Both EMS and CE are prevalent gynecological conditions. CE, characterized by chronic inflammation of the endometrium due to pathogenic microorganisms, is a common cause of female infertility [14]. Evidence supports this claim; for instance, the prevalence of CE among the general female population is approximately 10% to 11%. However, this prevalence can vary significantly, reaching up to 72% in patients with chronic PID. Among infertile women, the incidence rate of CE ranges from 2.8 to 60%, potentially due to the absence of standardized diagnostic criteria [13]. Pathogenic infections in the endometrium disrupt the equilibrium of local immune cells, resulting in the imbalanced expression of inflammatory factors, immune regulatory factors, chemokines, and other relevant components. Consequently, this imbalance diminishes endometrial receptivity and impedes embryo implantation, ultimately leading to infertility [26, 27].

Research has found that the prevalence of CE in patients receiving EMS treatment is 3.7 times higher compared to the control group. Additionally, the occurrence of EMS in CE patients is significantly higher compared to non-CE patients [15], indicating that EMS serves as an independent risk factor for CE development. This study’s findings demonstrate that the prevalence of CE in patients with EAI is 46.42% (318 out of 685), aligning with the results reported by Takebayashi et al. [28]. However, our study uniquely highlights the compounded risks of pregnancy complications in EMS patients with CE. While previous research primarily focused on implantation and early pregnancy outcomes, our study extends these findings to later stages of pregnancy, emphasizing the need for comprehensive prenatal care in this patient population. Although adenomyosis was identified in both groups (85 cases in the CE group and 97 cases in the non-CE group), the prevalence did not differ significantly (P = 0.999). Therefore, it was not included as an independent variable in the analysis, and it did not affect the study’s primary outcomes.

This extension is critical as it provides a more complete understanding of the impact of CE on pregnancy outcomes. Pelvic peritoneal inflammation can occur following the development of EMS lesions, subsequently spreading to the endometrium via the fallopian tubes. This process leads to aseptic inflammation in the endometrium and triggers the infiltration of plasma cells in the interstitial region [28]. Furthermore, research has demonstrated a notable increase in the microbial community within the endometrium of EMS patients compared to non-EMS patients [29]. Consequently, microbial infection may also contribute to the occurrence of CE in EMS patients [30]. However, the precise etiology and associated mechanisms of these conditions remain largely unknown, necessitating further investigation.

Research indicates that the pathogenesis of various EMS types may differ [31]. However, there is limited data available in the literature on the impact of r-AFS staging of EMS on the occurrence of CE. Takebayashi et al. [28] observed that the incidence of CE in EMS patients at stages 1 to 4 was 40.0%, 50.0%, 70.0%, and 46.7%, respectively. However, these differences did not reach statistical significance. Furthermore, no significant variation in CE incidence rates was observed across different clinicopathological types. In this study, the prevalence of CE in patients with EAI was 46.42% (318 out of 685). Among women with stage 1 to 4 EMS, the CE occurrence rates were 47.25% (103 out of 218), 46.59% (82 out of 176), 44.87% (70 out of 156), and 46.67% (63 out of 135), respectively.

Specifically, the CE incidence rate was 46.95% (185 out of 394) in patients with stage 1 to 4 EMS and 45.70% (133 out of 291) in those with stage 3 and 4 EMS, with no statistically significant differences (P = 0.513). Additionally, the CE incidence rate was slightly lower in patients with PEM (42.80%, or 101 out of 236) compared to those with ovarian EMS (48.58%, or 154 out of 317) and DIE (47.72%, or 63 out of 132), although these differences were not statistically significant (P = 0.142). These findings suggest that the presence of CE in EMS patients may not be associated with a specific clinicopathological type.

Due to its minimally invasive nature, laparoscopy is the preferred method for diagnosing and treating EAI. This procedure allows for the removal of lesions, restoration of pelvic anatomy, and assessment of r-AFS staging and EFI scoring, which can guide post-surgical pregnancy outcomes and improve the likelihood of conception. Additionally, hysteroscopy can be used to identify endometrial hyperemia, endometrial micropolyps (< 1 mm), and interstitial edema, providing valuable diagnostic information for CE [32, 33]. However, the sensitivity and specificity of hysteroscopy in accurately diagnosing CE remain uncertain, making it insufficient as a standalone diagnostic tool. Combining hysteroscopy with pathological examination is recommended, as this approach serves as the preferred method for diagnosing CE and enhancing diagnostic accuracy.

