Reproductive Sciences最新文献

Type 2 diabetes mellitus (T2DM) is a multifactorial disease that cannot be linked to a single pathway, causing the observed heterogeneity among T2DM patients. Despite this level of heterogeneity, T2DM is majorly managed by metformin (MET) monotherapy. However, recent findings have associated long-term metformin intake with progressive oxidative pancreatic β cell damage as the disease progresses. Hence, a significant number of patients treated with MET need an alternate therapy. Hence, identifying drug combinations that can effectively alleviate different diabetes complications would serve as a more promising therapy that can translate into active use. Hence, this study was designed to explore the possible synergistic effect of vitamin D and metformin on T2DM-induced testicular dysfunction. Thirty healthy male Wistar rats (weight: 120-150 g and age: 10 ± 2 weeks) were randomly divided into control, diabetes untreated (HFD+STZ), diabetes + vitamin D (1000 IU/kg), diabetes + metformin (180 mg/kg), and diabetes + vitamin D + metformin. All treatments lasted for 28 days and animals were sacrificed using IP injection of ketamine and xylaxine (40 and 4 mg/kg respectively). Vitamin D improved the ameliorative effect of metformin on T2DM-induced hyperglycemia and lipid dysmetabolism, accompanied by a significant decrease in testicular lactate dehydrogenase and lactate. Also, vitamin D + metformin significantly increased serum luteinizing hormone, follicle-stimulating hormone, testosterone, and testicular 5α reductase activities. Furthermore, vitamin D improved the anti-inflammatory and antioxidant effects of metformin by significantly decreasing T2DM-induced increase in testicular interleukin 1beta, interleukin 6, TNF-α, nitric oxide, and NF-κB and increasing T2DM-induced decrease in interleukin 10, glutathione, superoxide dismutase, catalase, GPx, and Nrf2. Vitamin D enhanced the ameliorative effect of metformin on T2DM-induced testicular dysfunction.

Platelet-rich plasma (PRP) has been suggested for the improvement of endometrial growth and receptivity in the patients with recurrent implantation failure (RIF). The aim of present study was to investigate the impact of different concentration of PRP on the expression of genes involved in the endometrial receptivity in the human endometrial cells from RIF and controls with thin and normal endometrium in vitro. In this cross-sectional study, endometrial biopsies were obtained from 14 healthy fertile women and 14 women with RIF. Endometrial cells from 4 different group (RIF and control with endometrial thickness < 7 mm and > 7 mm) were cultured with three different concentration of PRP 3%, 5% and 10%. Expression of leukemia inhibitory factor (LIF), COX2 and P53, estrogen receptors (ERs) and progesterone receptors (PRs) genes were measured using quantitative real-time polymerase chain reaction (PCR). Protein expression levels of LIF, COX2 and p53 were evaluated using Western Blot method (WB). There was a significant decrease in the expression of PROA/b, ER2/b, LIF/b, COX2/b and P53/b genes in the RIF groups compared to the controls. Treatment with 5% and 10% PRP caused a significant increase in the gene expression of PRs, ERs, LIF/b, COX2/b and p53 in the RIF groups. Moreover, protein expression of COX2/b, LIF/b and p53/b increased following treatment with PRP in the RIF group with the endometrium thickness < 7 mm. PRP enhances expression of LIF, COX2, p53, ERs and PRs in the RIF patients with thin endometrium which may improve endometrium receptivity.

