Gynecologic and Obstetric Investigation最新文献

Objective: Endometriosis is a chronic gynecological disorder that can cause infertility in women of reproductive age, and its clinical treatment still faces significant challenges. However, the pathogenesis of endometriosis remains unclear.

Methods: S1PR4 knockdown and overexpression were constructed in primary ectopic endometrial stromal cells (EESCs) with or without the glycolysis inhibitor 2-deoxy-D-glucose and normal endometrial stromal cells (ESCs) with or without the mTOR signaling pathway inhibitor AZD8055, respectively. CCK-8 and Transwell assays were used to evaluate the viability and invasive capabilities. The cellular glycolytic capacity was assessed by measuring the extracellular acidification rate and lactate levels in the cell culture supernatant. An endometriosis mouse model was established in vivo, and histopathological changes in the endometrium were analyzed by hematoxylin-eosin staining. The expression of S1PR4, LDHA, and p-mTOR in endometrium and ESCs was assessed using qRT-PCR, Western blotting, or immunofluorescence.

Results: Glycolytic levels were increased in EESCs, and inhibiting glycolysis in vitro reduced the viability and invasive capabilities of EESCs, as well as suppressed the growth of ectopic lesions in vivo. S1PR4 was abnormally overexpressed in endometriosis, and knocking down S1PR4 inhibited the viability, invasion, and glycolysis of EESCs, along with downregulation of p-mTOR expression. Conversely, overexpression of S1PR4 promoted the viability, invasion, and glycolysis of ESCs via the mTOR signaling pathway.

Conclusions: In endometriosis, S1PR4 enhances cellular glycolysis by activating the mTOR signaling pathway, thereby promoting the viability and invasion of EESCs.

Objective: This paper aimed to evaluate the influence of low-dose oxytocin (LDO) on pain intensity and delivery outcomes in primiparas who delivered vaginally with epidural block analgesia (EBA).

Methods: A total of 150 primiparas were retrospectively collected, and finally, 120 cases were included. They were divided into a control group (n = 60, received EBA) and an oxytocin group (n = 60, received EBA combined with LDO). Analgesic onset time, analgesic duration, time to flatus, and time to first bowel movement were compared. Pain intensity was assessed using the Visual Analog Scale (VAS) at pre-analgesia, cervical dilation of 3 cm, and fetal delivery. Serum levels of cortisol (Cor), norepinephrine (NE), and C-reactive protein (CRP) before and 24 h post-delivery, postpartum bleeding, Apgar scores, delivery outcomes, and adverse reactions were compared.

Results: The oxytocin group had shorter times for gas passage and first bowel movement, as well as shorter durations of the first, second, and third stages of labor (p < 0.05). VAS scores at cervical dilation of 3 cm and fetal delivery were lower than pre-analgesia in both groups (p < 0.05), with no inter-group differences at each time point (p > 0.05). Serum Cor and NE decreased, while CRP increased at 24 h postpartum (p < 0.05), with no inter-group differences (p > 0.05). The oxytocin group had less postpartum bleeding at 2 h (p < 0.05), a higher natural delivery rate, and a lower incidence of uterine atony (p < 0.05), with no significant difference in Apgar scores (p > 0.05).

Conclusion: EBA with LDO shortens labor duration, promotes gastrointestinal recovery, reduces uterine atony, postpartum hemorrhage, and vaginal assistive delivery rates, without affecting analgesia or stress response.

Objectives: Address and identify the sub-group of patients that might benefit from letrozole co-treatment throughout the entire ovarian stimulation (OS).

Design: A retrospective cohort study.

Patients: Patients who underwent two successive IVF cycle attempts, where the 2nd included the co-administration of 5 mg Letrozole from OS day 1 until trigger day.

Setting: IVF institute of a tertiary medical center.

Methods: First and second cycle attemtps were compared with regard to cycle characteristics and results. Different subroups according to ovarian response were considered.

