Background Unresponsive thin endometrium caused by Asherman syndrome (AS) is the major cause of uterine infertility. However, current therapies are ineffective. This study is to evaluate the effect of transplantation with collagen scaffold/umbilical cord mesenchymal stem cells (CS/UC-MSCs) on this refractory disease. Methods Eighteen infertile women with unresponsive thin endometrium, whose frozen–thawed embryo transfers (FETs) were cancelled due to reduced endometrial thickness (ET ≤ 5.5 mm), were enrolled in this before and after self-control prospective study. Hysteroscopic examination was performed to confirm no intrauterine adhesions, then twenty million UC-MSCs loaded onto a CS were transplanted into the uterine cavity in two consecutive menstrual cycles. Then uterine cavity was assessed through hysteroscopy after two transplants. FETs were performed in the following cycle. Pregnancy outcomes were followed up. Endometrial thickness, uterine receptivity and endometrial angiogenesis, proliferation and hormone response were compared before and after treatment. Results Sixteen patients completed the study. No treatment-related serious adverse events occurred. Three months after transplantation, the average ET increased from 4.08 ± 0.26 mm to 5.87 ± 0.77 mm (P < 0.001). Three of 15 patients after FET got pregnant, of whom 2 gave birth successfully and 1 had a miscarriage at 25 weeks’ gestation. One of 2 patients without FET had a natural pregnancy and gave birth normally after transplantation. Immunohistochemical analysis showed increased micro-vessel density, upregulated expression of Ki67, estrogen receptor alpha, and progesterone receptor, indicating an improvement in endometrial angiogenesis, proliferation, and response to hormones. Conclusion CS/UC-MSCs is a promising and potential approach for treating women with unresponsive thin endometrium caused by AS. Trial registration ClinicalTrials.gov NCT03724617. Registered on 26 October 2018—prospectively registered, https://register.clinicaltrials.gov/

ObjectiveThis nationwide population-based study aims to explore the relationship between polycystic ovarian syndrome (PCOS) and subsequent gestational diabetes mellitus (GDM).MethodsData from 1998–2012 Taiwan National Health Insurance Research Database were used for this study. ICD9-CM codes 256.4X and 648.X were used separately for the diagnoses of PCOS and GDM, which were further confirmed by records of blood tests or ultrasonography to ensure the accuracy of the diagnoses. Women diagnosed at < 15 or > 45 years of age, and those diagnosed with overt diabetes mellitus or GDM prior to PCOS were excluded. During pregnancy, each woman with a previous diagnosis of PCOS was age-matched to 10 women without PCOS. Odds ratios (ORs) for risk of GDM were calculated by logistic regression analysis with adjustment for economic status and co-morbidities.ResultsAmong 7,629 eligible women with a valid PCOS diagnosis, 3,109 (42.87%) had subsequent pregnancies. GDM occurred frequently among women with a history of PCOS as compared to those without PCOS (20.46% vs. 10.54%, p<0.0001). Logistic regression analysis revealed that PCOS was associated with GDM (adjusted OR = 2.15; 95% CI:1.96–2.37). Among 3,109 affected patients, 1,160 (37.31%) had used medications for PCOS and 261 (8.39%) were treated with an oral hypoglycemic agent (OHA). There was no significant difference in development of GDM between the medication and no medication sub-groups (p>0.05). If not used after conception, OHAs did not reduce the risk of GDM (adjusted OR = 1.20; 95% CI:0.88–1.62).ConclusionsA history of PCOS is a significant and independent risk factor for development of GDM. Medication for PCOS or pre-pregnancy use of OHAs does not reduce the risk of GDM. When at-risk women become pregnant, they require closer surveillance for maternal and fetal well-being, and should follow a strict diet and adhere to weight gain control to avoid obstetric complications due to GDM.

The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998–2012. Taiwan National Health Insurance Research Database, patients with IDA (case group (n = 35,751)) and individuals without IDA (control group (n = 178,755)) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to five individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p < 0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio (HR) = 1.74; 95% CI = 1.61–1.88) and remained similar after adjustment for covariates (adjusted HR = 1.81; 95% CI = 1.67–1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR = 2.21; 95% CI = 1.85–2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR = 1.47; 95% CI = 1.20–1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis.

Birth weight under 2500 g is a significant risk factor for IH repairs. Other risk factors are male gender, past history of lung diseases, and ventilator supports.