It is crucial to gain a better understanding of threatened and recurrent miscarriages, including the existing knowledge and unknowns, as well as to discuss medical approaches and assess the situation. These issues are outstanding problems, causing significant physical and emotional burdens on women and their families, not only in Turkey but also worldwide. This article aims to explore the topic of miscarriages, including the implications, challenges, and potential therapeutic approaches in Turkey. Nineteen statements were presented to 6 Turkish perinatologists and obstetricians and gynecologists to evaluate the management of threatened and recurrent miscarriage and to compare the results with literature recommendations in an expert opinion meeting. Turkish perinatologists and obstetricians & gynecologists provided their responses using a 5-point Likert scale and discussed every statement. Progesterone use, particularly oral dydrogesterone, was supported by most of the experts. Opinions varied on the preference for dydrogesterone in recurrent miscarriage treatment. Experts unanimously agreed on the efficacy and safety of dydrogesterone and its recommendation in guidelines for threatened and recurrent miscarriage. Regarding progesterone therapy, vaginal progesterone was not associated with an increased rate of live births. Side effects of vaginal and oral micronized progesterone were acknowledged, and compliance with oral progesterone treatment was generally agreed upon. Dydrogesterone activity and effectiveness in threatened miscarriage received positive responses, while opinions on its effectiveness in recurrent miscarriage were divided. The loading dose of dydrogesterone and the practice of checking blood progesterone levels had different opinions among experts.This manuscript provides valuable insights in the management of threatened and recurrent miscarriages, highlighting the role of progesterone therapy, specifically dydrogesterone, and the need for adherence to relevant guidelines. Further research and a national Turkish guideline are warranted to address areas of uncertainty and optimize the management of these conditions.
Objective: This study aimed to evaluate the effect of the rate of decline in serum estradiol (E2) levels between hCG injection and the day of embryo transfer (ET) on the success of assisted reproductive technology (ART) in women with infertility of different etiologies.
Materials and methods: Women 20-45 years of age who underwent a standard GnRH antagonist or long agonist protocol and fresh ET during day 3 of their first ART cycle were included. Group 1 was diagnosed with low ovarian reserve, group 2 comprised high ovarian responders, and group 3 consisted of normal responders. Both groups were divided into four subgroups according to the decrease in E2 levels between the day of hCG injection and the day of ET. Subgroup A patients had a decrease of <20%, subgroup B a decrease of 20-40%, subgroup C a decrease of 41-60%, and subgroup D a decrease >60%. The primary outcome measure was the effect of an E2 decline, based on the measurement of E2 on the day of hCG administration and day of ET, on the implantation rate. The secondary outcome was the change in E2 values in these three groups.
Results: The study was conducted on 1.928 women. Of these, 639 were poor responders (group 1), 502 were high responders (group 2), and 787 women had a normal ovarian response (group 3). Patients with a 60% decrease in their E2 levels on the ET day after hCG had a lower live birth rate (LBR) and higher miscarriage rate (MCR), except normoresponders, in whom a similar decline was significant only with respect to MCR.
Conclusion: We indicate that high ovarian responders who underwent fresh ET cycles with a 60% decrease in their E2 levels on the ET day after human chorionic gonadotropin had lower LBRs and higher miscarriage. However, in normoresponder women, this decline was only significant in miscarriage.
Objective: Adenomyosis is a benign uterine illness characterized by endometrial gland and stromal invasion into the myometrium. Acetyl-CoA acetyltransferase 1 (ACAT1) is an enzyme localized in mitochondria that is involved in ketogenesis and ketolysis processes by reversibly catalyzing the formation of acetoacetyl-CoA from two acetyl-CoA molecules. The current study investigated the expression of the ACAT1 molecule in tissue samples of patients diagnosed with adenomyosis and healthy endometrial tissues. It is aimed to determine the differences in ACAT1 gene expression and in this way to discover the first information about the role of ACAT1 in the development and molecular mechanism of adenomyosis.
Materials and methods: In the current retrospective study, formalin-fixed paraffin-embedded archival tissues were employed. A total of 76 patient samples were included in the study. Of these samples, 28 are adenomyotic tissue (Group I), 30 are eutopic endometrial tissue (Group II), and 18 are the Control Group. In these groups, the expression levels of the ACAT1 gene were determined by the reverse transcription-polymerase chain reaction method.
