Gynecologic and Obstetric Investigation

doi: 10.1159/000525622pmid: N/A

Zhang, Hui; Qi, Shasha; Liu, Zhao; Li, Chunyan; Li, Mingjiang; Zhao, Xingbo

doi: 10.1159/000522170pmid: 35130539

AbstractObjectives: Melatonin (MLT) shows antitumor effects in various tumor types, including endometrial carcinoma. However, the molecular mechanism involved is unclear. In the current study, we investigated the effect of MLT on the estrogen-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells and explored the pathway that might be involved. Design: Laboratory study was via cultured endometrial cancer cells. Design refers only to in vitro experiments. Methods: In cell culture experiments, cell growth was examined using CCK-8 assays. The expression of Numb and EMT markers in Ishikawa cells was examined using Western blot analysis and real-time PCR. Cell invasion was examined using transwell assays. Cell migration was examined using wound-healing assays and transwell assays. Using immunohistochemistry analysis, the expression of Numb in human endometrial cancers was examined. Results: In immunohistochemistry experiments, we found that 15.2% of atypical endometrial hyperplasia and 15.6% of endometrial carcinoma did not express Numb. In cell culture experiments, MLT inhibited cell proliferation, invasion, and migration induced by 17β-estradiol (E2) in endometrial cancer cells. MLT decreased the expression of vimentin and Slug and increased the expression of Numb and E-cadherin in Ishikawa cells. Numb knockdown in cancer cells significantly increased cell proliferation, invasion, and migration. Limitations: No animal experiments were performed. Conclusions: MLT blocked E2-induced cell growth and EMT in endometrial cancer cells via upregulating Numb expression.

Yaakov, Odelia; Ashwal, Eran; Gemer, Ofer; Peled, Yoav; Kapustian, Victoria; Namazov, Ahmet; Eitan, Ram; Krissi, Haim

doi: 10.1159/000522501pmid: 35139515

AbstractObjectives: We aimed to investigate whether surgery for adnexal detorsion within 6 h from admission to the hospital was associated with less adnexal ischemia. Design: This is a retrospective cohort study. Participants/Materials, Setting, and Methods: This retrospective study was conducted at two university-affiliated medical centers and assessed women aged 18–45 years with adnexal torsion who were hospitalized within 12 h from the pain onset and underwent surgery for detorsion within 24 h. The study group was divided into 2 groups: early, surgical intervention within less than 6 h and late, surgical intervention between 6 and 24 h. The primary outcome was the rate of macroscopic appearance of ischemic adnexa. Results: Two hundred and twenty women fulfilled the inclusion criteria. In 101 women, the adnexa with the torsion appeared macroscopically ischemic. There was no difference in ischemic adnexa between the early and late intervention groups (48% vs. 40%; p = 0.269). No significant association was found between the physical examination or ultrasonographic findings and the rate of ischemic adnexa within each group. Limitations: The main limitations of our study are its retrospective nature. Much of the clinical and ultrasonographic data are subjective and operator-dependent. The decision to operate may vary from one surgeon to another. Conclusion: Immediate surgical intervention in patients with adnexal torsion is not associated with a lower rate of adnexal ischemia. These findings suggest that in acute adnexal torsion, there is a wider time window for a thorough evaluation before surgery.

Ahn, Ji Yeon; Hong, Yeon Hee; Kim, Keun Cheon; Kim, Ji Hyang; Lee, Seo-Yeon; Lee, Jung Ryeol; Lee, Eun Ju

