Does chronic endometritis affect pregnancy outcomes in patients with endometriosis associated infertility? A retrospective cohort study

Does chronic endometritis affect pregnancy outcomes in patients with endometriosis associated infertility? 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A retrospective cohort study Shunhe Lin, Xi Xie, Yishan Chen, Penghui Huang, Jinna Zhang, Chaobin Liu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3866949/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Endometriosis (EMS) and chronic endometritis (CE) often coexist. Laparoscopic and hysteroscopic surgery surgery is one of the main methods for diagnosing and treating these conditions. The objectives of this study were to examine the clinical characteristics and prognosis of surgically diagnosed EMS complicated by CE and to assess the reproductive outcomes during subsequent pregnancies. Methods: A total of 1574 infertile patients were included in this study between January 2018 and December 2020. 685 patients were diagnosed with endometriosis who were further divided into two groups: a CE group consisting of 318 patients and a non-CE group consisting of 367 patients. Within the cohort who suffered from CE, a subset of postoperative care clinical pregnant women (n=123) was selected to form the study group. The control group consisted of women undergoing singleton pregnancy (n=369) who underwent delivery during the same period. Data on clinical statuses and complications during pregnancy and delivery were collected from hospitals and through telephone interviews. Results: The CE prevalence rate in women with EMS was 46.42%. Among the 318 women who were diagnosed with posterior CE, 135 achieved pregnancy. The cumulative clinical pregnancy rate was found to be significantly higher in groups with endometriosis fertility index (EFI) scores ranging from 7 to 8 and from 9 to 10 compared to groups with EFI scores below 7. Furthermore, women with both EMS and CE had a higher risk of experiencing complications during pregnancy, including placenta previa (13.01%), gestational hypertension (5.69%), and cesarean section delivery (59.34%). Conclusions: Patients diagnosed with endometriosis exhibited a heightened prevalence of chronic endometritis. Our investigation revealed that combined hysteroscopic and laparoscopic surgery proved to be a successful approach in augmenting the overall pregnancy rate. Furthermore, women afflicted by both EMS and CE face an independently escalated susceptibility to placenta previa, gestational hypertension, and cesarean delivery. Chronic endometritis Endometriosis Infertility Pregnancy outcome Figures Figure 1 Figure 2 Figure 3 Introduction Endometriosis (EMS) is characterized by the ectopic proliferation of endometrial tissue, encompassing both glands and stroma, beyond the confines of the uterine cavity’s endometrial and myometrial layers [ 1 ]. This pathological condition gives rise to the development of lesions, which subsequently result in local infiltration, recurrent hemorrhage, and the formation of nodules and masses. Moreover, EMS is one of the most common gynecological disorders that reduces the life quality and fertility of patients worldwide. The peak age-specific incidence of EMS is between 24 and 29 years old, and the incidence rate is up to 10–15% of the general population [ 2 , 3 ]. Additionally, EMS often causes patients to suffer long-standing pain, infertility, pelvic masses, etc., which can seriously affect their home and work life and result in a continuous increase in medical costs, leading to the economic burden of both the state and individuals [ 4 ]. In some cases, EMS has even been shown to be tied to bacterial infections [ 5 ] . Chronic endometritis (CE) and EMS are similar. The former refers to the persistent chronic inflammation of the endometrium, characterized by plasma cell infiltration into the endometrium stroma [ 6 ] . Among infertile women, the incidence of CE is up to 56.8% [ 7 ], among which the incidence rate of repeated implantation failure ranges from 4.0–67.5% [ 8 , 9 ] while the incidence rate of recurrent abortions is approximately 9.3%~67.6% [ 10 ]. Patients diagnosed with CE typically exhibit an absence of symptoms or display mild, non-specific manifestations, including abnormal uterine bleeding and abnormal leucorrhea. Additionally, CE exhibits a notable prevalence among individuals experiencing endometriosis associated infertility (EAI) [ 11,12 ] . The strikingly similar features of EMS and CE suggest that there may be a potential association between the two conditions. Thus far, it is not entirely clear whether CE is a risk factor or an etiologic factor of EAI. Previous studies have revealed a higher CE frequency in patients with EMS compared to those without the disease [ 13–15 ] . These studies collectively indicate that the presence of EMS may be significantly associated with CE. Currently, these types of disorders are leading to relatively high infertility occurrence rates, which are also ill defined. Both EMS and CE can both contribute to and give rise to infertility. It is widely accepted that EMS alters fertility during women’s reproductive age. Several factors affect overall fertility, including altered pelvic anatomy, extensive adhesions, hormonal alterations, and inflammation. In addition, speculative CE mechanisms that result in infertility include lesions that may promote intrauterine adhesions through endometrial fibrosis enhancement and those that mechanically interfere with sperm transport or through embryo implantation. As such, these two disorders collectively affect endometrium receptivity. The exact aetiology by which this occurs, however, is not completely understood [ 16 ]. The past two decades have witnessed a steady increase in the number of procedures performed via minimally invasive surgery, including laparoscopy and hysteroscopy. Along with the development and widespread application of minimally invasive surgery, it would be especially beneficial to treat patients with EAI through laparoscopy and hysteroscopy. Furthermore, it is important to consider the potential negative effects on maternal and neonatal health when examining the mechanisms that disrupt fertility in women with these disorders. The relationship between EMS and adverse pregnancy outcomes has started to gain significant attention [ 17 – 24 ]. Nevertheless, to the best of our knowledge, there is a lack of comprehensive clinical data regarding pregnancy complications and perinatal outcomes in postsurgical patients with these disorders who later conceive. This study aimed to investigate correlations between EMS and CE in individuals experiencing infertility, and to evaluate the pregnancy outcomes following a combined laparoscopy and hysteroscopy surgical intervention procedure. Specifically, the main objective is to provide a comprehensive treatment for patients facing EMS challenges accompanied by CE. Methods Participants and procedure Ethical approval for this study was obtained from the Fujian Provincial Maternal and Child Health Hospital (grant number 2018–4133). Prior to participation, all patients were provided with detailed information about the study before their permission was obtained by signing consent forms. This study included women who underwent laparoscopy combined with hysteroscopy due to tubal infertility, infertility associated with EMS, or unexplained infertility. In this study, infertility is defined as the inability of couples to conceive under normal coital practices for greater than one year. From January 2018 to December 2020, 1574 infertile patients who met the inclusion criteria were enrolled in the study. The inclusion criteria for this study were as follows: 1) the absence of hormone therapy within the 3 months preceding surgery; 2) normal ovarian reserve function; 3) regular menstruation without regular vaginal bleeding; 4) normal semen functionality of the patient's male partner; 5) the active intention to conceive after surgery; 6) participation in follow-up interviews over a 24 month period. Conversely, the exclusion criteria encompassed: 1) ovulation disorders, such as polycystic ovarian syndrome (PCOS); 2) uterine abnormalities, including uterus septum, uterine fibroid, and intrauterine adhesion; 3) acute pelvic inflammatory disease (PID), oligospermia, and asthenospermia; 4) other medical comorbidities, including thyroid disorders, diabetes, hypertension, hyperprolactinemia, and connective tissue diseases, were also considered as exclusion criteria; 5) the use of any antibiotics within the past four weeks was also a criterion for exclusion. All patients in this study underwent a combined laparoscopy and hysteroscopy surgical procedure to address menorrhagia during the menstruation cycle. The laparoscopic surgical procedure involved the exploration of the uterus, adnexa, and pelvic cavity. In cases where pelvic adhesion was present, the adhesion was separated prior to the removal of the ovarian cyst. Furthermore, pelvic ectopic foci excision and bilateral tubal fluidization were performed as necessary. Additionally, hysteroscopic surgical procedures involved the observation of various anatomical structures, such as internal cervix opening, cervical canal, uterine wall, uterine fundus, bilateral fallopian tube opening, etc. Special attention was given to the identification of endometrial congestion, interstitial edema, and the precise location of the endometrial biopsy. The histopathologic detection of plasma cells in the endometrium plays a crucial role in the diagnosis of CE, and the identification of typical features under hysteroscopy can be valuable for diagnostic purposes [ 25 ] . In this study, the diagnostic criteria included the presence of one or more CD138-stained