Results: When the expression results of the ACAT1 gene were evaluated, statistically significant differences were found between the groups (p<0.05). There was a difference between Group I-Group II and Group I-Control Group regarding the ACAT1 gene. No statistically significant change was observed between Group II and Control Group. It is a remarkable finding that the expression of ACAT1 in adenomyosis tissue is decreased compared with both eutopic endometrium and control groups tissues.
Conclusion: The results suggest that ACAT1 may be associated with the molecular pathogenesis of adenomyosis.
Objective: This study aimed to investigate the efficacy of metformin and ganirelix on subcutaneous endometriotic tissues created in an experimental mouse model.
Materials and methods: Five groups were formed with eight animals in each group. One of the groups was set as the control group. Endometriotic lesions were created by transplanting 40 mouse autologous endomyometrial tissues into the mouse subcutaneous tissue to a highly vascular surface. Gene expression analyzes of tissues were performed as HIF-1α, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7α, and WNT10α gene analyzes. Drug effects were examined by histological examination. HIF1a and WNT2 protein expressions were examined immunohistochemically. Gene expression coefficients of control, metformin day 1 (Met1g), metformin day 7 (Met7g), ganirelix day 1 (Gnx1g), and ganirelix day 7 (Gnx7g) groups are shown in tables. Data are presented as mean and standard error.
Results: Beclin2 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and general 7th day groups were found to have significantly decreased compared with the control group coefficient. Beclin1 gene expression coefficients of metformin 1st day, metformin 7th day, ganirelix 1st day, and genirelix 7th day groups were found to have significantly decreased compared with the control group coefficient. LC3BII gene expression coefficients of metformin 1st day and metformin 7th day groups were found to have significantly decreased compared with LC3BII gene expression coefficients of control, genirelix 1st day, and genirelix 7th day groups. These findings were supported by histological and immunohistochemical staining.
Conclusion: These genes are actively involved in the autophagy pathway, and we think that the use of metformin in endometriosis might create an autophagy-based suppression mechanism.
Objective: To compare the short-term results of classic single-layer uterine closure and double-layer purse-string uterine closure (Turan technique) techniques in cesarean section in terms of the incidence of ischiocele formation.
Materials and methods: This was a prospective randomized controlled trial study. Participants undergoing first-time cesarean delivery were randomized into two groups. Fifty-eight participants were included in the double-layered uterine closure group (study group), while 53 participants were randomized into the classical single-layered uterine closure group (control group). For comparison of isthmocele formation, transvaginal ultrasound examination was planned in all patients 6 weeks after surgery. The operation data,the formation of isthmocele, its dimensions and volume were recorded.
Results: A total of 111 women were included in the study. The incidence of ischiocele at 6 weeks after birth was not significantly different between the groups (p=0.128). Isthmosel was detected in 20.8% of single-layer closures, and this rate was determined as 10.3% in the purse technique. In the Kerr incision made during surgery, the uterine incision size did not differ in either group, but the uterine incision length after suturing was significantly smaller in the purse technique compared with the other group (p<0.001).
Conclusion: The incidence of ischiocele formation after cesarean section and the depth of the ischiocele was independent of the uterotomy closure technique.
Objective: Gynecological malignancies are significant causes of mortality and morbidity in women worldwide. Although surgery is an important treatment method, both the extent of the surgery and the factors related to the patient affect postoperative processes. The National Early Warning Score 2 (NEWS2) is a simple, inexpensive, and safe early warning score developed in 2012 and updated in 2017. Although it is not commonly used in surgical patients, its use in patients who will undergo major surgery may provide insights about the postoperative process. This study investigates the importance of NEWS2 and its relationship in patients with for major gynecologic oncology surgery.
Materials and methods: Forty-four patients with gynecologic malignancies scheduled for major abdominal surgery were included in this study. Patients with a NEWS-2 score of <3 were included in group 1, and patients with a NEWS-2 score of more than 3 were included in groups 2. NEWS2 Score, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation 2 scores (APACHE 2) were calculated. In addition, postoperative routine clinical and laboratory parameters were evaluated. Operation time, duration of intubation in the intensive care unit (ICU), the length of the intensive care stay, and length of hospitalization were recorded.