doi: 10.1159/000524232pmid: 35350012

AbstractObjectives: The persistently thin endometrium is a major cause of repeated implantation failure; however, there is no definite treatment for it yet. This study aimed to confirm the potential of human peripheral blood mononuclear cells (hPBMCs) as a therapeutic agent for endometrial regeneration. Design: An experimental study was carried out. Participants/Materials, Setting, Methods: To assess the in vitro effect of hPBMC, the human primary endometrial epithelial cell lines SNU-685 and SNU-1077 were co-cultured with or without 1 × 105 hPBMCs for 24 h. To evaluate the in vivo effect, either 1 × 105 hPBMCs in PBS or PBS alone were injected into the left uterine horn of nonobese diabetic-severe combined immune-deficient mice, and the right untreated uterine horn was used as control. Results: Co-culture with hPBMCs stimulated significant proliferation in both SNU-685 and SNU-1077 cell lines (p = 0.002 and 0.044, respectively). Moreover, treatment with hPBMCs significantly increased the thickness in all parts of the endometrium compared with that in the untreated control uterine horn (proximal: 1.69 ± 0.19 vs. 1.00 ± 0.10, p = 0.009; middle: 1.51 ± 0.14 vs. 1.00 ± 0.12, p = 0.010; distal: 1.72 ± 0.22 vs. 1.00 ± 0.12, p = 0.003, respectively). Compared with the PBS injection group, the hPBMC injection group had significantly thickened endometrium in the middle (p = 0.036) and distal segments (p = 0.002) of the uterine horn. Immunohistochemical analysis revealed the presence of exogenously injected hPBMCs in the uterus of recipient mice. hPBMC-recipient mice had cyclic uterus with normal histology in the endometrium. Limitations: hPBMCs were not applied directly to a mouse model with thin endometrium, so further study is needed. Conclusion: The beneficial effect of hPBMCs on endometrium may suggest their clinical feasibility for the safe treatment of infertile patients with persistently thin endometrium.

Benseler, Anouk; McDermott, Colleen D.

doi: 10.1159/000524266pmid: 35354149

AbstractObjectives: The objective of the study was to determine practice patterns of prescribing prophylactic antibiotics against urinary tract infection (UTI) for urodynamic studies (UDS) and outpatient cystoscopy in women. Design: A cross-sectional survey study was conducted of North American female pelvic medicine and reconstructive specialists (FPMRS). Methods: An online survey was used to assess prophylactic prescribing patterns of FPMRS that perform UDS and outpatient cystoscopy. This survey was developed and then electronically disseminated through the American Urogynecologic Society to 699 eligible physicians. Results: A total of 138 surveys were completed. Approximately half of physicians did not prescribe any antibiotic prophylaxis for UDS or for cystoscopy (54% and 43%, respectively). For patients with perceived risk factors (recurrent UTIs, immunosuppression, known neurogenic lower urinary tract dysfunction, indwelling catheter use, elevated postvoid residual/bladder outlet obstruction, genitourinary anomalies, and diabetes), 32% and 41% of physicians prescribed antibiotic prophylaxis for UDS and cystoscopy, respectively. A minority of physicians always prescribed antibiotics for UDS and cystoscopy (13% and 17%, respectively). Limitations: The response rate was a limitation of the study; however, this rate is in keeping with other physician survey studies published within this subspecialty. Selection and response biases may have contributed to the results of this survey study. Conclusion: There was no uniform approach to UTI prophylaxis for UDS and outpatient cystoscopy in women which reflects the lack of current guidelines and the low level of evidence on which they are based. This nonuniform practice calls for more research to better define an evidence-based standard of care.

Soto, Eleazar E.; Hernandez-Andrade, Edgar; Huntley, Erin S.; Blackwell, Sean C.

doi: 10.1159/000524361pmid: 35354147

AbstractObjective: The aim of the study was to describe changes in the acceptance of transvaginal (TV) cervical length (CL) assessment and in the variance of CL measurements among operators, after implementation of universal TV-CL screening at 18+0 – to 23+6 weeks/days of gestation. Design: Retrospective cohort. Participants/Materials, Setting, Methods: This study was performed after universal TV-CL screening was implemented at the University of Texas Health Science Center in Houston, TX, USA, for all women undergoing an anatomy ultrasound (US) between 18 0/6 and 23 6/7 weeks/days of gestation. Pregnant women carrying singletons without prior history of preterm delivery who underwent anatomy US evaluation between September 2017 and March 2020 (30 months) were included. The complete study period was divided into five epochs of 6 months each. Changes in patient’s acceptance for the TV scan, in CL distribution, in the prevalence of short cervix defined as ≤15, ≤20, or ≤25 mm, and in the performance of US operators across the five epochs were evaluated. Success rate was defined as the percentage of TV-CL measurements obtained in relation to the number of second-trimester anatomy scans. Results: A total of 22,207 low-risk pregnant women evaluated by 36 trained sonographers (operators) were analyzed. Overall, the acceptance for TV-CL measurement was 82.3% (18,289/22,207), increasing from 76.7% in the first epoch to 82.8% (p < 0.0001) in the last epoch. The mean CL did not significantly change from 38.6 mm in the first epoch to 38.5 mm in the last epoch (p = 0.7); however, the standard deviation decreased from 7.9 mm in the first epoch to 7.04 mm in the last epoch (p = <0.01). The prevalence of a short cervix ≤25 mm was 2.2% (n = 399/18,289), ≤20 mm was 1.2% (224/18,289), and ≤15 mm was 0.9% (162/18,289). This prevalence varied only for CL ≤25 mm from 3.02% (88/2,907) in the first epoch to 1.77% (64/3,615) in the last epoch (p = 0.0009). There was a variation in CL measurements among operators (mean 3.3 mm). Sonographers with less than 1 year of experience had a lower success rate for completing TV-CL examinations than more experienced sonographers (80.8% vs. 85.8%; p < 0.03). In general, 77% (27/35) of operators had a success rate ≥80% for completing TV-CL scans. Limitations: Characteristics of individuals who accepted versus those who declined TV-CL were not compared; CL values were not correlated with clinical outcomes. Conclusions: During the first 6 months after implementation of a universal CL screening program, there was greater variation in CL measurements, lower acceptance for TV US, and a higher number of women diagnosed with a CL ≤25 mm, as compared to subsequent epochs. After the first 6 months, these metrics improved and remained stable. Most operators improved their performance over time; however, there were a few with a low success rate for TV-CL and others who systematically over- or underestimate CL measurements.