and/or CD38-stained positive plasma cells in the endometrial stroma per × 400 high-power field of view. Pathological findings revealed that all patients diagnosed with CE were administered a single course of doxycycline (Chinese Guangdong Huanan Pharmaceutical, 100 mg orally twice a day for 14 days). Furthermore, gonadotropin releasing agonists (GnRH-a, triptorelin acetate, French IPSEN Pharmaceutical, 3.75 mg) were utilized in cases of advanced EMS stages (i.e., stages 3 and 4) for a 3-month duration, followed by active preparation for pregnancy after discontinuation. Outpatient and telephone follow-up assessments were conducted at 3-month intervals for a minimum 24-month duration to monitor postoperative recovery and pregnancy outcomes. The follow-up period extended until the end of December 2022. Statistical analysis Data analysis was conducted using SPSS 26.0 statistical analysis software (IBM, Armonk, NY, USA). Normally distributed continuous measurement data are shown as the mean ± standard deviation, while a t -test was employed to compare the two groups. Counting data were expressed as rates (%) while a chi-square test was used for group comparisons. In cases where chi-square test conditions could not be met, the corrected chi-square test and the Fisher’s exact test were employed along with the rank sum test. Kaplan-Meier survival analysis estimates were conducted to compare cumulative pregnancy rates between CE and Non-CE groups at different time periods. All p-values reported are two sided and a p < 0.05 was considered statistically significant. Results Among the cohort of 953 women experiencing infertility due to EMS, a total of 237 individuals (24.87%) were excluded from the study due to various factors, such as ovulation disorders (n=33), uterine fibroids (n=49), uterine abnormalities (n=65), male factor infertility (n=54), and other medical comorbidities (n=36). Additionally, 22 patients (12.66%) were lost to follow-up while nine individuals (2.53%) had postponed their conception plans during the 24-month observation period. Consequently, the final analysis included 685 cases of EAI (Figure 1). Among these patients, 318 individuals (24.38%) were diagnosed with CE, while the remaining cases did not exhibit this condition. The baseline characteristics of the CE and non-CE groups showed no significant differences (Table 1). Table 1 Baseline characteristics of women with and without endometriosis Variables Endometriosis (N=685) P value CE (N=318) Non-CE (N=367) Mean age (years) 28.1 ± 4.7 27.6 ± 4.9 0.398 BMI (kg/m 2 ) 20.5 ± 3.4 21.2 ± 2.6 0.175 Gravidity 1.92 ± 1.61 2.01 ± 1.23 0.235 Parity 1.73 ± 1.05 1.62 ± 1.32 0.374 Menarche Age (years) 12.1 ± 2.3 12.7 ± 1.9 0.856 Menstrual average cycle (days) 27.6 ± 2.7 28.3 ± 2.5 0.673 Table 1 Baseline characteristics of women with and without endometriosis Menstrual duration (days) 6.4 ± 1.5 6.1 ± 1.7 0.147 Infertility duration (years) 2.9 ± 1.3 3.1 ± 1.5 0.536 Primary infertility (n, %) 113 (55.39%) 142 (57.49%) 0.176 Secondary infertility (n, %) 91 (44.61%) 105 (42.51%) 0.287 Preoperative serum CA125 level (U /mL) 45.1 ± 6.5 51.2 ± 8.1 0.864 r-AFS total score 55.8 ± 16.3 61.1 ± 13.6 0.951 EFI score 7.98 ± 1.15 8.18 ± 0.93 0.188 NOTE: The probability of all values was above 0.05. BMI = Body mass index; r-AFS = Revised American Fertility Society; EFI = Endometriosis fertility index The prevalence of CE in patients with EAI was determined to be 46.42% (i.e., 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 (Figure 2). Specifically, the CE incidence rate was 46.95% (185 out of 394) in patients with stage 1 and 2 EMS and 45.70% (133 out of 291) in patients with stage 3 to 4 EMS, for which no statistically significant differences were observed ( P =0.513). Additionally, the CE incidence rate was slightly lower in patients with peritoneal endometriosis (PEM) (42.80%, or 101 out of 236) compared to those with ovarian endometriosis (OEM) (48.58%, or 154 out of 317) and deep infiltrating endometriosis (DIE) (47.72%, or 63 out of 132), although the difference was not statistically significant ( P =0.142) (Figure 3). In the CE group, women with stage 1 to 4 EMS experienced cumulative pregnancy rates of 52 (50.49%), 40 (48.78%), 25 (35.71%), and 18 (28.57%), respectively. The cumulative pregnancy rate for patients with stage 1 and 2 EMS were significantly higher compared to patients with stage 3 and 4 EMS (i.e., 49.73% [92/185] versus 32.33%, [43/133]). Furthermore, the cumulative pregnancy rate and live birth rate at different time periods for the CE group were consistently lower than those for the non-CE group, although the differences were not statistically significant (Table 2). Table 2 Comparison of the pregnancy status between CE and non-CE groups in women suffering from endometriosis Period （months） Cumulative pregnancy rate(n, %) Live birth rate (%) Miscarriage rate (n, %) CE Non-CE P value CE Non-CE P value CE Non-CE P value 3 1.26%(4/318) 1.09%(4/367) 0.838 1.26%(4/318) 1.09%(4/367) 0.838 0%(0/318) 0%(0/367) - 6 9.75%(31/318) 10.08%(37/367) 0.614 9.12%(29/318) 9.81%(36/367) 0.807 0.63%(2/318) 0.27%(1/367) 0.481 9 21.07%(67/318) 18.80%(69/367) 0.723 21.07%(62/318) 19.98%(66/367) 0.538 1.57%(5/318) 0.82%(3/367) 0.359 12 29.25%(93/318) 31.33%(115/367) 0.553 29.25%(87/318) 31.33%(109/367) 0.499 1.89%(6/318) 1.63%(6/367) 0.802 15 36.48%(116/318) 38.96%(143/367) 0.503 36.48%(108/318) 38.96%(133/367) 0.534 2.52%(8/318) 2.72%(10/367) 0.865 18 38.05%(121/318) 42.51%(156/367) 0.236 38.05%(111/318) 42.51%(144/367) 0.242 3.14%(10/318) 3.27%(12/367) 0.926 21 41.82%(133/318) 46.59%(171/367) 0.210 41.82%(121/318) 46.59%(156/367) 0.236 3.77%(12/318) 4.09%(15/367) 0.833 24 42.45%(135/318) 48.50%178/367） 0.113 42.45%(123/318) 48.50%（163/367) 0.129 3.77%(12/318) 4.09%(15/367) 0.833 NOTE: The probability of all values was above 0.05. CE = chronic endometritis Notably, postsurgical pregnancy outcomes of patients with PEM were slightly better compared to those with ovarian endometriosis or DIE, but the differences were not statistically significant ( P =0.823). Groups with EFI scores from 7 to 8 and from 9 to 10 exhibited significantly higher cumulative clinical pregnancy rates compared to groups with EFI scores below 7. However, no significant differences were observed when comparing the two subgroups (i.e., 7–8 and 9–10) ( P =0.729). Additionally, no significant differences ( P =0.138) were observed among the three subgroups (i.e., 5–6, 3–4, and 0–2) in relation to adverse pregnancy outcomes (Table 3). TABLE 3 Gestational comparison among the stages, types and endometriosis fertility index (EFI) scores of patients with endometriosis Items No. of cases Cumulative pregnancy (n, %) Miscarriage rate (n, %) Endometriosis types OEM PEM DIE 318 124（38.99%） 131（41.19%） 63（19.81%） 135 (42.45%) 52 (41.93%) 58 (44.27%) 25 (39.68%) 12 (3.37%) 5 (4.03%) 5 (3.81%) 2 (3.17%) P value 0.823 0.958 Endometriosis stages Stage 1 Stage 2 Stage 3 Stage 4 103（32.39%）82 (25.79% ) 70（22.01%） 63（19.81%） 52 (50.49%) 40 (48.78%) 25 (35.71%) 18 (28.57%) 2 (1.94%) 3 (3.66%) 4 (5.71%) 3 (4.76%) P value 0.016 0.604 EFI 9–10 7–8 5–6 3–4 0–2 37 144 95 33 9 28 (75.68%) a 73 (50.69%) a 28 (29.47%) 5 (15.15%) 1 (11.11%) 2 (5.41%) 5 (3.47%) 3 (3.16%) 2 (6.06%) 0 (0.00%) P value ＜0.001 0.872 Note: Data are shown as n (%) unless stated otherwise. EFI = endometriosis fertility index. PEM=peritoneal endometriosis, OEM=ovarian endometriosis, DIE=deep infiltrating endometriosis. The probability of most values was above 0.05. a The probability was below 0.05. Table 4 presents the main findings regarding the association between EMS and adverse pregnancy outcomes. In comparison to women experiencing a typical pregnancy, the study group exhibited an elevated likelihood of developing placenta previa, preeclampsia, and those that required a cesarean delivery. Additionally, our findings indicate no significant association between postpartum hemorrhaging, premature rupture of fetal membranes, infants with low birth weights, stillbirths, perinatal mortality, or fetal distress (Table 4). Table 4 Association between endometriosis and maternal and infant outcomes. Variables EMS and CE (n=123) Control (n=369) RR (95% CI) P value Maternal outcomes Placenta abruption Placental previa HDP Small for gestational age PPRM Cesarean delivery PPH Infant outcomes Preterm birth Perinatal asphyxia Perinatal death Low birth weight NICU admission 9（7.32%） 16（13.01%） 7（5.69%） 7（5.69%） 19（15.45%） 73（59.34%） 12（9.76%） 13（10.57%） 3（2.44%） 0（0%） 9（7.32%） 3（2.44%） 29（7.85） 15（4.07%） 8（2.17%） 15（4.07%） 61（16.53%） 132（35.77%） 20（5.42%） 38（10.30%） 11（2.98%） 0（0%） 22（5.96%） 8（2.17%） 0.92 (0.71, 1.28) 3.53（1.69,7.37） 2.72（0.97,7.67） 1.42（0.57,3.58） 0.92 (0.53,1.62) 2.62 (1.73,3.98) 1.89 (0.89,3.98) 1.03 (0.53,2.00) 0.81 (0.22,2.97) — 1.25 (0.56,2.78) 1.13 (0.30,4.32) 0.845 ＜0.001 0.049 0.450 0.778 ＜0.001 0.091 0.932 0.754 — 0.592 0.860 Note: Data are shown as n (%) unless stated otherwise. CI = confidence interval, HDP = hypertensive disorders in pregnancy, PPRM = Preterm premature rupture of membranes, PPH=Postpartum hemorrhaging, NICU = neonatal intensive care unit; RR = relative risk. The probability of most values was above 0.05. a The probability was below 0.05. Discussion 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. Abbreviations EMS Endometriosis CE Chronic endometritis EAI Endometriosis associated infertility GnRH-a Gonadotropin releasing agonists BMI Body mass index r-AFS Revised American Fertility Society EFI Endometriosis fertility index HDP hypertensive disorders in pregnancy PPRM Preterm premature rupture of membranes PPH Postpartum hemorrhaging NICU neonatal intensive care unit RR relative risk Declarations Acknowledgements The authors are grateful to their patients’ participation