Endogenous Microbacteria Can Contribute to Ovarian Carcinogenesis by Reducing Iron Concentration in Cysts: A Pilot Study.

Among epithelial ovarian cancer, clear cell carcinoma is common for chemo-resistance and high mortality. This cancer arises from benign ovarian endometrioma (OE), which is a high oxidative stress environment due to the cystic retention of menstrual blood produced during menstruation and the "iron" liberated from the cyst. There has been strong evidence that the iron concentration in OE decreases when they become cancerous. A decrease in iron concentration is a necessary condition for the formation of cancer. However, the mechanism of carcinogenesis is not yet clear. In the current study, the bacterial flora in endometriosis-associated ovarian cancer (EAOC), including clear cell carcinoma, and their origin, OE, were investigated using next-generation sequencing. The Shannon index in the genus level was significantly higher in EAOC than in OE fluids. Among several bacterial flora that were more abundant than benign chocolate cysts, a number of bacterial species that correlate very well with iron concentrations in the cysts were identified. These bacterial species are likely to be associated with decreased iron concentrations and cancer development.

The clinical trial of alternative relugolix administration for uterine leiomyoma prior to surgically treatment: a study protocol for Non-Adverse Relugolix Administration (NARA) trial.

BACKGROUND: Uterine leiomyomas are common for reproductive-aged women and affect women's quality of life due to heavy menstrual bleeding or dysmenorrhea. Leiomyomas grow according to estradiol exposure and decrease after post-menopause. In case serious symptoms are caused by leiomyomas, pharmacotherapy or surgical treatment is proposed. Prior to surgical treatment, pharmacotherapies aimed at the reduction of leiomyoma and uterine volume or improvement of anemia are introduced to conduct minimum invasive surgery (i.e., to reduce blood loss or surgical duration). Recently, relugolix (40 mg orally once daily) as a gonadotropin-releasing hormone (GnRH) receptor antagonist has proved its sufficient efficacy in suppressing estradiol levels without the transient estradiol flare-up compared with GnRH agonist. However, long-term administration should not be permitted liable to for climacteric disorder or osteoporosis, and evidence is lacking on the actual efficacy and extent of adverse effects of the every-other-day dosing regimen. This trial aimed to prove non-inferiority in volume reduction effect on leiomyoma and safety (i.e., reduction of adverse effects) by every-other-day administration after 2 months of everyday administration compared to daily administration throughout the duration. METHODS: A minimization adaptive randomized control trial (RCT) will be conducted. Patients (over 20 years old) harboring leiomyoma who will be undergoing surgical treatment will be invited to participate. Patients who are enrolled in the intervention group will receive every-other-day administration for 16 weeks after 8 weeks of daily administration. Patients who are enrolled in the control group will receive daily throughout the 24 weeks. The primary outcome is the leiomyoma volume reduction, and the secondary endpoints are the reduction of uterine volume, the occurrence of the climacteric disorder, genital bleeding days, change rate of serum hormone or bone turnover markers, and bone mineral density after 24 weeks compared to before administration. DISCUSSION: This study aims to prove both the non-inferiority in leiomyoma volume reduction and superiority in adverse effects occurrence reduction, which will provide a novel method to escape adverse effects while maintaining the effect of leiomyoma reduction. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs051230078. Registered on 26 July 2023.

Possible Molecular Mechanisms of Hypertension Induced by Sleep Apnea Syndrome/Intermittent Hypoxia.

Intermittent hypoxia (IH) is a central characteristic of sleep apnea syndrome (SAS), and it subjects cells in the body to repetitive apnea, chronic hypoxia, oxygen desaturation, and hypercapnia. Since SAS is linked to various serious cardiovascular complications, especially hypertension, many studies have been conducted to elucidate the mechanism of hypertension induced by SAS/IH. Hypertension in SAS is associated with numerous cardiovascular disorders. As hypertension is the most common complication of SAS, cell and animal models to study SAS/IH have developed and provided lots of hints for elucidating the molecular mechanisms of hypertension induced by IH. However, the detailed mechanisms are obscure and under investigation. This review outlines the molecular mechanisms of hypertension in IH, which include the regulation systems of reactive oxygen species (ROS) that activate the renin-angiotensin system (RAS) and catecholamine biosynthesis in the sympathetic nervous system, resulting in hypertension. And hypoxia-inducible factors (HIFs), Endotheline 1 (ET-1), and inflammatory factors are also mentioned. In addition, we will discuss the influences of SAS/IH in cardiovascular dysfunction and the relationship of microRNA (miRNA)s to regulate the key molecules in each mechanism, which has become more apparent in recent years. These findings provide insight into the pathogenesis of SAS and help in the development of future treatments.