Yamanaka, Shoichiro; Miyake, Ryuta; Yamada, Yuki; Kawaguchi, Ryuji; Ootake, Norihisa; Myoba, Shohei; Kobayashi, Hiroshi

doi: 10.1159/000524804pmid: 35613543

AbstractObjectives: Patients with asymptomatic venous thromboembolism (VTE) are associated with an increased risk of pulmonary thromboembolism events. However, due to low specificity and high false-positive rates, D-dimer testing cannot be used alone to diagnose VTE. Tissue factor pathway inhibitor 2 (TFPI2), a new serodiagnostic marker for ovarian cancer, plays a role in blood coagulation system regulation. We hypothesized that combining D-dimer and TFPI2 would improve its utility in diagnosing VTE. This study aimed to look into the clinical utility of serum D-dimer and TFPI2 levels in detecting asymptomatic VTE in patients with epithelial ovarian cancer (EOC). Design: From January 2008 to December 2015, researchers at Nara Medical University Hospital’s Department of Gynecology conducted a single-center retrospective study. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of preoperative D-dimer, TFPI2, and D-dimer combined with TFPI2 in distinguishing VTE patients from those who did not have VTE. Participants: This study included 122 patients with EOC who met the inclusion and exclusion criteria out of 223 admitted to the hospital with EOC. The patients were divided into two groups: VTE (n = 25) and non-VTE (n = 97). Results: There were significant differences in D-dimer, TFPI2, and CA125 levels and residual tumor between the VTE and non-VTE groups. The D-dimer level was found to be significantly related to age, body mass index, VTE, massive ascites, residual tumor, histology, and Federation of Gynecology and Obstetrics stage, whereas the TFPI2 level was only related to VTE. Multivariate analysis revealed that D-dimer (the optimal cutoff value, 3.5 μg/mL) and TFPI2 (the optimal cutoff value, 400 pg/mL) are independent risk factors for preoperative VTE. ROC analysis revealed that the area under the curve was 0.8266 for D-dimer, 0.7963 for TFPI2, and 0.8495 for the combination of D-dimer and TFPI2. When compared to the D-dimer test alone, the combination of D-dimer and TFPI2 had higher specificity (77.3–96.9%) and positive predictive value (48.8–81.2%) for the diagnosis of VTE. Limitations: This is a single-center retrospective study. Conclusion: The combination of D-dimer and TFPI2 may be useful to safely exclude VTE and select patients at high risk of VTE.

