Hyperin promotes proliferation, migration, and invasion of HTR-8/SVneo trophoblast cells via activation of JAK1/STAT3 pathway in recurrent spontaneous abortions.

The proliferation of extravillous trophoblasts (EVT) and their further migration, invasion, and differentiation into the decidual and myometrial vasculature are vital for spiral artery remodeling. These physiological functions of EVT are also essential steps in the implantation of the human embryo and the formation of the placenta and are closely related to pregnancy maintenance and the occurrence of abortion. Hyperin is a flavonoid with anti-inflammatory, pro-proliferative, and anti-apoptotic properties. Consequently, we investigated the previously unexplored effects of hyperin on the proliferation, migration, and invasion of HTR-8/SVneo cells. Human extravillous trophoblast-derived HTR-8/SVneo cells were incubated with different concentrations of hyperin (0, 5, 10, 25, 50, and 100 µM) to observe the changes in cell proliferation, migration, invasive capacity, and pathway activation. Proliferation, migration, and invasion were promoted by activating the JAK1/STAT3 pathway in HTR-8/SVneo cells treated with hyperin. In addition, brepocitinib (PF-06700841) significantly inhibited the proliferation, migration, and invasion effects of hyperin on HTR-8/SVneo cells. In vivo experiments confirmed that hyperin reduces the embryo loss rate in recurrent spontaneous abortion (RSA) model mice. Furthermore, our study revealed that hyperin promoted the proliferation, migration, and invasion of HTR-8/SVneo cells via activation of the JAK1/STAT3 pathway, further improving pregnancy outcomes in RSA.

Resistant ovary syndrome: Pathogenesis and management strategies.

Resistant ovary syndrome (ROS) is a rare and difficult gynecological endocrine disorder that poses a serious risk to women's reproductive health. The clinical features are normal sex characteristics, regular female karyotype, and usual ovarian reserve, but elevated endogenous gonadotropin levels and low estrogen levels with primary or secondary amenorrhea. Although there have been many case reports of the disease over the past 50 years, the pathogenesis of the disease is still poorly understood, and there are still no effective clinical management strategies. In this review, we have collected all the current reports on ROS and summarized the pathogenesis and treatment strategies for this disease, intending to provide some clinical references for the management and treatment of this group of patients and provide the foothold for future studies.

Ovulation induction with high progesterone levels may be more suitable for elderly patients with low ovarian response.

BACKGROUND: The objective of this study was to explore the outcomes of using the progestin-primed ovarian stimulation (PPOS) protocol in aged infertile women. The patients recruited in the study had displayed a poor ovarian response (POR) in the first IVF/ICSI-ET cycles with the ultra-short gonadotropin-releasing hormone agonist (GnRH-a) protocols. MATERIALS AND METHODS: A self-controlled retrospective study was conducted to investigate the clinical outcomes of 117 aged infertile women who met the inclusion criteria. The patients were grouped into two; group B included patients who had displayed a poor ovarian response (POR) in the first IVF/ICSI-ET cycle with the ultra-short GnRH-a protocol. Group A was made up of patients who underwent the PPOS protocol in the second cycle. The study was done between January 2015 to May 2018 in the reproductive and genetic centre of integrated traditional and western medicine, Affiliated hospital of Shandong University of traditional Chinese medicine. Reproduction-related clinical outcomes in the two groups were compared. RESULTS: There were no statistically significant differences in the serum levels of LH, E2, and P on the trigger day between group A and group B (P＞0.05). The number of follicles with a diameter > 14 mm was significantly higher in the PPOS protocol patients than in the ultra-short GnRH-a protocol group (4.83 ± 2.82 vs. 3.25 ± 2.53, P < 0.01). The duration and total dosage of gonadotropin of the PPOS protocol group were less than in the previous ultra-short GnRH-a protocol, although the statistical differences were not significant (P > 0.05). The number of eggs obtained in the PPOS group was significantly higher than that of the previous one (4.29 ± 3.11 vs. 2.76 ± 2.33, P < 0.05). The numbers of MII eggs, cleavage, 2 P N, transplantable embryos, and high quality embryos were higher in the PPOS protocol group than that in the ultra-short protocol group. However, the differences between the two groups in all the above parameters were not statistically significant (P > 0.05). The rate of high-quality embryos was significantly higher in the PPOS protocol group than in the ultra-short protocol group (38.61(100/259) vs. 32.02(65/203), P < 0.05). Although not statistically significant (P > 0.05), the abortion rate of the PPOS protocol group was higher than that of the ultra-short protocol group. The clinical pregnancy and live birth rates were significantly higher in the PPOS protocol group than in the ultra-short protocol group (p < 0.05). The clinical pregnancy rates in the PPOS protocol group and the ultra-short protocol group were 32.35 % and 25.53 % respectively while the live birth rates were 27.45 % and 21.28 % respectively. CONCLUSION: Compared with the ultra-short protocol, the PPOS protocol improves the number of follicles, the number of eggs, clinical pregnancy, and live birth rates in POR patients. The PPOS protocol could, therefore, provide a novel treatment strategy for inducing ovulation in POR patients.

Successful live birth in a woman with resistant ovary syndrome treated with letrozole and HMG: A case report.