Results: Two hundred patients met the inclusion criteria and were included in the study. Of whom, 65 were poor responders (oocytes ≤3) during the first IVF cycle attempt, 85 were sub-optimal responders (4-9 oocytes), and 50 were normal responders (≥10 oocytes). The total dose of gonadotropins (4,525 ± 1,553 vs. 4,293 ± 2,166, p = NS) and length of stimulation (11.3 ± 2.2 vs. 11.1 ± 2.3, p = NS) were comparable between the two cycle attempts. Numbers of follicles ≥13 mm (7.2 ± 4.7 vs. 6.2 ± 4.3, p < 0.001), retrieved oocytes (8.6 ± 6.1 vs. 6.9 ± 5.5, p < 0.001), zygotes (5.7 ± 4.5 vs. 4.5 ± 3.7, p < 0.001) and number of top quality embryos (TQE) (2.5 ± 2.5 vs. 1.8 ± 1.9, p < 0.001) were significantly higher in letrozole cycles. Sub-analysis according to patients' ovarian response during the first attempt revealed that the poor and sub-optimal responders significantly benefit from the letrozole co-administration, while the normal responders did not.

Conclusions: Letrozole co-administration during OS for IVF increases the number of retrieved oocytes, zygotes, and TQE in poor and sub-optimal responders but not in normal responders.

Objectives: The aim of the study was to compare maternal, neonatal, and microbiological outcomes among patients with unknown group B Streptococcus (GBS) status and prolonged rupture of membranes (ROM ≥18 h) who received intrapartum prophylaxis with either ampicillin or clindamycin.

Design: A retrospective comparative cohort.

Materials: A total of 1,507 term singleton pregnancies with ROM ≥18 h and unknown GBS colonization status were included in the study: 1,418 received ampicillin, and 89 received clindamycin due to reported penicillin allergy.

Setting: The study was conducted in a tertiary university-affiliated hospital in northern Israel, from March 2020 to May 2024.

Methods: Patients were stratified by antibiotic regimen. The co-primary outcomes were clinical chorioamnionitis and neonatal intensive care unit (NICU) admission. Secondary outcomes included maternal complications (intrapartum fever, endometritis, cesarean delivery) and neonatal morbidities (Apgar <7, cord pH <7.1, respiratory distress, and ventilation support). Post-delivery chorioamniotic membrane swabs were cultured. Multivariate logistic regression was used to identify independent predictors of outcomes.

Results: Compared to ampicillin, clindamycin treatment was associated with higher rates of clinical chorioamnionitis (14.6% vs. 2.3%, p < 0.001), intrapartum fever (28.1% vs. 4.1%, p < 0.001), maternal sepsis (2.2% vs. 0.3%, p = 0.011), puerperal endometritis (13.5% vs. 2.6%, p < 0.001), cesarean delivery (36.0% vs. 18.1%, p < 0.001), and postpartum antibiotic use (14.6% vs. 5.4%, p < 0.001). Among neonates of patients treated with clindamycin compared to ampicillin, the rates were higher for NICU admission (19.1% vs. 4.4%, p < 0.001), Apgar <7 at 5 min (4.5% vs. 0.8%, p = 0.001), cord pH <7.1 (7.9% vs. 2.0%, p < 0.001), respiratory distress (13.5% vs. 5.4%, p < 0.001), and ventilation support (invasive 2.2% vs. 0.2%, p = 0.019; non-invasive 7.9% vs. 1.1%, p < 0.001). Hypoxic brain injury occurred more frequently in the clindamycin group (2.2% vs. 0.1%, p = 0.016). GBS was isolated more often in chorioamniotic cultures of patients treated with clindamycin (19.1% vs. 1.1%, p < 0.001). In multivariable analysis, clindamycin treatment (adjusted odds ratio [aOR] 7.7, 95% CI: 3.8-15.5, p < 0.001) and artificial ROM (aOR 2.6, 95% CI: 1.1-6.3, p = 0.031) were independently associated with clinical chorioamnionitis. Clindamycin treatment was also independently associated with NICU admission (aOR 3.71, 95% CI: 1.9-7.1, p < 0.001). Other factors associated with NICU admission were the presence of meconium-stained amniotic fluid (aOR 3.28, 95% CI: 1.7-6.2, p < 0.001), clinical chorioamnionitis (aOR 3.11, 95% CI: 1.3-7.2, p = 0.009), and umbilical cord pH <7.1 (aOR 4.76, 95% CI: 1.9-11.4, p < 0.001).