and the medical staff for retrieving the case files. Authors’ contributions SHL and YYG contributed to designing the study. SHL, CBL, YSC and PHH collected the data and wrote the manuscript. YYG, JNZ, GL, YW and XX contributed to data collection and data analyzing. All authors read and approved the final manuscript. Funding Nature Foundation of Fujian Province ( No. 2021J01421, No. 2021J01412 ). Fujian Provincial Health Commission Young and Middle-aged Backbone Personnel Training Project ( No. 2022GGB004 ). Data Availability All data related to this study are available from the corresponding author upon reasonable request. Declarations Ethical approval and consent to participate The research was performed in accordance with the Declaration of Helsinki and relevant guidelines and regulations. The study was approved by the Ethics Committee of Fujian Maternity and Child Health Hospital (grant number 2018-4133), College of Clinical Medical for Obstetrics & Gynecology and Pediatrics, Fujian Medical University. As this study is a retrospective study, it will not adversely affect the health of patients, nor will it involve the privacy and personal identity information of patients. The Ethics Committee of Fujian Maternity and Child Health Hospital has waived the requirement of informed consent of patients. Consent for publication All data were anonymized, therefore individual consent for publication was not required. Competing of interests All authors of this study declare no conflicts of interest. Author details 1 Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medical for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian, P.R. China. 2 Physical examination center, Fujian Medical University Union Hospital, Fujian, 35000, P.R. China References Ye L, Whitaker LHR, Mawson RL et al. Endometriosis. BMJ (Clinical research ed.). 2022;379: e068950. 10.1136/bmj-2021-068950 . Zondervan KT, Becker CM, Missmer SA, Endometriosis. N Engl J Med. 2020;382:1244–56. 10.1056/NEJMra1810764 . Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: Clinical challenges and novel innovations. Lancet. 2021;397:839–52. 10.1016/s0140-6736(21)00389-5 . Shafrir AL, Farland LV, Shah DK, et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018;51:1–15. 10.1016/j.bpobgyn.2018.06.001 . Harris Emily. Study: Bacterial Infection Tied to Some Endometriosis Cases. JAMA-J AM MED ASSOC. 2023-07-11;330(2):112. 10.1001/jama.2023.10747 . Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022;379:e070750. 10.1136/bmj–2022 . 070750. Cicinelli E, Matteo M, Tinelli R, et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015;30(2):323–30. 10.1093/humrep/deu292 . McQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014;101(4):1026–30. 10.1016/j.fertnstert.2013.12.031 . Chen Peigen C, Panyu G. Interaction Between Chronic Endometritis Caused Endometrial Microbiota Disorder and Endometrial Immune Environment Change in Recurrent Implantation Failure. Front Immunol. 2021;12:748447. 10.3389/fimmu.2021.748447 . Pirtea P, Cicinelli E, De NR, et al. Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis. Fertil Steril. 2021;115(3):546–560doi. 10.1016/j.fertnstert.2020.12.010 . Ettore C, Giuseppe T, Marcella M et al. Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link.Fertil Steril, 2017, 108(2): 289–95. 10.1016/j.fertnstert.2017.05.016 . Kimura F, Takebayashi A, Ishida M, et al. Review:chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res. 2019;45(5):951–60. 10.1111/jog.13937 . Kitaya K, Matsubayashi H, Yamaguchi K, et al. Chronic Endometritis: Potential Cause of Infertility and Obstetric and Neonatal Complications. Am J Reprod Immunol. 2016;75(1):13–22. 10.1111/aji.12438 . Qiao X, Wu L, Liu D et al. Existence of chronic endometritis and its influence on pregnancy outcomes in infertile women with minimal/mild endometriosis. INT J GYNECOL OBSTET. 2023-02-01;160(2):628–34. 10.1002/ijgo.14326 . Ticconi C, Pietropolli A, Di Simone N et al. Endometrial immune dysfunction in recurrent pregnancy loss. Int J Mol Sci, 2019, 20 (21): 5332. doi: 10. 3390 /ijms20215332. Broi MGD, Ferriani RA, Navarro PA. Ethiopathogenic mechanisms of endometriosis-related infertility. JBRA Assist Reprod. 2019;23:273–80. 10.5935/1518-0557.20190029 . Koninckx PR, Zupi E, Martin DC. Endometriosis and pregnancy outcome. Fertil Steril. 2018;110(3):406–7. 10.1016/j.fertnstert.2018.06.029 . Wang Y, Hwa-Fen YY-CG, et al. Impact of adenomyosis and endometriosis on IVF/ICSI pregnancy outcome in patients undergoing gonadotropin-releasing hormone agonist treatment and frozen embryo transfer. Sci Rep. 2023;13(1):6741. 10.1038/s41598-023-34045-7 . Sorrentino Felice DE, Padova Maristella F, Maddalena et al. Endometriosis and adverse pregnancy outcome.Minerva Obstetrics and Gynecology. 2022; 74 (1): 31–44. 10.23736/S2724-606X.20.04718-8 . Schliep Karen C, Farland Leslie V, Pollack Anna Z, et al. Endometriosis diagnosis, staging and typology and adverse pregnancy outcome history. Paediatr Perinat Epidemiol. 2022;36(6):771–81. 10.1111/ppe.12887 . Supermaniam S, Thye WL. Laparoscopic cystectomy in treating women with endometrioma and pregnancy outcome-a case series. Med J Malay. 2021;76(1):29–34. doi:null. PMID:33510105. Benaglia Laura C, Giorgio P, Enrico, et al. Pregnancy outcome in women with endometriosis achieving pregnancy with IVF. Hum Reprod. 2016;31(12):2730–6. 10.1093/humrep/dew210 . Sindan Namita B, Adheesh S, Namrata, et al. Clinical factors influencing the pregnancy outcome after laparoscopic treatment in endometriosis-associated infertility patients: a retrospective study. Am J Transl Res. 2021;13(4):2399–409. doi:null.PMID:34017398. Breintoft Kjerstine P, Regitze HT, Brink, et al. Endometriosis and Risk of Adverse Pregnancy Outcome: A Systematic Review and Meta-Analysis. J Clin Med. 2021;10(4). 10.3390/jcm10040667 . Kitaya K, Takeuchi T, Mizuta S, et al. Endometritis: new time, new concepts. Fertil Steril. 2018;110:344–50. 10.1016/j.fertnstert.2018.04.012 . Kitaya K, Matsubayashi H, Yamaguchi K, et al. Chronic Endometritis: Potential Cause of Infertility and Obstetric and Neonatal Complications. Am J Reprod Immunol. 2016;75(1):13–22. 10.1111/aji.12438 . Giulini S, Grisendi V, Sighinolfi G, et al. Chronic endometritis in recurrent implantation failure: Use of prednisone and IVF outcome. J REPROD IMMUNOL. 2022;153:103673. 10.1016/j.jri.2022.103673 . Li J, Li X, Ding J, et al. Analysis of pregnancy outcomes in patients with recurrent implantation failure complicated with chronic endometritis. Front Cell Dev Biol. 2023;11:1088586. 10.3389/fcell.2023.1088586 . Ticconi C, Pietropolli A, Di Simone N et al. Endometrial immune dysfunction in recurrent pregnancy loss. Int J Mol Sci, 2019, 20 (21): 5332. doi: 10. 3390 /ijms20215332. Takebayashi A, Kimura F, Kishi Y, et al. The association between endometriosis and chronic endometritis. PLoS ONE. 2014;9(2):e88354. 10.1371/journal.pone.0088354 . Kotaro K. Yasuo Tadahiro. Commonalities and Disparities between Endometriosis and Chronic Endometritis: Therapeutic Potential of Novel Antibiotic Treatment Strategy against Ectopic Endometrium. Int J Mol Sci. 2023;24(3). 10.3390/ijms24032059 . Freitag Nadine, Pour Sarah J, Fehm Tanja N et al. Are uterine natural killer and plasma cells in infertility patients associated with endometriosis, repeated implantation failure, or recurrent pregnancy loss?ARCH GYNECOL OBSTET. 2020;302 (6): 1487–94. 10.1007/s00404-020-05679-z . Imperiale Ludovica N, Michelle, Noël, Jean-Christophe et al. Three Types of Endometriosis: Pathogenesis, Diagnosis and Treatment. State of the Art. J Clin Med. 2023;12 (3). 10.3390/jcm12030994 . SONG D, LI TC, ZHANG Y et al. Correlation between hysteroscopy findings and chronic endometritis. Fertil Steril, 2019, 111(4): 772–779. 10.1016/j. fertnstert. 2018. 12. 007. LIU H, SONG J, ZHANG FF, et al. A new hysteroscopic scoring system for diagnosing chronic endometritis. J MINIM INVAS GYN. 2020;27(5):1127–32. 10.1016/j.jmig.2019.08.035 . McQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014;101(4):1026–30. 10.1016/j.fertnstert.2013.12.031 . Chen Peigen C, Panyu G. Interaction Between Chronic Endometritis Caused Endometrial Microbiota Disorder and Endometrial Immune Environment Change in Recurrent Implantation Failure. Front Immunol. 2021;12:748447. 10.3389/fimmu.2021.748447 . Song D, He Y, Wang Y et al. Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial. Fertil Steril. 2021, 115(6):1549–1556. doi: 10.1016/j.fertnstert. 2020. 12. 019. Cicinelli E, Resta L, Loizzi V, et al. Antibiotic therapy versus no treatment for chronic endometritis: a case-control study. Fertil Steril. 2021;115(6):1541–8. 10.1016/j.fertnstert.2021.01.018 . Kim JS, Lee CW, Yun J, et al. Use of the endometriosis fertility index to predict natural pregnancy after endometriosis surgery: a single-center study. Gynecol Obstet Invest. 2018;20:1–8. 10.1159/000493264 . Garavaglia E, Pagliardini L, Tandoi I, et al. External validation of the endometriosis fertility index (EFI) for predicting spontaneous pregnancy after surgery: further considerations on its validity. Gynecol Obstet Invest. 2015;79:113–8. 10.1159/000366443 . Shi JDYZ, Junji, et al. Pregnancy outcomes in women with infertility and coexisting endometriosis and adenomyosis after laparoscopic surgery: a long-term retrospective follow-up study. BMC Pregnancy Childbirth. 2021;21(1):383. 10.1186/s12884-021-03851-0 . Rodrigues Daisy Martins, de Ávila, Ivete et al. Amorim Leci Veiga Caetano,. Endometriosis fertility index predicts pregnancy in women operated on for moderate and severe symptomatic endometriosis. WOMEN HEALTH. 2022;62 (1): 3–11. 10.1080/03630242.2021.1986458 . Fruscalzo A, Dayer A, Londero AP, et al. Endometriosis and Infertility: Prognostic Value of #Enzian Classification Compared to rASRM and EFI Score. J Pers Med. 2022;12(10). 