Immunohistochemical Analysis of the Tissue Factor Pathway Inhibitor-2 in Endometrial Clear Cell Carcinoma: A Single-center Retrospective Study.

The tissue factor pathway inhibitor-2 (TFPI2) was recently identified as a diagnostic serum marker for ovarian clear cell carcinoma. Moreover, the immunohistochemical expression of TFPI2 in ovarian clear cell carcinoma was recently reported. This single-center retrospective study aimed to evaluate whether TFPI2 can be a specific biomarker for immunohistological diagnosis of endometrial clear cell carcinoma (ECCC). Immunohistochemical staining of TFPI2 in 55 endometrial carcinomas was evaluated at Nara Medical University Hospital. Thirteen ECCC samples were included as cases and 42 samples were included as a control (endometrioid carcinoma grade 1, 11 cases; grade 2, 11 cases; grade 3, 10 cases; serous carcinoma, 10 cases). The mean ± SD TFPI2 histoscore for diagnosing ECCC was 115.4 ± 87.9, which was significantly higher than that of non-ECCC (21.3 ± 45.9, P = 0.002). The best TFPI2 histoscore value obtained from the analyses of receiver operating characteristic curves for immunohistochemical diagnosis of ECCC was 15. With TFPI2 histoscores ≥15.0 as positive and <15.0 as negative, all 13 ECCC cases (100%) were positive for TFPI2, whereas 11 (26.2%) non-ECCC cases were positive for TFPI2. The sensitivity and specificity of TFPI2 for diagnosing ECCC were 100% and 73.8%, respectively. TFPI2 is expressed in ECCC and is useful for histopathological diagnosis.

The Prognosis Predictive Score around Neo Adjuvant Chemotherapy (PPSN) Improves Diagnostic Efficacy in Predicting the Prognosis of Epithelial Ovarian Cancer Patients.

BACKGROUND: Recent studies have shown that pretreatment inflammatory responses can predict prognosis. However, no reports have analyzed the combined effect of the inflammatory response with pre-treatment and post-neo adjuvant chemotherapy (NACT). This retrospective study aims to identify factors predicting prognosis and create a novel predictive scoring system. METHODS: The study was conducted at our institution between June 2006 and March 2020. Demographic and clinicopathological data were collected from patients with advanced epithelial ovarian cancer who underwent neoadjuvant chemotherapy after sample collection by laparoscopic or laparotomy surgery, followed by interval debulking surgery. We created a scoring system, called the Predictive Prognosis Score around NACT (PPSN), using factors extracted from a receiver operating characteristic curve analysis. Univariate and multivariate analyses were conducted to assess the efficacy of PPSN in predicting progression-free survival and overall survival. Kaplan-Meier and log-rank tests were used to compare the PFS or OS rate. RESULTS: Our study included 72 patients, with a cut-off value of four for the scoring system. Our analysis showed that high PPSN (≥4) significantly predicts poor prognosis. Moreover, CD3+ and CD8+ tumor-infiltrating lymphocytes with low PPSN (<4) showed higher aggregation than those with high PPSN (≥4) cases. CONCLUSION: Our study shows that PPSN could be a useful prognostic tool for advanced EOC patients who undergo NACT followed by IDS.

Preoperative serum tissue factor pathway inhibitor­2 level as a prognostic marker for endometrial cancer.