Limitations: Limitations include

Objectives: This study aimed to combine dynamic magnetic resonance imaging (MRI) with three-dimensional (3D) reconstruction and form a plane based on osseous structures to evaluate the degree of pelvic organ prolapse (POP). The correlation of this novel evaluation approach with the POP-Q system was assessed.

Methods: A retrospective analysis was conducted on 71 POP patients with POP-Q stage ≥II. The dynamic MRI images of those patients were reconstructed in three dimensions. A plane was created by using the midpoint of the line between the inferior margins of the two pubic bones and the starting points of the superior margins of the bilateral sacrotuberous ligaments (the pubic inferior midpoint - sacrotuberous ligament starting point superior edge plane). Distances from the lowest point of the anterior vaginal wall, cervix, and rectal ampulla to this evaluation plane were measured, modeled, and categorized. The consistency and correlation of the categorized results with POP-Q scores were verified by performing a kappa analysis and Spearman's rank correlation analysis, respectively.

Results: The highest consistency with POP-Q scores was found in the prolapse of the central pelvic cavity (kappa = 0.713, p < 0.05), followed by the anterior POP (kappa = 0.427, p < 0.05), and posterior POP (kappa = 0.261, p < 0.05), with all showing statistically significant differences. The strongest positive correlation was observed between central POP and POP-Q scores (r = 0.864, p < 0.01), followed by posterior POP and POP-Q scores (r = 0.710, p < 0.01), with both exhibiting a strong positive correlation. Anterior POP and POP-Q scores showed a moderate positive correlation (r = 0.586, p < 0.01).

Conclusions: The results of the proposed evaluation method were highly consistent in the anterior and central pelvic cavities and strongly correlated in the central and posterior pelvic cavities. In particular, the assessment of the posterior cavity showed a strong positive correlation with that of the POP-Q system. The evaluation plane demonstrated high consistency and correlation with the POP-Q system.

Objectives: The objective of this study was to explore the lymph node metastasis (LNM) and related risk factors of low-grade endometrioid endometrial carcinomas (EECs) and analyse the efficacy of related risk factors in predicting LNM.

Design: Data from 424 patients with low-grade EEC treated between January 2019 and June 2024 were retrospectively analysed, according to the International Federation of Gynecology and Obstetrics (FIGO) 2009.

Methods: Univariate and multivariate logistic regression analyses were used to examine the factors associated with LNM. Receiver operating characteristic (ROC) curves were plotted to assess the predictive efficacy of independent risk factors for LNM.

Results: The rate of LNM was 7.8% (33/424). Histological grade, tumour size, depth of myometrial invasion, cervical stromal invasion, lymphovascular space invasion (LVSI), microcystic, elongated, fragmented (MELF) pattern, carbohydrate antigen 125 (CA125), carbohydrate antigen 199, and human epididymis protein 4 were associated with LNM. However, only LVSI, MELF pattern, depth of myometrial invasion, and CA125 were identified as independent risk factors. The area under the ROC curve for CA125 and depth of myometrial invasion was 0.796 and 0.734, respectively. The optimal cut-off value for CA125 was 31.36 U/mL, with a maximum Youden index of 53.9%. Combining CA125 with depth of myometrial invasion improved diagnostic accuracy compared to either parameter alone.

Limitations: This is a single-center retrospective study.

Conclusions: LNM is more likely with independent risk factors. Combining CA125 and depth of myometrial invasion enhances diagnostic accuracy for LNM. This study provides valuable insights for predicting LNM risk in low-grade EEC patients and guiding stratified management.

Objective: The objective of this study was to investigate the impact of localization of diffuse adenomyosis on reproductive outcomes after frozen embryo transfer (FET).

Design: This prospective cohort study was conducted between January 2019 and December 2022. A total of 585 infertile women undergoing the first FET cycle were recruited.