10.3390/jpm12101623 . Ferrier Clément B, Jérémy P, Christophe, et al. Use of the EFI score in endometriosis-associated infertility: A cost-effectiveness study. EUR J OBSTET GYN R B. 2020;253:296–303. / j.ejogrb. 2020.08.031. Lin S, Xie X, Guo Y, et al. Clinical characteristics and pregnancy outcomes of infertile patients with endometriosis and endometrial polyps: A retrospective cohort study. TAIWAN J OBSTET GYNE. 2020;59(6):916–21. 10.1016/j.tjog.2020.09.020 . Emine D, Zeynep S. Kelekci Sefa. Outcomes between non-IVF and IVF treatment after laparoscopic conservative surgery of advanced endometriosis with Endometriosis Fertility Index score > 3. MEDICINE.2022;101 (37): e30602. 10.1097/MD.0000000000030602 . Berlac JF, Hartwell D, Skovlund CW, et al. Endometriosis increases the risk of obstetrical and neonatal complications. Acta Obstet Gynecol Scand. 2017;96(6):751–60. 10.1111/aogs.13111 . Chen I, Lalani S, Xie RH, et al. Association between surgically diagnosed endometriosis and adverse pregnancy outcomes. Fertil Steril. 2017;109:142–7. 10.1016/j.fertnstert.2017.09.028 . Miura Mayo U, Takafumi I, Kenji, et al. Adverse effects of endometriosis on pregnancy: a case-control study. BMC Pregnancy Childbirth. 2019;19(1):373. 10.1186/s12884-019-2514-1 . Additional Declarations No competing interests reported. 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15:29:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3866949/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3866949/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50183579,"identity":"6d1d0472-aad4-4204-9acb-9dec456567c3","added_by":"auto","created_at":"2024-01-25 19:27:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":260019,"visible":true,"origin":"","legend":"\u003cp\u003ePatients inclusion flow chart.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-3866949/v1/fb5bff4fdd385658c808a0e0.png"},{"id":50183578,"identity":"78ee24ec-f00f-4fc4-b8fc-5bfb9038a382","added_by":"auto","created_at":"2024-01-25 19:27:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":138864,"visible":true,"origin":"","legend":"\u003cp\u003eThe CE incidence rate of different stage EAI patients.\u003c/p\u003e\n\u003cp\u003eNote: CE=chronic endometritis, EAI= endometriosis associated infertility\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-3866949/v1/9a563ee22fceed94ea1abb90.png"},{"id":50183577,"identity":"72fd2c6d-0629-471a-b258-7cb7985494d5","added_by":"auto","created_at":"2024-01-25 19:27:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":100842,"visible":true,"origin":"","legend":"\u003cp\u003eThe CE incidence rate of different stage EAI patients.\u003c/p\u003e\n\u003cp\u003eNote: PEM=peritoneal endometriosis, OEM=ovarian endometriosis, DIE=deep infiltrating endometriosis\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-3866949/v1/6bde5544e264ea85dc8b45f2.png"},{"id":57320402,"identity":"26dd198a-672b-4de4-b131-b29098e1516a","added_by":"auto","created_at":"2024-05-29 06:04:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1016263,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3866949/v1/06907721-5aa4-4d6e-93f2-5dc6d165ff67.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Does chronic endometritis affect pregnancy outcomes in patients with endometriosis associated infertility? A retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometriosis (EMS) is characterized by the ectopic proliferation of endometrial tissue, encompassing both glands and stroma, beyond the confines of the uterine cavity\u0026rsquo;s endometrial and myometrial layers [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This pathological condition gives rise to the development of lesions, which subsequently result in local infiltration, recurrent hemorrhage, and the formation of nodules and masses. Moreover, EMS is one of the most common gynecological disorders that reduces the life quality and fertility of patients worldwide. The peak age-specific incidence of EMS is between 24 and 29 years old, and the incidence rate is up to 10\u0026ndash;15% of the general population [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Additionally, EMS often causes patients to suffer long-standing pain, infertility, pelvic masses, etc., which can seriously affect their home and work life and result in a continuous increase in medical costs, leading to the economic burden of both the state and individuals [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In some cases, EMS has even been shown to be tied to bacterial infections \u003csup\u003e[\u003c/sup\u003e5\u003csup\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eChronic endometritis (CE) and EMS are similar. The former refers to the persistent chronic inflammation of the endometrium, characterized by plasma cell infiltration into the endometrium stroma \u003csup\u003e[\u003c/sup\u003e6\u003csup\u003e]\u003c/sup\u003e. Among infertile women, the incidence of CE is up to 56.8% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], among which the incidence rate of repeated implantation failure ranges from 4.0\u0026ndash;67.5% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] while the incidence rate of recurrent abortions is approximately 9.3%~67.6% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Patients diagnosed with CE typically exhibit an absence of symptoms or display mild, non-specific manifestations, including abnormal uterine bleeding and abnormal leucorrhea. Additionally, CE exhibits a notable prevalence among individuals experiencing endometriosis associated infertility (EAI) \u003csup\u003e[\u003c/sup\u003e11,12\u003csup\u003e]\u003c/sup\u003e. The strikingly similar features of EMS and CE suggest that there may be a potential association between the two conditions. Thus far, it is not entirely clear whether CE is a risk factor or an etiologic factor of EAI. Previous studies have revealed a higher CE frequency in patients with EMS compared to those without the disease \u003csup\u003e[\u003c/sup\u003e13\u0026ndash;15\u003csup\u003e]\u003c/sup\u003e. These studies collectively indicate that the presence of EMS may be significantly associated with CE.\u003c/p\u003e \u003cp\u003eCurrently, these types of disorders are leading to relatively high infertility occurrence rates, which are also ill defined. Both EMS and CE can both contribute to and give rise to infertility. It is widely accepted that EMS alters fertility during women\u0026rsquo;s reproductive age. Several factors affect overall fertility, including altered pelvic anatomy, extensive adhesions, hormonal alterations, and inflammation. In addition, speculative CE mechanisms that result in infertility include lesions that may promote intrauterine adhesions through endometrial fibrosis enhancement and those that mechanically interfere with sperm transport or through embryo implantation. As such, these two disorders collectively affect endometrium receptivity. The exact aetiology by which this occurs, however, is not completely understood [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The past two decades have witnessed a steady increase in the number of procedures performed via minimally invasive surgery, including laparoscopy and hysteroscopy. Along with the development and widespread application of minimally invasive surgery, it would be especially beneficial to treat patients with EAI through laparoscopy and hysteroscopy. Furthermore, it is important to consider the potential negative effects on maternal and neonatal health when examining the mechanisms that disrupt fertility in women with these disorders. The relationship between EMS and adverse pregnancy outcomes has started to gain significant attention [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22 CR23\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Nevertheless, to the best of our knowledge, there is a lack of comprehensive clinical data regarding pregnancy complications and perinatal outcomes in postsurgical patients with these disorders who later conceive.\u003c/p\u003e \u003cp\u003eThis study aimed to investigate correlations between EMS and CE in individuals experiencing infertility, and to evaluate the pregnancy outcomes following a combined laparoscopy and hysteroscopy surgical intervention procedure. Specifically, the main objective is to provide a comprehensive treatment for patients facing EMS challenges accompanied by CE.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants and procedure\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003e for this study was obtained from the Fujian Provincial Maternal and Child Health Hospital (grant number 2018\u0026ndash;4133). Prior to participation, all patients were provided with detailed information about the study before their permission was obtained by signing consent forms. This study included women who underwent laparoscopy combined with hysteroscopy due to tubal infertility, infertility associated with EMS, or unexplained infertility.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn this study, infertility is defined as the inability of couples to conceive under normal coital practices for greater than one year. From January 2018 to December 2020, 1574 infertile patients who met the inclusion criteria were enrolled in the study. The inclusion criteria for this study were as follows: 1) the absence of hormone therapy within the 3 months preceding surgery; 2) normal ovarian reserve function; 3) regular menstruation without regular vaginal bleeding; 4) normal semen functionality of the patient's male partner; 5) the active intention to conceive after surgery; 6) participation in follow-up interviews over a 24 month period. Conversely, the exclusion criteria encompassed: 1) ovulation disorders, such as polycystic ovarian syndrome (PCOS); 2) uterine abnormalities, including uterus septum, uterine fibroid, and intrauterine adhesion; 3) acute pelvic inflammatory disease (PID), oligospermia, and asthenospermia; 4) other medical comorbidities, including thyroid disorders, diabetes, hypertension, hyperprolactinemia, and connective tissue diseases, were also considered as exclusion criteria; 5) the use of any antibiotics within the past four weeks was also a criterion for exclusion.