Sun, Wenping; Wang, Pinghua; Wang, Shenglan

doi: 10.1159/000513670pmid: 35605584

AbstractObjectives: Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM). In this study, we aimed to determine the expression of circulating circRNAs in humans, which may be promising biomarkers for the diagnosis of GDM or predicting the macrosomia in GDM patients. Design: A multi-stage validation and risk score formula analysis was applied for validation. Participants/Materials, Setting, Methods: A total of 26 circRNAs previously reported highly expressed in placenta tissues or umbilical cord blood of GDM patients during the pregnancy were enrolled. We recruited a total of 200 patients with GDM with or without macrosomia, 200 healthy pregnant woman, and 200 healthy volunteers. Results: We discovered that four circRNAs including circRNA_1030, circRNA_23658, circRNA_0009049, and circRNA_32231 were upregulated in plasmatic samples of patients with GDM with or without macrosomia in training set and validation set compared with the healthy pregnant woman and healthy volunteers. Further receiver operating characteristic (ROC) curve analysis in risk score formula indicated a high diagnostic ability and area under ROC curve value (AUC) of 0.950 and 0.815 in training set and validation set for predicting GDM from controls group, for predicting macrosomia from GDM, the AUC was 0.975 and 0.820, respectively. The four circRNAs were further investigated with stable expression in human plasma samples. Limitations: The study was limited by larger scale of sample validation and the detailed mechanism investigation. Conclusion: The circRNA_1030, circRNA_23658, circRNA_0009049, and circRNA_32231 might be the potential biomarkers for predicting the GDM and macrosomia during the perinatal period.

Qiu, Yu; Zhang, Xueqin; Ni, Yan

doi: 10.1159/000521728pmid: 35172306

AbstractObjectives: The results of studies regarding the association between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) are controversial. Design: This meta-analysis was conducted to evaluate the relationship between PCOS and GDM. Methods: English language articles published before July 2021 were included by searching in databases: PubMed, EMBASE, Web of Science, Medline, and Google Scholar. All these results were computed using STATA 12.0 software. The random-effects models were used to calculate summary odds ratio (OR) or relative risk (RR) and 95% confidence interval (CI) when the heterogeneity was high; Inversely, the fixed-effects models were used to calculate summary OR/RR and 95% CI when the heterogeneity was low. Results: The present study showed that PCOS was significantly associated with an increased risk of GDM with a random-effects model (OR/RR = 2.02, 95% CI: 1.74–2.34, I2 = 79.5%, p < 0.0001). Subgroup analysis indicated an elevated risk of GDM in PCOS patients in both retrospective and prospective studies (retrospective studies: OR = 1.89, 95% CI: 1.62–2.20; prospective studies: RR = 2.85, 95% CI: 1.77–4.60). In addition, subgroup analysis indicated an elevated risk of GDM in PCOS patients in both Caucasian and Asian populations (Caucasian populations: OR/RR = 2.47, 95% CI: 1.99–3.07; prospective studies: OR/RR = 1.58, 95% CI: 1.23–2.02). Conclusion: Overall, findings of the meta-analysis showed that women with PCOS have an elevated risk of GDM compared to women without PCOS. Limitations: First, on account of sources of information, the role of several variables including BMI, the severity of GDM and serum lipid level in the association between PCOS and GDM cannot be evaluated. Second, only studies published in English and Chinese were included, and the publish bias is impossible to avoid.

Cucinella, Giuseppe; Sozzi, Giulio; Di Donna, Mariano Catello; Unti, Elettra; Mariani, Andrea; Chiantera, Vito

doi: 10.1159/000520983pmid: 35108708

AbstractIntroduction: Squamous cell carcinoma (SCC) arising from endometriosis is very rare. Moreover, endometriosis located on the pelvic side wall is uncommon, while its cancerization is quite unusual. We herein report the first case of retroperitoneal SCC arising from endometriosis. Case Presentation: A case of a 52-year-old woman with retroperitoneal pararectal right mass is presented. The pelvic magnetic resonance imaging showed a retroperitoneal tumor extended to the right pelvic side wall. The neuropelveological examination completed the preoperative assessment, showing a right-sided sciatica and overactive bladder symptoms. Tumor removal was completely managed by a minimally invasive technique through the laparoscopic laterally extended endopelvic resection procedure and pelvic neurolysis. Final histology revealed a SCC in a context of diffuse endometriosis with a histologic continuity between the SCC and the endometriosis. The patient underwent adjuvant chemotherapy with no recurrence after 6 months. Conclusion: To the best of our knowledge, the present case represents the first evidence of retroperitoneal SCC of the pelvic side wall arising from endometriosis completely resected by laparoscopic approach. Although its rare occurrence, the gynecologist oncologist should maintain a high index of suspicion for malignant endometriosis transformation in case of retroperitoneal pelvic mass and history of endometriosis.