Adverse effect of lactobacilli-depauperate cervicovaginal microbiota on pregnancy outcomes in women undergoing frozen-thawed embryo transfer.

Purpose: The cervicovaginal microbiota is essential for maintaining the health of the female reproductive tract. However, whether cervicovaginal microbiota status prior to frozen embryo transfer (FET) associates with pregnancy outcomes is largely unexplored. Methods: Cervical mucus from 29 women who had undergone FET was collected. Microbial composition was analyzed using 16 S rRNA gene sequence to assess the correlation to the pregnancy outcomes. Results: CST-categorized Lactobacillus was the most dominant (41.71%) in the pregnant group, while CST-IV-based and BV-related Gardnerella (34.96%) prevailed in the non-pregnant group. The average abundance of Gardnerella compared non-pregnant to pregnant women was the highest (34.96% vs. 4.22%, p = 0.0015) among other CST-IV indicator bacteria. Multivariate analysis revealed that CST-IV-related bacteria have a significantly adverse effect on ongoing pregnancy outcomes (odds ratio, 0.083; 95% confidence index, 0.012-0.589, p = 0.013*). Conclusions: The study found that the CST-IV microbiota, with significantly increasing Gardnerella and the loss of Lactobacilli as the dominant bacteria, can potentially contribute to pregnancy failure. Therefore, dysbiotic microbiota may be a risk factor in women undergoing FET. Assessing the health of the cervicovaginal microbiota prior to FET would enable couples to make a more thoughtful decision on the timing and might improve pregnancy outcomes.

Artificial oocyte activation may improve embryo quality in older patients with diminished ovarian reserve undergoing IVF-ICSI cycles.

BACKGROUND: Artificial oocyte activation (AOA) is used to improve fertilization rate following fertilization failure after intracytoplasmic sperm injection (ICSI). Several studies have also shown that AOA may be involved in embryo development. Women with poor ovarian response are more likely to encounter in vitro fertilization (IVF) failure due to poor embryo quality. The aim of this study was to investigate whether AOA could improve embryo quality in older patients with diminished ovarian reserve undergoing IVF-ICSI cycles. METHODS: The retrospective cohort study consisted of 308 patients who fulfilled the POSEIDON Group 4 criteria and received IVF-ICSI cycles. The study group included 91 patients receiving AOA with calcium ionophores following ICSI. A total of 168 patients in the control group underwent ICSI without AOA. The baseline and cycle characteristics and embryo quality were compared between the two groups. RESULTS: At baseline, there were more IVF attempts, greater primary infertility, higher basal FSH levels and lower anti-Müllerian hormone (AMH) levels in the AOA group than in the non-AOA group. In terms of embryo quality, there were higher cleavage rates and top-quality Day 3 embryo (TQE) rates, as well as higher percentages of more than 1 TQE and TQE rates ≥50 in the AOA group than in the non-AOA group. The multivariate analysis revealed that AOA was positively associated with more than 1 TQE (adjusted OR 3.24, 95% CI 1.63-6.45, P = 0.001) and a TQE rate ≥ 50 (adjusted OR 2.14, 95% CI 1.20-3.80, P = 0.010). When the study population was divided into 2 subgroups based on the age of 40 years old, the beneficial effects of AOA on embryo quality were only observed in the subgroup of age ≥ 40 years old. CONCLUSIONS: Our data suggest that AOA with calcium ionophores may improve embryo quality in older patients with diminished ovarian reserve undergoing IVF-ICSI cycles, especially in women aged ≥40 years.

Expression status and prognostic significance of mitochondrial dynamics OPA3 in human ovarian cancer.