Participants/materials, setting, methods: The study population included 368 women with diffuse adenomyosis where 167 women had diffuse adenomyosis of outer myometrium (OM) (group A) and 201 women had diffuse adenomyosis of the junctional zone (JZ) (group B). 217 women with male infertility were taken as controls. Adenomyosis was diagnosed on transvaginal ultrasound using MUSA criteria where diffuse adenomyosis patients with two or more features were included. These patients were further divided based on the localization of adenomyotic lesions in OM or JZ. All the patients underwent FET cycle. Pregnancy outcomes and complications were compared between different groups. Additionally, adenomyosis patients as a whole were compared with the control group.

Results: Women with diffuse adenomyosis have similar (p > 0.05) pregnancy rates (36.14% vs. 35.94%), biochemical pregnancy rates (11.27% vs. 3.84%), and clinical pregnancy rates (32.06% vs. 35.02%) but higher miscarriage rates (22.03% vs. 9.21%; OR: 2.79, 95% CI: 1.14-6.79, p = 0.024) and a lower live birth rates (20.65% vs. 29.95%; OR: 0.61, 95% CI: 0.41-0.89, p = 0.011) than women without adenomyosis. However, women with diffuse adenomyotic lesions affecting the JZ (group B) exhibited significantly lower positive pregnancy (26.37% vs. 47.9%; OR: 0.39, 95% CI: 0.25-0.60, p < 0.0001), clinical pregnancy (23.38% vs. 42.51%; OR: 0.41, 95% CI: 0.26-0.65, p = 0.0001), and live birth (16.42% vs. 25.75%; OR: 0.57, 95% CI: 0.34-0.94, p = 0.029) compared to those with adenomyosis of the OM (group A) but comparable (p > 0.05) biochemical pregnancy (11.32% vs. 11.25%) and miscarriage (23.4% vs. 21.13%). Pregnancy complications were comparable between the adenomyosis groups; however, there was a significantly higher incidence of pregnancy complications, particularly gestational hypertension (OR: 6.41, 95% CI: 1.79-22.92, p = 0.0042), IUGR (OR: 9.08, 95% CI: 2.01-40.99, p = 0.0041), and preterm labor (OR: 9.41, 95% CI: 3.09-28.62, p = 0.0001) in adenomyosis patients compared to the controls.

Limitations: It is an observational prospective study, and the study included patients with endometriosis as a comorbidity. The population size is limited to ascertain the effect of diffuse adenomyosis on pregnancy complications, particularly between subgroups.

Conclusion: This study emphasizes the importance of evaluation and localization of adenomyotic lesions before initiating ART, which can aid in effective counseling and personalized treatment strategies

Objectives: To explore the relationship between brain structural connectivity and polycystic ovary syndrome (PCOS).

Design: Two-sample Mendelian randomization (2SMR) was conducted by querying a relevant European population genome-wide association studies (GWAS) database about the anatomical connections of the brain and polycystic ovarian syndrome from the Ieu Open GWAS Project database. Two hundred six brain structural connectivity-related single-nucleotide polymorphisms (SNPs) were evaluated as instrumental variables (IVs).

Methods: To investigate the potential causal effect between brain structure and PCOS, we applied several statistical models, including inverse variance weighting (IVW), weighted median (WME), MR-Egger regression, simple mode, and weighted mode approaches.

Results: IVW analysis indicated significant associations between certain white matter tracts and PCOS risk, including the connection between the right default mode network and the amygdala (OR = 1.559; 95% CI = 1.028-2.36; p = 0.037), as well as the pathway linking the right somatomotor and limbic networks (OR = 1.800; 95% CI = 1.077-3.009; p = 0.025). Additionally, negative correlations with PCOS risk were observed in white matter tracts involving limbic-control and limbic-thalamic connections across both hemispheres, as well as in the left somatomotor-control circuit. Horizontal pleiotropy was not detected by heterogeneity tests or sensitivity analyses that used the leave-one-out approach.

Limitations: More research involving bigger and more heterogeneous cohorts is necessary to evaluate the functional consequences of anatomical brain changes in PCOS.

Conclusion: The structural integrity of white matter tracts linking the right default mode network to the amygdala and connecting the right somatomotor and limbic networks appears to be causally associated with the development of PCOS.

