Whole exome sequencing reveals novel candidate variants for endometriosis utilizing multiple affected members in a single family.

BACKGROUND: Endometriosis is an estrogen-dependent, chronic inflammatory disease that affects 10% of women during the reproductive ages. Despite the estimated 50% heritability for the condition, only 26% was associated with common genetic variants. Thus, necessity of identifying rare variants for the missing heritability is implicated in the literature. Therefore, our study aimed to identify novel rare genetic variants involved in the pathogenesis of endometriosis utilizing a family of multiple affected members. METHODS: A family composed of four affected women along with their two unaffected mothers were recruited at a single gynecology and infertility clinic specialized in endometriosis. All patients presented with endometriomas, which was visualized by transvaginal ultrasonography. Two affected individuals had received laparoscopic endometrioma excision and therefore were diagnosed with recurrent disease. One mother had a history of endometrial serous adenocarcinoma (ESC) for which she underwent hysterectomy with bilateral oophorectomy. Three endometriosis cases were whole exome sequenced on Illumina NextSeq 550 platform with an average of 90% coverage. Candidate genes were confirmed by Sanger sequencing and followed-up with family segregation. RESULTS: Novel rare variants were identified in TNFRSF1B (NM_001066.3: c.1072G>A, p.(Ala358Thr)) and GEN1 (NM_001130009.3: c.1574C>T, p.(Ser525Leu)) as possible genetic causes of endometriosis. A third novel rare variant was identified in CRABP1 (NM_004378.3:c.54G>C, p.(Glu18Asp)) only on the mother with ESC history and her daughters. CONCLUSION: Novel candidate genetic variants that might contribute to endometriosis were suggested that need replication through independent cohorts or validation by functional studies. The family has also received genetic counseling and that the affected daughters are on clinical follow-up, accordingly.

A comparison of the effects of oral dydrogesterone and levonorgestrel-releasing intrauterine device on quality of life and sexual function in patients with abnormal uterine bleeding.

OBJECTIVE: The purpose of this study is to compare the effects of cyclic oral dydrogesterone treatment and levonorgestrel-releasing intrauterine device (LNG_IUD) on quality of life (QoL) and sexual function in patients diagnosed with abnormal uterine bleeding (AUB). STUDY DESIGN: The study was conducted at the University of Health Sciences Turkey Health Istanbul Kanuni Sultan Süleyman Training and Research Hospital, on 171 sexually active patients, aged 18-45, who were under a minimum of 6 months of treatment for AUB. 85 patients were treated with oral cyclic dydrogesterone, and 86 patients received LNG-IUD. Following a minimum of 6 months of treatment, these patients were recruited to the study and were asked to complete a 36-Item Short Form Survey (SF-36) and the Female Sexual Function Index (FSFI). RESULTS: When the FSFI scores of the patients were compared, it was observed that the total FSFI score was significantly higher in the cyclic dydrogesterone group (p < 0.05). Likewise, it was observed that sexual desire, arousal, and lubrication domains were significantly higher in the cyclic dydrogesterone group (p < 0.05). No significant differences were found between the treatment groups in 7 out of the 8 dimensions of SF-36. The energy/vitality dimension was found to be significantly higher in the cyclic dydrogesterone group. CONCLUSION: Total FSFI score, as well as sexual desire, arousal, and lubrication scores, were significantly higher in the cyclic dydrogesterone group compared to the LNG-IUD group indicating that cyclic dydrogesterone has a more positive impact on sexual function when compared to LNG-IUD.

Increased levels of nerve growth factor accompany oxidative load in recurrent pregnancy loss. Machine learning applied to FT-Raman spectra study.