Early diagnosis of ovarian cancer and the discovery of prognostic markers can significantly improve survival and reduce mortality. OPA3 protein exists in a structure called mitochondria, which is the energy production center of cells, but its molecular and biological functions in ovarian cancer are still unclear. Here, the expression of OPA3 mRNA in ovarian cancer was estimated using TCGA, Oncomine, TIMER databases. We found that functional OPA3 activation caused by mutations and profound deletions predicted poor prognosis in OV patients. OPA3 was highly expressed in both OV tissues and cells compared to normal ovarian tissues/cells. High OPA3 expression is associated with poorer overall survival (OS). The association between OPA3 and immune infiltration of ovarian cancer was assessed by TIMER and CIBERSORT algorithms. OPA3 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of OV cell lines revealed that OPA3 inactivation was associated with increased sensitivity to PFI-1, and WZ4003. Therefore, we investigated the clinical application of OPA3 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of ovarian cancer.

Phosphoglycerate mutase family member 5 maintains oocyte quality via mitochondrial dynamic rearrangement during aging.

Decline in ovarian reserve with aging is associated with reduced fertility and the development of metabolic abnormalities. Once mitochondrial homeostasis is imbalanced, it may lead to poor reproductive cell quality and aging. However, Phosphoglycerate translocase 5 (PGAM5), located in the mitochondrial membrane, is associated with necroptosis, apoptosis, and mitophagy, although the underlying mechanisms associated with ovarian aging remain unknown. Therefore, we attempted to uncover whether the high phosphoglycerate mutant enzyme family member 5 (PGAM5) expression is associated with female infertility in cumulus cells, and aims to find out the underlying mechanism of action of PGAM5. We found that PGAM5 is highly expressed and positively associated with aging, and has the potential to help maintain and regulate mitochondrial dynamics and metabolic reprogramming in aging granulosa cells, ovaries of aged female mice, and elderly patients. PGAM5 undergoes activation in the aging group and translocated to the outer membrane of mitochondria, co-regulating DRP1; thereby increasing mitochondrial fission. A significant reduction in the quality of mitochondria in the aging group, a serious imbalance, and a significant reduction in energy, causing metabolism shift toward glycolysis, were also reported. Since PGAM5 is eliminated, the mitochondrial function and metabolism of aging cells are partially reversed. A total of 70 patients undergoing in vitro fertilization (IVF) treatment were recruited in this clinical study. The high expression of PGAM5 in the cumulus cells is negatively correlated with the pregnancy rate of infertile patients. Hence, PGAM5 has immense potential to be used as a diagnostic marker.

High serum anti-Müllerian hormone concentrations have a negative impact on fertilization and embryo development rates.

RESEARCH QUESTION: What is the impact of high serum anti-Müllerian hormone (AMH) concentrations on fertilization and embryo development among infertile women undergoing treatment with assisted reproductive technology (ART)? DESIGN: Retrospective study of 1036 infertile women undergoing ART; women were divided into three groups according to serum AMH concentrations: AMH <1.1 ng/ml, 1.1-5.0 ng/ml and >5.0 ng/ml. The fertilization and embryo development rates of patients with different AMH concentrations and after stratification according to age were compared. RESULTS: Women with high AMH concentrations were younger and had higher testosterone concentrations (0.4 ± 0.13 versus 0.3 ± 0.12 versus 0.3 ± 0.08 µg/dl, P < 0.001) than women with low AMH concentrations. However, analysis of the embryo development rate showed negative outcomes for women with high AMH concentrations, including a poor fertilization rate (76.3 ± 17.36 versus 82.1 ± 19.15 versus 82.4 ± 25.38, P = 0.003), and poor day 3 embryo development rate (55.6 ± 23.88 versus 62.6 ± 26.52 versus 62.8 ± 32.65, P = 0.014). Multivariate linear regression analysis showed significantly negative correlations of the AMH concentrations with the fertilization rate (P < 0.001) and day 3 embryo development rate (P = 0.006). Subgroup analysis showed that age 30 years or younger had a significant negative correlation with AMH and the embryo development rate, including the fertilization rate (P < 0.001) and day 3 embryo development rate (P = 0.037). CONCLUSION: These results suggest that high serum AMH concentrations, contributing to a hyperandrogenic environment and leading to decreased oocyte developmental competence, may have a negative impact on fertilization and the early stage of embryo development in women undergoing treatment with ART.

The Molecular Regulation in the Pathophysiology in Ovarian Aging.