This study’s findings revealed a cumulative postoperative pregnancy count of 135 in patients with EAI and CE, resulting in a cumulative pregnancy rate of 42.45%. These results are consistent with findings in the literature [8, 21]. Women with stage 1 to 4 EMS in the CE group had cumulative pregnancy rates of 52 (50.49%), 40 (48.78%), 25 (35.71%), and 18 (28.57%), respectively. Notably, the pregnancy rates in our study were higher than those reported in previous studies, particularly for stage 4 endometriosis, where rates typically hover around 20%. This discrepancy may be attributed to several factors: first, our study population was carefully selected, excluding patients with significant comorbidities and focusing on those intending to conceive naturally post-surgery. Second, the comprehensive post-surgical management and follow-up protocols implemented in our study likely contributed to the enhanced fertility outcomes observed. The cumulative pregnancy rate of patients with stage 1 and 2 EMS was significantly higher than that of patients with stage 3 and 4 EMS (49.73% [92/185] versus 32.33% [43/133]), indicating that the pregnancy rates of patients with mild to moderate EAI and CE are superior to those of patients with moderate to severe EAI and CE. The cumulative pregnancy rate and live birth rate in the CE group were consistently lower compared to the non-CE group at various time periods, with these differences being statistically significant (P < 0.05). Conversely, no statistically significant differences were observed in the postoperative pregnancy status among patients with combined EAI and CE across different clinicopathological types. This suggests a significant increase in the postoperative pregnancy rate of patients with combined EAI and CE irrespective of the clinicopathological type, warranting further prospective studies.

Microbial pathogen infection is the primary cause of CE, with Streptococcus, Escherichia coli (E. coli), Proteus, Mycoplasma genitalium (M. genitalium), and Chlamydia being the most common pathogens [8]. Antibiotics are the cornerstone of CE treatment, effectively eliminating plasma cells that infiltrate the interstitium. After treatment, hysteroscopic-based endometrial biopsy has shown a plasma cell clearance rate ranging from 70 to 96% [9]. The most commonly used therapeutic regimen is doxycycline (200 mg/day) administered for 14 days. In cases of doxycycline resistance, a combination of ciprofloxacin (800 mg/day) and metronidazole (1000 mg/day) for 14 days may also be considered. Most antibiotic treatments are effective after one to two courses; however, patients should undergo a hysteroscopic review and repeat endometrial biopsy to confirm efficacy. In a prospective, double-blind cohort study by Song et al., 120 patients with CE were randomly assigned to either an antibiotic treatment group (60 cases) or a control group (60 cases). The treatment group received oral antibiotics for 14 days, followed by a repeat endometrial biopsy after 4 to 8 weeks. The endometrial conversion rate was 89.8% in the treatment group, compared to only 12.3% in the control group. Based on these findings, a 14-day course of broad-spectrum oral antibiotics is recommended to significantly improve chronic endometrial inflammation [34]. The study also found that the cumulative endometrial conversion rate among patients with CE who received antibiotic treatment was 81.3%, significantly higher than the 6% observed in the untreated group [35]. Our study’s results further demonstrate the effectiveness of antibiotic therapy, as evidenced by the similar cumulative pregnancy rates observed in patients with CE after antibiotic treatment compared to those without the condition. Thus, appropriate post-surgery antibiotic treatment can enhance the reproductive prognosis of patients with EAI and CE. Moreover, this investigation revealed that women with elevated EFI scores exhibited superior fertility outcomes, particularly those with EFI scores ranging from 5 to 10, resulting in significantly higher pregnancy rates. This suggests that a higher EFI score correlates with a greater cumulative pregnancy rate, supporting the efficacy of the EFI scoring system in accurately predicting spontaneous pregnancy in patients with EAI following surgical intervention. These findings align with previous studies [36,37,38,39,40,41,42,43]. The prognostic value of the EFI score in predicting pregnancy outcomes underscores its utility in clinical practice. Clinicians should consider incorporating EFI scores in the management of EMS patients to better predict and improve pregnancy outcomes. However, further research is needed to confirm these observations.