The presented article is focused on developing and validating an efficient, credible, minimally invasive technique based on spectral signatures of blood serum samples in patients with diagnosed recurrent pregnancy loss (RPL) versus healthy individuals who were followed at the Gynecology department. A total of 120 participants, RPL disease (n = 60) and healthy individuals (n = 60), participated in the study. First, we investigated the effect of circulating nerve growth factor (NGF) in RPL and healthy groups. To show NGF's effect, we measured the level of oxidative loads such as Total Antioxidant Level (TAS), Total Oxidant Level (TOS), and Oxidative Stress Index (OSI) with Beckman Coulter AU system and biochemical assays. We find a correlation between oxidative load and NGF level. Oxidative load mainly causes structural changes in the blood. Therefore, we obtained Raman measurements of the participant's serum. Then we selected two Raman regions, 800 and 1800 cm-1, and between 2700 cm-1 and 3000 cm-1, to see chemical changes. We noted that Raman spectra obtained for RPL and healthy women differed. The findings confirm that the imbalance between reactive oxygen species and antioxidants has important implications for the pathogenesis of RPL and that NGF levels accompany the level of oxidative load in the RPL state. Biomolecular structure and composition were determined using Raman spectroscopy and machine learning methods, and the correlation of these parameters was studied alongside machine learning technologies to advance toward clinical translation. Here we determined and validated the development of instrumentation for the Analysis of RPL patients' serum that can differentiate from control individuals with an accuracy of 100% using the Raman region corresponding to structural changes. Furthermore, this study found a correlation between traditional biochemical parameters and Raman data. This suggests that Raman spectroscopy is a sensitive tool for detecting biochemical changes in serum caused by RPL or other diseases.

Blood serum lipid profiling may improve the management of recurrent miscarriage: a combination of machine learning of mid-infrared spectra and biochemical assays.

The present article is focused on developing and validating an efficient, credible, minimally invasive technique based on spectral signatures of blood samples of women with recurrent miscarriage vs. those of healthy individuals who were followed in the Department of Obstetrics and Gynecology for 2 years. For this purpose, blood samples from a total of 120 participants, including healthy women (n=60) and women with diagnosed recurrent miscarriage (n=60), were obtained. The lipid profile (high-density lipoprotein, low-density lipoprotein, triglyceride, and total cholesterol levels) and lipid peroxidation (malondialdehyde and glutathione levels) were evaluated with a Beckman Coulter analyzer system for chemical analysis. Biomolecular structure and composition were determined using an attenuated total reflectance sampling methodology with Fourier transform infrared spectroscopy alongside machine learning technology to advance toward clinical translation. Here, we developed and validated instrumentation for the analysis of recurrent miscarriage patient serum that was able to differentiate recurrent miscarriage and control patients with an accuracy of 100% using a Fourier transform infrared region corresponding to lipids. We found that predictors of lipid profile abnormalities in maternal serum could significantly improve this patient pathway. The study also presents preliminary results from the first prospective clinical validation study of its kind.

Comparison of enhanced recovery protocol with conventional care in patients undergoing urogynecological surgery.

OBJECTIVE: The impact of enhanced recovery after surgery (ERAS) protocol on postoperative outcomes after urogynecological surgery is yet to be a matter of investigation. This study sought to evaluate this issue by comparing the patients who had conventional or ERAS--guided perioperative care for several clinical end-points including ambulation, length of hospital stay (LOS), readmissions, and postoperative complications. MATERIALS AND METHODS: A total of 121 patients undergoing pelvic organ prolapse surgery were allocated to two study arms, ERAS protocol (Group E) or conventional care (Group C). Variables reflecting the restoration of appetite and bowel movements, bleeding events, other complications, LOS and readmissions were compared between the groups. RESULTS: The patients in Group C significantly received a more intensive intravenous fluid treatment compared to Group E (2,760 ± 656 vs. 1,045 ± 218 mL, P < 0.001). Time required for first flatus, first defecation, eating solid food, and ambulation (P < 0.001) were also longer in the former group of patients. Moreover, LOS was significantly reduced when the ERAS protocol was applied (2.5 ± 1.1 vs. 2.0 ± 0.6 days, P < 0.001). On the other hand, the two groups were similar with respect to the frequency of the postoperative complications, including surgical site infections, cardiovascular complications, non-specific abdominal pain, sub-ileus, blood loss and readmission rate. CONCLUSION: In our sample population, ERAS protocol led to early initiation of oral intake, early recovery of bowel function, early mobilization, and early discharge of patients without compromise in safety concerns after urogynecological surgery.