The female reproductive system is of great significance to women's health. Aging of the female reproductive system occurs approximately 10 years prior to the natural age-associated functional decline of other organ systems. With an increase in life expectancy worldwide, reproductive aging has gradually become a key health issue among women. Therefore, an adequate understanding of the causes and molecular mechanisms of ovarian aging is essential towards the inhibition of age-related diseases and the promotion of health and longevity in women. In general, women begin to experience a decline in ovarian function around the age of 35 years, which is mainly manifested as a decrease in the number of ovarian follicles and the quality of oocytes. Studies have revealed the occurrence of mitochondrial dysfunction, reduced DNA repair, epigenetic changes, and metabolic alterations in the cells within the ovaries as age increases. In the present work, we reviewed the possible factors of aging-induced ovarian insufficiency based on its clinical diagnosis and performed an in-depth investigation of the relevant molecular mechanisms and potential targets to provide novel approaches for the effective improvement of ovarian function in older women.

Identification of Novel Biomarkers and Candidate Drug in Ovarian Cancer.

This paper investigates the expression of the CREB1 gene in ovarian cancer (OV) by deeply excavating the gene information in the multiple databases and the mechanism thereof. In short, we found that the expression of the CREB1 gene in ovarian cancer tissue was significantly higher than that of normal ovarian tissue. Kaplan-Meier survival analysis showed that the overall survival was significantly shorter in patients with high expression of the CREB1 gene than those in patients with low expression of the CREB1 gene, and the prognosis of patients with low expression of the CREB1 gene was better. The CREB1 gene may play a role in the occurrence and development of ovarian cancer by regulating the process of protein. Based on differentially expressed genes, 20 small-molecule drugs that potentially target CREB1 with abnormal expression in OV were obtained from the CMap database. Among these compounds, we found that naloxone has the greatest therapeutic value for OV. The high expression of the CREB1 gene may be an indicator of poor prognosis in ovarian cancer patients. Targeting CREB1 may be a potential tool for the diagnosis and treatment of OV.

Combining Bioinformatics and Experiments to Identify CREB1 as a Key Regulator in Senescent Granulosa Cells.

Aging of functional ovaries occurs many years before aging of other organs in the female body. In recent years, a greater number of women continue to postpone their pregnancies to later stages in their lives, raising concerns of the effect of ovarian aging. Mitochondria play an important role in the connection between the aging granulosa cells and oocytes. However, the underlying mechanisms of mitochondrial dysfunction in these cells remain poorly understood. Therefore, we evaluated the molecular mechanism of the aging granulosa cells, including aspects such as accumulation of mitochondrial reactive oxygen species, reduction of mtDNA, imbalance of mitochondrial dynamics, and diminished cell proliferation. Here, we applied bioinformatics approaches, and integrated publicly available resources, to investigate the role of CREB1 gene expression in reproduction. Senescence hallmark enrichment and pathway analysis suggested that the downregulation of bioenergetic-related genes in CREB1. Gene expression analyses showed alterations in genes related to energy metabolism and ROS production in ovary tissue. We also demonstrate that the biogenesis of aging granulosa cells is subject to CREB1 binding to the PRKAA1 and PRKAA2 upstream promoters. In addition, cofactors that regulate biogenesis significantly increase the levels of SIRT1 and PPARGC1A mRNA in the aging granulosa cells. These findings demonstrate that CREB1 elevates an oxidative stress-induced senescence in granulosa cells by reducing the mitochondrial function.

Laser irradiation pretreatment improves endometrial preparation of frozen-thawed embryo transfer in recurrent implantation failure patients.

