Particulate matter exposure induces adverse effects on endometrium and fertility via aberrant inflammatory and apoptotic pathways in vitro and in vivo.

This study aimed to evaluate the adverse effects of particulate matter (PM) exposure on endometrial cells and fertility and to identify possible underlying mechanisms. Thirteen women (aged 15-52 years) were included in this study. Enrolled patients underwent laparoscopic surgery at Gangnam Severance Hospital between 1 January and 31 December 2021. For in vivo experiments, 36 female and nine male C57BL/6 mice were randomly divided into control(vehicle), low-dose(10 mg/kg/d), and high-dose exposure groups(20 mg/kg/d). PM was inhaled nasally for four weeks and natural mating was performed. NIST® SRM® 1648a was used for PM exposure. qRT-PCR, western blotting and Masson's trichrome staining were performed. PM treatment in human endometrial stromal cells induced inflammation with significant upregulation of IL-1ß, p-NF-kB, and p-c-Jun compared to those of controls. Additionally, PM treatment significantly increased apoptosis in human endometrial stromal cells by downregulating p-AKT and upregulating p-p53/p53, Cas-3, BAX/Bcl-2, p-AMPK, and p-ERK. After PM treatment, the relative expression of IL-1ß, IL-6, TNF-α, p-NF-κB, p-c-Jun, and p-Nrf2/Nrf2 significantly increased in murine endometrium compared to those of the controls. Expression of apoptotic proteins p53, p27, and Cas-3, was also significantly elevated in murine endometrium of the PM exposure group compared to that of the controls. A significant increase in expression of procollagen Ⅰ, and Masson's trichrome staining scores in the murine endometrium was noted after PM treatment. PM treatment significantly decreased ERα expression. After natural mating, all 3 female mice in the control group gave birth to 25 offspring (mean 8.1), whereas in the low-dose PM treatment group, two of three female mice gave birth to nine offspring (mean 4.5). No pregnant mice or offspring was present in the high-dose PM treatment group. PM exposure induces adverse effects on the endometrium through aberrant activation of inflammatory and apoptotic pathways and is associated with detrimental effects on murine fertility.

Effects of Hormone Replacement Therapy on Bone Mineral Density in Korean Adults With Turner Syndrome.

BACKGROUND: Turner syndrome (TS) is a common chromosomal abnormality, which is caused by loss of all or part of one X chromosome. Hormone replacement therapy in TS is important in terms of puberty, growth and prevention of osteoporosis however, such a study has never been conducted in Korea. Therefore, the purpose of our study was to determine relationship between the starting age, duration of estrogen replacement therapy (ERT) in TS and develop a hormone replacement protocol suitable for the situation in Korea. METHODS: This is retrospective study analyzed the medical records in TS patients treated at the Severance hospital, Yonsei University College of Medicine, Seoul, Korea from 1997 to 2019. Total of 188 subjects who had received a bone density test at least once were included in the study. Korean National Health and Nutrition Examination Survey (KNHANES) was used for achieving bone mineral density (BMD) of normal control group. Student's t-test, Mann-Whitney U test, ANOVA and correlation analysis were performed using SPSS 18.0. RESULTS: Each BMD measurement was significantly lower in women with TS than in healthy Korean women. Early start and longer duration of ERT is associated with higher lumbar spine BMD but not femur neck BMD. Femur neck BMD, but not lumbar spine BMD was significantly higher in women with mosaicism than 45XO group. CONCLUSION: Early onset and appropriate duration of hormone replacement therapy is important for increasing bone mineral density in patients with Turner syndrome. Also, ERT affects differently to TS patients according to mosaicism.

Comparison of Eastern and Western patients undergoing bariatric surgery at two US and Korean institutions: a retrospective analysis of differing bariatric patient populations.