Pseudo-pseudo Meig's syndrome presenting as an acute surgical abdomen: A rare entity and review of the literature.

AIM: Pseudo-pseudo Meigs' syndrome is a rare entity of systemic lupus erythematosus, which is defined with the combination of pleural effusion, elevated serum CA-125 levels, and ascites. It has similar clinical aspects with gynecological malignancies which may lead gynecologists to perform unnecessary surgeries and lab workouts. This review seeks to point out the importance of diagnosing pseudo-pseudo Meig's syndrome (PPMS) and endeavors to inform gynecologists about the differential diagnoses. METHODS: This article includes a review of the literature on different cases of PPMS. We searched the PubMed database using the search terms in various combinations "Pseudo-pseudo Meig's syndrome," "Tjalma syndrome," and "SLE." RESULTS: According to the current literature, a majority of internal medicine specialists recognized this clinical condition in the past few years and discussed PPMS as a new onset of systemic lupus erythematosus. PPMS is one of the disregarding entities where gynecologists do not consider it as a differential diagnosis in case of less awareness. When a gynecologist evaluates ascites manifesting as acute abdomen; ectopic pregnancy, ovarian hyperstimulation syndrome, cyst rupture, and malignancy come to mind first. Four-thirds of those patients evaluated by gynecologists were performed hysterectomy leading to unnecessary interventions and economic burden on the health system. CONCLUSION: Although the mechanism is unrevealed and remains unclear, PPMS has been noticed in the literature for the past few years. In order to prevent unnecessary interventions, this syndrome should be considered as a differential diagnosis.

Could sestrin protein in serum be a new marker of oxidative stress in patients with polycystic ovary syndrome?

OBJECTIVE: PCOS (polycystic ovary syndrome) is one of the most common endocrinological disorders and it is the threshold of many systemic disorders. There are many studies in the literature on the mechanisms that cause increased oxidation in PCOS. Sestrin protein is known to regulate the oxidation. In this study, it is aimed to examine the changes in the level of sestrin protein in women with PCOS. METHODS: A total of 60 women participated the study, 30 of whom were diagnosed with PCOS according to the Rotterdam criteria. Also, 30 women were included in the study as the control group. Demographic information, biochemical analysis results, and sestrin levels of the patients in each group were compared. RESULTS: The median sestrin level was 6.2 ± 0.8 in the PCOS group and 3.38 ± 0.4 in the control group (p < 0.001). As a result of the evaluation made with ROC analysis, it is observed that serum sestrin levels may be meaningful in the diagnosis of polycystic ovary syndrome. The area under the curve (AUC) value for the 4.69 level was 99.4% (p < 0.001, 95% CI: 96.7% vs. 100%, sensitivity: 100%, specificity: 96.7%). CONCLUSIONS: Sestrin protein is associated with oxidative stress. Sestrin protein can be used as an indicator of increased oxidative stress in PCOS.

Evaluation of relationship between HbA1c levels and ovarian reserve in patients with type 1 diabetes mellitus.

In organ or non-organ-specific autoimmune disorders, human ovary is usually the target of the autoimmune attack. We aimed to demonstrate the correlation between ovarian reserve and DM1, based on the view that women with type-1 diabetes mellitus (DM1) will have lower AMH levels secondary to poor glycemic control and autoimmune attacks. Ovarian functions of 42 patients diagnosed with DM1 who use insulin and 65 healthy volunteers were analyzed. Basal hormone and AMH levels were measured during the follicular phase. Fasting and postprandial blood glucose concentrations, HbA1c and C-peptide levels were evaluated. The mean antral follicle count (AFC) was significantly lower in DM1 patients than in healthy controls (p = .001). The AMH levels were lower in women with DM1 than in the controls (p = .001). The HbA1c values of DM1 patients, who formed the study group, was significantly higher than the control group. Ovarian reserve that is evaluated with serum AMH level is affected by poor glycemic control in type 1 diabetes. Due to the time of the autoimmune damage in the ovaries and the observable effects of this damage, more comprehensive and longer-term studies are needed to be conducted for the follow-up of reproductive abnormalities.