\u003c/p\u003e \u003cp\u003eAll patients in this study underwent a combined laparoscopy and hysteroscopy surgical procedure to address menorrhagia during the menstruation cycle. The laparoscopic surgical procedure involved the exploration of the uterus, adnexa, and pelvic cavity. In cases where pelvic adhesion was present, the adhesion was separated prior to the removal of the ovarian cyst. Furthermore, pelvic ectopic foci excision and bilateral tubal fluidization were performed as necessary. Additionally, hysteroscopic surgical procedures involved the observation of various anatomical structures, such as internal cervix opening, cervical canal, uterine wall, uterine fundus, bilateral fallopian tube opening, etc. Special attention was given to the identification of endometrial congestion, interstitial edema, and the precise location of the endometrial biopsy.\u003c/p\u003e \u003cp\u003eThe histopathologic detection of plasma cells in the endometrium plays a crucial role in the diagnosis of CE, and the identification of typical features under hysteroscopy can be valuable for diagnostic purposes \u003csup\u003e[\u003c/sup\u003e25\u003csup\u003e]\u003c/sup\u003e. In this study, the diagnostic criteria included the presence of one or more CD138-stained and/or CD38-stained positive plasma cells in the endometrial stroma per \u0026times; 400 high-power field of view.\u003c/p\u003e \u003cp\u003ePathological findings revealed that all patients diagnosed with CE were administered a single course of doxycycline (Chinese Guangdong Huanan Pharmaceutical, 100 mg orally twice a day for 14 days). Furthermore, gonadotropin releasing agonists (GnRH-a, triptorelin acetate, French IPSEN Pharmaceutical, 3.75 mg) were utilized in cases of advanced EMS stages (i.e., stages 3 and 4) for a 3-month duration, followed by active preparation for pregnancy after discontinuation. Outpatient and telephone follow-up assessments were conducted at 3-month intervals for a minimum 24-month duration to monitor postoperative recovery and pregnancy outcomes. The follow-up period extended until the end of December 2022.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analysis was conducted using SPSS 26.0 statistical analysis software (IBM, Armonk, NY, USA). Normally distributed continuous measurement data are shown as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, while a \u003cem\u003et\u003c/em\u003e-test was employed to compare the two groups. Counting data were expressed as rates (%) while a chi-square test was used for group comparisons. In cases where chi-square test conditions could not be met, the corrected chi-square test and the Fisher\u0026rsquo;s exact test were employed along with the rank sum test. Kaplan-Meier survival analysis estimates were conducted to compare cumulative pregnancy rates between CE and Non-CE groups at different time periods. All p-values reported are two sided and a \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong the cohort of 953 women experiencing infertility due to EMS, a total of 237 individuals (24.87%) were excluded from the study due to various factors, such as ovulation disorders (n=33), uterine fibroids (n=49), uterine abnormalities (n=65), male factor infertility (n=54), and other medical comorbidities (n=36). Additionally, 22 patients (12.66%) were lost to follow-up while nine individuals (2.53%) had postponed their conception plans during the 24-month observation period. Consequently, the final analysis included 685 cases of EAI (Figure 1). Among these patients, 318 individuals (24.38%) were diagnosed with CE, while the remaining cases did not exhibit this condition. The baseline characteristics of the CE and non-CE groups showed no significant differences (Table 1).\u003c/p\u003e\n\u003cp\u003eTable 1 Baseline characteristics of women with and without endometriosis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"551\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.745916515426494%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eEndometriosis\u0026nbsp;(N=685)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.662100456621005%\" valign=\"top\"\u003e\n \u003cp\u003eCE\u0026nbsp;(N=318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"54.337899543378995%\" valign=\"top\"\u003e\n \u003cp\u003eNon-CE\u0026nbsp;(N=367)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eMean age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e28.1 \u0026plusmn;\u0026nbsp;4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e27.6 \u0026plusmn;\u0026nbsp;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.398\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e20.5 \u0026plusmn; 3.4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e21.2 \u0026plusmn; 2.6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eGravidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e1.92 \u0026plusmn; 1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e2.01 \u0026plusmn;\u0026nbsp;1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.235\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eParity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e1.73 \u0026plusmn; 1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e1.62 \u0026plusmn; 1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.374\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eMenarche Age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e12.1 \u0026plusmn; 2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e12.7 \u0026plusmn;\u0026nbsp;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.856\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eMenstrual average cycle (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e27.6 \u0026plusmn; 2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e28.3 \u0026plusmn; 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.673\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 1 Baseline characteristics of women with and without endometriosis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"551\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eMenstrual duration (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e6.4 \u0026plusmn;\u0026nbsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e6.1 \u0026plusmn;\u0026nbsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eInfertility duration (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e2.9 \u0026plusmn; 1.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e3.1 \u0026plusmn; 1.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.536\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary infertility (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e113 (55.39%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e142 (57.49%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.176\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eSecondary infertility (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e91 (44.61%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e105 (42.51%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003ePreoperative serum CA125 level (U /mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e45.1 \u0026plusmn; 6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e51.2 \u0026plusmn; 8.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.864\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003er-AFS total score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e55.8 \u0026plusmn;\u0026nbsp;16.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e61.1 \u0026plusmn;\u0026nbsp;13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.951\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.63883847549909%\" valign=\"top\"\u003e\n \u003cp\u003eEFI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.148820326678766%\" valign=\"top\"\u003e\n \u003cp\u003e7.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59709618874773%\" valign=\"top\"\u003e\n \u003cp\u003e8.