GC-MS/MS analysis of metabolites derived from a single human blastocyst.

INTRODUCTION: The field of assisted reproductive technology (ART) has significantly advanced; however, morphological evaluation remains as the chosen method of assessment of embryo quality. OBJECTIVE: We aimed to examine metabolic changes in embryo culture medium to develop a non-invasive method for evaluation of embryo quality. METHODS: We performed metabolic analysis of culture medium obtained from a single blastocyst cultured for freezing. RESULTS: In total, 187 (39.8%) of the 469 detectable organic acid metabolites were identified. A significant change (p < 0.05) was observed in eight metabolites between the good-quality and poor-quality embryo groups. Differences were observed in several metabolic pathways between the good-quality and poor-quality embryo groups. Metabolites that showed significant changes were primarily involved in the metabolism of branched-chain amino acids. CONCLUSION: The quantification of metabolism in human embryos may assist in identification and selection of good-quality embryos with high rates of survival before freezing and implantation in conjunction with morphological classification. This may help to identify embryos with high rates of survival.

National survey of bladder endometriosis cases in Japan.

AIM: We aimed to describe the clinical presentation, operative or medical management, and postoperative recurrence of bladder endometriosis (BE). METHODS: We conducted a national survey to investigate BE cases from 2006 to 2016 in Japan. Histologically diagnosed cases were extracted and then investigated for the following factors: age at diagnosis, body mass index, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, and postoperative recurrence. RESULTS: Eighty-nine patients with pathologically benign BE were identified. Eighty patients underwent surgery, whereas nine did not. Moreover, 34 and 44 patients underwent transurethral resection (TUR) and partial cystectomy (PC), respectively. Cumulative recurrence rates were significantly higher with TUR than with PC (p < 0.05). The recurrence rate tended to be higher after laparoscopic PC (n = 24) than after open PC (n = 20), but the difference was not statistically significant (p = 0.0879). Of the nine nonsurgical patients, eight received hormonal therapy and one did not. Efficacy rates of dienogest, GnRH agonist, and OC were 85.7%, 66.7%, and 66.7%, respectively. Of five patients with BE extending to the ureter or ureteral orifices, two underwent PC and ureteroneocystostomy and one underwent total nephroureterectomy due to renal function loss. CONCLUSION: To our knowledge, this is the first study to compare the postoperative recurrence of BE after TUR and PC. We found that cumulative recurrence rate is significantly lower after PC than after TUR. BE extending to the ureter or ureteral orifices is a very challenging condition. Further studies are required for the optimal management of BE.

hsa-miR-100-5p, an overexpressed miRNA in human ovarian endometriotic stromal cells, promotes invasion through attenuation of SMARCD1 expression.

BACKGROUND: A number of microRNAs are aberrantly expressed in endometriosis and are involved in its pathogenesis. Our previous study demonstrated that has-miR-100-5p expression is enhanced in human endometriotic cyst stromal cells (ECSCs). The present study aimed to elucidate the roles of has-miR-100-5p in the pathogenesis of endometriosis. METHODS: Normal endometrial stromal cells (NESCs) were isolated from normal eutopic endometrium without endometriosis. Using hsa-miR-100-5p-transfected NESCs, we evaluated the effect of hsa-miR-100-5p on the invasiveness of these cells by Transwell invasion assay and in-vitro wound repair assay. We also investigated the downstream signal pathways of hsa-miR-100-5p by microarray analysis and Ingenuity pathways analysis. RESULTS: hsa-miR-100-5p transfection enhanced the invasion and motility of NESCs. After hsa-miR-100-5p transfection, mRNA expression of SWItch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 (SMARCD1) was significantly attenuated. Whereas, the expression of matrix metallopeptidase 1 (MMP1) mRNA and active MMP1 protein levels was upregulated. CONCLUSION: We found that SMARCD1/MMP-1 is a downstream pathway of hsa-miR-100-5p. hsa-miR-100-5p transfection enhanced the motility of NESCs by inhibiting SMARCD1 expression and MMP1 activation. These findings suggest that enhanced hsa-miR-100-5p expression in endometriosis is involved in promoting the acquisition of endometriosis-specific characteristics during endometriosis development. Our present findings on the roles of hsa-miR-100-5p may thus contribute to understand the epigenetic mechanisms involved in the pathogenesis of endometriosis.

A National Survey of Umbilical Endometriosis in Japan.