Combined laparoscopy and hysteroscopy were conducted to address EMS lesions impacting pregnancy and fertility, restore pelvic anatomy, and enhance the pelvic microenvironment. Following successful treatment, uterine inflammation can be effectively repaired. Consequently, women who conceive after this intervention should experience comparable pregnancy outcomes to those without a surgical history, thereby eliminating the need to consider delivery modes as a determinant. Nevertheless, there is a scarcity of studies on postoperative pregnancy complications and outcomes in patients with both EAI and CE.

This study’s findings indicated that pregnant women who underwent combined laparoscopy and hysteroscopy had higher occurrences of placenta previa, hypertensive disorders of pregnancy (HDPs), and cesarean delivery compared to the control group, which aligns to some extent with results from previous studies [44,45,46]. The synergistic effect of EMS and CE on the uterine environment may exacerbate inflammatory responses, leading to increased rates of pregnancy complications. This interaction warrants further investigation to elucidate the underlying mechanisms. The presence of CE likely intensifies the inflammatory milieu in the endometrium, which is already compromised in EMS patients. Chronic inflammation can disrupt endometrial receptivity, impair placental development, and elevate the risk of hypertensive disorders. Additionally, immune dysregulation associated with both EMS and CE can contribute to adverse pregnancy outcomes, necessitating targeted therapeutic interventions to modulate inflammatory pathways. For instance, persistent inflammation in CE may lead to increased expression of inflammatory cytokines and immune cells, further impairing endometrial receptivity and placental development. Understanding these mechanisms could help in developing targeted therapies to improve pregnancy outcomes in EMS patients with CE.

Furthermore, the incidence of full-term infants with low birth weights, perinatal asphyxia, stillbirth, and perinatal death in the combined surgery group was slightly lower than in the non-surgical group, while the incidence of premature birth was slightly higher, though these differences were not statistically significant. However, the cesarean section rate in the treatment group was significantly higher compared to the control group. This increase in cesarean section rates can be attributed to factors such as a prolonged history of infertility and the perceived higher value of the fetus. Additionally, concerns among obstetricians regarding potential labor-related accidents have led to a relaxation of cesarean section indications during trial labor, ultimately resulting in higher cesarean section rates influenced by societal factors. Therefore, it is important to consider enhancing pregnancy management for women who have undergone combined laparoscopy and hysteroscopy, with close monitoring of the post-delivery labor process. To prioritize the safety of both mother and child, it is inadvisable to consider cesarean section as a standard delivery method in the absence of specific circumstances. Given the compounded risks, clinicians must adopt a holistic management approach that addresses both EMS and CE, potentially involving specialists from obstetrics, gynecology, and immunology.

This study offers several notable strengths. First, the case data were obtained from a reputable medical center, and all surgical procedures were consistently performed by the same group of doctors, enhancing the reliability of the data and the clarity of diagnoses, effectively mitigating potential selection bias. Second, all women with EMS and CE underwent both surgical and pathological examinations to confirm their conditions, significantly reducing the risk of misclassification. Third, comprehensive clinical data on the stage, type, and EFI of EMS were readily accessible for thorough analysis. Fourth, the follow-up duration was sufficient, with a lost-to-follow-up rate of less than 5%. Finally, we implemented various strategies to mitigate potential confounding variables, including verification of data accuracy and reliability by two qualified experts. However, it is important to acknowledge that this study was observational in nature, and despite efforts to control for confounding factors, residual confounding variables may still exist. Furthermore, the sample size in this study was relatively limited. Considering these limitations, future research will involve comprehensive multi-center investigations with larger sample sizes and prospective cohort studies.

In summary, our findings substantiate the hypothesis that individuals with EMS exhibit a heightened prevalence of CE. However, further investigation into the underlying mechanisms is imperative. Additionally, our study demonstrates that the combined utilization of hysteroscopy and laparoscopy as a surgical procedure is highly efficacious for augmenting pregnancy rates. While both endometriosis alone and endometriosis combined with CE are associated with an increased risk of placenta previa, the presence of CE may further elevate the risks, particularly for gestational hypertension and cesarean delivery. Furthermore, to minimize the risk of cesarean delivery and prevent delivery-related complications, it is imperative to implement a more stringent monitoring system for these patients.