Recurrent implantation failure (RIF) remains a clinical dilemma. Helium-Neon (He-Ne) laser irradiation has recently become more popular under certain clinical conditions. Given the unique therapeutic effects, we were interested in determining whether pretreatment with He-Ne laser irradiation prior to frozen-thawed embryo transfer (FET) would improve the microcirculation and cause the release of growth factors and cytokines, thus improving endometrial receptivity and the clinical pregnancy rates. Patients chose for themselves whether to proceed with (n = 29) or without (n = 31) pretreatment with He-Ne laser irradiation prior to FET. The clinical pregnancy rate (37.9%) and implantation rate (20.3%) were higher in the laser-treatment group than in the control group (35.5% and 15.9%, respectively, p = .844 and .518, respectively). The live birth rate was higher in the laser-treatment group (27.6% vs. 25.8%, respectively, p = .876) and the miscarriage rate was lower in the laser-treatment group (18.2% and 27.3%, respectively, p = .611). No side effects or complications from laser irradiation were encountered in patients who received the laser treatment. We concluded that pretreatment with He-Ne laser prior to FET may be an alternative choice for RIF-affected women; however, additional well-designed prospective studies are necessary to determine the precise clinical value of this treatment.

Low plasma levels of decoy receptor 3 (DcR3) in the third trimester of pregnancy with preeclampsia.

OBJECTIVE: The pathophysiology of preeclampsia, a major threat during pregnancy characterized by excessive inflammatory status, remains unclear. Decoy receptor 3 (DcR3), a soluble member of the tumor necrosis factor receptor (TNFR) superfamily, is capable of inducing anti-apoptosis via binding with TL1A and anti-inflammation by driving Th2 immune reactions. DcR3 may, therefore, play a role in immune modulation during pregnancy. The purpose of this study is to explore the role of DcR3 in normal and preeclamptic pregnancies. MATERIALS AND METHODS: Plasma samples from 104 normal pregnant women (26, 42, and 36 in the first, second, and third trimester, respectively) and 10 patients with preeclampsia in the third trimester were collected. Plasma DcR3 levels were determined by using commercial ELISA kits. ANOVA and linear regression analysis were performed to analyze the relationship between gestational age and DcR3 levels. After adjusting for gestational days, the levels of plasma DcR3 in preeclamptic and non-preeclamptic women in the third trimester were compared. RESULTS: The plasma levels of DcR3 gradually decreased as the gestational days increased during pregnancy (p < 0.05). In the third trimester, pregnant women with preeclampsia had significantly lower plasma DcR3 levels compared to non-preeclamptic women (p < 0.05). CONCLUSIONS: We found that plasma DcR3 levels gradually decreased as gestation progressed. The levels of plasma DcR3 in preeclamptic women were significantly lower than those of normal pregnant women, suggesting that a potential involvement of DcR3 in normal pregnancy and decreased levels of DcR3 may be related to preeclampsia.

MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities.

Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein.

Long-term compliance of vaginal pessaries: Does stress urinary incontinence matter?

Vaginal pessary treatment for pelvic organ prolapse (POP) is relatively safe and cost-effective. Since long-term use is an important key to keep the benefit of pessary treatment, we would like to investigate the factors which might affect the compliance of vaginal pessaries. In this retrospective study, 65 women were included, and we found poor compliance in women with severe stress urinary incontinence (SUI) after reduction (1-hour pad test >10 gm vs ≦10 gm, 57.1% vs. 84.3%, P = .027). Besides, women younger than 60 years-old also had poor compliance (age ≦60-year-old vs >60-year-old, 58.3% vs 83.0%, P = .04). Other factors such as POP stage, history of hysterectomy, and types of pessaries, did not show significant influence on the long-term compliance in this study. Therefore, to evaluate the severity of SUI after reduction before providing pessary treatment is important to predict long-term compliance. Meanwhile, long-term pessary treatment seems to be more acceptable to elderly patients.

Maternal pregnancy-induced hypertension increases the subsequent risk of neonatal candidiasis: A nationwide population-based cohort study.

