Gynecologic and Obstetric Investigation最新文献

Objectives: Endometriotic stromal cells (ESCs) are extensively found in endometriosis (EM). This study aims to investigate the effects and regulatory mechanisms of KLF10 on the proliferation of ESCs in EM.

Methods: Human ESCs from eutopic and ectopic endometrium were isolated and identified. Levels of KLF10, miR-200c-3p, and lncRNA NEAT1 in cells were detected by reverse transcription-quantitative polymerase chain reaction and Western blot analysis. Expression of KLF10, miR-200c-3p, and NEAT1 were silenced in ectopic ESCs, followed by an assessment of cell proliferation. Chromatin immunoprecipitation and dual-luciferase reporter assays were conducted to analyze the binding of KLF10 to the miR-200c-3p promoter. RNA immunoprecipitation and dual-luciferase reporter assays were performed to analyze the interaction between miR-200c-3p and NEAT1. NEAT1 RNA stability was measured.

Results: Compared to Eut-ESCs, Ect-ESCs exhibited decreased KLF10 and miR-200c-3p expression and increased NEAT1 expression. Overexpression of KLF10 inhibited the proliferation of Ect-ESCs. Mechanistically, KLF10 transcriptionally promoted miR-200c-3p expression, reducing the binding of miR-200c-3p to NEAT1 and downregulating NEAT1 expression. Combined experimental results showed that miR-200c-3p downregulation or NEAT1 overexpression could alleviate the inhibitory effect of KLF10 overexpression on the proliferation of Ect-ESCs.

Limitations: We only investigated the function of KLF10 in Ect-ESC proliferation of EM on the cellular level, but the effect of KLF10 on abnormal Ect-ESC migration and invasion remains to be explored. Besides, there is no interference experiments performed on Eut-ESCs, and no animal experiment was included.

Conclusions: KLF10 transcriptionally promoted miR-200c-3p expression reduced the binding of miR-200c-3p to NEAT1, thus downregulating NEAT1 expression and inhibiting the proliferation of Ect-ESCs.

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

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: 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

Objectives: The aim of the study was to report the first cases of surgical staging for apparently early-stage endometrial cancer performed using the Versius® next-generation robotic surgical system (Cambridge Medical Robots [CMR] Surgical, Cambridge, UK).

Design: The study used a prospective case series. Participants/Materials: Women who underwent surgical staging, including total hysterectomy, bilateral adnexectomy, and sentinel lymph node (SLN) biopsy, for apparently early-stage endometrial cancer using the Versius® next-generation robotic surgical system (CMR Surgical, Cambridge, UK) were included.

Setting: The study was conducted at a Gynecologic Oncology Referral Center.

Methods: We prospectively recorded data of all consecutive women who underwent the investigated surgical procedure.

Results: Fourteen endometrial cancer patients were treated between March and August 2024 at the Azienda Ospedaliera Universitaria Integrata of Verona. The mean age was 69.4 ± 8.7 years, and the average body mass index was 27.2 ± 4.8. SLN biopsy was performed on all patients: 5 patients had unilateral and 9 bilateral successful SLN detection; 6 women underwent systematic pelvic lymphadenectomy in the unmapped areas. The median operative time was 122 (min-max, 77-185) minutes, and the median hysterectomy time was 34 (min-max, 18-68) minutes. None of the surgical procedures required conversion to conventional laparoscopic or open surgery for technical reasons, and no intraoperative complications were recorded. No readmissions, reoperations, or deaths were observed during the follow-up (median 102 days, min-max 39-249).

Limitations: The limitations of the study are the first experience in a limited study population and the use of methylene blue for SLN mapping.

Conclusions: Our preliminary results with the Versius® platform appear encouraging regarding surgical time, blood loss, rate of completion of the robotic procedures, and complications risk. Further studies will confirm the indications, feasibility, and safety of the Versius® surgical robot system for treating apparently early-stage endometrial cancer.

Introduction: Variants of the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene have been investigated for their close associations with assisted reproductive technology (ART) outcomes. However, available data are controversial. This meta-analysis aimed to elucidate the associations of LHCGR N312S polymorphism (rs2293275) with ART outcomes.

Methods: A thorough search was performed in the databases of PubMed, EMBASE, Web of Science, and Cochrane Library from their inception to July 19, 2024. The analysis included five studies, encompassing 2,692 patients with infertility and subfertility. RevMan 5.4 was used for further comprehensive data analysis.

Results: In this study, A allele homozygotes encoded asparagine (N/N), and G allele homozygotes encoded serine (S/S). The number of oocytes retrieved was higher in AA homozygotes than in GG homozygotes (mean difference [MD] 1.07, 95% confidence interval [CI] 0.09-2.05, I2 = 7%, p = 0.03) or AG heterozygotes (MD 1.26, 95% CI 0.32-2.20, I2 = 45%, p = 0.008). The number of mature oocytes and the distribution of the LHCGR (rs2293275) genotype (MD 0.60, 95% CI -0.25 to 1.45, I2 = 49%, p = 0.17; MD 0.85, 95% CI 0.02-1.68, I2 = 76%, p = 0.05; MD -0.36, 95% CI -1.20 to 0.49, I2 = 56%, p = 0.41) were not significantly different. G allele homozygotes and heterozygotes exhibited an increasing trend in the number of clinical pregnancies compared with A allele homozygotes (odds ratio [OR] 1.69, 95% CI 1.21-2.36, I2 = 0%, p = 0.002; OR 1.30, 95% CI 1.09-1.54, I2 = 0%, p = 0.003).

Conclusion: This study revealed associations of LHCGR polymorphism with ART outcomes, implying that the LHCGR N312S polymorphism (rs2293275) may serve as a predictor of certain ART outcomes.