STUDY OBJECTIVE: To identify the clinical presentation, diagnostic evaluation, operative or medical management, and postoperative recurrence of umbilical endometriosis. DESIGN: A retrospective national survey. SETTING: Obstetrics and Gynecology and Plastic Surgery Departments at a teaching hospital in Japan. PATIENTS: Patients with umbilical endometriosis or malignant transformation. INTERVENTIONS: A national survey was conducted to identify and evaluate cases of umbilical endometriosis or malignant transformation documented between 2006 and 2016. MEASUREMENTS AND MAIN RESULTS: The following were evaluated for each patient: age at diagnosis, body mass index, medical history, presence of extragenital endometriosis, surgical history, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, postoperative recurrence, and time to recurrence. Ninety-six patients were identified with pathologically diagnosed benign umbilical endometriosis. The patients frequently had swelling (86.5%), pain (81.3%), or bleeding (44.8%) in the umbilicus. Sensitivity was 87.1% for physical examination, 76.5% for transabdominal ultrasonography, 75.6% for computed tomography, and 81.8% for magnetic resonance imaging. The cumulative recurrence rate was 1.34% at 6 months, 6.35% at 12 months, and 6.35% at 60 months after surgery. Importantly, there was no recurrence after wide resection including of the peritoneum (0 of 37 cases). The efficacy of dienogest (an oral progestin), gonadotropin-releasing hormone agonists, and oral contraceptives was 91.7%, 81.8%, and 57.1%, respectively. Finally, 2 cases of malignant transformation were identified. CONCLUSION: There was a low recurrence rate following surgery, and hormonal treatment is an option, although the current findings suggest surgical therapy as the first choice of treatment for umbilical endometriosis.

Clinical practice guidelines for the treatment of extragenital endometriosis in Japan, 2018.

The aim of this publication is to disseminate the clinical practice guidelines for the treatment of intestinal, bladder/ureteral, thoracic and umbilical endometriosis, already published in Japanese, to non-Japanese speakers. For developing the original Japanese guidelines, the clinical practice guideline committee was formed by the research team for extragenital endometriosis, which is part of the research program of intractable disease of the Japanese Ministry of Health, Labor and Welfare. The clinical practice guideline committee formulated eight clinical questions for the treatment of extragenital endometriosis, which were intestinal, bladder/ureteral, thoracic and umbilical endometriosis. The committee performed a systematic review of the literature to provide responses to clinical questions and developed clinical guidelines for extragenital endometriosis, according to the process proposed by the Medical Information Network Distribution Service. The recommendation level was determined using modified Delphi methods. The clinical practice guidelines were officially approved by the Japan Society of Obstetrics and Gynecology and the Japan Society of Endometriosis. This English version was translated from the Japanese version.

[Successful delivery after chemotherapy for acute myeloid leukemia diagnosed in the second trimester].

Development of acute myeloid leukemia (AML) during pregnancy is rare, and the available data are limited to small retrospective reports. Currently, no guidelines exist for the management of AML during pregnancy in Japan. A 26-year-old female was diagnosed with AML at 19 weeks of gestation, received chemotherapy with daunorubicin and cytarabine, and achieved complete remission. Following the first consolidation therapy, she gave birth to a 1964-g female infant by cesarean section at 33 weeks of gestation. One week later, she was initiated on the second consolidation therapy; however, she developed a pelvic abscess during neutropenia. She underwent urgent surgery for open drainage and recovered soon after surgery. She has been in complete remission for eight months, and the daughter is healthy. Chemotherapy delivered after the second trimester rarely causes congenital malformations and may not require the termination of pregnancy. The clinical course of the present case suggests that chemotherapy can be performed safely and effectively in pregnant patients with AML after the trimester and babies.

ATM expression is attenuated by promoter hypermethylation in human ovarian endometriotic stromal cells.