OBJECTIVE: Neonatal candidiasis is a leading infectious cause of significant morbidity and mortality in premature birth mainly due to impaired physical barriers and immature immune system of fetus. Maternal pregnancy-induced hypertension (PIH) has been reported to be able to disturb the neonatal immune system, which could cause the increased possibility of neonatal infection. Therefore, we hypothesized that maternal PIH may increase the risk of neonatal candidiasis. The aim of this study was to evaluate whether PIH increased the risk of neonatal candidiasis and identify the predictive risk factors. MATERIALS AND METHODS: Patients with newly diagnosed PIH between January 1, 2000, and December 31, 2013 were selected from the Taiwan National Health Insurance Research Database (NHIRD). For each patient in the PIH cohort, 4 subjects without PIH, matched for age and year of delivery, were randomly selected as the comparison cohort. A Cox proportional regression model was used to estimate the risks of neonatal candidiasis in both cohorts. RESULTS: Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. Patients with PIH had a higher incidence of neonatal candidiasis than did those without PIH. According to the multivariate analysis, PIH (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11-3.19, p < 0.0228), single parity (OR = 1.91, 95% CI = 1.00-3.65, p < 0.0499), and preterm birth (OR = 3.57, 95% CI = 1.84-6.93, p = 0.0002) were independent risk factors for the development of neonatal candidiasis. CONCLUSION: Patients who had a history of PIH was associated with an increased risk of having infants who develop neonatal candidiasis compared with those without PIH. Additionally, preterm birth was an independent risk factor for the development of neonatal candidiasis.

The short-term outcome of laser in the management of female pelvic floor disorders: Focus on stress urine incontinence and sexual dysfunction.

OBJECTIVE: Female pelvic floor disorders, including female stress urinary incontinence (SUI) or sexual dysfunction are notorious for affecting the quality of women's life. It is reported that laser therapy might result in collagen remodeling and improvement in tissue firmness. The study was conducted to evaluate the short-term outcome of female pelvic floor disorders treated by laser therapy. MATERIALS AND METHODS: Women with self-reported symptoms of female pelvic floor disorders (limited to SUI and sexual dysfunction) were included in the study. The participants were treated with the Er:YAG laser or the fractional microablative carbon dioxide (CO2) laser system. The therapeutic effect was focused on SUI symptoms and sexual dysfunction. RESULTS: There were 31 women underwent laser treatment, including 21 patients treated with Erbium:YAG laser and 10 treated with CO2 laser. In the Erbium:YAG laser group, International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ- SF) scores were dropped from 8.25 ± 5.66 to 5.00 ± 3.99 (P = 0.007); and in the CO2 laser group, scores were dropped from 11.11 ± 6.85 to 6.44 ± 4.25 (P = 0.035), contributing to the drop of ICI-Q-SF scores from 9.14 ± 6.08 to 5.45 ± 4.05 for all enrolled patients (P = 0.001). However, objective measure using pad test did not show a statistically significant difference between before and after treatment (from 3.20 ± 5.84 g to 1.54 ± 3.18 g, P = 0.224). Sexual dysfunction was improved in 13 patients (44.83%), but Female Sexual Function Index (FSFI) scores were not different before and after laser treatment (44.22 ± 23.36 vs. 44.09 ± 24.51, P = 0.389). CONCLUSION: Laser therapy either by Erbium:YAG laser or CO2 laser seemed to be useful for female pelvic floor disorders, especially on improvement of SUI symptoms; however, the effectiveness needs further confirmation.

Dehydroepiandrosterone (DHEA) supplementation improves in vitro fertilization outcomes of poor ovarian responders, especially in women with low serum concentration of DHEA-S: a retrospective cohort study.

