Recurrent pregnancy loss is associated with increased red cell distribution width and platelet distribution width.

AIM: The present study aims to evaluate how components of complete blood count are altered in women with a history of recurrent pregnancy loss. MATERIAL AND METHODS: This was a retrospective evaluation of 60 women who had a history of recurrent pregnancy loss, 60 healthy women who had a first trimester pregnancy and 60 healthy parous women. RESULTS: When compared with pregnant women and healthy controls, the women with a history of recurrent pregnancy loss had significantly higher red cell distribution width (RDW) and platelet distribution width (PDW) (P = 0.001 for both). Thrombophilia was detected in 31.7% of the women who had a history of recurrent pregnancy loss (19 out of 60). When compared to the women without thrombophilia, the women with thrombophilia had significantly lower body mass index (P = 0.034) but significantly higher RDW, PDW and plateletcrit (respectively, P = 0.043, P = 0.001 and P = 0.002). There were significant and positive correlations between RDW and PDW (r = 0.615, P = 0.001), RDW and plateletcrit (r = 0.343, P = 0.007) and PDW and plateletcrit (r = 0.340, P = 0.008) in women with a history of recurrent pregnancy loss. CONCLUSION: An elevation in PDW and RDW values was found to be associated with recurrent pregnancy loss.

Evaluation of endocervical canal in women with minimal cervical cytological abnormalities.

OBJECTIVE: This study aimed to examine the endocervical canal curettage (ECC) results of patients with atypical squamous cells of undetermined significance (ASC-US) or low-grade intraepithelial lesion (LSIL) and secondarily to explore the features of patients who are at greatest risk for endocervical involvement. MATERIALS AND METHODS: This is a retrospective analysis of 846 women who underwent ECC with ASC-US or LSIL on cervical cytology between January 2003 and April 2011. Records of demographic data and colposcopic impression were evaluated. Histopathological results of biopsies and ECC were classified into 2 categories as less than cervical intraepithelial lesion 2 (CIN 2) and CIN 2+ lesions for comparison. Multivariate analysis was performed using binary logistic regression analysis to identify predictors of ECC results. RESULTS: CIN 1 lesions were detected in 8.9% of patients, and the rates of CIN 2 or 3 and invasive/microinvasive cancers in ECC were 3.8% and 0.7%, respectively. Cervical intraepithelial lesion 2 or worse lesions were detected in 1.6% (7/419) of the patients with normal colposcopic findings. There was no statistically significant difference in the rate of CIN 2+ lesion in endocervical canal between the patients with or without satisfactory colposcopic examination (4.4% vs 4.1% p = .69). A total of 1.7% of the patients who did not have cervical biopsy and also 1.1% of the patients who had less than CIN 2 biopsy results were diagnosed with CIN 2+ lesion by ECC despite the satisfactory colposcopy. Only a positive biopsy result for dysplasia was found to be an independent factor for the detection of a dysplastic lesion in endocervical canal (odds ratio = 0.06; 95% CI = 0.01-0.35; p = .02). CONCLUSIONS: Endocervical canal curettage had minimal diagnostic utility for the detection of CIN 2 or worse lesions in women with ASC-US or LSIL smear result and normal colposcopic findings. In addition to this, the presence or absence of CIN 2+ lesions diagnosed by means of endocervical curettage was independent of a satisfactory or unsatisfactory colposcopic examination.

The novel criteria for predicting pelvic lymph node metastasis in endometrioid adenocarcinoma of endometrium.

OBJECTIVE: To identify clinicopathological risk factors for pelvic lymph node metastasis, and to evaluate the clinical validity of these factors in selecting patients who need pelvic lymph node dissection. METHODS: The data of 466 patients who had lymphadenectomy for endometrioid adenocarcinoma of the endometrium between January 2002 and December 2010 were reviewed retrospectively. RESULTS: All patients underwent pelvic lymphadenectomy and 192 (41.2%) patients also underwent paraaortic lymphadenectomy. The median number of pelvic lymph node was 16 (range: 2-46) and of paraaortic lymph node was 5 (range: 2-16). 10.1% (47/466) of all patients had pelvic lymph node involvement and 7.8% (15/192) of the patients had paraaortic lymph node involvement (LNI). Pelvic LNI was significantly more common in the presence of higher grades of tumor, LVSI, deep myometrial invasion, positive peritoneal cytology and cervical involvement. The logistic regression analysis revealed that LVSI, cervical glandular invasion and cervical stromal invasion remained to be the independent risk factors for LNI. When the LVSI and/or cervical involvement were considered as high risk for pelvic lymph node metastasis, NPV and specificity were found to be 96.3% and 68.4%, respectively. LNI was correctly estimated in 323 women (69%), overestimated in 132 women (28%) and underestimated in 11 women (2%). CONCLUSION: LVSI, cervical glandular and stromal involvement were independent risk factors for pelvic LNI. These variables can be assessed pre- or intraoperatively with a high rate of accuracy, the model which uses these variables may be successfully used in the prediction of pelvic lymph node metastasis.

