Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation.

CXCR4 is a key regulator of the development of NK cells and DCs, both of which play an important role in early placental development and immune tolerance at the maternal-fetal interface. However, the role of CXCR4 in pregnancy is not well understood. Our study demonstrates that adult-induced global genetic CXCR4 deletion, but not uterine-specific CXCR4 deletion, was associated with increased pregnancy resorptions and decreased litter size. CXCR4-deficient mice had decreased NK cells and increased granulocytes in the decidua, along with increased leukocyte numbers in peripheral blood. We found that CXCR4-deficient mice had abnormal decidual NK cell aggregates and NK cell infiltration into trophoblast areas beyond the giant cell layer. This was associated with low NK cell expression of granzyme B, a NK cell granule effector, indicative of NK cell dysfunction. Pregnancy failure in these mice was associated with abnormalities in placental vascular development and increased placental expression of inflammatory genes. Importantly, adoptive BM transfer of WT CXCR4+ BM cells into CXCR4-deficient mice rescued the reproductive deficits by normalizing NK cell function and mediating normal placental vascular development. Collectively, our study found an important role for maternal CXCR4 expression in immune cell function, placental development, and pregnancy maintenance.

AMH predicts miscarriage in non-PCOS but not in PCOS related infertility ART cycles.

BACKGROUND: To study whether AMH levels were associated with miscarriage rates in index ART cycles undergoing fresh autologous transfers in PCOS and non-PCOS related infertility. METHODS: In the SART CORS database 66,793 index cycles underwent fresh autologous embryo transfers with AMH values reported within the last 1-year between 2014 and 2016. Cycles that resulted in ectopic or heterotopic pregnancies, or were performed for embryo/oocyte banking were excluded. Data were analyzed using Graphpad Prism-9. Odds ratios (OR) were calculated with 95% confidence intervals (CI) along with multivariate regression analysis adjusting for age, body mass index (BMI), and number of embryos transferred. Miscarriage rates were calculated as miscarriage per clinical pregnancies. RESULTS: Of the total 66,793 cycles, the mean AMH was 3.2 ng/ml and were not associated with increased miscarriage rates for AMH < 1 ng/ml (OR 1.1, CI 0.9-1.4, p = 0.3). Of the 8,490 PCOS patients, the mean AMH was 6.1 ng/ml and were not associated with increased miscarriage rates for AMH < 1 ng/ml (OR 0.8, CI 0.5-1.1, p = 0.2). Of the 58,303 non-PCOS patients, the mean AMH was 2.8 ng/ml and there was a significant difference in miscarriage rates for AMH < 1 ng/ml (OR 1.2, CI 1.1-1.3, p < 0.01). All findings were independent of age, BMI and number of embryos transferred. This statistical significance did not persist at higher thresholds of AMH. The overall miscarriage rate for all cycles, and cycles with and without PCOS were each 16%. DISCUSSION: The clinical utility of AMH continues to increase as more studies investigate its predictive abilities regarding reproductive outcomes. This study adds clarity to the mixed findings of prior studies that have examined the relationship between AMH and miscarriage in ART cycles. AMH values of the PCOS population are higher than the non-PCOS. The elevated AMH associated with PCOS decreases its utility in predicting miscarriages in IVF cycles as it may be representing the number of developing follicles rather than oocyte quality in the PCOS patient population. The elevated AMH associated with PCOS may have skewed the data; removing this sub-population may have unmasked significance within the non-PCOS associated infertility. CONCLUSIONS: AMH < 1 ng/mL is an independent predictor of increased miscarriage rate in patients with non-PCOS infertility.

AMH independently predicts aneuploidy but not live birth per transfer in IVF PGT-A cycles.