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.61524500907441%\" valign=\"top\"\u003e\n \u003cp\u003e0.188\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNOTE: The probability of all values was above 0.05. BMI = Body mass index;\u003c/p\u003e\n\u003cp\u003er-AFS = Revised American Fertility Society; EFI = Endometriosis fertility index\u003c/p\u003e\n\u003cp\u003eThe prevalence of CE in patients with EAI was determined to be 46.42% (i.e., 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 (Figure 2). Specifically, the CE incidence rate was 46.95% (185 out of 394) in patients with stage 1 and 2 EMS and 45.70% (133 out of 291) in patients with stage 3 to 4 EMS, for which no statistically significant differences were observed (\u003cem\u003eP\u003c/em\u003e=0.513). Additionally, the CE incidence rate was slightly lower in patients with peritoneal endometriosis (PEM) (42.80%, or 101 out of 236) compared to those with ovarian endometriosis (OEM) (48.58%, or 154 out of 317) and deep infiltrating endometriosis (DIE) (47.72%, or 63 out of 132), although the difference was not statistically significant (\u003cem\u003eP\u003c/em\u003e=0.142) (Figure 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the CE group, women with stage 1 to 4 EMS experienced cumulative pregnancy rates of 52 (50.49%), 40 (48.78%), 25 (35.71%), and 18 (28.57%), respectively. The cumulative pregnancy rate for patients with stage 1 and 2 EMS were significantly higher compared to patients with stage 3 and 4 EMS (i.e., 49.73% [92/185] versus 32.33%, [43/133]). Furthermore, the cumulative pregnancy rate and live birth rate at different time periods for the CE group were consistently lower than those for the non-CE group, although the differences were not statistically significant (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 Comparison of the pregnancy status between CE and non-CE groups in women suffering from endometriosis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"780\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.242618741976893%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePeriod\u003c/p\u003e\n \u003cp\u003e（months）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.83568677792041%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eCumulative pregnancy rate(n, %)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.065468549422338%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eLive birth rate (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85622593068036%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eMiscarriage rate (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.135593220338983%\" valign=\"top\"\u003e\n \u003cp\u003eCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.27683615819209%\" valign=\"top\"\u003e\n \u003cp\u003eNon-CE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.757062146892656%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.853107344632768%\" valign=\"top\"\u003e\n \u003cp\u003eCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.559322033898304%\" valign=\"top\"\u003e\n \u003cp\u003eNon-CE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.768361581920904%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.440677966101696%\" valign=\"top\"\u003e\n \u003cp\u003eCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.440677966101696%\" valign=\"top\"\u003e\n \u003cp\u003eNon-CE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.768361581920904%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.923076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e1.26%(4/318)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e1.09%(4/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.948717948717949%\" valign=\"top\"\u003e\n \u003cp\u003e0.838\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.666666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e1.26%(4/318)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e1.09%(4/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.838\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e0%(0/318)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e0%(0/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.923076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e9.75%(31/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e10.08%(37/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.948717948717949%\" valign=\"top\"\u003e\n \u003cp\u003e0.614\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.666666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e9.12%(29/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e9.81%(36/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.807\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e0.63%(2/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e0.27%(1/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.481\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.923076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e21.07%(67/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e18.80%(69/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.948717948717949%\" valign=\"top\"\u003e\n \u003cp\u003e0.723\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.666666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e21.07%(62/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e19.98%(66/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.538\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e1.57%(5/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e0.82%(3/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.359\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.923076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e29.25%(93/318)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e31.33%(115/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.948717948717949%\" valign=\"top\"\u003e\n \u003cp\u003e0.553\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.666666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e29.25%(87/318)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e31.33%(109/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e1.89%(6/318)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e1.63%(6/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.802\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.923076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e36.48%(116/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e38.96%(143/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.948717948717949%\" valign=\"top\"\u003e\n \u003cp\u003e0.503\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.666666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e36.48%(108/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e38.96%(133/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.534\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e2.52%(8/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e2.72%(10/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.865\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.923076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e38.05%(121/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e42.51%(156/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.948717948717949%\" valign=\"top\"\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.666666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e38.05%(111/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e42.51%(144/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e3.14%(10/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e3.27%(12/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.926\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.923076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e41.82%(133/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e46.59%(171/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.948717948717949%\" valign=\"top\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.666666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e41.82%(121/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e46.59%(156/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e3.77%(12/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e4.09%(15/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.833\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.923076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e42.45%(135/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e48.50%178/367）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.948717948717949%\" valign=\"top\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.666666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e42.45%(123/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e48.50%（163/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e3.77%(12/318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e4.09%(15/367)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.051282051282051%\" valign=\"top\"\u003e\n \u003cp\u003e0.833\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNOTE: The probability of all values was above 0.05. CE = chronic endometritis\u003c/p\u003e\n\u003cp\u003eNotably, postsurgical pregnancy outcomes of patients with PEM were slightly better compared to those with ovarian endometriosis or DIE, but the differences were not statistically significant (\u003cem\u003eP\u003c/em\u003e=0.823). Groups with EFI scores from 7 to 8 and from 9 to 10 exhibited significantly higher cumulative clinical pregnancy rates compared to groups with EFI scores below 7. However, no significant differences were observed when comparing the two subgroups (i.e., 7\u0026ndash;8 and 9\u0026ndash;10) (\u003cem\u003eP\u003c/em\u003e=0.729). Additionally, no significant differences (\u003cem\u003eP\u003c/em\u003e=0.138)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ewere observed among the three subgroups (i.e., 5\u0026ndash;6, 3\u0026ndash;4, and 0\u0026ndash;2) in relation to adverse pregnancy outcomes (Table 3).