Although numerous studies have explored the link between polycystic ovary syndrome (PCOS) and thyroid dysfunction, the relationship between polycystic ovary morphology (PCOM) and thyroid issues remains unclear. This study aimed to examine the association between PCOM and subclinical hypothyroidism (SCH) as well as the threshold for thyroid-stimulating hormone (TSH). Data were drawn from the Iranian PCOS prevalence study and the Khuzestan PCOS prevalence study. Eligible participants were divided into two groups: those with PCOM (n = 120) and a control group (n = 630). A logistic regression model was employed to assess the impact of PCOM on SCH, with odds ratios and 95% confidence intervals calculated. Additionally, a quantile regression model was used to evaluate the effect of PCOS on TSH levels. The results indicated no significant association between PCOM and SCH (adjusted OR: 1.38, 95% CI: 0.80-2.37; p = 0.243). Furthermore, after adjusting for confounding factors such as age, body mass index (BMI), and number of pregnancies, no significant differences were found in TSH levels between the PCOM and control groups. The prevalence of SCH and the TSH threshold were similar in both groups. Further comprehensive population-based studies with detailed thyroid evaluations are recommended.

Surgical intervention for endometriosis is an important treatment modality, yet incomplete resection resulting from poor visibility of affected tissue and consequently recurrence of disease remains a prevalent challenge. Intra-operative visualization of endometriosis, enabling fluorescence-guided surgery (FGS), could help to optimize surgical treatment. A biomarker, upregulated in endometriosis compared to adjacent tissue, is required to use as a target for FGS. Immunohistochemistry was used to evaluate protein expression of a selection of previously identified potential biomarkers. Ten biomarkers were stained in a large cohort of 84 tissues, both deep and peritoneal endometriosis and tissue without endometriosis, all from patients with confirmed endometriosis. MMP11 and VCAN showed the largest upregulation in endometriosis compared to adjacent tissue and showed a membranous or extracellular staining pattern. MMP11 is a promising target for glandular and stromal visualization, VCAN for stromal visualization only. For both biomarkers, upregulation was high in both peritoneal and deep endometriosis and for patients with and without hormonal medication. Other stained biomarkers showed non-beneficial characteristics based on staining pattern or upregulation. Analysis of all endometriosis samples showed that combined glandular and stromal targeting is expected to result in optimal visualization of endometriosis. Further research is needed to determine whether targeting one biomarker is sufficient for this goal, or if dual targeting is necessary. Development of clinical tracers for VCAN and MMP11 is necessary.

To evaluate the effectiveness of Letrozole and Clomiphene (CC) combination versus Letrozole alone for ovulation induction in infertile women with PCOS. This was an open label randomized controlled trial conducted between September 2020 and March 2023 at a tertiary level hospital. Women with a diagnosis of infertility and PCOS were included. Participants were randomized in a 1:1 ratio, to either the combination of 2.5 mg letrozole and 50 mg Clomiphene Citrate (CC) daily or 2.5 mg letrozole alone from 2nd to 6^thday of menstrual cycle for up to three treatment cycles. The primary outcome was ovulation rate per cycle. The secondary outcomes included ovulation rate per woman randomised, cumulative pregnancy and live birth rates. A total of the 120 participants, 59 women in Letrozole and CC arm (intervention) and 61 women in the Letrozole alone arm (control) were recruited. The woman per cycle ovulation rate following Letrozole and CC combination versus Letrozole alone (71/92 (77.2%) vs. 52/83 (62.6%), RR 1.43, 95%CI 0.99 to 2.06) but was not statistically significant. A per ITT analysis, the clinical pregnancy rate per woman randomized (16/61(26.2%) vs. 13/59(22%), RR 1.12, 95%CI 0.76 to 1.64) and live birth rate per woman randomized (10/61(16.4%) vs 11/59(18.6%), RR 0.92, 095%CI 0.57 to 1.50) did not differ significantly between Letrozole and CC versus Letrozole group. There was no significant improvement in ovulation, clinical pregnancy, or live birth rates with a combination of letrozole and CC versus letrozole alone in per woman randomized with PCOS. Trial RegistrationThe trial was prospectively registered in the clinical trial registry of India (CTRI registration number CTRI/2020/07/026263), Registration dated: February 26, 2020.