BACKGROUND: While anti-Müllerian hormone (AMH) predicts quantitative IVF outcomes such as oocyte yield, it is not certain whether AMH predicts markers of oocyte quality such as aneuploidy. METHODS: Retrospective case-control analysis of the SART-CORS database, 2014-2016, to determine whether anti-Müllerian hormone (AMH) predicts aneuploidy and live birth in IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A). RESULTS: Of 51,273 cycles utilizing PGT-A for all embryos, 10,878 cycles were included in the final analysis; of these, 2,100 cycles resulted in canceled transfer due to lack of normal embryos and 8,778 cycles resulted in primary FET. AMH levels of cycles with ≥ 1 euploid embryo were greater than those of cycles with no normal embryos, stratifying by number of embryos biopsied (1-2, 3-4, 5-6, and ≥ 7), P < 0.017 for each stratum. Adjusting for age and number of embryos biopsied, AMH was a significant independent predictor of ≥ 1 euploid embryo for all age groups: < 35 yrs (aOR 1.074; 95%CI 1.005-1.163), 35-37 years (aOR 1.085; 95%CI 1.018-1.165) and ≥ 38 years (aOR 1.055; 95%CI 1.020-1.093). In comparative model analysis, AMH was superior to age as a predictor of  ≥ 1 euploid embryo for age groups < 35 years and 35-37 years, but not  ≥ 38 years. Across all cycles, age (aOR 0.945, 95% CI 0.935-0.956) and number of embryos (aOR 1.144, 95%CI 1.127-1.162) were associated with live birth per transfer, but AMH was not (aOR 0.995, 95%CI 0.983-1.008). In the subset of cycles resulting in ≥ 1 euploid embryo for transfer, neither age nor AMH were associated with live birth. CONCLUSIONS: Adjusting for age and number of embryos biopsied, AMH independently predicted likelihood of obtaining ≥ 1 euploid embryo for transfer in IVF PGT-A cycles. However, neither age nor AMH were predictive of live birth once a euploid embryo was identified by PGT-A for transfer. This analysis suggests a predictive role of AMH for oocyte quality (aneuploidy risk), but not live birth per transfer once a euploid embryo is identified following PGT-A.

Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus†.

Bone marrow-derived progenitor cells (BMDPCs) are mobilized to the circulation in pregnancy and get recruited to the pregnant decidua where they contribute functionally to decidualization and successful implantation. However, the molecular mechanisms underlying BMDPCs recruitment to the decidua are unknown. CXCL12 ligand and its CXCR4 receptor play crucial roles in the mobilization and homing of stem/progenitor cells to various tissues. To investigate the role of CXCL12-CXCR4 axis in BMDPCs recruitment to decidua, we created transgenic GFP mice harboring CXCR4 gene susceptible to tamoxifen-inducible Cre-mediated ablation. These mice served as BM donors into wild-type C57BL/6 J female recipients using a 5-fluorouracil-based nongonadotoxic submyeloablation to achieve BM-specific CXCR4 knockout (CXCR4KO). Successful CXCR4 ablation was confirmed by RT-PCR and in vitro cell migration assays. Flow cytometry and immunohistochemistry showed a significant increase in GFP+ BM-derived cells (BMDCs) in the implantation site as compared to the nonpregnant uterus of control (2.7-fold) and CXCR4KO (1.8-fold) mice. This increase was uterus-specific and was not observed in other organs. This pregnancy-induced increase occurred in both hematopoietic (CD45+) and nonhematopoietic (CD45-) uterine BMDCs in control mice. In contrast, in CXCR4KO mice there was no increase in nonhematopoietic BMDCs in the pregnant uterus. Moreover, decidual recruitment of myeloid cells but not NK cells was diminished by BM CXCR4 deletion. Immunofluorescence showed the presence of nonhematopoietic GFP+ cells that were negative for CD45 (panleukocyte) and DBA (NK) markers in control but not CXCR4KO decidua. In conclusion, we report that CXCR4 expression in nonhematopoietic BMDPCs is essential for their recruitment to the pregnant decidua.

Bone marrow-derived progenitor cells contribute to remodeling of the postpartum uterus.

Endometrial stem/progenitor cells play a role in postpartum uterine tissue regeneration, but the underlying mechanisms are poorly understood. While circulating bone marrow (BM)-derived cells (BMDCs) contribute to nonhematopoietic endometrial cells, the contribution of BMDCs to postpartum uterus remodeling is unknown. We investigated the contribution of BMDCs to the postpartum uterus using 5-fluorouracil-based nongonadotoxic BM transplant from green fluorescent protein (GFP) donors into wild-type C57BL/6J female mice. Flow cytometry showed an influx of GFP+ cells to the uterus immediately postpartum accounting for 28.7% of total uterine cells, followed by a rapid decrease to prepregnancy levels. The majority of uterine GFP+ cells were CD45+ leukocytes, and the proportion of nonhematopoietic CD45-GFP+ cells peaked on postpartum day (PPD) 1 (17.5%). Immunofluorescence colocalization of GFP with CD45 pan-leukocyte and F4/80 macrophage markers corroborated these findings. GFP+ cells were found mostly in subepithelial stromal location. Importantly, GFP+ cytokeratin-positive epithelial cells were found within the luminal epithelium exclusively on PPD1, demonstrating direct contribution to postpartum re-epithelialization. A subset (3.2%) of GFP+ cells were CD31+CD45- endothelial cells, and found integrated within blood vessel endothelium. Notably, BM-derived GFP+ cells demonstrated preferential proliferation (PCNA+) and apoptosis (TUNEL+) on PPD1 vs resident GFP- cells, suggesting an active role for BMDCs in rapid tissue turnover. Moreover, GFP+ cells gradually acquired cell senescence together with decreased proliferation throughout the postpartum. In conclusion, BM-derived progenitors were found to have a novel nonhematopoietic cellular contribution to postpartum uterus remodeling. This contribution may have an important functional role in physiological as well as pathological postpartum endometrial regeneration.

