Both EMS and CE are prevalent gynecological conditions. Moreover, CE, which is characterized by chronic inflammation of the endometrium due to pathogenic microorganisms, is a common cause of female infertility [14]. Evidence supports this claim. For example, the prevalence of CE among the general female population is 10–11%. This prevalence of CE can vary. For example, it can reach up to 72% in patients with chronic PID. In infertile women, the incidence rate of CE ranges from 2.8–60%, which is potentially attributed to the absence of standardized diagnostic criteria [26]. Pathogenic infections in the endometrium disrupts 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 while impeding embryo implantation, ultimately leading to infertility [27,28].
Research has found that the prevalence of CE in patients receiving EMS treatment is greater by a factor of 3.7 compared to the control group. Additionally, the occurrence of EMS in CE patients is significantly higher compared to non-CE patients [29], 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), which agrees with results reported by Takebayashi et al. [30], emphasizing the need for clinicians to exercise heightened vigilance regarding the potential occurrence of CE in patients with EAI. Pelvic peritoneal inflammation can occur following the development of EMS lesions, which subsequently spreads to the endometrium via the fallopian tube. This process leads to aseptic inflammation in the endometrium and triggers the infiltration of plasma cells in the interstitial region [30]. Furthermore, research has demonstrated a notable microbial community increase within the endometrium of EMS patients compared to non-EMS patients [31]. Consequently, microbial infection may also contribute to the occurrence of CE in EMS patients [32]. However, the precise etiology and associated mechanisms of these conditions remain largely unknown, which necessitates further investigation.
Based on research, the pathogenesis of various EMS types may vary [33]. However, only limited data is available in the literature on the impact of r-AFS staging of EMS on the occurrence of CE. Takebayashi et al. [30] observed that the incidence of CE in EMS patients at stages 1–4 was 40.0%, 50.0%, 70.0%, and 46.7%, respectively, but these differences did not reach statistical significance. Furthermore, no significant variation in CE incidence rates was observed across different clinicopathological types. In this study, CE prevalence in patients with EAI was 46.42% (318 out of 685). Among women with stage 1 to 4 EMS, CE occurrence rates were 47.25% (103 out of 218), 46.59% (82 out of 176), 44.87% (70 out of 156), and 46.677% (63 out of 135), respectively. Specifically, the CE incidence rate was 46.95% (185 out of 394) in patients with stage 1–4 EMS and 45.70% (133 out of 291) in patients with stage 3–4 EMS, where no statistically significant differences were observed (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 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, the restoration of the pelvic anatomical structure, and the ability to assess 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 diagnosis [34, 35]. However, the sensitivity and specificity of hysteroscopy in accurately diagnosing CE remain uncertain, and hysteroscopy alone is insufficient as a standalone diagnostic tool for CE. It is recommended to combine hysteroscopy with a pathological examination, which 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 42.45% cumulative pregnancy rate. These results agree with findings in the literature [8, 21]. Women suffering from stage 1 to 4 EMS in the CE group had a 52 (50.49%), 40 (48.78%), 25 (35.71%), and 18 (28.57%) cumulative pregnancy rate, respectively. The cumulative pregnancy rate of patients with stage 1 and 2 EMS was wholly 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 the live birth rate of the CE group were consistently lower compared to the non-CE group at various time periods, and these differences were 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, which warrants further prospective studies.
Microbial pathogen infection is the primary etiology of CE, with streptococcus, Escherichia coli (E. coli), Proteus, Mycoplasma genitalium (M. genitalium), and chlamydia being the most common pathogens [36]. Antibiotics constitute the CE treatment mainstay, effectively eliminating plasma cells that infiltrate the interstitium. Following treatment, hysteroscopic based endometrial biopsy has shown a plasma cell clearance rate ranging from 70–96% [37]. The most frequently employed therapeutic regimen consists of 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 demonstrate effectiveness after 1 to 2 courses; however, it is necessary for patients to undergo an hysteroscopic review and a repeated endometrial biopsy to ascertain efficacy. In a prospective, double-blind, cohort study conducted by Song et al., a total of 120 patients with CE were randomly assigned to either an antibiotic treatment group (60 cases) or a blank control group (60 cases). The case group received oral antibiotics for a duration of 14 days, followed by a repeat endometrial biopsy after 4 to 8 weeks. The endometrial conversion rate was 89.8% in the case group, whereas it was only 12.3% in the control group. According to previous findings, it is recommended that a 14-day course of broad-spectrum oral antibiotics can lead to a significant improvement in chronic endometrial inflammation [38]. This study also revealed that the cumulative endometrial conversion rate among patients with CE who received antibiotic treatment was 81.3%, which was significantly higher compared to the group that did not receive the antibiotic treatment (6%) [39]. Our study’s results 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. Hence, the administration of suitable post-surgery antibiotic treatments can enhance the reproductive prognosis of patients with EAI and CE to varying degrees. Furthermore, this investigation also revealed that women with elevated EFI scores exhibited superior fertility outcomes, particularly among those with EFI scores ranging from 5 to 10, resulting in significantly heightened pregnancy rates. This suggests that a higher EFI score corresponds to a greater cumulative pregnancy rate, indicative of the efficacy of the EFI scoring system in accurately predicting spontaneous pregnancy in patients with EAI following surgical intervention, which is consistent with findings from previous studies [40–47]. However, this observation must be confirmed by further research.