Despite evidence in previous literature regarding vaccine safety, more data were needed as concerns about COVID-19 vaccines were raised, particularly regarding their effects on female fertility, exacerbated by the widespread dissemination of information without scientific evidence. This study aims to answer the question: does COVID-19 vaccination have any impact on female fertility at a population level. In this ecological study, vaccination rates against COVID-19 and birth rates in 100 different countries were correlated. In addition, the correlation between these two rates of interest and the Gini index were also analyzed. Data were retrieved from the World Population Prospects document produced by the Population Division of the United Nations Department of Economic and Social Affairs, from the World Health Organization (WHO) website, and from the World Bank website. Statistical analyses were conducted using the ANOVA test, and Pearson's correlation using the JASP software. For all analyses, results were considered significant if P < 0.05. In evaluating the trend of the birth rate in the countries included in the study, a persistent reduction of approximately 1.66% per year was observed between 2010 and 2022. From 2019 to 2022, the decline was close to 5%, resulting in an annual average reduction of 1.68%, which is similar to previous years. Among the selected countries, until December 2021, the average number of vaccine doses administered was 137 per 100 inhabitants. There was no observed correlation between the number of vaccine doses administered in different countries and the variation in the birth rate per thousand inhabitants between 2019 and 2022 (Pearson's r = 0.075; P = 0.455). A correlation was found between the Gini index and the birth rate, considering the base year of 2022, with a Pearson's r value of 0.376 (P < 0.01). This correlation remained consistent for all other years. A negative correlation was found between vaccine doses and the Gini index, with a Pearson's r value of -0.219 (P = 0.040). The findings of this article, as well as previous scientific evidence, do not identify any correlation between COVID-19 vaccines and female fertility issues. The associations analyzed in this study indicate the safety of vaccines for reproductive health and contribute to reducing vaccine hesitancy among the population of childbearing age.

We aimed to analyze the prevalence of isthmocele and factors associated with its onset within a cohort of women with previous history of cesarean section. A cross-sectional study with 90 women assessed from 2020 to 2022. Isthmocele was a composite variable diagnosed by transvaginal ultrasound (TVUS), magnetic resonance imaging (MRI) and/or diagnostic hysteroscopy (DxHys) and were asked about clinical symptoms, sociodemographic and obstetrical history and quality of life by the WHO-QOL questionnaire. Univariate and multivariate analysis (odds ratio (OR) plus 95% confidence intervals-CI) were performed to seek factors associated with the presence of isthmocele (5% significance level).The prevalence of isthmocele after combining MRI, TVUS and DxHys was 63.3% (n = 57). Women with isthmocele presented a higher body mass index (BMI) measured during delivery (32.70 ± 6.07 vs. 28.28 ± 9.86 kg/m²;p < 0.05) than women without isthmocele. Other sociodemographic variables, obstetrical history and WHO-QOL subdomains did not differ between groups. Within women with isthmocele, the residual myometrial mantle had an average of 4.97 ± 1.57 cm. Uterine volume was higher in the isthmocele group (103.95 vs. 81.34 cm³; p = 0.08), but with no statistical difference. Multivariate analysis (logistic regression) has reported that the factors associated with isthmocele were: higher BMI during delivery (aOR = 1.26[1.07-1.49];p < 0.05); longer interpartum interval (aOR = 1.22[1.03-1.46];p = 0.02) and presence of more than two cesarean sections (aOR = 2.16[1.16-4.01];p = 0.02). We concluded that a high prevalence of isthmocele was found. Women with previous cesarean section, with higher BMI during delivery and longer interdelivery interval were risk factors for the presence of isthmocele.

Uterine leiomyomas are the most common benign, monoclonal, gynaecological tumors in a woman's uterus, while leiomyosarcoma is a rare but aggressive condition caused by the malignant transformation of the myometrium. To overcome the common obstacles related to the methods usually used to study these pathologies, we aimed to devise three-dimensional models of myometrium, uterine leiomyoma and leiomyosarcoma cell lines, using two different types of biocompatible scaffolds. Specifically, we exploited the agarose gel matrix in common 6-well plates and the alginate matrix using Bioprinting INKREDIBLE + (CELLINK), a pneumatic extruded base equipped with a system with double printheads, and a UV printer LED curing system. Both methods allowed the development of 3D spheroids of all three cell types, that were also suitable for morphological investigations. We showed that all cell types embedded in both agarose and alginate formed spheroids in their growth medium. The spheroids successfully proliferated and self-organized into complex structures, developing a sustainable system that emulated the condition of the tissues through the accumulation of extracellular matrix. These models could be useful for a better understanding of pathophysiology, etiopathogenesis, and testing new methods or molecules from a preventive and therapeutic point of view.