Loss of Cxcr4 in Endometriosis Reduces Proliferation and Lesion Number while Increasing Intraepithelial Lymphocyte Infiltration.

Hyperactivation of the CXCL12-CXCR4 axis occurs in endometriosis; the therapeutic potential of treatments aimed at global inhibition of the axis was recently reported. Because CXCR4 is predominantly expressed on epithelial cells in the uterus, this study explored the effects of targeted disruption of CXCR4 in endometriosis lesions. Uteri derived from adult female mice homozygous for a floxed allele of CXCR4 and co-expressing Cre recombinase under control of progesterone receptor promoter were sutured onto the peritoneum of cycling host mice expressing the green fluorescent protein. Four weeks after endometriosis induction, significantly lower number of lesions developed in Cxcr4-conditional knockout lesions relative to those in controls (37.5% vs. 68.8%, respectively). In lesions that developed in Cxcr4-knockout, reduced epithelial proliferation was associated with a lower ratio of epithelial to total lesion area compared with controls. Furthermore, while CD3+ lymphocytes were largely excluded from the epithelial compartment in control lesions, in Cxcr4-knockout lesions, CD3+ lymphocytes infiltrated the Cxcr4-deficient epithelium in the diestrus and proestrus stages. Current data demonstrate that local CXCR4 expression is necessary for proliferation of the epithelial compartment of endometriosis lesions, that its downregulation compromises lesion numbers, and suggest a role for epithelial CXCR4 in lesion immune evasion.

Endometrial stem cells: origin, biological function, and therapeutic applications for reproductive disorders.

PURPOSE OF REVIEW: Endometrial stem cells (ESCs) are multipotent cells that are thought to originate locally in the endometrium as well as in the bone marrow (BM). They have remarkable plasticity and hold promise as an autologous source for regenerative medicine. This review focuses on recent studies that have advanced our understanding of the biology and function of ESCs and BM-derived stem cells (BMDSCs) as related to physiological reproductive processes and pathologies. Moreover, it reviews recent data on potential therapeutic applications of stem cells to endometrial disorders that lead to reproductive failure. RECENT FINDINGS: Growing evidence from basic and preclinical studies suggests that ESCs participate in endometrial tissue regeneration and repair. Recent evidence also suggests that ESCs and BMDSCs play important roles in physiological reproductive functions including decidualization, implantation, pregnancy maintenance, and postpartum uterine remodeling. Initial preclinical and clinical studies with ESCs and BMDSCs suggest they have the potential to provide new therapies for various endometrial disorders associated with reproductive failure. SUMMARY: Uterine ESCs and BMDSCs appear to play an important biological role in reproductive success and failure, and have the potential to become treatment targets for reproductive diseases including recurrent implantation failure, thin endometrium, Asherman, and recurrent pregnancy loss.

AMH Highly Correlates With Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve Independent of Age.

CONTEXT: Antimüllerian hormone (AMH) level is strongly associated with ovarian response in assisted reproductive technology (ART) cycles but is a poor predictor of live birth. It is unknown whether AMH is associated with cumulative live birth rates (CLBRs) in women with diminished ovarian reserve (DOR). OBJECTIVE: To examine the association between serum AMH and CLBR among women with DOR undergoing ART. METHODS: Retrospective analysis of Society for Assisted Reproductive Technology Clinic Outcome Reporting System database 2014-16. A total of 34 540 index retrieval cycles of women with AMH <1 ng/mL. The main outcome measure was cumulative live birth. RESULTS: A total of 34 540 (25.9%) cycles with AMH <1 ng/mL out of 133 442 autologous index retrieval cycles were analyzed. Cycles with preimplantation genetic testing or egg/embryo banking were excluded. Data were stratified according to AMH and, age and regression analysis of AMH and CLBR was performed for each age stratum. Multiple logistic regression demonstrated that AMH is an independent predictor of CLBR (odds ratio [OR] 1.39, 95% CI 1.18-1.64). Serum AMH was strongly associated with number of oocytes retrieved, embryos cryopreserved, mean number of cumulative embryos transferred, and percentage of cycles that had an embryo transfer. Linear regression analysis demonstrated that AMH highly correlated with CLBR in each age stratum. CONCLUSION: Serum AMH is highly correlated with CLBR in women with DOR independent of age. The addition of AMH to current age-based prognostication counseling particularly in women with DOR would provide more informative and personalized CLBR prediction prior to ART.

Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to conduct a systematic review of the current literature to determine estimates of vertical transmission of coronavirus disease 2019 based on early RNA detection of severe acute respiratory syndrome coronavirus 2 after birth from various neonatal or fetal sources and neonatal serology. DATA SOURCES: Eligible studies published until May 28, 2020, were retrieved from PubMed, EMBASE, medRxiv, and bioRxiv collection databases. STUDY ELIGIBILITY CRITERIA: This systematic review included cohort studies, case series, and case reports of pregnant women who received a coronavirus disease 2019 diagnosis using severe acute respiratory syndrome coronavirus 2 viral RNA test and had reported data regarding the testing of neonates or fetuses for severe acute respiratory syndrome coronavirus 2 immediately after birth and within 48 hours of birth. A total of 30 eligible case reports describing 43 tested neonates and 38 cohort or case series studies describing 936 tested neonates were included. STUDY APPRAISAL AND SYNTHESIS METHODS: The methodological quality of all included studies was evaluated by a modified version of the Newcastle-Ottawa scale. Quantitative synthesis was performed on cohort or case series studies according to the neonatal biological specimen site to reach pooled proportions of vertical transmission. RESULTS: Our quantitative synthesis revealed that of 936 neonates from mothers with coronavirus disease 2019, 27 neonates had a positive result for severe acute respiratory syndrome coronavirus 2 viral RNA test using nasopharyngeal swab, indicating a pooled proportion of 3.2% (95% confidence interval, 2.2-4.3) for vertical transmission. Of note, the pooled proportion of severe acute respiratory syndrome coronavirus 2 positivity in neonates by nasopharyngeal swab in studies from China was 2.0% (8/397), which was similar to the pooled proportion of 2.7% (14/517) in studies from outside of China. Severe acute respiratory syndrome coronavirus 2 viral RNA testing in neonatal cord blood was positive in 2.9% of samples (1/34), 7.7% of placenta samples (2/26), 0% of amniotic fluid (0/51), 0% of urine samples (0/17), and 9.7% of fecal or rectal swabs (3/31). Neonatal serology was positive in 3 of 82 samples (3.7%) (based on the presence of immunoglobulin M). CONCLUSION: Vertical transmission of severe acute respiratory syndrome coronavirus 2 is possible and seems to occur in a minority of cases of maternal coronavirus disease 2019 infection in the third trimester. The rates of infection are similar to those of other pathogens that cause congenital infections. However, given the paucity of early trimester data, no assessment can yet be made regarding the rates of vertical transmission in early pregnancy and potential risk for consequent fetal morbidity and mortality.

The Association between Vitamin D and Anti-Müllerian Hormone: A Systematic Review and Meta-Analysis.

Accumulating evidence from animal and human studies indicates a role for vitamin D in female reproductive physiology, and numerous clinical studies have suggested its potential benefit for various aspects of human reproduction. Anti-Müllerian hormone (AMH) is an ovarian biomarker that plays an important role in folliculogenesis. It is the most sensitive ovarian reserve marker and is widely used clinically in reproductive medicine. While initial studies have suggested that vitamin D may be associated with ovarian reserve markers, including AMH, evidence has been conflicting. Currently, there is considerable debate in the field whether vitamin D has the capacity to influence ovarian reserve, as indicated by the AMH level. The current systematic review aims to evaluate and summarize the available evidence regarding the relationship between vitamin D and AMH. In total, 18 observational studies and 6 interventional studies were included in this systematic review. Cross-sectional studies have reported largely discrepant findings regarding an association between serum vitamin D and AMH levels, which are likely due to the heterogeneity in study populations, as well as the apparently complex relationship that may exist between vitamin D and AMH. However, meta-analysis of interventional studies performed herein that examined the effects of vitamin D supplementation on serum AMH levels indicates a cause-effect relationship between vitamin D and AMH, the direction of which appears to depend on a woman's ovulatory status. Serum AMH was significantly decreased following vitamin D supplementation in polycystic ovarian syndrome (PCOS) women (standardized mean difference (SMD) -0.53, 95% CI -0.91 to -0.15, p < 0.007), while it was significantly increased following vitamin D supplementation in ovulatory women without PCOS (SMD 0.49, 95% CI 0.17 to 0.80, p = 0.003). In conclusion, the results of this systematic review demonstrate that the relationship between vitamin D and AMH is a complex one, and large, randomized trials of vitamin D supplementation focusing on different vitamin D status ranges are necessary to gain more insight into the nature of this relationship and the potential benefit of vitamin D to female reproduction in general.