Objectives: Alterations in 17β-estradiol metabolism are known to potentially impair endometrial receptivity. Previous pioneering studies have investigated the role of endometrial steroid metabolism by determining steroid hormone levels and steroid-metabolizing enzyme activity in endometrial biopsies of patients undergoing IVF. The activity of oxidative and reductive 17β-hydroxysteroid dehydrogenases (17β-HSDs), which catalyze the interconversion between estrone and 17β-estradiol, was found to be similar between IVF patients who - after fresh embryo transfer in the cycle following endometrial biopsy - did and did not become pregnant. However, inhibition of the reductive enzyme 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), the most prominent 17β-HSD type in 17β-estradiol formation, was found to differ between groups. The primary objective of this study was to determine oxidative and reductive 17β-HSD enzyme activity in the endometrium of two well-defined groups: IVF patients with recurrent implantation failure (RIF) and control patients.

Design: This is a prospective observational study of IVF patients with RIF (n = 52) and controls (n = 25). Patients undergoing treatment because of pre-implantation genetic testing, a severe male factor, or bilateral tubal pathology were recruited as controls since these conditions did not suggest an endometrial contribution to infertility.

Participants/materials, setting, methods: Endometrial biopsies were obtained 5-8 days after a positive urine ovulation test in a natural cycle using a Pipelle catheter. Activity of oxidative and reductive enzymes, inhibition of 17β-HSD1, 5, 7, and 12, and immunostaining of 17β-HSD7 were performed. The formation of 17β-estradiol by reduction of estrone (reductive enzymes), formation of estrone by oxidation of 17β-estradiol (oxidative enzymes), and inhibition of specific 17β-HSD enzymes were determined using high-performance liquid chromatography. Formalin-fixed paraffin-embedded tissue was used for immunostaining. The Student's t test and Mann-Whitney U test were used for statistical analysis. Multivariate analysis was used to determine the influence of confounders.

Results: No differences were found in activity of oxidative and reductive 17β-HSD enzymes in RIF patients and controls. Combined inhibition of 17β-HSD5, 7, and 12 was significantly lower in the RIF group compared to controls (p = 0.04). Inhibition of 17β-HSD1 and 17β-HSD7 combined was also significantly lower (more production of 17β-estradiol remained) in the RIF group compared to controls (p < 0.01). However, solely inhibiting 17β-HSD1 or 17β-HSD7 showed no significant difference between groups. Immunostaining revealed the expression of 17β-HSD7 in all endometrial samples.

Limitations: Results should be interpreted carefully due to possible cycle-to-cycle variation, challenges to translate in vitro fi

Introduction: Oxytocin has long been used for the induction of labor, but it can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labor. We performed this meta-analysis to determine whether discontinuation of oxytocin, once the active phase of induced labor is achieved, affects the second stage of labor and the rate of various maternal and fetal outcomes.

Methods: We searched for randomized controlled trials (RCTs) comparing discontinuing oxytocin after the active stage of labor is established versus continuing to give oxytocin throughout the labor process using databases like PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from the inception till February 1, 2025. Results were pooled using RevMan 5.4, and the effect metric was the risk ratio (RR). Our systematic review and meta-analysis was registered with PROSPERO (CRD42024534076).

Results: Pooled analysis of fifteen RCTs included in our review showed that discontinuation of oxytocin, once the active stage of labor is established, did not reduce the primary outcome of incidence of cesarean delivery (RR = 0.91; 95% CI, 0.77-1.07; p = 0.21). The incidence of uterine tachysystole, postpartum hemorrhage, and non-reassuring fetal heart rate was significantly lower in the oxytocin discontinuation group compared to oxytocin continuation. The rates of uterine rupture, vaginal instrument use, epidural use, and neonatal intensive care unit admission did not differ among both groups. The duration of the active stage of labor was significantly prolonged in the oxytocin-discontinued group; however, the duration of the second stage of labor and total delivery time remained comparable between the two groups.

Conclusions: Discontinuation of oxytocin during the active phase of labor did not reduce the incidence of cesarean section or neonatal morbidity. We therefore recommend an individualized approach regarding oxytocin discontinuation while factoring in patient-specific factors. New large-scale RCTs focusing on identifying subgroups that might benefit from one approach over the other are required to provide more reliable results.