Relationship Between Recurrent Pregnancy Loss With Unknown Etiology and Endoplasmic Reticulum Stress.

INTRODUCTION: Recurrent pregnancy loss (RPL) is characterized by consecutive pregnancy losses before 20 weeks of gestation, with evolving definitions necessitating adjustments to prevent delays in couples' evaluation. Limited etiological data on RPL prompts comprehensive evaluations, often yielding no pathological findings. Emerging research implicates endoplasmic reticulum (ER) stress in various reproductive processes, yet its association with RPL remains understudied. AIM: To evaluate ER stress in patients with RPL with unknown etiology by determining the plasma concentration of X-box binding protein-1 (XBP-1). MATERIALS AND METHODS: A total of 45 patients aged 18 to 35 years with at least two pregnancy losses with unknown etiology before the completion of 20 weeks of gestation between March 2020 and September 2020 were included in the study group. The control group consisted of 45 healthy women with at least two previous live births, no pregnancy-associated complications, and no history of pregnancy loss or infertility. The XBP-1 levels were determined from serum samples. Statistical analyses assessed differences between groups, and receiver operating characteristic (ROC) curve analysis determined XBP-1's predictive value for RPL. RESULTS: The mean XBP-1 concentration in the RPL group was significantly higher than in the control group (p < 0.001). The mean values were 2243.65 ± 9425.27 pg/mL and 1196.32 ± 4378.81 pg/mL, respectively. The use of XBP-1 levels for the prediction of RPL was evaluated. In an ROC curve analysis, the area under the curve was found to be 87% (95% CI: 80% to 94.8%). The specificity was 78%, the sensitivity was 88%, the positive likelihood ratio (LR) was 4, the negative LR was 0.15, the positive predictive value was 80%, and the negative predictive value was 87% for the cut-off XBP-1 level at 1364.68 pg/mL. CONCLUSION: This study highlights the potential role of ER stress in RPL and proposes XBP-1 as a predictive biomarker for pregnancy loss. Understanding ER stress mechanisms in RPL could inform diagnostic and therapeutic strategies. Further research is essential to validate these findings and explore their clinical implications.

Effects of Dienogest Therapy on Endometriosis-Related Dysmenorrhea, Dyspareunia, and Endometrioma Size.

INTRODUCTION: Endometriosis is an estrogen-dependent chronic inflammatory disease that is defined by the presence of endometrial-like tissue outside of the uterus. The most common localization is the ovaries, and endometriosis in this location is then called an endometrioma. According to the European Society of Human Reproduction and Embryology (ESHRE) (2022) guidelines, the most commonly prescribed treatments for endometriosis include drugs that alter the hormonal milieu. Dienogest is a new generation of progestin used in the treatment of endometriosis. The aim of this study was to assess the effect of Dienogest treatment on endometrioma size and endometriosis-related pain symptoms over a six-month follow-up period. METHODS: This prospective observational study was conducted at a tertiary clinic in Turkey between March 2020 and March 2021. Here, 64 patients aged 17-49 years with unilateral or bilateral endometriomas without any hormone-dependent cancers and any medical conditions contraindicating the onset of hormonal treatment, such as active venous thromboembolism, previous or current cardiovascular disease, diabetes with cardiovascular complications, current severe liver disease, and not being pregnant, were included. Endometrioma sizes were determined by transvaginal ultrasonography (TVUS). Dysmenorrhea and dyspareunia symptoms were evaluated using the visual analogue scale (VAS). Patients received Dienogest 2 mg/day continuously for six months. At the three- and six-month follow-ups, the patients were re-evaluated. RESULTS: The mean endometrioma size decreased significantly from an initial measurement of 44.0 ± 13 mm to 39.5 ± 15 mm at three months and to 34.4 ± 18 mm at the six-month follow-up. The mean dysmenorrhea VAS scores before treatment, at the three-month follow-up, and at the six-month follow-up were 6.9 ± 2.6, 4.3 ± 2.8, and 3.8 ± 2.7, respectively. Dysmenorrhea VAS scores decreased significantly over the first three months (p<0.01). Similarly, the mean VAS score for dyspareunia decreased at three and six months compared with the pretreatment value (p<0.01). CONCLUSION: This study shows that dienogest treatment reduced the symptoms of dysmenorrhea and dyspareunia and the size of endometriomas. However, the main significant decrease in dysmenorrhea and dyspareunia symptoms was noted in the first three months, making it a good treatment option, especially in young patients with a fertility wish.

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Evaluating the effects of the COVID-19 pandemic on the physical and mental well-being of obstetricians and gynecologists in Turkey.

OBJECTIVE: To apply online surveying to assess the general physical and mental well-being of obstetricians/gynecologists (OB/GYNs) working in COVID-19 designated hospitals in Turkey. METHODS: A prospective survey-based study using an online survey platform. Three hundred participants working at COVID-19 designated hospitals in Turkey identified from a hospital database were sent a link to the survey by email between April 29 and May 20, 2020. RESULTS: A total of 253 OB/GYNs (31 consultants and 222 residents) completed the survey, for a response rate of 84.3%. Of respondents, 191 (76.4%) were anxious about coming into contact with pregnant women infected with COVID-19. 74.4% stated that they were afraid of getting sick. 64.8% reported that they had fallen into despair at times because of the pandemic. 66.5% stated that their family lives were affected. 72.4% started living separately from their families because of the pandemic. CONCLUSION: Despite the difficulties in patient care during the pandemic, OB/GYNs continued providing for their patients, which reflected positively on their perceptions of the profession. The importance of trust in the national healthcare system, presence of adequate PPE, finding a suitable coping mechanism, and family support were essential for Turkish OB/GYNs during the COVID-19 pandemic. ClinicalTrials.gov identifier: NCT04327531. Turkish obstetricians/gynecologists reported anxiety and stress caused by the current situation and future implications of the COVID-19 pandemic.

Micronutrients in COVID-19 Positive Pregnancies.

Pregnant women are considered among the high-risk population for COVID-19. Therefore, research for methods of treatment and prevention of COVID-19 positive pregnancies carries an importance. The aim of this study was to measure serum 25(OH)D, vitamin B12, and zinc levels in COVID-19 positive pregnant women to evaluate the role of these micronutrients in treatment and prevention. A total of 44 COVID-19 positive pregnant women who were hospitalized and treated at a tertiary clinic were included in this study. The mean serum 25(OH)D level was measured to be 9.70 ± 59.14. The mean serum zinc level was 62.58 ± 2.63, and the mean serum vitamin B12 level was 295.55 ± 302.48. All these variables were significantly lower than the accepted cut-off values (p < 0.001). These low values might have contributed to a deficiency in their immune response and thus made these patients susceptible to COVID-19 infection. Supplementation of micronutrients during the pandemic could be beneficial during pregnancy for prevention.