Genital tuberculosis screening at an academic fertility center in the United States.

BACKGROUND: Infertility is a common presentation of female genital tuberculosis in endemic areas. Female genital tuberculosis-related maternal and neonatal complications have increased in recent years after assisted reproductive technology treatments. Despite rising emigration rates to the United States, guidelines to identify those with latent tuberculosis or female genital tuberculosis in fertility centers do not exist. OBJECTIVE: This study aimed to characterize the prevalence of female genital tuberculosis in infertile patients at our academic fertility center. STUDY DESIGN: This is a prospective cohort study. All patients presenting for infertility evaluation between January 2014 and January 2017 were assessed for risk factors for latent tuberculosis. Patients at risk for latent tuberculosis underwent screening using QuantiFERON-TB Gold serum assay. QuantiFERON-TB Gold-positive patients underwent further testing for female genital tuberculosis consisting of endometrial biopsy with histopathologic examination by a clinical pathologist, polymerase chain reaction for tuberculosis, and culture for acid-fast Mycobacterium tuberculosis. RESULTS: Twenty-five of 323 infertility patients (7.7%) screened for latent tuberculosis had positive QuantiFERON-TB Gold results. A greater number of patients with a positive test result for QuantiFERON-TB Gold were foreign born than those with a negative test result for QuantiFERON-TB Gold (92% vs 29%; P<.001). Of note, the QuantiFERON-TB Gold-positive population had a higher incidence of both recurrent pregnancy loss (28% vs 7%; P=.003) and Asherman syndrome (8% vs 0.3%; P<.001). Among those with a positive test result for QuantiFERON-TB Gold, chest x-ray was abnormal in only 2 patients (8.0%). Endometrium evaluation revealed abnormalities in 2 patients (8.0%), in whom chest x-ray was normal, with 1 showing evidence of female genital tuberculosis. This was indicated by histology consistent with chronic granulomatous endometritis and positive endometrial testing for tuberculosis by polymerase chain reaction, acid-fast bacilli smear, and culture for Mycobacterium tuberculosis. CONCLUSION: Although the prevalence of female genital tuberculosis in infertile women in the United States seems to be low, this study indicates that it can be underdiagnosed without utilization of multiple diagnostic modalities including endometrial sampling. Given the potential for serious maternal and neonatal morbidity in affected patients utilizing assisted reproductive technology, we propose that all at-risk women seeking infertility care in the United States be screened for latent tuberculosis. In patients who screen positive, endometrial biopsy should be obtained for evaluation by histology, polymerase chain reaction, and culture for Mycobacterium tuberculosis to rule out female genital tuberculosis before infertility treatments are initiated.

SARS-CoV-2 infection of the placenta.

BACKGROUNDThe effects of the novel coronavirus disease 2019 (COVID-19) in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic COVID-19 complicated by severe preeclampsia and placental abruption.METHODSWe analyzed the placenta for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through molecular and immunohistochemical assays and by and electron microscopy and measured the maternal antibody response in the blood to this infection.RESULTSSARS-CoV-2 localized predominantly to syncytiotrophoblast cells at the materno-fetal interface of the placenta. Histological examination of the placenta revealed a dense macrophage infiltrate, but no evidence for the vasculopathy typically associated with preeclampsia.CONCLUSIONThis case demonstrates SARS-CoV-2 invasion of the placenta, highlighting the potential for severe morbidity among pregnant women with COVID-19.FUNDINGBeatrice Kleinberg Neuwirth Fund and Fast Grant Emergent Ventures funding from the Mercatus Center at George Mason University. The funding bodies did not have roles in the design of the study or data collection, analysis, and interpretation and played no role in writing the manuscript.