A number of genes involved in the pathogenesis of endometriosis are silenced by the hypermethylation of their promoter regions. We assessed the effect and mechanism of the DNA demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC) (10 µM) on the cell cycle in human endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) by flow cytometry. The DNA methylation status of G2/M checkpoint regulators were investigated by methylation-specific PCR. The expression of ataxia telangiectasia mutated (ATM) and the effect of 5-aza-dC on its expression were also evaluated by quantitative RT-PCR and western blotting analysis. 5-aza-dC treatment resulted in the cell cycle arrest of ECSCs at the G2/M phase. In contrast, 5-aza-dC did not affect the cell cycle of NESCs. The promoter region of the ATM gene was hypermethylated in ECSCs, but not in NESCs. ATM mRNA expression was attenuated in ECSCs compared to that in NESCs. Further, 5-aza-dC was found to restore ATM expression in ECSCs by its promoter demethylation. Our findings indicate that ATM promoter hypermethylation occurs in endometriosis, and that ATM silencing is involved in tumorigenesis during this disease; moreover, selective DNA demethylating agents and molecular target drugs against ATM silencing are promising for the treatment of endometriosis.

Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma.

Endometrial endometrioid carcinoma is usually divided into three histological subgroups: grade 1 (G1), grade 2 (G2), and grade 3 (G3). Most cases of endometrial endometrioid carcinoma G1/2 have a favorable prognosis, although some can have unfavorable outcomes, especially when they involve elderly patients, with similarities to endometrioid carcinoma G3 and serous carcinoma. This retrospective study evaluated whether TP53 abnormalities in endometrial endometrioid carcinoma could be used to supplement the current grading system and improve its ability to predict clinical outcomes. Immunohistochemical expression of TP53 was analyzed using tissue microarrays from the surgically resected specimens of 475 patients with endometrial endometrioid carcinoma. Weak or moderate expression was defined as TP53-normal expression, while absent or strongly positive expression was defined as TP53-aberrant expression. The endometrial endometrioid carcinomas had originally been diagnosed as G1 (69%), G2 (18%), and G3 (13%). Univariate analyses revealed that TP53-aberrant expression was associated with poor survival in G1 and G2 cases, but not G3 cases. In addition, age (<60 years vs. ≥60 years) was correlated with TP53-aberrant expression in G1 cases (3% vs. 16%, p = 0.001), but not in G2 or G3 cases. Based on immunohistochemical TP53 expression, the endometrial endometrioid carcinomas were reclassified using a prognostic grading system as high-grade (G1 or G2 with TP53- aberrant expression, and G3 with TP53-normal or -aberrant expression) or low-grade (G1 or G2 with TP53-normal expression). The multivariate analyses revealed that the prognostic grading system (using histological grade and TP53 expression) could independently predict poor progression-free survival (hazard ratio: 2.91, p < 0.001) and overall survival (hazard ratio: 3.62, p < 0.001). Therefore, combining immunohistochemical TP53 expression with the traditional histological grading system for endometrial endometrioid carcinoma may help improve its ability to accurately predict the patient's prognosis.

Detection of DNA double-strand breaks by pulsed-field gel electrophoresis.

A DNA double-strand break (DSB) is one of the most cytotoxic DNA lesions because unrepaired DSBs cause chromosomal aberrations and cell death. Although many physiological DSBs occur at DNA replication sites, the molecular mechanisms underlying this remain poorly understood. There was therefore a need to develop a highly specific method to detect DSB fragments containing DNA replication sites. Here we investigated whether pulsed-field gel electrophoresis (PFGE) combined with visualization of DNA replication sites by immunoblotting using halogenized deoxyuridines, such as BrdU and IdU, was sufficient for this detection. Our methodology enabled us to reproduce previously reported data. In addition, this methodology was also applied to the detection of bacterial infection-induced DSBs on human chromosomal DNA. Based on our findings, we propose that this strategy combining PFGE with immunoblot analysis will be applicable to studies analyzing the mechanistic details of DNA repair, the DNA damage response and the activity of DNA-damaging agents.

Asymptomatic Bartholin Cyst: Evaluation With Multidetector Row Computed Tomography.

OBJECTIVE: The aim of this study was to determine the frequency, morphology, and attenuation characteristics of Bartholin cysts on multidetector computed tomography (MDCT) in asymptomatic women. METHODS: A total of 3280 consecutive MDCT examinations were assessed for Bartholin cysts. The diagnosis was based on shape, contrast enhancement, and anatomical location. Age, laterality, size, and attenuation patterns were recorded. Scans from patients with paravaginal-related symptoms were excluded, and any available follow-up MDCT scans or magnetic resonance images were evaluated. RESULTS: Asymptomatic Bartholin cysts were seen in 17 patients (0.52%) (mean age, 56 years). The mean maximum cyst diameter was 21.8 mm. High-attenuation cysts comprised 47% of cases, all in older (≥50 years) patients. Follow-up MDCT scans showed minimal changes over time. CONCLUSIONS: High-attenuation Bartholin cysts are more common than previously thought and are usually seen in older women. The size and attenuation of Bartholin cysts show only minimal changes over time.

