8,24\u003c/sup\u003e Ibiebele et al. reported a modest increase in preterm birth among women with endometriosis who conceived without ART compared with controls (adjusted risk ratio (aRR) 1.24; 99% CI 1.06–1.44). \u003csup\u003e24\u003c/sup\u003e Similarly, Velez et al. observed comparable estimates independent of mode of conception (aRR 1.26; 95% CI 1.20–1.33). \u003csup\u003e8\u003c/sup\u003e Notably, these studies included mixed-parity populations. Findings from clinical cohorts with histologically confirmed endometriosis are heterogeneous with respect to preterm birth. Lin et al. observed increased rates of preterm birth among nulliparous women with spontaneously conceived singleton pregnancies (adjusted OR 2.42; 95% CI 1.05–5.57).\u003csup\u003e13\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eMannini and Sorbi et al. reported higher overall rates of preterm birth among women with surgically and histologically confirmed endometriosis (OR 0.32 for the non-event; 95% CI 0.20–0.52); however, estimates were not adjusted for mode of conception, and parity was mixed.\u003csup\u003e26\u003c/sup\u003e In our cohort, overall rates of preterm birth were high in both groups (\u003cstrong\u003eTable S3\u003c/strong\u003e), which may have limited the ability to detect an additional effect attributable to endometriosis.\u0026nbsp;Evidence from registry–based cohorts and meta-analyses suggests that preterm delivery in women with endometriosis is frequently associated with placental pathology, particularly placenta previa, rather than reflecting a primary tendency toward spontaneous preterm labor.\u003csup\u003e5,24\u003c/sup\u003e This interpretation is supported by lesion-specific analyses indicating that elevated preterm birth rates often co-occur with placental abnormalities or disease severity rather than representing a uniform effect of endometriosis across all pregnancies.\u003csup\u003e25,26\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eSimilarly, although caesarean delivery was more frequent among women with endometriosis in unadjusted analyses, this association was no longer independent after adjustment. Comparable patterns have been reported in smaller clinically defined cohorts, where higher caesarean section rates were largely observed in conjunction with placental complications or disease severity.\u003csup\u003e12,13\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese observations are consistent with population-based studies demonstrating attenuation after accounting for maternal age, infertility, mode of conception and placental pathology.\u003csup\u003e8,24\u003c/sup\u003e In the present cohort, all cases of placenta previa were delivered by caesarean section, underscoring that caesarean delivery represents a downstream consequence of abnormal placentation.\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this analysis, endometriosis was associated with an increased risk of placenta previa, whereas no independent associations were observed with preterm birth or caesarean delivery after adjustment. These findings suggest that endometriosis may be linked to abnormal placentation rather than to a generalized obstetric risk profile. Together, the results underscore the importance of careful cohort definition and conception\u0026ndash;mode stratification when evaluating pregnancy outcomes associated with endometriosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMAR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMedically assisted reproduction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdjusted Odds Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eDisclosure of Interests\u003c/p\u003e\n\u003cp\u003eThe authors report no conflict of interests.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe authors thank Prof. Dr. rer. nat. Thomas Friedl for their statistical advice.\u003c/p\u003e\n\u003cp\u003eContribution to Authorship\u003c/p\u003e\n\u003cp\u003eJT, KH and KB conceived and designed the study. JT was responsible for data acquisition and statistical analysis. LZ and SA contributed to interpretation of the data and critically revised the manuscript.