BACKGROUND: Currently, there are differences in both demographics and indications for bariatric surgery between Eastern and Western countries. We compared postoperative outcomes between Korean and American bariatric programs in order to assess how bariatric surgery differently affects these populations. METHODS: We enrolled 540 patients who underwent bariatric surgery at University of California, Los Angeles (UCLA) and 85 patients who underwent surgery at Kosin University Gospel Hospital (KUGH) between January 2019 and December 2020. We compared demographics, complications, weight loss, and metabolic parameters between these groups. RESULTS: There was a difference in age between the UCLA and KUGH patient groups (44.3 years vs 37.6 years, P < 0.01). Frequencies of T2DM and OSA were also different (4.2% vs 50.6%, 34.1% vs 85.9% P < 0.01. Length of hospital stay varied (1.55 days vs 6.68 days, P < 0.01), but there was no difference in operating time and complications. There was no difference in percent of excess weight loss between the two groups at 6 months (29.7 vs 33.8, P = 0.13). Hepatic steatosis index (HSI) was higher in the UCLA group both before (54.2 vs 51.5, P < 0.01) and after (44.4 vs 40.0, P = 0.02) surgery. LSG was the most frequently performed operation, and robotic surgery and revisions were performed only in the UCLA program. CONCLUSION: There were differences in age, BMI, length of stay, and choice of operation between Korean and American bariatric patients. Also, there were differences in the degree of fatty liver disease using HSI and liver enzymes before and after surgery. There was no significant differences in operation time and complications. These findings suggest differences in bariatric practices and reactions to bariatric surgery in Eastern and Western settings.

Postoperative outcomes of ovarian preserving surgery in premenopausal women with adnexal torsion.

OBJECTIVE: We aimed to determine whether ovarian-preserving surgery for adnexal torsion helps preserve ovarian function without increasing the risk of postoperative complications. METHODS: We retrospectively evaluated 71 women who were surgically diagnosed with adnexal torsion between January 2015 and December 2019 at Severance Hospital, Yonsei University College of Medicine (ovarian preservation group, 56; oophorectomy, 15). Serum anti-Müllerian hormone (AMH) levels measured within 6 months before surgery were compared to levels measured 6-24 months after surgery. Surgical findings and postoperative complications were compared between the groups. RESULTS: There was a borderline significant difference in the decrease in serum AMH levels between the oophorectomy group and ovarian preservation group before and after surgery. There were no significant differences between the groups in terms of fever, infection, or duration of admission. Discoloration of the twisted ovary was found in 27.3% and 33.3% of the patients in the ovarian preservation and oophorectomy groups, respectively. There was no difference in the decrease in serum AMH levels between patients with and those without discoloration. CONCLUSION: Ovarian-preserving surgery may not increase postoperative complications in patients with adnexal torsion, even if a twisted mass is suspected to be necrotic. Moreover, the ovarian reserve may not be affected by torsion if the ovary is preserved. Conservative ovarian surgery can be safely performed to preserve the reproductive potential of women with adnexal torsion and cystic masses.

Formononetin Inhibits Progression of Endometriosis via Regulation of p27, pSTAT3, and Progesterone Receptor: In Vitro and In Vivo Studies.