Advanced endometrial cancer (EC) often recurs and has a poor prognosis. Various serum markers have been used for EC but their usefulness as biomarkers is still unclear; therefore, identifying new biomarkers is important. The present study aimed to investigate whether the tissue factor pathway inhibitor-2 (TFPI2) level was elevated in the preoperative serum of patients with EC and if it may be a prognostic factor. The present retrospective study included 207 patients who had a confirmed pathological diagnosis of EC and received surgical therapy as the initial treatment between January 2011 and December 2017. Survival analysis was performed using Kaplan-Meier analysis and the Cox proportional hazards regression model. The 5-year disease-free survival and overall survival (OS) rates were 73.3 and 83.7%, respectively. The cut-off value for predicting OS for TFPI2 level was 177 pg/ml as determined from the receiver operating characteristic curve. A TFPI2 value ≥177 pg/ml was significantly associated with age ≥65 years (P<0.001), diabetes (P=0.035), stage (P<0.001), myometrial invasion (P<0.001), lymphovascular invasion (P=0.004), lymph node metastasis (P=0.010), distant metastasis (P<0.001), cancer antigen (CA) 125 ≥36 U/ml (P<0.001) and CA 19-9 ≥38 U/ml (P<0.001). In multivariate analysis, high-grade carcinoma [hazard ratio (HR), 2.439; P=0.041], lymph node metastasis (HR, 2.116; P=0.038), distant metastasis (HR, 3.604; P=0.009) and TFPI2 level ≥177 pg/ml (HR, 2.42; P=0.043) were significant prognostic factors affecting OS in patients with EC. These results suggest that the preoperative serum TFPI2 level, along with its histological type, lymph node metastasis and distant metastasis, was a prognostic factor for OS in patients with endometrial cancer.

Impact of Lactobacillus in the uterine microbiota on in vitro fertilization outcomes.

Abundant intrauterine Lactobacillus is associated with good in vitro fertilization (IVF) outcomes; however, whether specific species of Lactobacillus have any benefit remains unclear. So we examine the effect of Lactobacillus on the clinical outcomes of IVF at the species level. Uterine microbiota were classified as either Lactobacillus-dominant (LD) or non-Lactobacillus-dominant. In the LD group, we further investigated the clinical results for each Lactobacillus species and evaluated them in relation to IVF outcomes. In Uterine microbiome analysis, Lactobacillus was the most abundant, with the four species of L. crispatus, L. iners, L. gasseri, and L. jensenii accounting for the great majority. We compared the clinical outcomes of single frozen-thawed embryo transfer conducted by Lactobacillus species and found that the implantation rate was lowest in those in whom L. iners was dominant. This study is the first to conduct a species-level analysis of the uterine microbiota and report on a detailed investigation of Lactobacillus, which was believed to be particularly helpful for pregnancy.

Effect of a web-based fertility preservation training program for medical professionals in Japan.

BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.

Verification of selective and individual pulmonary thromboembolism prophylaxes for cesarean delivery.

OBJECTIVE: This study aimed to verify the utility of simple, safe, and effective venous thromboembolism (VTE) prophylaxis and implement it with few adverse events during cesarean delivery. METHODS: This single-center, prospective study involved pregnant women who underwent cesarean deliveries from August 3, 2020 to March 31, 2022. Patients with VTE risk factors were initially administered unfractionated heparin (5,000 international unit [IU] subcutaneously, twice daily), 6 hours after cesarean delivery. Subsequently, they were administered enoxaparin (2,000 IU subcutaneously, twice daily). They were not administered anticoagulants if one or more of the exclusion criteria were met. The primary efficacy outcome was the incidence of symptomatic VTE. The primary safety outcome was the incidence of major bleeding. RESULTS: Out of the 850 women eligible for this study, 551 (64.9%) had one or more VTE risk factors and 299 (35.1%) had no risk factors. Of the 551 women with one or more VTE risk factors, 15 met one or more exclusion criteria for enoxaparin administration. A total of 314 women received only perioperative mechanical prophylaxis, including 15 who met the exclusion criteria for anticoagulants and 299 without VTE risk factors. During implementation of the protocol, no woman developed symptomatic VTE after cesarean delivery. Major bleeding occurred in only one woman who received postoperative anticoagulants. CONCLUSION: This protocol, which clarified the administration of anticoagulants according to VTE risk factors and dose reduction/discontinuation criteria, may be an effective and safe VTE prophylaxis for cesarean deliveries.

