Obstetric outcomes in women with endometriosis: A retrospective cohort study

Background: Endometriosis is a chronic gynecological condition affecting approximately 10% of reproductive-age women and has been increasingly associated with adverse pregnancy outcomes. However, the extent to which endometriosis influences obstetric compl ications remains incompletely understood. This study aimed to evaluate obstetric outcomes in women with a confirmed diagnosis of endometriosis compared to women without the condition.

A retrospective cohort study was conducted at a tertiary care h ospital between. A total of 684 pregnant women were included: 228 with a confirmed diagnosis of endometriosis (exposed group) and 456 without endometriosis (unexposed group) , matched by age and parity in a 1:2 ratio. Obstetric outcomes including preterm bi rth, preeclampsia, placenta previa, cesarean delivery, small for gestational age (SGA) neonates, gestational diabetes mellitus (GDM), and postpartum hemorrhage (PPH) were compared between groups. Statistical analyses included chi -square tests , independent t-tests, and multivariable logistic regression.

Women with endometriosis demonstrated significantly higher rates of preterm birth (18.4% vs. 9.6%, p = 0.001) , placenta previa (6.1% vs. 1.8% , p = 0.003) , preeclampsia (12.7% vs. 7.0% , p = 0.014) , and cesarean delivery (58.3% vs. 39.0% , p<0.001). The mean gestational age at delivery was significantly lower in the endometriosis group (37.2 ± 2.8 weeks vs. 38.6 ± 1.9 weeks , p<0.001). After multivariable adjustment, endometriosis remained an independ ent predictor of preterm birth (aOR 2.14 , 95% CI 1.38 - 3.32), placenta previa (aOR 3.47, 95% CI 1.52-7.93), and cesarean delivery (aOR 2.21, 95% CI 1.58-3.09).

Endometriosis is significantly associated with multiple adverse obstetric outcomes , particularly preterm birth , placenta previa , and cesarean delivery. Enhanced antenatal surveillance and multidisciplinary management are warranted for pregnant women with endometriosis.