OBJECTIVES: Formononetin is one of the phytoestrogens that functions like a selective estrogen receptor modulator (SERM). In this study, we evaluated the effects of formononetin on endometriosis progression in vitro and in vivo. MATERIALS AND METHODS: After pathological confirmation, 10 eutopic and ectopic endometria were collected from patients with endometriosis. Ten eutopic endometria samples were collected from patients who did not have endometriosis. To determine the cytotoxic dose and therapeutic dose of formononetin, the concentration of 70% of the cells that survived after formononetin administration was estimated using a Cell counting kit-8 (CCK 8) assay. Western blot analysis was used to determine the relative expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 in the eutopic endometria without endometriosis, eutopic endometria with endometriosis, and ectopic endometria with endometriosis as the formononetin concentration was increased. We confirmed the effect of formononetin on apoptosis and migration in endometriosis using fluorescence-activated cell sorting (FACS) and wound healing assays, respectively. A mouse model of endometriosis was prepared using a non-surgical method, as previously described. The mice were intraperitoneally administered formononetin for four weeks after dividing them into control, low-dose formononetin (40 mg/kg/day) treatment, and high-dose (80 mg/kg/day) formononetin treatment groups. All the mice were euthanized after formononetin treatment. Endometriotic lesions were retrieved and confirmed using hematoxylin and eosin (H&E) staining. Immunohistochemical (IHC) staining of p27 was performed. RESULTS: We set the maximum concentration of formononetin administration to 80 µM through the CCK8 assay. Based on formononetin concentration, the expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 proteins were measured using Western blot analysis (N = 4 per group). The expression level of pERK, p27, and pSTAT3 in eutopic endometrium with endometriosis tended to decrease with increasing formononetin concentration, and a significant decrease was noted at 80 µM. The expression of p27 in ectopic endometrium with endometriosis was also significantly decreased at 80 µM of formononetin. FACS analysis revealed that formononetin did not significantly affect apoptosis. In the wound healing assay, formononetin treatment revealed a more significant decrease in the proliferation of the eutopic endometrium in patients with endometriosis than in the eutopic endometrium without endometriosis. Relative expression of sex hormone receptors decreased with increasing formononetin doses. Although no significant differences were observed in the ER, PR-A, ERß/ERα, and PR-B/PR-A, significant down-regulation of PR-B expression was noted after formononetin treatment at 80 µM. In the in vivo study, endometriotic lesions in the formononetin-treated group significantly decreased compared to those in the control group. The relative expression of p27 using IHC was highest in the control group and lowest in the high-dose formononetin treatment group. CONCLUSIONS: Formononetin treatment was shown to inhibit the proliferation of eutopic and ectopic endometria in patients with endometriosis through the regulation of p27, pSTAT3, and PR-B. In an endometriosis mouse model, formononetin treatment significantly reduced the number of endometriotic lesions with decreased p27 expression. The results of this study suggest that formononetin may be used as a non-hormonal treatment option for endometriosis.

Transcriptomic patterns in early-secretory and mid-secretory endometrium in a natural menstrual cycle immediately before in vitro fertilization and embryo transfer.

OBJECTIVE: This study aimed to evaluate the endometrial transcriptomic patterns in the early secretory phase (ESP) and mid-secretory phase (MSP) of the natural menstrual cycle before in vitro fertilization and embryo transfer (IVF-ET). METHODS: Thirty patients whose endometrial tissues were obtained from the ESP or MSP of a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle days 16-18) or MSP (cycle days 19-21), according to the noyes criteria. The patients were divided into two groups depending on the IVF-ET outcome: pregnant (n=14; 7 in ESP and 7 in MSP) or non-pregnant (n=16; 8 in ESP and 8 in MSP). Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter (NanoString Technologies, Seattle, WA, USA) data for both the pregnant and non-pregnant groups. RESULTS: Thirteen DEGs in the pregnant group and 11 DEGs in the non-pregnant group were identified in the MSP compared to those in the ESP. In both groups, adrenoceptor alpha 2A, interleukin 1 receptor-associated kinase 2, a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1, integrin subunit beta 3, transmembrane protein 252 (TMEM252), huntingtin associated protein 1, C2 calcium-dependent domain containing 4A, and integrin subunit alpha 2 were upregulated in the MSP, compared to the ESP. TMEM37, galactosidase beta 1 like 2, Rho family GTPase 3, and cytochrome P450 family 24 subfamily A member 1 were upregulated in the MSP only in the pregnant group. ADAMTS8 was downregulated and monoamine oxidase A was upregulated in the MSP only in the non-pregnant group. CONCLUSION: Transcriptomic patterns in the endometrium immediately before IVF-ET appear to differ according to the IVF-ET outcome. These novel DEGs, which have not been previously studied, may have functional significance during the window of implantation and serve as potential biomarkers of endometrial receptivity.