\u003c/p\u003e\n\u003cp\u003eTABLE 3 Gestational comparison among the stages, types and endometriosis fertility index (EFI) scores of patients with endometriosis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.442477876106196%\" valign=\"top\"\u003e\n \u003cp\u003eItems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003eNo. of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.309734513274336%\" valign=\"top\"\u003e\n \u003cp\u003eCumulative pregnancy (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.24778761061947%\" valign=\"top\"\u003e\n \u003cp\u003eMiscarriage rate (n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.442477876106196%\" valign=\"top\"\u003e\n \u003cp\u003eEndometriosis types\u003c/p\u003e\n \u003cp\u003eOEM\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePEM\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDIE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e318\u003c/p\u003e\n \u003cp\u003e124（38.99%）\u003c/p\u003e\n \u003cp\u003e131（41.19%）\u003c/p\u003e\n \u003cp\u003e63（19.81%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.309734513274336%\" valign=\"top\"\u003e\n \u003cp\u003e135 (42.45%)\u003c/p\u003e\n \u003cp\u003e52 (41.93%)\u003c/p\u003e\n \u003cp\u003e58 (44.27%)\u003c/p\u003e\n \u003cp\u003e25 (39.68%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.24778761061947%\" valign=\"top\"\u003e\n \u003cp\u003e12 (3.37%)\u003c/p\u003e\n \u003cp\u003e5 (4.03%)\u003c/p\u003e\n \u003cp\u003e5 (3.81%)\u003c/p\u003e\n \u003cp\u003e2 (3.17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.442477876106196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.309734513274336%\" valign=\"top\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.24778761061947%\" valign=\"top\"\u003e\n \u003cp\u003e0.958\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.442477876106196%\" valign=\"top\"\u003e\n \u003cp\u003eEndometriosis stages\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eStage 1\u003c/p\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003eStage 3\u003c/p\u003e\n \u003cp\u003eStage 4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e103（32.39%）82 (25.79% )\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e70（22.01%）\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63（19.81%）\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.309734513274336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52 (50.49%)\u003c/p\u003e\n \u003cp\u003e40 (48.78%)\u003c/p\u003e\n \u003cp\u003e25 (35.71%)\u003c/p\u003e\n \u003cp\u003e18 (28.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.24778761061947%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (1.94%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3.66%)\u003c/p\u003e\n \u003cp\u003e4 (5.71%)\u003c/p\u003e\n \u003cp\u003e3 (4.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.442477876106196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.309734513274336%\" valign=\"top\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.24778761061947%\" valign=\"top\"\u003e\n \u003cp\u003e0.604\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.442477876106196%\" valign=\"top\"\u003e\n \u003cp\u003eEFI\u003c/p\u003e\n \u003cp\u003e9\u0026ndash;10\u003c/p\u003e\n \u003cp\u003e7\u0026ndash;8\u003c/p\u003e\n \u003cp\u003e5\u0026ndash;6\u003c/p\u003e\n \u003cp\u003e3\u0026ndash;4\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.309734513274336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28 (75.68%)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e73 (50.69%)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e28 (29.47%)\u003c/p\u003e\n \u003cp\u003e5 (15.15%)\u003c/p\u003e\n \u003cp\u003e1 (11.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.24778761061947%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (5.41%)\u003c/p\u003e\n \u003cp\u003e5 (3.47%)\u003c/p\u003e\n \u003cp\u003e3 (3.16%)\u003c/p\u003e\n \u003cp\u003e2 (6.06%)\u003c/p\u003e\n \u003cp\u003e0 (0.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.442477876106196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.309734513274336%\" valign=\"top\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.24778761061947%\" valign=\"top\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Data are shown as \u003cem\u003en\u003c/em\u003e (%) unless stated otherwise. EFI = endometriosis fertility index. PEM=peritoneal endometriosis, OEM=ovarian endometriosis, DIE=deep infiltrating endometriosis. The probability of most values was above 0.05. \u003csup\u003ea\u003c/sup\u003e The probability was below 0.05.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 presents the main findings regarding the association between EMS and adverse pregnancy outcomes. In comparison to women experiencing a typical pregnancy, the study group exhibited an elevated likelihood of developing placenta previa, preeclampsia, and those that required a cesarean delivery. Additionally, our findings indicate no significant association between postpartum hemorrhaging, premature rupture of fetal membranes, infants with low birth weights, stillbirths, perinatal mortality, or fetal distress (Table 4).\u003c/p\u003e\n\u003cp\u003eTable 4\u0026nbsp;Association between endometriosis and maternal and infant outcomes.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"597\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.096989966555185%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.558528428093645%\" valign=\"top\"\u003e\n \u003cp\u003eEMS and CE\u003c/p\u003e\n \u003cp\u003e(n=123)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.725752508361204%\" valign=\"top\"\u003e\n \u003cp\u003eControl\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n=369)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.073578595317727%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;RR\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.545150501672241%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.096989966555185%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaternal outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePlacenta abruption\u003c/p\u003e\n \u003cp\u003ePlacental previa\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHDP\u003c/p\u003e\n \u003cp\u003eSmall for gestational age\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePPRM\u003c/p\u003e\n \u003cp\u003eCesarean delivery\u003c/p\u003e\n \u003cp\u003ePPH\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eInfant outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePreterm birth\u003c/p\u003e\n \u003cp\u003ePerinatal asphyxia\u003c/p\u003e\n \u003cp\u003ePerinatal death\u003c/p\u003e\n \u003cp\u003eLow birth weight \u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNICU admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.558528428093645%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9（7.32%）\u003c/p\u003e\n \u003cp\u003e16（13.01%）\u003c/p\u003e\n \u003cp\u003e7（5.69%）\u003c/p\u003e\n \u003cp\u003e7（5.69%）\u003c/p\u003e\n \u003cp\u003e19（15.45%）\u003c/p\u003e\n \u003cp\u003e73（59.34%）\u003c/p\u003e\n \u003cp\u003e12（9.76%）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13（10.57%）\u003c/p\u003e\n \u003cp\u003e3（2.44%）\u003c/p\u003e\n \u003cp\u003e0（0%）\u003c/p\u003e\n \u003cp\u003e9（7.32%）\u003c/p\u003e\n \u003cp\u003e3（2.44%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.725752508361204%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29（7.85）\u003c/p\u003e\n \u003cp\u003e15（4.07%）\u003c/p\u003e\n \u003cp\u003e8（2.17%）\u003c/p\u003e\n \u003cp\u003e15（4.07%）\u003c/p\u003e\n \u003cp\u003e61（16.53%）\u003c/p\u003e\n \u003cp\u003e132（35.77%）\u003c/p\u003e\n \u003cp\u003e20（5.42%）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38（10.30%）\u003c/p\u003e\n \u003cp\u003e11（2.98%）\u003c/p\u003e\n \u003cp\u003e0（0%）\u003c/p\u003e\n \u003cp\u003e22（5.96%）\u003c/p\u003e\n \u003cp\u003e8（2.17%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.073578595317727%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.92 (0.71, 1.28)\u003c/p\u003e\n \u003cp\u003e3.53（1.69,7.37）\u003c/p\u003e\n \u003cp\u003e2.72（0.97,7.67）\u003c/p\u003e\n \u003cp\u003e1.42（0.57,3.58）\u003c/p\u003e\n \u003cp\u003e0.92 (0.53,1.62)\u003c/p\u003e\n \u003cp\u003e2.62 (1.73,3.98)\u003c/p\u003e\n \u003cp\u003e1.89 (0.89,3.98)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.03 (0.53,2.00)\u003c/p\u003e\n \u003cp\u003e0.81 (0.22,2.97)\u003c/p\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003cp\u003e1.25 (0.56,2.78) \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.13 (0.30,4.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.545150501672241%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.845\u003c/p\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003cp\u003e0.450\u003c/p\u003e\n \u003cp\u003e0.778\u003c/p\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.932\u003c/p\u003e\n \u003cp\u003e0.754\u003c/p\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003cp\u003e0.592\u003c/p\u003e\n \u003cp\u003e0.860\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Data are shown as n (%) unless stated otherwise. CI = confidence interval, HDP = hypertensive disorders in pregnancy, PPRM = Preterm premature rupture of membranes, PPH=Postpartum hemorrhaging, NICU = neonatal intensive care unit; RR = relative risk. The probability of most values was above 0.05.\u003csup\u003ea\u003c/sup\u003e The probability was below 0.05.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBoth 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 \u003csup\u003e[\u003c/sup\u003e14\u003csup\u003e]\u003c/sup\u003e. Evidence supports this claim. For example, the prevalence of CE among the general female population is 10\u0026ndash;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\u0026ndash;60%, which is potentially attributed to the absence of standardized diagnostic criteria \u003csup\u003e[\u003c/sup\u003e26\u003csup\u003e]\u003c/sup\u003e. 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 \u003csup\u003e[\u003c/sup\u003e27,28\u003csup\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eResearch 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 [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], indicating that EMS serves as an independent risk factor for CE development. This study\u0026rsquo;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. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], 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 [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Furthermore, research has demonstrated a notable microbial community increase within the endometrium of EMS patients compared to non-EMS patients [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Consequently, microbial infection may also contribute to the occurrence of CE in EMS patients [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, the precise etiology and associated mechanisms of these conditions remain largely unknown, which necessitates further investigation.