Successful vaginoscopic excision of the vaginal septum in a virgin girl of obstructed hemivagina and ipsilateral renal anomaly: Case report and review of literature.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) is a rare malformation that not only causes severe menstrual cramps shortly after menarche but can also lead to endometriosis and infection in the future. We report a case of OHVIRA successfully managed by vaginoscopic excision of the vaginal septum. A 12-year-old virgin girl presented to our hospital with dysmenorrhea and lower abdominal pain. OHVIRA was diagnosed using magnetic resonance imaging. Vaginoscopic surgery was performed for drainage of hematocolpos and excision of the vaginal septum. Vaginoscopic excision of the vaginal septum was performed using a resectoscope, without a vaginal speculum. The procedure was completed safely without injuring the hymen. This is the first case report of successful excision of the vaginal septum by vaginoscopic surgery for OHVIRA in Japan. Vaginoscopic excision may be one of the effective options for the treatment of vaginal obstruction.

Exploratory Study of Serum Lactoferrin and Anti-Lactoferrin Antibody Concentrations in Patients with Endometriosis.

Endometriosis is a disease that is characterized by the ectopic presence of the endometrium or its similar cells. A high prevalence of patients with autoimmune diseases has been reported among patients with endometriosis although the cause of endometriosis remained unknown. Recently, the anti-lactoferrin antibody is reported to be highly detected in autoimmune diseases. This study focused on lactoferrin and anti-lactoferrin antibodies to explore the pathology of endometriosis. Lactoferrin is a substance that regulates inflammation and is produced by neutrophils. Anti-lactoferrin antibody is a type of perinuclear antineutrophil cytoplasmic antibody. The serum lactoferrin and anti-lactoferrin antibody levels were compared among patients with or without endometriosis, revealing significantly higher levels in patients with endometriosis. Additionally, a decreased serum anti-lactoferrin antibody level was observed after surgical endometriosis resection. The receiver operating characteristic curve analysis determined the reference values for the serum lactoferrin and anti-lactoferrin antibody levels. Patients whose serum level exceeded the reference anti-lactoferrin antibody value were significantly higher in more than 40% of cases in the endometriosis group. The rate is comparable to that of autoimmune diseases. This is the first report that anti-lactoferrin antibody is frequently observed in patients with endometriosis, adding a new perspective to the understanding of the pathology of endometriosis although precisely elucidating the mechanism by which lactoferrin and anti-lactoferrin antibody appear in endometriosis in the future is necessary.

A Nationwide Survey Aimed at Establishing an Appropriate Long-Term Storage and Management System for Fertility Preserving Specimens in Japan.

Purpose: The demand for fertility preservation continues to grow as cancer treatment outcomes improve. The specimen storage period is longer for fertility preservation than for conventional fertility treatment; therefore, a robust management system for stored specimens is required. We conducted the first national survey in Japan on the management of cryopreserved specimens in fertility preservation facilities. Methods: Questionnaires were mailed to 130 fertility preservation facilities. Primary outcomes included the official position of the storage manager, support system in case of facility closure, disaster countermeasures, management and operating system for liquid nitrogen storage containers, preservation costs, and method to confirm the intention to continue storage. Results: The response rate was 63.8%. The facility director most commonly functioned as the storage manager (59.0%). In case of facility closure, 20.5% had an approved transfer site; 59.0% had not made any decisions. In the management of liquid nitrogen containers, 83.1% regularly replenished the liquid nitrogen, 65.1% regularly checked the amount, and 16.9% had alarm monitoring systems. Regarding disaster countermeasures, 70.9% had taken measures to protect specimens. Conclusion: This survey revealed issues such as disparities among facilities regarding long-term specimen storage systems. Accordingly, management standards for fertility preservation facilities should be established.

The prognosis predictive score around primary debulking surgery (PPSP) improves diagnostic efficacy in predicting the prognosis of ovarian cancer.

In recent years, the pretreatment inflammatory responses have proven to predict the prognosis, but no report exists analyzing the combined inflammatory response of the pre- and postsurgical treatment. The current study aims to extract the factors predicting the recurrence and create novel predictive scoring. This retrospective study was conducted at our institution between November 2006 and December 2020, with follow-up until September 2022. Demographic and clinicopathological data were collected from women who underwent primary debulking surgery. We created the scoring system named the prognosis predictive score around primary debulking surgery(PPSP) for progression-free survival(PFS). Univariate and multivariate analyses were performed to assess its efficacy in predicting PFS and overall survival(OS). Cox regression analyses were used to assess its time-dependent efficacy. Kaplan-Meier and the log-rank test were used to compare the survival rate. A total of 235 patients were included in the current study. The cut-off value of the scoring system was six. Multivariate analyses revealed that an advanced International Federation of Gynecology and Obstetrics(FIGO) stage (p < 0.001 for PFS; p = 0.038 for OS), the decreased white blood cell count difference (p = 0.026 for PFS) and the high-PPSP (p = 0.004 for PFS; p = 0.002 for OS) were the independent prognostic factors. Cox regression analysis also supported the above results. The PPSP showed good prognostic efficacy not only in predicting the PFS but also OS of ovarian cancer patients comparable to FIGO staging.