Human Endometrium Derived Induced Pluripotent Stem Cells Are Amenable to Directed Erythroid Differentiation.

BACKGROUND: A protocol for using human endometrium derived induced pluripotent stem cells (iPSCs) to derive hematopoietic and erythroid lineages will be elaborated, through a two-phase culture system. METHODS: Discarded endometrial tissues were obtained from women receiving hysterectomy in their 4th to 5th decade due to benign uterine conditions. pCE-Sox2, Oct4, Klf4, L-Myc and Lin28 episomal vectors were used to electrotransfect the endometrial stromal cells. The first 8 days involves commitment to hematopoietic stem cells through embryoid body with robust expansion on murine bone marrow stromal cells. The second phase involves feeder free conditions with hydrocortisone, stem cell factor, interleukin-3, and recombinant EPO. After 22 days of feeder free culture, the expression profiles of CD235a+, CD34+, CD43+ and CD 71+ were analyzed by flow cytometry and Wright-Giemsa staining for differential counting. The oxygen carrying capacity of cultured RBCs was measured using a hemoxanalyser. RESULTS: As a result of inducing these cells via co-culture with murine stromal fibroblasts, all endometrium derived iPSCs were differentiated into erythroblasts with a stable yield of approximately 80% for polychromatic and orthochromatic normoblasts. The protocol for complete induction of erythroid lineage cells starting from human endometrial tissue via iPS cells has been optimized. CONCLUSION: Successful directed erythroid differentiation has occurred from human endometrium-derived iPS cells. A comprehensive process of actually deriving iPS cells using discarded surgical hysterectomy specimens to the erythroid fate has significance in that the scope of using human iPSC cell lines for tissue regeneration could be expanded in the future.

Melatonin Protects Bone Microarchitecture against Deterioration due to High-Fat Diet-Induced Obesity.

BACKGROUND: We evaluated the protective effects of melatonin against high-fat diet (HFD)-induced deterioration of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Four-week-old male C57BL/6 mice were divided into control (chow diet group), HFD, and HFD + melatonin-administered groups. Mice were sacrificed after 14 weeks, and the right femur was extracted. The microskeletal structure of the femur was analyzed using SkyScan1173 (version 1.6). A 3-dimensional image was reconstructed using the Nrecon (version 1.7.0.4) program. RESULTS: Bone volume (BV) was significantly increased in the HFD group compared with that in the normal diet group, and that of the melatonin group also increased significantly compared with BV of the normal diet group (p<0.05). Percent BV/total volume [TV] and bone surface/BV were significantly higher in both the HFD and melatonin groups than in the normal diet group (p<0.05), and the melatonin group had the highest BV/total volume (TV). BMD was lower in the HFD than in the normal diet group and was the highest in the melatonin group. CONCLUSIONS: This study shows that melatonin inhibited the deterioration of microarchitecture induced by a HFD. A better understanding of the protective effect of melatonin on bone microarchitecture and mechanisms could provide fracture prevention for people who are obese.

Prediction of type 2 diabetes using genome-wide polygenic risk score and metabolic profiles: A machine learning analysis of population-based 10-year prospective cohort study.