INTRODUCTION: Resistance ovary syndrome (ROS) is a disease characterized by hypergonadotropic amenorrhea but with normal ovarian reserve. Currently, its pathogenesis is still unclear and the treatment methods are complex. Nevertheless, there are evident negative effects of this disease on females' physical and mental health such as gonadal dysplasia, infertility, anxiety, and depression. This article reports a case of successful ovulation induction and pregnancy with letrozole combined with HMG. This can provide clinical treatment guidelines for the disease. PATIENT CONCERNS: The patient underwent several hormone replacement cycles and ovulation induction cycles. But the dominant follicles were not extracted even after using large doses of gonadotropin. DIAGNOSIS: Resistant ovary syndrome; Primary infertility INTERVENTIONS:: Larger doses of letrozole combined with HMG were injected to stimulate ovulation and sensitize the ovaries during menstruation. This helped to examine the peripheral effects of letrozole in relation to gonadotropin. OUTCOMES: The patient displayed a dominant follicular growth and notable ovulation which resulted in a full-term pregnancy and successful delivery. CONCLUSIONS: The resistance ovary syndrome (ROS) can be treated and the findings from this case provides a possible treatment for ROS patients with infertility.

Relation of Chlamydia trachomatis infections to ectopic pregnancy: A meta-analysis and systematic review.

BACKGROUND: In a multitude of previous studies, Chlamydia trachomatis (CT) plays an important role in the occurrence of ectopic pregnancy (EP). However, the predictive value of CT infections in the occurrence of EP has not been estimated worldwide. We thus evaluated, by means of a meta-analysis, the current status of the association between CT infections with EP and the potential predictive value of CT infections in EP. METHODS: We evaluated studies performed between the database construction time and August 2018 published in PubMed, the Cochrane Library, EMBASE, and the Web of Science (SCI). The relationship between CT and EP was calculated based upon the predetermined entry criteria for control group selection and the original data. The related articles were analyzed using a random-effects model, and the heterogeneity of the studies was assessed using the I index. Data were analyzed with the STATA 12.0 software. RESULTS: Twenty-five studies that recruited 11960 patients were included in the present meta-analysis, and the relation of CT infections with EP were assessed. The association between CT infections and EP risk showed an odds ratio (OR) of 3.03, with a 95% confidence interval (CI) of 2.37 to 3.89. Our results showed that there was a statistically significant difference between the intervention and control groups. The prevalence of CT infections in EP was then calculated by a subgroup analysis: African (OR, 2.22; 95% CI, 1.14-4.31), European (OR, 3.16; 95% CI, 2.10-4.47), North American (OR, 3.07; 95% CI, 1.78-5.31), and Asian (OR, 3.39; 95% CI, 1.95-5.90). CONCLUSIONS: From the results of numerous studies conducted on different continents, this meta-analysis showed a clear association between EP and prior CT infections, that is, CT infections increase the risk of EP occurrence.

Effect of duration of gonadotropin releasing hormone agonist on the outcome of in vitro fertilization-embryo transfer in a short-acting long regimen.

Objective: To investigate the effect of the duration of gonadotropin releasing hormone agonist (GnRH-a) use on the outcome of in vitro fertilization and embryo transfer (IVF-ET) during the short-acting long-term hyperstimulation cycle. Methodology: Clinical data from 776 patients receiving controlled ovarian stimulation (COS) after short-term regimen downregulation were retrospectively analyzed. According to the duration of GnRH-a, the patients were divided into 3 groups: Group A, 14 days for GnRH-a; Group B, 15-17 days for GnRH-a; and Group C, >18 days for GnRH-a. The clinical data, treatment and clinical outcomes were compared among the groups. Results: There were no significant differences in fertilization rate, implantation rate, clinical pregnancy rate, abortion rate, ovarian hyperstimulation syndrome (OHSS) rate(P > 0.05). The total costs in group A were significantly less than those in group B and C(P < 0.001). The number of eggs and quality embryos generated in group A was significantly higher than that in groups B and C (P = 0.014, P = 0.005). Conclusions: In the short-acting GnRH agonist long protocol, satisfactory IVF-ET pregnancy outcome was obtained with the use of GnRH-a for 14 days under the premise of lowering the receptor-regulating standard. Excessive application of GnRH-a will affect the number of eggs and embryos and increase the cost of medical treatment.

Effectiveness and safety of Chinese herbal medicine Xiaoyao san for the treatment of insomnia: Protocol for a systematic review and meta-analysis.

BACKGROUND: Insomnia is one of the most common sleep problems, which can impact physical and mental quality of life, resulting in a heavy social and economic burden. Xiaoyao san, a Chinese Herbal Medicine product, has been widely used as an alternative to recommended treatments for insomnia, but still lack of evidence of evidence-based medicine, which the clinical efficacy and its safety are questioned. Accordingly, we provide a protocol to evaluate the efficacy and safety of Xiaoyao san to update the search and evaluation for the best available and security treatment for insomnia. METHODS: This review systematic and comprehensive retrieves of 8 related databases at home and abroad. Only randomized controlled trials (RCTs) of Xiaoyao san on Insomnia published in English and Chinese will be included. The quality of the included trials including randomization, allocation concealment, blinding, withdrawal, and loss of follow-up which was evaluated using internationally accepted evaluation criteria. And then systematically comprehensive analysis of the efficacy. RESULTS: This review will be to assess the efficacy and safety of Xiaoyao san for insomnia. CONCLUSION: This systematic review will provide strong evidence for the effectiveness and safety of Xiaoyao san in the treatment of insomnia. PROSPERO REGISTRATION NUMBER: CRD42019127326.