The Endometriotic Neoplasm Algorithm for Risk Assessment (e-NARA) Index Sheds Light on the Discrimination of Endometriosis-Associated Ovarian Cancer from Ovarian Endometrioma.

BACKGROUND: Magnetic resonance (MR) relaxometry provides a noninvasive tool to discriminate endometriosis-associated ovarian cancer (EAOC) from ovarian endometrioma (OE) with high accuracy. However, this method has a limitation in discriminating malignancy in clinical use because the R2 value depends on the device manufacturer and repeated imaging is unrealistic. The current study aimed to reassess the diagnostic accuracy of MR relaxometry and investigate a more powerful tool to distinguish EAOC from OE. METHODS: This retrospective study was conducted at our institution from December, 2012, to May, 2022. A total of 150 patients were included in this study. Patients with benign ovarian tumors (n = 108) mainly received laparoscopic surgery, and cases with suspected malignancy (n = 42) underwent laparotomy. Information from a chart review of the patients' medical records was collected. RESULTS: A multiple regression analysis revealed that the age, the tumor diameter, and the R2 value were independent malignant predicting factors. The endometriotic neoplasm algorithm for risk assessment (e-NARA) index provided high accuracy (sensitivity, 85.7%; specificity, 87.0%) to discriminate EAOC from OE. CONCLUSIONS: The e-NARA index is a reliable tool to assess the probability of malignant transformation of endometrioma.

Bovine lactoferrin suppresses inflammatory cytokine expression in endometrial stromal cells in chronic endometritis.

Chronic endometritis (CE) is a type of chronic inflammation in the endometrium that is associated with infertility, which is primarily due to implantation failure. Antibiotics are the most common treatment for CE. However, some patients with CE are resistant to antibiotic treatment, while others refuse this treatment. Therefore, we focused on lactoferrin (Lf), which exhibits antimicrobial and anti-inflammatory properties, and studied its effect on inflammation in endometrial stromal cells (ESCs) from patients with CE. Endometrial tissue was collected from patients with CE, and ESCs were isolated and cultured. When ESCs were cultured with bovine lactoferrin (bLf: 1 mg/mL), the mRNA expression of TNF-α (p < 0.05) and IL-1ß (p < 0.01) was significantly decreased compared with that in cells cultured without bLf. The level of TNF-α protein in the culture medium was significantly decreased (p < 0.01), while that of IL-1ß was also decreased, but not significantly (p < 0.10), when 1 mg/mL of bLf was added to the culture medium. When more inflammation was induced artificially by adding 0.1 ng/mL of TNF-αto ESCs, the addition of bLf (1 mg/mL) to ESCs decreased IL-6 and IL-1ß mRNA expression to levels similar to those in ESCs without TNF-α treatment. Furthermore, it was revealed that the actions of bLf are mediated by the AKT and MAPK intracellular signaling pathways, which are mechanisms by which the increase in TNF-α-induced cytokine expression is suppressed in ESCs. bLf suppresses the expression of inflammatory cytokines in human ESCs and may be a new therapeutic candidate for CE.

Tissue factor pathway inhibitor 2: A potential diagnostic marker for discriminating benign from malignant ovarian tumors.