Combined laparoscopy and hysteroscopy surgery was conducted to address EMS lesions that impact pregnancy and fertility, to restore the typical anatomical structure of the pelvic cavity, and to enhance the pelvic microenvironment. Following successful treatment, uterine inflammation can be effectively repaired. Consequently, women who conceive after undergoing 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 showed that pregnant women who underwent combined laparoscopy and hysteroscopy surgery had higher occurrences of placental previa, hypertensive disorders of pregnancy (HDPs), and cesarean delivery compared to the control group, which is to some extent consistent with results reported in previous studies [48–50]. Additionally, the incidence of full-term infants with low birth weights, perinatal asphyxia, stillbirth, and perinatal death within the combined uterine and laparoscopic surgery group was slightly lower than in the non-surgical group, while the incidence of premature birth was slightly higher, although these differences were not statistically significant. However, the treatment group’s cesarean section rate was higher when compared to the control group, and the difference was statistically significant. The rise in cesarean section rates can be primarily attributed to factors such as a patient’s prolonged history of infertility and the perceived higher value of the fetus. Furthermore, obstetricians have expressed concerns regarding potential labor-related accidents, leading to a relaxation of cesarean section indications during trial labor, which have ultimately resulted in an increase in cesarean section rates that are influenced by societal factors. Consequently, it is imperative to enhance pregnancy management for women who have undergone combined laparoscopy and hysteroscopy surgery, while closely monitoring the post-delivery labor process. To prioritize the safety of both the mother and child, it is inadvisable to consider cesarean section as a standard delivery method in the absence of specific circumstances.
This study offers several notable advantages. Firstly, the case data employed in this study was obtained from a reputable medical center, and the surgical procedures were consistently performed by the same group of doctors. Consequently, the reliability of the case data source and the clarity of the diagnoses effectively mitigated any potential case selection bias. Secondly, all women affected by EMS and CE underwent surgical and pathological examinations to confirm their conditions, significantly minimizing the risk of misclassification. Thirdly, comprehensive clinical data pertaining to the stage, type, and EFI of EMS was readily accessible for thorough analysis. Fourthly, the follow-up duration was deemed sufficient because the proportion of lost follow-up cases was below 5%. Lastly, we implemented diverse strategies to mitigate potential confounding variables, including data accuracy and reliability verification by two qualified experts. However, it is important to acknowledge that our study was observational in nature, and despite our efforts to control confounding factors, residual confounding variables may still be present. Furthermore, it should be noted that the sample size used in this study was relatively limited. Taking this into account, our future research endeavors will include comprehensive multi-center investigations with larger sample sizes, as well as prospective cohort studies.
In summary, our findings have substantiated the hypothesis that individuals afflicted with EMS exhibit a heightened prevalence of CE. Nevertheless, further investigation into the underlying mechanisms is imperative. Additionally, our study has demonstrated that the combined utilization of hysteroscopy and laparoscopy as a surgical procedure is a highly efficacious approach for augmenting pregnancy rates. However, it is important to acknowledge that women affected by EMS and CE face an independent escalation in the risk of placenta previa, gestational hypertension, and cesarean section delivery during pregnancy. Consequently, our findings provide strong evidence supporting the recommendation for infertile patients with EMS and CE to undergo a combined hysteroscopy and laparoscopy surgical procedure coupled with appropriate antibiotic therapy to enhance their likelihood of achieving pregnancy. 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.