Ruptured external iliac artery pseudoaneurysm following surgery for ovarian cancer: A case report and literature review.

Ruptured pseudoaneurysm following pelvic surgery is a rare and fatal complication. Because of its rarity, existing evidence is limited to a small case series. A 60-year-old woman underwent staging laparotomy, including pelvic and para-aortic lymphadenectomy, for ovarian cancer. On the 11th day, the patient developed a sudden lumbar pain and loss of consciousness, which resulted in a state of shock. She was diagnosed as having a pelvic abscess and ruptured external iliac artery pseudoaneurysm. We performed ligation of the external iliac artery to restrain hemorrhage and femoro-femoral artery bypass to prevent infection, which saved the patient's life. Our study had two findings. First, this is the first reported case of ruptured external iliac artery pseudoaneurysm following surgery for ovarian cancer. Second, treatment of ruptured pseudoaneurysm requires rapid hemostasis, prevention of infection, and revascularization.

Expression of angiogenic factors in sclerosing stromal tumours of the ovary.

Sclerosing stromal tumours (SSTs) are rare benign tumours and are generally observed in individuals in their teens to 20 s. Many cases are suspected as malignant tumours pre-operatively, owing to their high vascularity on diagnostic imaging. Herein, we aimed to evaluate the expressions of various angiogenic factors in SSTs. The expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) were examined by immunohistochemical staining. Upon immunohistochemistry, overexpressions of VEGF, bFGF, and HGF in the ovarian stroma were observed in SSTs. In the normal ovary, the expressions were strong around the vessels and weak in the stroma of the ovary, while a Sertoli-Leydig cell tumour showed weak staining with VEGF, locally strong staining with bFGF and negative staining with HGF. This is the first report about angiogenic factors such as bFGF, and HGF in SST. Impact statement What is already known on this subject? Sclerosing stromal tumour (SST) is a rare benign tumour with high vascularity. The high vascularity of SSTs are reported to be related to the overexpression of vascular endothelial growth factor (VEGF). But there is no study on the expressions of other angiogenic factors in SST. What do the results this study add? In the immunohistochemical analysis, VEGF, bFGF and HGF were found to be widely stained in SSTs. This results suggest the possibility that the high vascularity seen on diagnostic imaging, and the many small vessels observed microscopically may be related to the expressions of VEGF, bFGF and HGF in SSTs. What are the implications of these findings for clinical practice and/or further research? Our results suggest the possibility that the combined expression pattern of VEGF, bFGF, and HGF may be used as marker of SSTs.

Arcyriaflavin a, a cyclin D1-cyclin-dependent kinase4 inhibitor, induces apoptosis and inhibits proliferation of human endometriotic stromal cells: a potential therapeutic agent in endometriosis.

BACKGROUND: We previously showed that microRNA-503 (miR-503) transfection into endometriotic cyst stromal cells (ECSCs) induced cell cycle arrest at the G0/G1 phase by suppressing cyclin D1. This finding prompted us to evaluate the potential therapeutic effects of cyclin D1 inhibitors in endometriotic cells. This study aimed to determine whether arcyriaflavin A, a representative inhibitor of cyclin D1-cyclin-dependent kinase 4 (CDK4), is beneficial in the treatment of endometriosis. METHODS: ECSCs were isolated from the ovarian endometriotic tissues of 32 women. The effects of arcyriaflavin A on cell viability and proliferation, vascular endothelial growth factor A expression, apoptosis, and cell cycle progression were evaluated using a modified methylthiazoletetrazolium assay, enzyme-linked immunosorbent assay (ELISA), Caspase-Glo® 3/7 assay, and flow cytometry. RESULTS: Arcyriaflavin A significantly inhibited cell viability, proliferation, and angiogenesis of ECSCs as assessed using the 5-bromo-2-deoxyuridine (BrdU) and methylthiazoletetrazolium bromide (MTT) assays, and vascular endothelial growth factor (VEGF) ELISA. Arcyriaflavin A induced apoptosis as shown in the Caspase-Glo® 3/7 assay and cell death detection ELISA whilethe cell cycle was arrested at the G0/G1 phase. CONCLUSION: The findings indicate that cyclin D1-CDK4 inhibitors may be promising candidates for the treatment of endometriosis. This is the first study to demonstrate the potential usefulness of arcyriaflavin A as a therapeutic agent for endometriosis. Further studies of the effects of cyclin D1-CDK4 inhibitors on endometriosis may provide useful information on pathogenesis and treatment.

miR-503, a microRNA epigenetically repressed in endometriosis, induces apoptosis and cell-cycle arrest and inhibits cell proliferation, angiogenesis, and contractility of human ovarian endometriotic stromal cells.