Influence of body mass index on clinicopathologic features, surgical morbidity and outcome in patients with endometrial cancer.

AIM: To examine the influence of obesity on the patient characteristics and clinicopathologic features of endometrial cancer, and to find how treatment and prognosis were affected by obesity in women with endometrial cancer. METHODS: The data of 370 consecutive women operated for endometrial cancer were retrospectively reviewed. Patients were divided into three categories as <25, 25-29.9 and ≥30 according to BMI. All patients underwent primary surgical treatment including total abdominal hysterectomy, bilateral oophorectomy and peritoneal cytology. Pelvic lymphadenectomy was carried out for all patients except for those with no myometrial invasion regardless of the tumor grade or for whom it was technically impossible. Paraaortic lymphadenectomy was performed when pre- and intraoperative assessments suggested non-endometrioid or grade 3 endometrioid cancer, >50 % myometrial invasion and cervical involvement. RESULTS: Patients with a BMI (body mass index) of <25 were significantly younger. Patients with a BMI of ≥30 were statistically less likely to have >50 % myometrial invasion and more likely to have stage I disease. There were no significant differences in the incidences of positive pelvic and paraaortic lymph nodes and tumor grades between the three groups. Also, there were no differences in surgery type, the mean of removed pelvic and paraaortic lymph node number, hospital stay, blood loss and complications between the groups. The patients with a BMI of ≥30 had significantly longer operating time. There were no statistically significant differences in recurrences, the median number of months at recurrence or the site of recurrence between the three groups, as well as the 5-year overall and disease-free survival of patients. Multivariate proportional hazard models identified stage III and IV disease as significant covariates for mortality rates, while stage III and IV disease, hypertension and pelvic irradiation were identified as significant covariates for recurrence rates. CONCLUSION: Positive peritoneal cytology, deep myometrial invasion and stage II-IV endometrial cancer were significantly more common in patients with a BMI of <25. There were no significant differences in tumor grade, surgical technique, surgical morbidity or adjuvant radiotherapy between the BMI groups. Recurrence and cancer-related mortality rates were not affected by the BMI.

Safety of Intraovarian Injection of Human Mesenchymal Stem Cells in a Premature Ovarian Insufficiency Mouse Model.

Primary ovarian insufficiency (POI), a condition in which there is a loss of ovarian function before the age of 40 years, leads to amenorrhea and infertility. In our previously published studies, we demonstrated recovery of POI, correction of serum sex hormone levels, increase in the granulosa cell population, and restoration of fertility in a chemotherapy-induced POI mouse model after intraovarian transplantation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). While hBM-MSC may be a promising cell source for treatment of POI, there are few reports on the safety of stem cell-based therapy for POI. For future clinical applications, the safety of allogenic hBM-MSCs for the treatment of POI through intraovarian engraftment needs to be addressed and verified in appropriate preclinical models. In this study, we induced POI in C57/BL6 mice using chemotherapy, then treated the mice with hBM-MSCs (500,000 cells/ovary) by intraovarian injection. After hBM-MSC treatment, we analyzed the migration of engrafted cells by genomic DNA polymerase chain reaction (PCR) using a human-specific ALU repeat and by whole-body sectioning on a cryo-imaging system. We examined the possibility of transfer of human DNA from the hBM-MSCs to the resulting offspring, and compared the growth rate of offspring to that of normal mice and hBM-MSC-treated mice. We found that engrafted hBM-MSCs were detected only in mouse ovaries and did not migrate into any other major organs including the heart, lungs, and liver. Further, we found that no human DNA was transferred into the fetus. Interestingly, the engrafted cells gradually decreased in number and had mostly disappeared after 4 weeks. Our study demonstrates that intraovarian transplantation of hBM-MSCs could be a safe stem cell-based therapy to restore fertility in POI patients.

Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models. METHODS: For in vitro experiment, we treated conditioned media from BM-hMSC to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into letrozole (LTZ)-induced PCOS mouse model. BM-hMSC effect in androgen-producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery. RESULTS: BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improved in metabolic and reproductive markers in our PCOS model and able to restore fertility. CONCLUSION: Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.