OBJECTIVES: Carbohydrate antigen 125 (CA125), CA19-9, carcinoembryonic antigen (CEA), human epididymis protein 4 (HE4), and the Risk of Ovarian Malignancy Algorithm (ROMA) are widely used as tumor markers and algorithms for the diagnosis of ovarian cancer (OC). Tissue factor pathway inhibitor 2 (TFPI2) has been developed as a potential serodiagnostic marker for OC in Japan. The aim of this study is to evaluate the diagnostic accuracy of the six markers alone and in combination to find the best marker for discriminating between benign and malignant ovarian tumors. METHODS: Frozen serum samples collected from 484 patients were divided into three groups based on histopathological results: OC (n = 119), borderline ovarian tumors (BR) (n = 48), and benign ovarian tumors (BN) (n = 317). Diagnostic accuracy was calculated with an area under a receiver operating characteristic (AUC) curve. RESULTS: TFPI2 achieved the highest discrimination between the OC + BR group versus the BN group (AUC 0.8076). ROMA values best discriminated patients with OC from those with BN (AUC, 0.8966), which was equivalent to TFPI2 (AUC, 0.8937). For discriminating the OC group from the BR + BN group, the highest AUC value was achieved by ROMA values (AUC, 0.8884), and TFPI2 also showed comparable diagnostic accuracy (AUC, 0.8845). Combining TFPI2 with ROMA had the highest AUC (0.8420-0.9357). CONCLUSION: TFPI2 may be a clinically useful single marker comparable to conventional ROMA values for discriminating between benign and malignant ovarian tumors.

The Comparison of Three Predictive Indexes to Discriminate Malignant Ovarian Tumors from Benign Ovarian Endometrioma: The Characteristics and Efficacy.

This study aimed to evaluate the prediction efficacy of malignant transformation of ovarian endometrioma (OE) using the Copenhagen Index (CPH-I), the risk of ovarian malignancy algorithm (ROMA), and the R2 predictive index. This retrospective study was conducted at the Department of Gynecology, Nara Medical University Hospital, from January 2008 to July 2021. A total of 171 patients were included in the study. In the current study, cases were divided into three cohorts: pre-menopausal, post-menopausal, and a combined cohort. Patients with benign ovarian tumor mainly received laparoscopic surgery, and patients with suspected malignant tumors underwent laparotomy. Information from a review chart of the patients' medical records was collected. In the combined cohort, a multivariate analysis confirmed that the ROMA index, the R2 predictive index, and tumor laterality were extracted as independent factors for predicting malignant tumors (hazard ratio (HR): 222.14, 95% confidence interval (CI): 22.27−2215.50, p < 0.001; HR: 9.80, 95% CI: 2.90−33.13, p < 0.001; HR: 0.15, 95% CI: 0.03−0.75, p = 0.021, respectively). In the pre-menopausal cohort, a multivariate analysis confirmed that the CPH index and the R2 predictive index were extracted as independent factors for predicting malignant tumors (HR: 6.45, 95% CI: 1.47−28.22, p = 0.013; HR: 31.19, 95% CI: 8.48−114.74, p < 0.001, respectively). Moreover, the R2 predictive index was only extracted as an independent factor for predicting borderline tumors (HR: 45.00, 95% CI: 7.43−272.52, p < 0.001) in the combined cohort. In pre-menopausal cases or borderline cases, the R2 predictive index is useful; while, in post-menopausal cases, the ROMA index is better than the other indexes.

Histopathological evaluation of cesarean scar defect in women with cesarean scar syndrome.

Purpose: To explore the histopathological findings of cesarean scar defect (CSD) and the immunological component in women with cesarean scar syndrome (CSS). Methods: This retrospective study was conducted in a university hospital and a public hospital. A total of 63 patients with secondary infertility due to CSS who underwent laparoscopic resection of the CSD lesion were enrolled (CSS group), and 21 patients who underwent hysterectomy with a history of cesarean section were enrolled as control (non-CSS group). We compared the differences in histopathological findings of CSD lesions by hematoxylin and eosin staining and immunohistochemistry for CD3, CD20, CD56, CD68, CD138, myeloperoxidase, and tryptase between the two groups. Results: The frequency of presence of endometrium on the CSD surface was significantly lower (p = 0.0023) and that of adenomyosis was significantly higher (p = 0.0195) in the CSS group than in the non-CSS group. The number of CD3-, CD20-, CD68-, and tryptase-positive cells was significantly lower in the CSS group than in the non-CSS group; however, the number of CD138-positive cells was significantly higher in the CSS group (p = 0.0042). Conclusions: This study suggested that the absence of endometrium, presence of adenomyosis, and chronic inflammation in CSD contributes to secondary infertility due to CSS.