This systematic review and meta-analysis aimed to investigate the effect of letrozole alone or in combination with Methotrexate on the management of ectopic pregnancy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied for reporting. The EMBASE, PubMed, Scopus, and Web of Science databases were searched for relevant studies focused on women diagnosed with ectopic pregnancy and managed non-surgically with letrozole alone or in combination with methotrexate (MTX) until April 2024. The success rate, laboratory findings, and complications were analyzed and reported. Meta-analysis was done using RevMan 5.4.1 software. Out of 129 unique studies obtained, 7 of them were found eligible for final review; of which, 3 were nonrandomized prospective cohort studies, 2 were randomized clinical trials, and 2 study were case studies. In 5 studies letrozole was used as monotherapy. While in another study letrozole was used with MTX. The meta-analysis showed a significantly lower level of β-HCG in the letrozole group compared to MTX, 7 days after initiation of treatment (Fixed effect model, MD = -92.22, 95%CI: [-159.39, -25.04], P = 0.007, I2 = 0%). There was no significant difference in the level of anti-mullerian hormone (AMH) between groups (Fixed effect model, MD = 0.18, 95%CI: [-0.09, 0.45], P = 0.20, I2 = 0%). Success rate, platelet count, and level of liver enzymes seemed to be better or similar among patients receiving Letrozole compared to patients receiving Methotrexate. Letrozole exhibits potential as a therapeutic option for ectopic pregnancies; however, further randomized clinical trials are necessary to establish strong evidence.

Can the best culture medium be determined by mouse embryo testing? Zygotes/embryos of four different mouse strains: inbred Balb/c (n = 79) and C57Bl/6 (n = 95), F1 hybrid DBA/2*C57Bl/6 (n = 133), and outbred ICR (n = 69) were incubated in vitro in four culture media: 1-Step Culture Medium (VitaVitro), CSC medium (Irvine Scientific), Sage 1-Step medium (Origio), G-TL medium (Vitrolife). The embryos were cultured under standard conditions at atmospheric oxygen: 37℃; 6% CO2, 100% humidity. Standard MEA-test parameters (number of expanded blastocysts on E4.5), as well as additional characteristics (embryo development on E2.5-E4.5, number of hatching and hatched blastocysts on E4.5, embryo arrest and degeneration) were assessed for each of the strain-medium combinations. The results were compared across strains as well as across media. Embryo development depended on both the media and the mouse strain. Embryos from inbred and outbred mice were more sensitive to suboptimal culture conditions compared to the hybrid strain; this was reflected in reduced blastocyst and hatching rates, as well as an increased percentage of arrested and degraded embryos. The choice of optimal media depended strongly on the strain: CSC was better for Balb/c, Sage 1-step for C57Bl/6, while both were preferred for hybrids, and G-TL for outbreds. VitaVitro was quite good for hybrids and performed worse for other strains. Overall, the embryos of each strain behaved differently in different media, and it was not possible to make a real preference for any of them over human embryos based on the results of any single mouse strain. Only a pooled sample of different mouse strains can be used for comprehensive media MEA testing. MEA testing with any strain of mice is doomed to error due to their specific culture requirements. Hybrid mice are too reproductively efficient and cannot be used to distinguish media based on their subtle differences. Outbred and inbred mice are too sensitive and may be delayed or degraded in culture media that is well suited to the requirements of human embryos. Combined analysis of multiple mouse strains should be used to test media more fully and may serve as a model for the heterogeneity of human embryos in IVF clinics.