BACKGROUND: Dehydroepiandrosterone (DHEA) is now widely used as an adjuvant for in vitro fertilization (IVF) cycles in poor ovarian responders (PORs). Several studies showed that DHEA supplementation could improve IVF outcomes of PORs. However, most of the PORs do not respond to DHEA clinically. Therefore, the aim of this study is to confirm the beneficial effects of DHEA on IVF outcomes of PORs and to investigate which subgroups of PORs can best benefit from DHEA supplementation. METHODS: This retrospective cohort study was performed between January 2015 and December 2017. A total of 151 PORs who fulfilled the Bologna criteria and underwent IVF cycles with the gonadotropin-releasing hormone antagonist protocol were identified. The study group (n = 67) received 90 mg of DHEA daily for an average of 3 months before the IVF cycles. The control group (n = 84) underwent the IVF cycles without DHEA pretreatment. The basic and cycle characteristics and IVF outcomes between the two groups were compared using independent t-tests, Chi-Square tests and binary logistic regression. RESULTS: The study and control groups did not show significant differences in terms of basic characteristics. The study group demonstrated a significantly greater number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality embryos at day 3 and a higher clinical pregnancy rate, ongoing pregnancy rate and live birth rate than those measures in the control group. The multivariate analysis revealed that DHEA supplementation was positively associated with clinical pregnancy rate (OR = 4.93, 95% CI 1.68-14.43, p = 0.004). Additionally, in the study group, the multivariate analysis showed that serum dehydroepiandrosterone-sulfate (DHEA-S) levels < 180 µg/dl were significantly associated with a rate of retrieved oocytes > 3 (OR = 5.92, 95% CI 1.48-23.26, p = 0.012). CONCLUSIONS: DHEA supplementation improves IVF outcomes of PORs. In PORs with DHEA pretreatment, women with lower DHEA-S level may have greater possibility of attaining more than 3 oocytes.

Luteal Phase Ovarian Stimulation May Improve Oocyte Retrieval and Oocyte Quality in Poor Ovarian Responders Undergoing In Vitro Fertilization: Preliminary Results from a Single-Center Prospective Pilot Study.

INTRODUCTION: Luteal phase ovarian stimulation (LPOS) has been proven a feasible protocol for infertile patients. High progesterone level in the luteal phase could physiologically inhibit premature luteinizing hormone surge, from which poor ovarian responders (PORs) could obtain benefits. Therefore, we aimed to compare clinical outcomes between LPOS and follicular phase ovarian stimulation (FPOS) protocol in PORs undergoing in vitro fertilization (IVF). METHODS: This prospective pilot study was performed at one tertiary center from January 2016 to October 2017. A total of 60 PORs who met Bologna criteria and undergoing IVF were enrolled. Thirty PORs were allocated to the LPOS group and 30 PORs were allocated to the FPOS group. Basic characteristics, cycle characteristics, and pregnancy outcomes were compared between the two groups. RESULTS: The length of stimulation was significantly longer in the LPOS group than in the FPOS group. The numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, and day-3 embryos were significantly higher in the LPOS group than in the FPOS group. Conversely, we could not find any significant difference for clinical pregnancy rate, ongoing pregnancy rate, abortion rate, and cancellation rate. The multivariate analysis showed that only LPOS (p = 0.007) was significantly associated the possibility to retrieve three or more oocytes, whereas basal follicle-stimulating hormone (FSH) < 8 IU/l (p = 0.103) and antral follicle count (AFC) ≥ 3 (p = 0.143) did not significantly affect this event. CONCLUSION: LPOS allows improved oocyte retrieval and oocyte quality in PORs with respect to FPOS, despite comparable pregnancy outcomes. LPOS may be considered a feasible option for oocytes accumulation in PORs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03238833.

Decoy receptor 3 promotes cell adhesion and enhances endometriosis development.

Endometriosis is a multifactorial inflammatory disease with persistent activation of the nuclear factor-κB (NF-κB) signalling pathway. Aberrant adhesion of endometrium is the essential step in the progression of endometriosis, but the molecular mechanism of ectopic growth of endometrium is still unclear. Decoy receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by oestrogen, is able to activate focal adhesion kinase to promote cell adhesion. We found that DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt-NF-κB signalling pathway, and its expression level correlates positively with that of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and homing cell adhesion molecule (HCAM; CD44). In a multivariate regression model, DcR3 expression level was the most significant parameter associated with endometriosis severity. Knockdown of DcR3 not only downregulated the expression of ICAM-1 and HCAM, but also reduced cell adhesion and migration. In vivo investigation further showed that DcR3 promoted the growth and spread of endometrium, whereas knockdown of DcR3 by lentivirus-delivered short hairpin RNA inhibited ectopic adhesion of endometrium and abrogated endometriosis progression. These observations are in support of DcR3 playing a critical role in the pathogenesis of endometriosis, and the inhibition of DcR3 expression being a promising approach for the treatment of endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Using gonadotropin-releasing hormone agonist before frozen embryo transfer may improve ongoing pregnancy rates in hyperandrogenic polycystic ovary syndrome women.