BACKGROUND: Previous work on predicting type 2 diabetes by integrating clinical and genetic factors has mostly focused on the Western population. In this study, we use genome-wide polygenic risk score (gPRS) and serum metabolite data for type 2 diabetes risk prediction in the Asian population. METHODS: Data of 1425 participants from the Korean Genome and Epidemiology Study (KoGES) Ansan-Ansung cohort were used in this study. For gPRS analysis, genotypic and clinical information from KoGES health examinee (n = 58,701) and KoGES cardiovascular disease association (n = 8105) sub-cohorts were included. Linkage disequilibrium analysis identified 239,062 genetic variants that were used to determine the gPRS, while the metabolites were selected using the Boruta algorithm. We used bootstrapped cross-validation to evaluate logistic regression and random forest (RF)-based machine learning models. Finally, associations of gPRS and selected metabolites with the values of homeostatic model assessment of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) were further estimated. FINDINGS: During the follow-up period (8.3 ± 2.8 years), 331 participants (23.2%) were diagnosed with type 2 diabetes. The areas under the curves of the RF-based models were 0.844, 0.876, and 0.883 for the model using only demographic and clinical factors, model including the gPRS, and model with both gPRS and metabolites, respectively. Incorporation of additional parameters in the latter two models improved the classification by 11.7% and 4.2% respectively. While gPRS was significantly associated with HOMA-B value, most metabolites had a significant association with HOMA-IR value. INTERPRETATION: Incorporating both gPRS and metabolite data led to enhanced type 2 diabetes risk prediction by capturing distinct etiologies of type 2 diabetes development. An RF-based model using clinical factors, gPRS, and metabolites predicted type 2 diabetes risk more accurately than the logistic regression-based model. FUNDING: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2019M3E5D1A02070863 and 2022R1C1C1005458). This work was also supported by the 2020 Research Fund (1.200098.01) of UNIST (Ulsan National Institute of Science & Technology).

Kimchi improves irritable bowel syndrome: results of a randomized, double-blind placebo-controlled study.

Background: Irritable bowel syndrome (IBS) can be caused by abnormal bowel movements, altered brain-gut axis, gut microbiota change, and low levels of inflammation or immune activation. The intake of food containing much fiber and lactic acid bacteria (LABs) can alleviate IBS. Objective: This study was undertaken to confirm the alleviative effect of kimchi on symptoms of IBS. Design: Three types of kimchi (standard kimchi, SK; dead nano-sized Lactobacillus plantarum nF1 (nLp) added to standard kimchi, nLpSK; or functional kimchi, FK) were given to 30 individuals in each of three groups, that is, the SK group (n = 30), the nLpSK group (n = 30), or the FK group (n = 30) at 210 g a day for 12 weeks. Food intake records, serum levels of inflammatory factors, fecal levels of harmful enzymes, and microbiome changes were investigated over the 12-week study period. Results: After intervention, dietary fiber intake was increased in all groups. Typical IBS symptoms (abdominal pain or inconvenience, desperation, incomplete evacuation, and bloating), defecation time, and stool type were also improved. In serum, all groups showed reductions in tumor necrosis factor (TNF)-α (P < 0.001) levels. In addition, serum IL-4 (P < 0.001), IL-10 (P < 0.001), and IL-12 (P < 0.01) were significantly reduced in the nLpSK and FK groups, and serum monocyte chemotactic protein (MCP)-1 (P < 0.05) was significantly reduced in the nLpSK group. Furthermore, activities of fecal ß-glucosidase and ß-glucuronidase were significantly decreased in all three groups, and these reductions were greatest in the nLpSK group. Gut microbiome analysis showed that kimchi consumption increased Firmicutes populations at the expense of Bacteroidetes and Tenericutes populations. In addition, the Bifidobacterium adolescentis population increased significantly in the FK group (P = 0.026). Conclusion: Kimchi intake helps alleviate IBS by increasing dietary fiber intake and reducing serum inflammatory cytokine levels and harmful fecal enzyme activities. Notably, nLp improved the immune system, and several functional ingredients in FK promoted the growth of Bifidobacterium adolescentis in gut.

BRAK and APRIL as novel biomarkers for ovarian tumors.

Aims: To evaluate BRAK and APRIL in serum samples from healthy patients and an ovarian tumor group and analyze their effective value as biomarkers. Materials & methods: BRAK and APRIL were measured in 197 serum samples including 34 healthy controls, 48 patients with benign ovarian cysts and 115 patients with ovarian cancer, and the best statistical cut-off values were calculated. Then, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value for selected cut-off points were assessed. Results: The healthy control group had statistically significant higher BRAK and lower APRIL than the ovarian tumor group. BRAK was excellent for differentiating healthy patients from patients with ovarian tumors, showing area under the receiver operating characteristic curve 0.983, 98.16% sensitivity and 100% specificity. When BRAK was combined with APRIL and CA-125, it also played a role in distinguishing benign cysts from malignancies with area under the curve 0.864, 81.74% sensitivity and 79.17% specificity. Conclusions: BRAK and APRIL are good candidates for ovarian tumor biomarkers.