Endometriosis, obstetric outcomes, preterm birth, placenta previa, cesarean delivery, pregnancy complications, retrospective cohort study 1. Introduction Endometriosis is a chronic , estrogen-dependent inflammatory disorder characterized by the presence of endometrial -like tissue outside the uterine cavity , most com monly affecting the ovaries, peritoneum, and rectovaginal septum [1]. It affects an estimated 6 -10% of women of reproductive age worldwide and represents one of the most prevalent gynecological conditions encountered in clinical practice [2]. The cardinal symptoms include chronic pelvic pain , dysmenorrhea, dyspareunia, and subfertility, collectively contributing to substantial impairment in quality of life and significant healthcare expenditure [3]. While the relationship between endometriosis and infertili ty has been extensively investigated and well-established, the impact of endometriosis on obstetric outcomes has garnered increasing scientific attention over the past two decades [4]. Several pathophysiological mechanisms have been proposed to explain how endometriosis may adversely influence pregnancy , including impaired decidualization, aberrant placentation, chronic inflammatory milieu, and altered uterine contractility [5]. The eutopic endometrium of women with endometriosis exhibits molecular and cellular abnormalities that may compromise implantation and subsequent placental development, potentially predisposing to complications such as preeclampsia , placenta previa, and preterm birth [6]. A systematic review and meta -analysis by Zullo et al. (2017) d emonstrated that endometriosis was associated with increased risks of preterm birth , cesarean section , and placenta previa , although substantial heterogeneity existed across included studies [7]. Similarly, a large International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 1090 ~ population-based cohort study from Sweden reported elevated risks of preeclampsia and antepartum hemorrhage among women with endometriosis [8]. More recently , Berlac et al . (2017) found that women with endometriosis had higher rates of gestational hypertensive disorders and adverse perinatal outcomes, although the magnitude of associations varied by endometriosis phenotype [9]. A comprehensive meta -analysis by Horton et al . (2019) further confirmed these associations and emphasized the need for additional well -designed studies to clarify the independent contribution of endometriosis to obstetric morbidity after controlling for confounders such as assisted reproductive technology (ART) utilization [10]. Despite the growing body of evidence, several gaps persist in the literature. Many previous studies did not adequately differentiate between spontaneous and ART -conceived pregnancies, making it difficult to disentangle the independent effects of endometriosis from those attributable to fertility treatments [11]. Furthermore, data from Middle Eastern a nd developing country populations remain limited , and the influence of endometriosis stage and phenotype on specific obstetric outcomes requires further investigation [12]. Additionally , postpartum outcomes such as postpartum hemorrhage have been inconsist ently evaluated across existing studies [13]. The aim of this study was to compare obstetric outcomes between pregnant women with a confirmed diagnosis of endometriosis and those without endometriosis in a tertiary care setting, while controlling for poten tial confounders including mode of conception, maternal age, body mass index (BMI) , and parity. 2. Materials and Methods 2.1 Study Design and Setting This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology of a tertiar y university -affiliated hospital. 2.2 Study Population The exposed group comprised 228 women with a confirmed diagnosis of endometriosis established prior to or during early pregnancy. Diagnosis was based on surgical confirmation (laparoscopy or laparotomy) with or without histopathological verification, or imaging -confirmed endometriomas (≥2 cm) identified on transvaginal ultrasonography or magnetic resonance imaging. The unexposed group consisted of 456 women without any documented history or cl inical evidence of endometriosis, matched to the exposed group in a 1:2 ratio by maternal age (±2 years) and parity. 2.3 Inclusion and Exclusion Criteria Inclusion criteria were: singleton pregnancy , delivery at ≥24 weeks of gestation , and complete medical records documenting antenatal, intrapartum, and postpartum course. Exclusion criteria included: multiple gestations , major fetal congenital anomalies , chronic hypertension diagnosed prior to pregnancy , pre- gestational diabetes mellitus, chronic renal disease, autoimmune disorders requiring immunosuppressive therapy , and incomplete medical records. 2.4 Data Collection and Variables Data were extracted from electronic health records by trained research assistants using a standardized data collection form. Maternal demographic variables included age , pre-pregnancy BMI, parity, smoking status , and mode of conception (spontaneous vs. ART). For the endometriosis group , additional data regarding disease stage (revised American Society for Reproductive Medicine [rA SRM] classification: stages I -II vs. III-IV) and phenotype (peritoneal , ovarian endometrioma, deep infiltrating endometriosis [DIE]) were recorded when available. Primary obstetric outcomes included: preterm birth (28 weeks) , cesarean delivery, small for gestational age (SGA; birth weight <10th percentile for gestational age) , gestational diabetes mellitus (GDM; diagnosed by 75 -g oral glucose tolerance test per IADPSG criteria), and postpartum hemorrhage (PPH; estimated blood loss ≥500 mL for vaginal delivery or ≥1000 mL for cesarean delivery). Secondary outcomes included gestational age at delivery, neonatal birth weight, Apgar score at 5 minutes , and neonatal intensive care unit (NICU) admission. 2.5 Statistical Analysis Continuous variables were expressed as mean ± standard deviation (SD) and compared using independent -sample t-tests. Categorical variables were presented as frequencies and percentages and analyzed using chi-square tests or Fisher's exact test as appropriate. Multivariable logistic regression analysis was performed to identify independent associations between endometriosis and adverse obstetric outcomes after adjusting for potential confounders (maternal age , BMI, smoking, parity, mode of conception , and history of prior cesarean delivery).