STUDY QUESTION: Is the micro-RNA (miRNA) miR-503, downregulated in endometriotic cyst stromal cells (ECSCs) and does this affect the cell cycle, cell proliferation, angiogenesis and contractility of these cells? SUMMARY ANSWER: miR-503 expression is downregulated in ECSCs by DNA hypermethylation and this contributes to their proliferation, resistance to apoptosis, extracellular matrix (ECM) contractility and angiogenesis through effects on cyclin D1, B-cell lymphoma/leukemia (Bcl)-2, Ras homology A  and vascular endothelial growth factor A (VEGF-A). WHAT IS KNOWN ALREADY: A variety of miRNAs are demonstrated to involve in the pathogenesis of endometriosis. miR-503 is a miRNA with tumor-suppressor functions, whose expression is suppressed in ECSCs. STUDY DESIGN, SIZE, DURATION: We isolated ECSCs and normal endometrial stromal cells (NESCs) from ovarian endometriotic tissues (n = 32) and eutopic endometrial tissues without endometriosis (n = 8), respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: We investigated the functions of miR-503 by using miR-503-transfected ECSCs and the DNA methylation status of miR-503 gene in ECSCs and NESCs by combined bisulfite restriction analysis. MAIN RESULTS AND THE ROLE OF CHANCE: In ECSCs, miR-503 is downregulated by the DNA hypermethylation of its gene. The transfection of miR-503 into ECSCs resulted in the inhibition of cell proliferation and induction of cell-cycle arrest at G0/G1 phase through the suppression of cyclin D1, the induction of apoptosis through Bcl-2 suppression, the inhibition of VEGF-A production and the attenuation of ECM contractility via the suppression of Rho/Rho-associated coiled-coil-forming protein kinase-pathways. LARGE SCALE DATA: NA. LIMITATIONS, REASONS FOR CAUTION: The present experiments were carried out only with the stromal component of endometriosis and eutopic endometrium. The experiments with the eutopic endometrial stromal cells from women with endometriosis are not performed. WIDER IMPLICATIONS OF THE FINDINGS: Our findings indicate that epigenetically repressed miR-503 in ECSCs is involved in the acquisition of endometriosis-specific cellular functions. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 13237327 to K.N., no. 26861335 to K.K. and no. 23592407 to H.N.) and the Kanzawa Medical Research Foundation (to K.K.). There are no conflicts of interest to declare.

A prospective observational study on chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer by the CINV Study Group of Japan.

OBJECTIVE: This study was performed to investigate the occurrence of and risk factors for chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer. METHODS: In total, 214 patients with gynecologic cancer who underwent highly emetogenic (HEC) or moderately emetogenic chemotherapy (MEC) were evaluated. We investigated the relationship between CINV and clinical factors and the accuracy of estimation of CINV by medical staff in the acute and late phases. Vomiting was evaluated in terms of frequency, and nausea was evaluated with a 100-mm visual analog scale on days 1 to 7. We also analyzed the risk factors and changes in CINV over time using a generalized linear mixed (GLM) model. RESULTS: The multivariate analysis revealed no significant risk factors for acute CINV. The independent risk factors for delayed nausea were a morning sickness history (odds ratio [OR], 2.687; 95% confidence interval [95% CI], 1.450-4.976; p=0.0017), age (each 1-year increment) (OR, 0.97; 95% CI, 0.944-0.996; p=0.0235), and HEC (OR, 2.134; 95% CI, 1.039-4.383; p=0.0391). The GLM model demonstrated that the independent factors affecting nausea were significant morning sickness (p=0.0101) and HEC (p=0.0136). These data also showed more severe nausea from days 3 to 5, but the negative predictive value for estimation of delayed nausea by medical staff was 57.8%. CONCLUSION: Our data suggest that improvement of preventive antiemetic administration is needed for patients with risk factors to manage delayed CINV caused by HEC and by MEC.