Results: Duration of intubation in the ICU in group 1 with a NEWS2 <3 [8.2 (0-18) vs 16.2 (3-39), respectively; p<0.01], ICU length of stay [21.6 (4-27) vs 47.3 (4-113), respectively; p<0.01], length of hospitalization [11.6 (5-56) vs 18.6 (8-67), respectively; p<0.01]. NEWS2 >3 was significantly higher compared to group 2. The SOFA score was significantly higher in group 2 compared with group 1 [1.2±0.5 vs 4.1±1.9; respectively; p<0.01]. In the correlation analysis, the NEWS2 score level was positively correlated with the SOFA score (p<0.001, r=0.81) and hospitalization time (p<0.001, r=0.60) and neutrophil lymphocyte ratio (NLR) (p<0.001, r=0.47).
Conclusion: These findings suggest that the NEWS2 score may be correlated with the length of intensive care intubation, length of intensive care stay, and length of hospitalization. NEWS2 is an effective and simple scoring system that provides information about postoperative outcomes in gynecologic oncology patients scheduled for major surgery.
Objective: We conducted a biochemical and histological evaluation of whether berberine has a protective and/or therapeutic effect in a cyclophosphamide-induced premature ovarian failure (POF) model.
Materials and methods: We divided 28 Wistar albino female rats into 4 groups [control group, POF group, cyclophosphamide (CP)+berberine (Bb) group, and POF+Bb group]. The POF model was established by intraperitoneal administration of 50 mg/kg CP on day 1 followed by 8 mg/kg/day CP dissolved in saline for the following 14 days. The CP+Bb group received Bb concurrently for two weeks with CP. The POF+Bb group received berberine for two weeks following the completion of CP administration. Left ovaries were used for histopathological evaluation and right ovaries were used for biochemical analysis [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-6 levels in tissue].
Results: Ovarian damage scoring was significantly higher in the POF group than in the other groups (p<0.005). In the POF group, primordial and primary follicle counts were the lowest, while secondary and corpus luteum counts were the highest (p<0.005). There was no significant difference between the other groups. The POF group had significantly elevated levels of TNF-α, IL-1, and IL-6 in the biochemistry results (p<0.005).
Conclusion: We demonstrated that berberine could be effective in the protection and treatment of POF by reducing proinflammatory cytokines. We believe that our study can make a considerable contribution to the literature in terms of POF protection and/or treatment.
Objective: This study aims to investigate the impact of maternal albumin and serum electrolyte levels on the efficacy of single-dose methotrexate (SDMtx) therapy for ectopic pregnancies. Building on previous research, recommendations are provided to enhance the success of SD-Mtx therapy in the management of ectopic pregnancy.
Materials and methods: Conducted at a tertiary center gynecology clinic, the study included 353 patients diagnosed with ectopic pregnancy and treated with SD-Mtx from 2012 to 2023. Patients who responded positively to SD-Mtx treatment comprised Group 1 (n=313), while those requiring surgical intervention due to failed SD-Mtx therapy constituted Group 2 (n=40). Through the hospital's digital database, patient data including complete blood count, biochemistry, and hormone test results were retrospectively examined.
Results: The mean β-hCG value was 1996 IU/mL for Group 1 in contrast to 2058 IU/mL for Group 2. There was no statistically significant difference in β-hCG levels between the two groups. Notably, Group 1 patients exhibited lower serum magnesium levels but higher potassium levels compared to Group 2 patients, with statistically significant differences. Furthermore, Group 1 patients had higher albumin levels than those in Group 2, with a statistically significant difference.
Conclusion: Successful SD-Mtx treatment was associated with lower maternal serum magnesium levels and higher potassium and albumin levels. Considering electrolyte levels before administering SD-Mtx and addressing any imbalances could potentially enhance treatment success. Additionally, restoring low albumin levels might improve the efficacy of SD-Mtx treatment for ectopic pregnancies. While this study suggests these trends, further extensive studies with a larger sample size are necessary to establish more definitive evidence.