\u003c/p\u003e \u003cp\u003eBased on research, the pathogenesis of various EMS types may vary [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. 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. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] observed that the incidence of CE in EMS patients at stages 1\u0026ndash;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\u0026ndash;4 EMS and 45.70% (133 out of 291) in patients with stage 3\u0026ndash;4 EMS, where no statistically significant differences were observed (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;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 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.142). These findings suggest that the presence of CE in EMS patients may not be associated with a specific clinicopathological type.\u003c/p\u003e \u003cp\u003eDue 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 (\u0026lt;\u0026thinsp;1 mm), and interstitial edema, providing valuable diagnostic information for CE diagnosis [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. 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.\u003c/p\u003e \u003cp\u003eThis study\u0026rsquo;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 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. 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 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;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.\u003c/p\u003e \u003cp\u003eMicrobial 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 [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. 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\u0026ndash;96% [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. 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%) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Our study\u0026rsquo;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 [\u003cspan additionalcitationids=\"CR41 CR42 CR43 CR44 CR45 CR46\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. However, this observation must be confirmed by further research.\u003c/p\u003e \u003cp\u003eCombined 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.\u003c/p\u003e \u003cp\u003eThis study\u0026rsquo;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 [\u003cspan additionalcitationids=\"CR49\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. 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\u0026rsquo;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\u0026rsquo;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.\u003c/p\u003e \u003cp\u003eThis 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.\u003c/p\u003e \u003cp\u003eIn 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.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eEMS \u0026nbsp; \u0026nbsp; \u0026nbsp;Endometriosis\u003c/p\u003e\n\u003cp\u003eCE \u0026nbsp; \u0026nbsp; \u0026nbsp; Chronic endometritis\u003c/p\u003e\n\u003cp\u003eEAI \u0026nbsp; \u0026nbsp; \u0026nbsp; Endometriosis associated infertility\u003c/p\u003e\n\u003cp\u003eGnRH-a \u0026nbsp; Gonadotropin releasing agonists\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI \u0026nbsp; \u0026nbsp; \u0026nbsp; Body mass index\u003c/p\u003e\n\u003cp\u003er-AFS \u0026nbsp; \u0026nbsp; Revised American Fertility Society\u003c/p\u003e\n\u003cp\u003eEFI \u0026nbsp; \u0026nbsp; \u0026nbsp; Endometriosis fertility index\u003c/p\u003e\n\u003cp\u003eHDP \u0026nbsp; \u0026nbsp; \u0026nbsp;hypertensive disorders in pregnancy\u003c/p\u003e\n\u003cp\u003ePPRM \u0026nbsp; \u0026nbsp;Preterm premature rupture of membranes\u003c/p\u003e\n\u003cp\u003ePPH \u0026nbsp; \u0026nbsp; \u0026nbsp;Postpartum hemorrhaging\u003c/p\u003e\n\u003cp\u003eNICU \u0026nbsp; \u0026nbsp; neonatal intensive care unit\u003c/p\u003e\n\u003cp\u003eRR \u0026nbsp; \u0026nbsp; \u0026nbsp; relative risk\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful to their patients’ participation and\u0026nbsp;the medical staff for retrieving the case files.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSHL and YYG contributed to designing the study. SHL, CBL, YSC and PHH collected the data and wrote the manuscript. YYG, JNZ, GL, YW and XX contributed to data collection and data analyzing. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNature Foundation of Fujian Province ( No. 2021J01421, No. 2021J01412 ). Fujian Provincial Health Commission Young and Middle-aged Backbone Personnel Training Project ( No. 2022GGB004 ).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data related to this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research was performed in accordance with the Declaration of Helsinki\u003c/p\u003e\n\u003cp\u003eand relevant guidelines and regulations. The study was approved by the\u003c/p\u003e\n\u003cp\u003eEthics Committee of Fujian Maternity and Child Health Hospital\u0026nbsp;(grant number 2018-4133), College of Clinical Medical for Obstetrics \u0026amp; Gynecology and Pediatrics, Fujian Medical University. As this study is a retrospective study, it will not adversely affect the health of patients, nor will it involve the privacy and personal identity information of patients. The Ethics Committee of Fujian Maternity and Child Health Hospital has waived the requirement of informed consent of patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data were anonymized, therefore individual consent for publication was\u003c/p\u003e\n\u003cp\u003enot required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors of this study declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medical for Obstetrics \u0026amp; Gynecology and Pediatrics, Fujian Medical University, Fujian, P.R. China. \u003csup\u003e2\u003c/sup\u003ePhysical examination center, Fujian Medical University Union Hospital, Fujian, 35000, P.R. China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYe L, Whitaker LHR, Mawson RL et al. Endometriosis. BMJ (Clinical research ed.). 2022;379: e068950.\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj-2021-068950\u003c/span\u003e\u003cspan address=\"10.1136/bmj-2021-068950\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZondervan KT, Becker CM, Missmer SA, Endometriosis. 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Adverse effects of endometriosis on pregnancy: a case-control study. BMC Pregnancy Childbirth. 2019;19(1):373. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12884-019-2514-1\u003c/span\u003e\u003cspan address=\"10.1186/s12884-019-2514-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chronic endometritis, Endometriosis, Infertility, Pregnancy outcome","lastPublishedDoi":"10.21203/rs.3.rs-3866949/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3866949/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eEndometriosis (EMS) and chronic endometritis (CE) often coexist. Laparoscopic and hysteroscopic surgery surgery is one of the main methods for diagnosing and treating these conditions. The objectives of this study were to examine the clinical characteristics and prognosis of surgically diagnosed EMS complicated by CE and to assess the reproductive outcomes during subsequent pregnancies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003eA total of 1574 infertile patients were included in this study between January 2018 and December 2020. 685 patients were diagnosed with endometriosis who were further divided into two groups: a CE group consisting of 318 patients and a non-CE group consisting of 367 patients. Within the cohort who suffered from CE, a subset of postoperative care clinical pregnant women (n=123) was selected to form the study group. The control group consisted of women undergoing singleton pregnancy (n=369) who underwent delivery during the same period. Data on clinical statuses and complications during pregnancy and delivery were collected from hospitals and through telephone interviews.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The CE prevalence rate in women with EMS was 46.42%. Among the 318 women who were diagnosed with posterior CE, 135 achieved pregnancy. The cumulative clinical pregnancy rate was found to be significantly higher in groups with endometriosis fertility index (EFI) scores ranging from 7 to 8 and from 9 to 10 compared to groups with EFI scores below 7. Furthermore, women with both EMS and CE had a higher risk of experiencing complications during pregnancy, including placenta previa (13.01%), gestational hypertension (5.69%), and cesarean section delivery (59.34%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003ePatients diagnosed with endometriosis exhibited a heightened prevalence of chronic endometritis. Our investigation revealed that combined hysteroscopic and laparoscopic surgery proved to be a successful approach in augmenting the overall pregnancy rate. Furthermore, women afflicted by both EMS and CE face an independently escalated susceptibility to placenta previa, gestational hypertension, and cesarean delivery.\u003c/p\u003e","manuscriptTitle":"Does chronic endometritis affect pregnancy outcomes in patients with endometriosis associated infertility? A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-25 19:27:43","doi":"10.21203/rs.3.rs-3866949/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"386372a1-9d59-42be-b8ee-5d912fee450e","owner":[],"postedDate":"January 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-29T05:55:53+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-25 19:27:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3866949","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3866949","identity":"rs-3866949","version":["v1"]},"buildId":"0SHbDDIpRTBOrFPTvp6pu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}