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research received no external funding, and no funding body had any role in study design, data collection, analysis, interpretation, or manuscript preparation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eParazzini F, Esposito G, Tozzi L, Noli S, Bianchi S. Epidemiology of endometriosis and its comorbidities. \u003cem\u003eEur J Obstet Gynecol Reprod Biol\u003c/em\u003e. 2017;209:3-7. doi:10.1016/j.ejogrb.2016.04.021\u003c/li\u003e\n \u003cli\u003eZullo F, Spagnolo E, Saccone G, et al. Endometriosis and obstetrics complications: a systematic review and meta-analysis. \u003cem\u003eFertil Steril\u003c/em\u003e. 2017;108(4):667-672.e5. doi:10.1016/j.fertnstert.2017.07.019\u003c/li\u003e\n \u003cli\u003eNagase Y, Matsuzaki S, Ueda Y, et al. Association between Endometriosis and Delivery Outcomes: A Systematic Review and Meta-Analysis. \u003cem\u003eBiomedicines\u003c/em\u003e. 2022;10(2):478. doi:10.3390/biomedicines10020478\u003c/li\u003e\n \u003cli\u003eBreintoft K, Arendt LH, Uldbjerg N, Glavind MT, Forman A, Henriksen TB. Endometriosis and preterm birth: A Danish cohort study. \u003cem\u003eActa Obstet Gynecol Scand\u003c/em\u003e. 2022;101(4):417-423. doi:10.1111/aogs.14336\u003c/li\u003e\n \u003cli\u003eMatsuzaki S, Nagase Y, Ueda Y, et al. The association of endometriosis with placenta previa and postpartum hemorrhage: a systematic review and meta-analysis. \u003cem\u003eAm J Obstet Gynecol MFM\u003c/em\u003e. 2021;3(5):100417. doi:10.1016/j.ajogmf.2021.100417\u003c/li\u003e\n \u003cli\u003eHorton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. \u003cem\u003eHuman Reproduction Update\u003c/em\u003e. 2019;25(5):593-633. doi:10.1093/humupd/dmz012\u003c/li\u003e\n \u003cli\u003eBerlac JF, Hartwell D, Skovlund CW, Langhoff-Roos J, Lidegaard \u0026Oslash;. Endometriosis increases the risk of obstetrical and neonatal complications. \u003cem\u003eActa Obstetricia et Gynecologica Scandinavica\u003c/em\u003e. 2017;96(6):751-760. doi:10.1111/aogs.13111\u003c/li\u003e\n \u003cli\u003eVelez MP, Bougie O, Bahta L, et al. Mode of conception in patients with endometriosis and adverse pregnancy outcomes: a population-based cohort study. \u003cem\u003eFertility and Sterility\u003c/em\u003e. 2022;118(6):1090-1099. doi:10.1016/j.fertnstert.2022.09.015\u003c/li\u003e\n \u003cli\u003eMacer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. \u003cem\u003eObstet Gynecol Clin North Am\u003c/em\u003e. 2012;39(4):535-549. doi:10.1016/j.ogc.2012.10.002\u003c/li\u003e\n \u003cli\u003ePandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. \u003cem\u003eHum Reprod Update\u003c/em\u003e. 2012;18(5):485-503. doi:10.1093/humupd/dms018\u003c/li\u003e\n \u003cli\u003eQin J, Liu X, Sheng X, Wang H, Gao S. Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies. \u003cem\u003eFertil Steril\u003c/em\u003e. 2016;105(1):73-85.e1-6. doi:10.1016/j.fertnstert.2015.09.007\u003c/li\u003e\n \u003cli\u003eVercellini P, Parazzini F, Pietropaolo G, Cipriani S, Frattaruolo MP, Fedele L. Pregnancy outcome in women with peritoneal, ovarian and rectovaginal endometriosis: a retrospective cohort study. \u003cem\u003eBJOG\u003c/em\u003e. 2012;119(12):1538-1543. doi:10.1111/j.1471-0528.2012.03466.x\u003c/li\u003e\n \u003cli\u003eLin H, Leng JH, Liu JT, Lang JH. Obstetric Outcomes in Chinese Women with Endometriosis: A Retrospective Cohort Study. \u003cem\u003eChin Med J (Engl)\u003c/em\u003e. 2015;128(4):455-458. doi:10.4103/0366-6999.151077\u003c/li\u003e\n \u003cli\u003eJauniaux E, Alfirevic Z, Bhide A, et al. Placenta Praevia and Placenta Accreta: Diagnosis and Management. \u003cem\u003eBJOG: An International Journal of Obstetrics \u0026amp; Gynaecology\u003c/em\u003e. 2019;126(1):e1-e48. doi:10.1111/1471-0528.15306\u003c/li\u003e\n \u003cli\u003eJain V, Bos H, Bujold E. Guideline No. 402: Diagnosis and Management of Placenta Previa. \u003cem\u003eJournal of Obstetrics and Gynaecology Canada\u003c/em\u003e. 2020;42(7):906-917.e1. doi:10.1016/j.jogc.2019.07.019\u003c/li\u003e\n \u003cli\u003eHarb HM, Gallos ID, Chu J, Harb M, Coomarasamy A. The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis. \u003cem\u003eBJOG\u003c/em\u003e. 2013;120(11):1308-1320. doi:10.1111/1471-0528.12366\u003c/li\u003e\n \u003cli\u003eTan Y, Flynn WF, Sivajothi S, et al. Single-cell analysis of endometriosis reveals a coordinated transcriptional programme driving immunotolerance and angiogenesis across eutopic and ectopic tissues. \u003cem\u003eNat Cell Biol\u003c/em\u003e. 2022;24(8):1306-1318. doi:10.1038/s41556-022-00961-5\u003c/li\u003e\n \u003cli\u003ePirtea P, Ziegler D de, Ayoubi JM. Endometrial receptivity in adenomyosis and/or endometriosis. \u003cem\u003eFertility and Sterility\u003c/em\u003e. 2023;119(5):741-745. doi:10.1016/j.fertnstert.2023.03.004\u003c/li\u003e\n \u003cli\u003eWang S, Duan H. The role of the junctional zone in the management of adenomyosis with infertility. \u003cem\u003eFront Endocrinol\u003c/em\u003e. 2023;14. doi:10.3389/fendo.2023.1246819\u003c/li\u003e\n \u003cli\u003eMaggiore ULR, Inversetti A, Schimberni M, Vigan\u0026ograve; P, Giorgione V, Candiani M. Obstetrical complications of endometriosis, particularly deep endometriosis. \u003cem\u003eFertility and Sterility\u003c/em\u003e. 2017;108(6):895-912. doi:10.1016/j.fertnstert.2017.10.035\u003c/li\u003e\n \u003cli\u003eSaraswat L, Ayansina D, Cooper K, et al. Pregnancy outcomes in women with endometriosis: a national record linkage