Identification of Single Nucleotide Polymorphisms as Biomarkers for Recurrent Pregnancy Loss in Korean Women.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls. METHODS: In 53 women of RPL group and 50 controls, the genetic analysis was performed. The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed. RESULTS: The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively). CONCLUSION: There is a significant association between the risk of RPL and miR-449b/TNF-α combination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.

Delayed postpartum regression of theca lutein cysts with maternal virilization: A case report.

Theca lutein cysts are rare, benign lesions responsible for gross cystic enlargement of both ovaries during pregnancy. This condition is also termed hyperreactio luteinalis. Elevated human chorionic gonadotropin (hCG) levels or states of hCG hypersensitivity seem to promote these changes, which in up to 30% of patients produce clinical signs of hyperandrogenism. Given the self-limiting course of theca lutein cysts, which are subject to spontaneous postpartum resolution, conservative treatment is the mainstay of patient management. Described herein is a rare case of theca lutein cysts with maternal virilization that failed to regress by 9 months after childbirth. Surgical intervention was eventually undertaken, necessitated by adnexal torsion.

Cytokines in culture media of preimplantation embryos during in vitro fertilization: Impact on embryo quality.

Cytokine support of embryonic development includes promotion of implantation and protection of blastomeres from cell stress and apoptosis. Correlations between embryo quality and concentrations of specific cytokines in culture media of human embryos have been investigated for many years. The aim of this study was to assess the concentrations of cytokines in preimplantation embryo culture media and to investigate their relationships with embryo quality and in vitro fertilization (IVF) outcomes. Seventy-two samples were obtained from 39 infertile couples undergoing IVF or intracytoplasmic sperm injection treatment between October 2018 and May 2019. Each embryo was cultured separately, and the embryo culture medium was collected 72 h after fertilization. Before embryo transfer on day 3, a morphological evaluation of each embryo was performed. Cytokine concentrations of each culture medium were analyzed for 23 selected cytokines using the Multiplex Cytokine/Chemokine Panel II Assay (Merck Millipore®). The results were categorized into two groups (top-quality and non-top-quality embryos). The median age of the 39 patients was 34 years. Nine of 23 cytokines were quantified and compared between the top-quality embryo group and non-top-quality embryo group. Among the nine cytokines, CCL15, CCL27, and CXCL-12 were significantly elevated in the top-quality embryo group. These results suggested that specific cytokines measured in human embryo culture media can be used to predict embryo quality and IVF outcomes.

Vulvar Crohn's disease in an adolescent diagnosed after unsuccessful surgical treatment.

BACKGROUND: This case report presents a case of Vulvar Crohn's disease (VCD) in an adolescent, that is an uncommon manifestation of Crohn's disease (CD) without gastrointestinal symptoms. Before treating CD itself with proper medication, vulvar abscess continued to recur without improvement. CASE PRESENTATION: We report the case of an 18-year-old woman with VCD. After treatment with azathioprine 50 mg daily and mesalazine 1 g three times daily, vulvar lesions resolved after 6 weeks. We collected electronic medical data on patient characteristics, and evaluated findings of physical examinations, pelvic MRI, and biopsy specimen obtained from gastroduodenoscopy/colonoscopy. CONCLUSIONS: VCD is a rare manifestation of CD that may be misdiagnosed in the absence of gastrointestinal symptoms leading to delayed treatment. If a patient has an unexplained vulvar inflammatory lesion and with repeated failed surgical treatment, gynecologists should consider the possibility of a VCD.