were reported as adjusted odds ratios (aOR) with 95% confidence interval s (CI). A two -tailed p -value <0.05 was considered statistically significant. All analyses were performed using SPSS version 28.0 (IBM Corporation , Armonk, NY, USA). 3. Results 3.1 Baseline Characteristics A total of 684 women were included in the final an alysis: 228 in the endometriosis group and 456 in the control group. Baseline demographic and clinical characteristics are presented in Table 1. The two groups were comparable with respect to maternal age, parity, and smoking status. However , the endometri osis group had a significantly higher proportion of ART -conceived pregnancies (34.2% vs. 8.1% , p<0.001) and a slightly higher mean BMI (26.3 ± 4.1 vs. 25.4 ± 3.8 kg/m², p = 0.006). Table 1: Baseline Demographic and Clinical Characteristics Variable Endometriosis (n = 228) Control (n = 456) p-value Age (years), mean ± SD 32.4 ± 4.6 31.9 ± 4.3 0.163 Pre-pregnancy BMI (kg/m²), mean ± SD 26.3 ± 4.1 25.4 ± 3.8 0.006 Nulliparous, n (%) 142 (62.3) 278 (61.0) 0.737 Smoking, n (%) 19 (8.3) 31 (6.8) 0.462 ART conception, n (%) 78 (34.2) 37 (8.1) <0.001 Prior cesarean delivery, n (%) 38 (16.7) 64 (14.0) 0.362 rASRM Stage III-IV, n (%) 131 (57.5) — — Deep infiltrating endometriosis, n (%) 67 (29.4) — — International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 1091 ~ 3.2 Obstetric Outcomes Comparison of obstetric outcomes between the two groups is summarized in Table 2 . Women with endometriosis had significantly higher rates of preterm birth (18.4% vs. 9.6% , p = 0.001), preeclampsia (12.7% vs. 7.0% , p = 0.014) , placenta previa (6.1% vs. 1.8% , p = 0.003), cesarean delivery (58.3% vs. 39.0%, p<0.001), and PPH (9.6% vs. 5.5% , p = 0.038). The rate of GDM was numerically higher in the endometriosis group but did not reach statistical significance (14.0% vs. 10.3% , p = 0.151). The rate of SGA neonates was significantly higher in the endometriosis group (13.2% vs. 8.1% , p = 0.036). Mean gestational age at delivery was significantly lower (37. 2 ± 2.8 vs. 38.6 ± 1.9 weeks , p<0.001), and mean neonatal birth weight was also significantly lower (2 , 918 ± 548 g vs. 3 , 187 ± 462 g , p<0.001) in the endometriosis group. NICU admission was more frequent among neonates born to women with endometriosis (14.5% vs. 7.7%, p = 0.004). Table 2: Comparison of Obstetric and Neonatal Outcomes Outcome Endometriosis (n = 228) Control (n = 456) p-value Preterm birth (<37 weeks), n (%) 42 (18.4) 44 (9.6) 0.001 Preeclampsia, n (%) 29 (12.7) 32 (7.0) 0.014 Placenta previa, n (%) 14 (6.1) 8 (1.8) 0.003 Cesarean delivery, n (%) 133 (58.3) 178 (39.0) <0.001 GDM, n (%) 32 (14.0) 47 (10.3) 0.151 SGA (<10th percentile), n (%) 30 (13.2) 37 (8.1) 0.036 PPH, n (%) 22 (9.6) 25 (5.5) 0.038 Gestational age at delivery (weeks), mean ± SD 37.2 ± 2.8 38.6 ± 1.9 <0.001 Birth weight (g), mean ± SD 2, 918 ± 548 3, 187 ± 462 <0.001 Apgar <7 at 5 min, n (%) 12 (5.3) 15 (3.3) 0.208 NICU admission, n (%) 33 (14.5) 35 (7.7) 0.004 3.3 Multivariable Analysis After adjusting for maternal age, BMI, parity, smoking, mode of conception, and prior cesarean delivery, endometriosis remained independently associated with several adverse outcomes (Table 3). The strongest associations were observed for placenta previa (aOR 3.47, 95% CI 1.52 -7.93, p = 0.003) and cesarean delivery (aOR 2.21 , 95% CI 1.58 -3.09, p<0.001). Preterm birth (aOR 2.14, 95% CI 1.38 -3.32, p = 0.001) , preeclampsia (aOR 1.82 , 95% CI 1.06 -3.13, p = 0.029) , and SGA (aOR 1.71 , 95% CI 1.03-2.84, p = 0.038) also remained statistically significant. The association with PPH was attenuated and became borderline significant after adjustment (aOR 1.68 , 95% CI 0.93 -3.04, p = 0.086). Table 3: Multivariable Logistic Regression Analysis for Adverse Obstetric Outcomes Outcome Adjusted OR 95% CI p-value Preterm birth 2.14 1.38-3.32 0.001 Preeclampsia 1.82 1.06-3.13 0.029 Placenta previa 3.47 1.52-7.93 0.003 Cesarean delivery 2.21 1.58-3.09 <0.001 SGA 1.71 1.03-2.84 0.038 PPH 1.68 0.93-3.04 0.086 GDM 1.34 0.82-2.19 0.241 4. Discussion The findings of this retrospective cohort study demonstrate that women with endometriosis face significantly elevated risks of multiple adverse obstetric outcomes , including preterm birth , preeclampsia, placenta previa , cesarean delivery , and SGA neonates. These associations persisted after multivariable adjustment for key confounders , including mode of conception , supporting the concept that endometriosis exerts independent deleterious effects on pregnancy outcomes through intrinsic disease-related mechanisms. Our findings are consistent with the results of a landmark meta - analysis by Zullo et al . (2017) , which reported significan tly increased risks of preterm birth (OR 1.63) , placenta previa (OR 3.03), and cesarean section (OR 1.57) among women with endometriosis [14]. The magnitude of our observed associations was somewhat greater , particularly for placenta previa (aOR 3.47), which may reflect the relatively high proportion of advanced-stage disease (57.5% with rASRM stages III -IV) and deep infiltrating endometriosis (29.4%) in our cohort , as disease severity has been correlated with worse obstetric outcomes in prior investigations [15]. The pathophysiology underlying the association between endometriosis and adverse obstetric outcomes is multifactorial. Endometriosis is characterized by a state of chronic pelvic inflammation with elevated levels of pro -inflammatory cytokines, including interleukin -6, tumor necrosis factor -alpha, and interleukin-1β, which may interfere with normal trophoblast invasion and spiral artery remodeling , thereby predisposing to defective placentation [16]. This impaired placentation may manifest clinically as preeclampsia , fetal growth restriction , or placental abruption. Furthermore , the eutopic endometrium of women with endometriosis exhibits progesterone resistance and altered gene expression profiles that compromise decidualization, a process critical f or successful implantation and early placental development [17]. The elevated rate of placenta previa observed in our study deserves particular attention. Several studies have reported this association, and it has been hypothesized that endometriosis- related anatomical distortion of the pelvic structures , along with altered endometrial receptivity in the upper uterine segment , may promote lower uterine segment implantation [18]. Additionally, prior surgical interventions for endometriosis , including laparoscopic excision or ablation , may contribute to uterine scarring and subsequent abnormal placentation [19]. The significantly higher cesarean delivery rate in the endometriosis group (58.3% vs. 39.0%) aligns with previous reports and may b e attributable to multiple factors , including obstetrician awareness of potential complications , pelvic adhesive disease limiting labor progress , higher incidence of malpresentation, and elective cesarean deliveries planned due to prior endometriosis surge ry [20]. Saraswat et al. (2017) similarly reported a cesarean delivery rate exceeding 50% among women with endometriosis in a large Scottish population -based study [21]. The borderline association between endometriosis and International Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com ~ 1092 ~ postpartum hemorrhage (aOR 1.68 , p = 0.086) is noteworthy , though it did not achieve conventional statistical significance after adjustment. This finding is consistent with the findings of Mannini et al . (2022) , who reported a modest but inconsistent association between endometriosis and PPH across different study populations [22]. The potential mechanisms may include impaired myometrial contractility due to adenomyosis (frequently coexisting with endometriosis) , inflammatory mediator-related uterine atony , or surgical complications during cesarean delivery in the setting of severe pelvic adhesions [23]. Our study did not find a statistically significant association between endometriosis and GDM (aOR 1.34 , p = 0.241), which is concordant with the majority of published literature. A recent systematic review by Pérez -López et al . (2018) similarly concluded that the evidence linking endometriosis to GDM is inconclusive, with most studies reporting null or weakly positive associations [24]. An important strength of this study is the adjustment for mode of conception, which a critical confounder is given that ART itself has been independently associated with adverse obstetric outcomes including preterm birth , preeclampsia, and placenta previa [25]. Many prior studies failed to adequately account f or this variable , making it challenging to determine whether observed associations reflected the effects of endometriosis per se or ART -related factors. In our multivariable models , the associations remained robust after including ART as a covariate , suggesting that endometriosis contributes to adverse outcomes through pathways independent of fertility treatment. This study has several limitations that must be acknowledged. First, the retrospective design is inherently susceptible to selection bias and resi dual confounding. Second , the diagnosis of endometriosis was based on surgical or imaging criteria , and women with undiagnosed or asymptomatic endometriosis in the control group may have led to misclassification bias , potentially attenuating the observed a ssociations. Third , the study was conducted at a single tertiary referral center , which may limit generalizability, as the patient population likely represents a skewed distribution toward more severe disease. Fourth , the relatively modest sample size prec luded robust subgroup analyses by endometriosis stage or phenotype. Finally , information regarding endometriosis -specific treatments received prior to pregnancy (hormonal suppression , surgical excision) was incompletely documented , limiting our ability to evaluate the potential modifying effect of preconception treatment. Future prospective multicenter studies with larger sample sizes and detailed phenotypic characterization of endometriosis are needed to further delineate the impact of disease severity , phenotype, and prior treatment on specific obstetric outcomes. Additionally, investigations into potential biomarkers that could identify women with endometriosis at highest risk for obstetric complications would be of considerable clinical value. 5. Conclusion This retrospective cohort study demonstrates that endometriosis is independently associated with significantly increased risks of preterm birth, preeclampsia, placenta previa, cesarean delivery, and small for gestational age neonates. These findings underscore the importance of recognizing endometriosis as a clinically significant risk factor for adverse obstetric outcomes. Pregnant women with a history of endometriosis should be classified as high -risk and may benefit from enhanced antenatal surveillance, including serial ultrasonographic assessment of placental location and fetal growth , along with multidisciplinary care involving both gynecologists with expertise in endometriosis and maternal -fetal medicine specialists. Early identification and proac tive management of potential complications may contribute to improved maternal and neonatal outcomes in this vulnerable population.

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