study. \u003cem\u003eBJOG: An International Journal of Obstetrics \u0026amp; Gynaecology\u003c/em\u003e. 2017;124(3):444-452. doi:10.1111/1471-0528.13920\u003c/li\u003e\n \u003cli\u003eYi KW, Cho GJ, Park K, et al. Endometriosis Is Associated with Adverse Pregnancy Outcomes: a National Population-Based Study. \u003cem\u003eReprod Sci\u003c/em\u003e. 2020;27(5):1175-1180. doi:10.1007/s43032-019-00109-1\u003c/li\u003e\n \u003cli\u003eLalani S, Choudhry AJ, Firth B, et al. Endometriosis and adverse maternal, fetal and neonatal outcomes, a systematic review and meta-analysis. \u003cem\u003eHum Reprod\u003c/em\u003e. 2018;33(10):1854-1865. doi:10.1093/humrep/dey269\u003c/li\u003e\n \u003cli\u003eIbiebele I, Nippita T, Baber R, Torvaldsen S. Pregnancy outcomes in women with endometriosis and/or ART use: a population-based cohort study. \u003cem\u003eHum Reprod\u003c/em\u003e. 2022;37(10):2350-2358. doi:10.1093/humrep/deac186\u003c/li\u003e\n \u003cli\u003eVercellini P, DE Matteis S, Somigliana E, Buggio L, Frattaruolo MP, Fedele L. Long-term adjuvant therapy for the prevention of postoperative endometrioma recurrence: a systematic review and meta-analysis. \u003cem\u003eActa Obstet Gynecol Scand\u003c/em\u003e. 2013;92(1):8-16. doi:10.1111/j.1600-0412.2012.01470.x\u003c/li\u003e\n \u003cli\u003eMannini L, Sorbi F, Noci I, et al. New adverse obstetrics outcomes associated with endometriosis: a retrospective cohort study. \u003cem\u003eArch Gynecol Obstet\u003c/em\u003e. 2017;295(1):141-151. doi:10.1007/s00404-016-4222-7\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Medically Assisted reproduction (MAR), endometriosis, placenta previa, pregnancy outcomes, primiparity","lastPublishedDoi":"10.21203/rs.3.rs-9234842/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9234842/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective\u003c/p\u003e\n\u003cp\u003eTo assess whether pre-existing endometriosis is associated with specific adverse pregnancy and delivery outcomes in primiparous women\u003c/p\u003e\n\u003cp\u003eDesign\u003c/p\u003e\n\u003cp\u003eRetrospective cohort study\u003c/p\u003e\n\u003cp\u003eSetting\u003c/p\u003e\n\u003cp\u003eTertiary care university hospital\u003c/p\u003e\n\u003cp\u003ePopulation or Sample\u003c/p\u003e\n\u003cp\u003ePrimiparous women with singleton pregnancies.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eWomen with endometriosis were compared with primiparous controls without endometriosis. Primary outcomes were preterm birth and caesarean delivery; placenta previa was examined as a key secondary outcome. Multivariable logistic regression models adjusted for maternal age and mode of conception were used.\u003c/p\u003e\n\u003cp\u003eMain Outcome Measures\u003c/p\u003e\n\u003cp\u003ePreterm birth, caesarean delivery, placenta previa.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eAmong 16,033 primiparous women, 118 had a diagnosis of endometriosis prior to pregnancy. After adjustment for maternal age and mode of conception, endometriosis was not independently associated with preterm birth (adjusted odds ratio 0.75; 95% confidence interval 0.44-1.28) or caesarean delivery (adjusted odds ratio, 1.17; 95% confidence interval, 0.81–1.71). In contrast, endometriosis was associated with placenta previa (adjusted odds ratio, 5.90; 95% confidence interval, 2.37–14.71).\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003eIn primiparous women, pre-existing endometriosis was independently associated with placenta previa, but not with preterm birth or caesarean delivery. These findings support abnormal early placentation as a potential mechanism linking endometriosis to adverse obstetric outcomes.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e","manuscriptTitle":"Endometriosis and adverse pregnancy outcomes in primiparous women: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 09:10:34","doi":"10.21203/rs.3.rs-9234842/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-21T15:20:32+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-21T14:20:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"247972878072538783682270466107752836667","date":"2026-04-09T13:03:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-03T11:16:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-27T20:04:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-27T10:15:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2026-03-26T13:33:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c3ad865e-ddbc-4c01-9c17-3ffadcfccbea","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T11:56:31+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 09:10:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9234842","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9234842","identity":"rs-9234842","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}