Polycystic ovary syndrome (PCOS), affecting more than 5-10% of woman at reproductive childbearing age, is characterized by anovulation and hyperandrogenism. Frozen-thawed embryo transfer (ET) has been widely used for PCOS women to minimize the risk of ovarian hyperstimulation syndrome. However, the hyperandrogenic status of PCOS women deteriorates endometrial function, which has subsequently increased miscarriage rates in PCOS women. Therefore, we conducted this retrospective study to compare the pregnancy outcomes of hyperandrogenic PCOS women with (n = 29) and without (n = 31, controls) pretreatment of gonadotropin-releasing hormone (GnRH) agonist before frozen-thawed ET. We found that pretreatment with GnRH agonist before frozen-thawed ETs could not significantly improve the clinical pregnancy rate in these hyperandrogenic PCOS women. However, the ongoing pregnancy rate was significantly increased in women with GnRH agonist pretreatment (odds ratio: 3.98, 95% confidence interval: 1.12-14.20, p = 0.033). We concluded that androgen deprivation status due to pretreatment with GnRH agonist might improve the ongoing pregnancy rate in hyperandrogenic PCOS women. Additional large, well-designed prospective studies are worthwhile and necessary.

Postoperative maintenance levonorgestrel-releasing intrauterine system and endometrioma recurrence: a randomized controlled study.

BACKGROUND: According to 3 randomized trials, the levonorgestrel-releasing intrauterine system significantly reduced recurrent endometriosis-related pelvic pain at postoperative year 1. Only a few studies have evaluated the long-term effectiveness of the device for preventing endometrioma recurrence, and the effects of a levonorgestrel-releasing intrauterine system as a maintenance therapy remain unclear. OBJECTIVE: The objective of the study was to evaluate whether a maintenance levonorgestrel-releasing intrauterine system is effective for preventing postoperative endometrioma recurrence. STUDY DESIGN: From May 2011 through March 2012, a randomized controlled trial including 80 patients with endometriomas undergoing laparoscopic cystectomy followed by six cycles of gonadotropin-releasing hormone agonist treatment was conducted. After surgery, the patients were randomized to groups that did or did not receive a levonorgestrel-releasing intrauterine system (intervention group, n = 40, vs control group, n = 40). The primary outcome was endometrioma recurrence 30 months after surgery. The secondary outcomes included dysmenorrhea, CA125 levels, noncyclic pelvic pain, and side effects. RESULTS: Endometrioma recurrence at 30 months did not significantly differ between the 2 groups (the intervention group, 10 of 40, 25% vs the control group 15 of 40, 37.5%; hazard ratio, 0.60, 95% confidence interval, 0.27-1.33, P = .209). The intervention group exhibited a lower dysmenorrhea recurrence rate, with an estimated hazard ratio of 0.32 (95% confidence interval, 0.12-0.83, P = .019). Over a 30 month follow-up, the intervention group exhibited a greater reduction in dysmenorrhea as assessed with a visual analog scale score (mean ± SD, 60.8 ± 25.5 vs 38.7 ± 25.9, P < .001, 95% confidence interval, 10.7-33.5), noncyclic pelvic pain visual analog scale score (39.1 ± 10.9 vs 30.1 ± 14.7, P = .014, 95% confidence interval, 1.9-16.1), and CA125 (median [interquartile range], -32.1 [-59.1 to 14.9], vs -15.6 [-33.0 to 5.0], P = .001) compared with the control group. The number-needed-to-treat benefit for dysmenorrhea recurrence at 30 months was 5. The number of recurrent cases requiring further surgical or hormone treatment in the intervention group (1 of 40, 2.5%, 95% confidence interval, -2.3% to 7.3%) was significantly lower than that in the control group (8 of 40, 20%, 95% confidence interval, 7.6-32.4%; P = .031). CONCLUSION: Long-term maintenance therapy using a levonorgestrel-releasing intrauterine system is not effective for preventing endometrioma recurrence.