MicroRNA-139-5p Regulates Fibrotic Potentials via Modulation of Collagen Type 1 and Phosphorylated p38 MAPK in Uterine Leiomyoma.

PURPOSE: This study aimed to elucidate whether microRNA-139-5p is involved in the pathogenesis of uterine leiomyoma. MATERIALS AND METHODS: Human leiomyoma and matched human smooth muscle samples were obtained from 10 women who underwent hysterectomy for uterine leiomyoma. MicroRNA (miRNA) expression was analyzed by quantitative real-time polymerase chain reaction. To assess the effects of miR-139-5p on cultured leiomyoma cells, cell migration, collagen gel contraction, wound healing, and the expression levels of hallmark proteins were evaluated in cells transfected with a miR-139-5p mimic. RESULTS: The expression of miR-139-5p was significantly lower in leiomyoma tissues than in matched smooth muscle tissues. Restored miR-139-5p expression in miR-139-5p mimic-transfected human leiomyoma cells resulted in decreased contractility of the ECM and cell migration. In addition, upregulation of miR-139-5p decreased the protein expression of collagen type 1 and phosphorylated p38 MAPK. CONCLUSION: Expression of miR-139-5p is downregulated in leiomyoma cells and modulation of miR-139-5p may be involved inthe pathogenesis of leiomyomas through the regulation of collagen type 1 and phosphorylated p38 MAPK. Therefore, miR-139-5p is a potential therapeutic target for leiomyoma.

Predictive Factors of Conception and the Cumulative Pregnancy Rate in Subfertile Couples Undergoing Timed Intercourse With Ultrasound.

The aim of this study was to determine predictive factors for pregnancy and assess the cumulative pregnancy rate (CPR) and live birth rate (CLBR) in subfertile couples undergoing timed intercourse (TI) using ultrasound. This retrospective cohort study included 285 women (854 cycles) who started TI with ultrasound between January 2017 and October 2019. The overall clinical pregnancy rate was 28.1% (80/285) per couple and 9.4% (80/854) per cycle. Pregnant women had a higher body mass index (BMI), higher percentage of irregular menstrual cycles, a shorter duration of subfertility, lower serum follicle-stimulating hormone levels, and higher anti-Müllerian hormone levels than non-pregnant women. A longer duration of subfertility (≥24 months vs. <12 months; odds ratio: 0.193; 95% confidence interval: 0.043-0.859) and endometriosis (vs. ovulatory factors; odds ratio: 0.282; 95% confidence interval: 0.106-0.746) as causes of subfertility were unfavorable factors that independently affected clinical pregnancy. In subgroup analysis, old age ≥ 35 years [vs. < 35 years; odds ratio: 0.279; 95% confidence interval: 0.083-0.938), a longer duration of infertility ≥24 months (vs. <24 months; odds ratio: 0.182; 95% confidence interval: 0.036-0.913) and a higher BMI ≥ 25 kg/m2(vs. >25 kg/m2; odds ratio: 3.202; 95% confidence interval: 1.020-10.046) in couples with ovulatory factor and a longer duration of infertility ≥24 months (vs. <24 months; odds ratio: 0.185; 95% confidence interval: 0.042-0.819) in couples with non-ovulatory factors were significant independent predictive factors for pregnancy. No significant differences were found in the cycle characteristics between pregnant and non-pregnant women. The CPR substantially increased during the first three cycles and significantly increased until the sixth cycle. No significant increase was observed in the CPR after the sixth cycle. The CLBRs substantially increased during the first three cycles and significantly increased until the fourth cycle. No significant increase was observed in the CLBRs after the fifth cycle. When comparing CPRs and CLBRs according to subfertile causes, CRPs was significantly different and CLBRs was different with borderline significance. Our findings may indicate that women with a longer duration of subfertility or subfertility due to endometriosis have poor outcomes during TI with ultrasound. Women who failed to achieve conception by the fourth or fifth cycle of TI with ultrasound may be encouraged to consider advancing to the next treatment strategy.