High serum Antimullerian hormone levels are associated with lower live birth rates in women with polycystic ovarian syndrome undergoing assisted reproductive technology.

INTRODUCTION: Antimullerian hormone (AMH) strongly correlates with ovarian reserve and response to controlled ovarian stimulation. Emerging data suggests that serum AMH level may also predict ART outcomes. However, AMH is characteristically elevated in PCOS women and it is unknown whether it may predict live birth outcomes in this population. METHODS: This was a retrospective cohort study of 184 PCOS women (Rotterdam criteria) who underwent their first fresh IVF/ICSI cycle. Women were divided into 3 groups according to the <25th (low), 25 to 75th (average), or > 75th (high) percentile of serum AMH concentration. Cycle stimulation parameters and reproductive outcomes were compared between groups. RESULTS: Women in the low serum AMH group were older than those in the average or high AMH (p < 0.05), and required greater gonadotropin dose for stimulation compared to the high AMH group (p < 0.05). Women with high AMH had greater testosterone level compared to women in the low or average AMH groups. No differences were noted between groups in terms of maximal E2, oocytes retrieved and fertilization rate. However, low serum AMH women had significantly greater live birth rates (p < 0.05) and showed a trend towards greater clinical pregnancy rates compared to women in the average and high AMH groups (p = 0.09). The significant association of AMH with live birth rate remained after adjusting for age, BMI, day of transfer and number of embryos transferred. CONCLUSIONS: In PCOS women, elevated AMH concentrations are associated with hyperandrogenism and lower live birth rates.

Vitamin D Supplementation Ameliorates Metabolic Dysfunction in Patients with PCOS: A SystematicReview of RCTs and Insight into the Underlying Mechanism.

OBJECTIVE: Evidence suggests that vitamin D deficiency correlated with metabolic disorders in women with polycystic ovary syndrome (PCOS). We conducted this systematic review and meta-analysis to evaluate the impact of vitamin D supplementation alone on glucose, lipid, and androgen parameters and inflammation biomarkers in women with PCOS. METHODS: Literature research was conducted in Pubmed, Embase, Web of Science, Clinical Trials, and Cochrane Library to identify relevant randomized controlled trials (RCTs) up to March 2020. The effect of vitamin D supplementation alone on women with PCOS was compared with administration of placebo. The systematic review and meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews (Prospero) as number CRD42020157444. RESULTS: Thirteen randomized controlled trials with 824 patients in total were included. Serum FPG, fasting insulin, HOMA-IR, and VLDL-C were significantly decreased in the vitamin D group versus placebo. Vitamin D supplementation group also showed a significantly elevated level of QUICKI. No significant impact was seen on serum triglyceride, total-C, LDL-C, HDL-C, total testosterone, DHEAS, SHBG, or hs-CRP. Subgroup analysis demonstrated that oral vitamin D intake had significantly decreased serum triglyceride and total-C level in women with PCOS who have vitamin D deficiency (serum vitamin D < 20 ng/ml). CONCLUSION: The findings of the present meta-analysis indicate that vitamin D supplementation exerted favorable effects among women with PCOS on glucose metabolism and lipid metabolism, especially in vitamin D deficient women, but had no significant effect on the androgenic profile or inflammation status.

Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy.

Decidua is a transient uterine tissue shared by mammals with hemochorial placenta and is essential for pregnancy. The decidua is infiltrated by many immune cells promoting pregnancy. Adult bone marrow (BM)-derived cells (BMDCs) differentiate into rare populations of nonhematopoietic endometrial cells in the uterus. However, whether adult BMDCs become nonhematopoietic decidual cells and contribute functionally to pregnancy is unknown. Here, we show that pregnancy mobilizes mesenchymal stem cells (MSCs) to the circulation and that pregnancy induces considerable adult BMDCs recruitment to decidua, where some differentiate into nonhematopoietic prolactin-expressing decidual cells. To explore the functional importance of nonhematopoietic BMDCs to pregnancy, we used Homeobox a11 (Hoxa11)-deficient mice, having endometrial stromal-specific defects precluding decidualization and successful pregnancy. Hoxa11 expression in BM is restricted to nonhematopoietic cells. BM transplant (BMT) from wild-type (WT) to Hoxa11-/- mice results in stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11-/- mice. Moreover, in Hoxa11+/- mice, which have increased pregnancy losses, BMT from WT donors leads to normalized uterine expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that adult BMDCs have a previously unrecognized nonhematopoietic physiologic contribution to decidual stroma, thereby playing important roles in decidualization and pregnancy.