Intravenous leiomyomatosis treated with radical hysterectomy and adjuvant aromatase inhibitor therapy.

Intravenous leiomyomatosis (IVL), a rare disease that is histologically benign but clinically aggressive, is characterized by the intraluminal growth of benign leiomyoma in the intrauterine and systemic veins. Preoperative diagnosis of IVL is difficult, because the symptoms of early stage IVL are similar to those of uterine leiomyoma. The efficacy of adjuvant hormone therapy after surgical resection of IVL remains unclear. Herein is described a case of IVL that was diagnosed preoperatively, in which successful total resection of the tumor was achieved by radical hysterectomy. The patient, a 50-year-old premenopausal Japanese woman, also underwent aromatase inhibitor treatment and was free of disease at 36 months after surgery. Contrast-enhanced computed tomography is suggested as the best assessment for identifying and diagnosing IVL. Radical hysterectomy can be considered a successful therapy for total resection. Aromatase inhibitor treatment may be effective, especially when the patient has not yet entered menopause.

Combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium: A case report and survey of related literature.

Primary large-cell neuroendocrine carcinoma of the endometrium is extremely rare and has a poor prognosis. This report describes a case of combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium diagnosed as stage IIIA. The patient underwent surgery and chemotherapy and has been well with no evidence of disease for 20 months. The optimal treatment for this rare tumor has not been established. Considering its rarity and variability, it is difficult to establish an evidence-based therapeutic regimen.

A possible role for AMP-activated protein kinase activated by metformin and AICAR in human granulosa cells.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are generally insulin- resistant and are consequently often treated with metformin. We investigated the effect of metformin and AICAR on the AMP-activated protein kinase (AMPK) pathway. METHODS: We evaluated the effects of 5-amino-imidazole-4-carboxyamide-1- beta-D-ribofuranoside (AICAR) and metformin on tumor necrosis factor (TNF)-alpha- stimulated chemokine production in human granulosa cells. The phosphorylations of AMPK, I-kappaB, 4E-BP-1, p70S6K were analyzed by western immunoblotting. RESULTS: AICAR and metformin markedly reduced the IL-8 and GROalpha production induced by TNF-alpha. AICAR and metformin also reduced the TNF-alpha-induced phosphorylation of I-kappaB. The phosphorylations of I-kappaB, 4EBP-1, p70S6K were inhibited via an AMPK-dependent signal transduction. CONCLUSIONS: These results suggest that metformin promotes granulosa cell function by reducing a TNF-alpha- and chemokine-mediated inflammatory reaction through an AMPK-dependent pathway. These finding may have implications for metformin's actions during the treatment of PCOS with metformin.

Management of secondary infertility following cesarean section: Report from the Subcommittee of the Reproductive Endocrinology Committee of the Japan Society of Obstetrics and Gynecology.

AIM: The aim of this study was to examine the current status and management of secondary infertility following cesarean section in Japan. MATERIAL AND METHODS: A two-step questionnaire survey was performed in 1092 facilities, including teaching hospitals and artificial reproductive technology clinics, registered with the Japan Society of Obstetrics and Gynecology. In our questionnaires, we obtained data about symptoms, clinical findings, diagnostic methods, and pregnancy outcomes. Treatments were sorted into three groups, namely typical infertility treatment (group A), conservative treatment (group B), and operative treatment (group C). RESULTS: Of the 1092 facilities, 616 (56%) sent back reply forms to the first questionnaire; 56 (32%) of 176 facilities answered the second questionnaire, and 189 cases were able to be analyzed after completion of the two questionnaires. The commonest symptom was abnormal uterine bleeding during the follicular phase (91 cases; 48% of the 189 eligible cases), and the commonest clinical finding was fluid pooling in the area of cesarean scar dehiscence during the ovulatory phase (142 cases; 75%). The most commonly used diagnostic method was transvaginal ultrasound (153 cases, 81%). The pregnancy rate was 33% in group A, 50% in group B, and 60% in group C. In patients with abnormal uterine bleeding, painful symptoms and fluid pooling at the cesarean scar dehiscence, the pregnancy rate was significantly higher in group C (64%) than in group A (16%; P = 0.0063). CONCLUSIONS: We recommend operative treatment for secondary infertility following cesarean section with painful symptoms and fluid pooling at the site of cesarean scar dehiscence.