Application of Biomarkers in Obese Infertile Women: A Genetic Tool for a Personalized Treatment.

This study investigates links between CART and leptin gene expression, FSH receptor Asn680Ser polymorphism, and reproductive hormones in morbidly obese patients under 40 years old, facing infertility, and undergoing bariatric surgery. A total of 29 women were included in this study. A hormonal profile along with detection of CART and leptin gene expression was evaluated before and after bariatric surgery. Additionally, the presence or absence of Asn680Ser of the FSHR gene was studied. Following bariatric surgery, a mean reduction in BMI (16.03 kg/m2) was observed in all women. FSH levels preoperatively varied significantly among genotypes, with medians of 8.1, 9.5, and 10.3 for individuals without polymorphism, heterozygotes, and homozygotes, respectively (p = 0.0408). Post surgery, marginal differences in FSH levels were observed (5.8, 7.1, and 8.2, respectively) (p = 0.0356). E2 and LH levels exhibited no significant genotype-based differences pre and post surgery. Presurgical E2 levels were 29.6, 29.8, and 29.6, respectively (p = 0.91634), while postsurgical levels were 51.2, 47.8, and 47 (p = 0.7720). LH levels followed similar patterns. Our findings highlight bariatric surgery's positive impact on BMI reduction and its potential connection to genetic markers, hormones, and infertility. This suggests personalized treatments and offers a valuable genetic tool for better fertility outcomes in obese individuals.

Cracking the Code: Investigating the Correlation between Aerobic Vaginitis and Preterm Labor.

Aerobic vaginitis (AV) is a distinct clinical entity characterized by inflammation and abnormal vaginal microflora. Often mistaken for bacterial vaginosis, AV remains relatively unknown and underdiagnosed. AV's understanding is evolving, with some experts suggesting it may primarily be an immunological disorder, the prevalence of which has a range of 7-13% in non-pregnant women and 4.1-8.3% during pregnancy. Pregnancy can affect susceptibility to vaginal infections, leading to adverse outcomes for the woman and the newborn. This review summarizes the correlation between AV and adverse pregnancy outcomes, particularly preterm birth, the leading cause of morbidity and mortality among neonates. An improved understanding of AV's impact on pregnancy outcomes can lead to early recognition, proper management, and effective interventions. While some studies support an association between AV and preterm labor, the existing knowledge of this relationship remains limited. The evidence suggests that AV may contribute to adverse pregnancy outcomes, mainly preterm birth, but further research is needed to establish a definitive link. Further studies are needed to investigate the underlying mechanisms and clarify AV's role in premature labor. A comprehensive understanding of AV's impact on pregnancy outcomes is crucial for early recognition, appropriate management, and effective interventions.

Prospective Study on the Correlation between CART and Leptin Gene Expression, Obesity, and Reproductive Hormones in Individuals Undergoing Bariatric Surgery.

Obesity, a global health concern affecting 650 million individuals of all ages worldwide, prompts health complications, including fertility issues. This research investigates the impact of bariatric surgery on morbidly obese females under 40, examining the relationship between CART and leptin gene expressions and reproductive hormones. Post-surgery, a significant reduction in BMI (16.03 kg/m2, n = 29) was observed, accompanied by notable hormonal changes. FSH levels showed a mean difference of 3.18 ± 1.19 pre- and post-surgery (p < 0.001), LH levels exhibited a mean difference of 2.62 ± 1.1 (p < 0.001), E2 levels demonstrated a mean difference of 18.62 ± 5.02 (p < 0.001), and AMH levels showed a mean difference of 3.18 ± 1.19 (p < 0.001). High CART and leptin expressions before treatment correlated with lower expressions after treatment. These findings, rooted in statistically significant correlations (CART: rs = 0.51, p = 0.005; leptin: rs = 0.75, p < 0.001), shed light on potential molecular pathways connecting gene expressions with reproductive hormones post-bariatric surgery. Our study uniquely investigates the interplay between genetic markers, infertility, and bariatric surgery in women. It stands out by providing distinctive insights into the development of personalized treatment strategies for obesity-related infertility, contributing to a deeper understanding of this complex medical issue.

Choriocarcinoma After Term Pregnancy With a Subsequent Successful Pregnancy: A Rare Entity.

Gestational trophoblastic neoplasia (GTN) is a group of pregnancy-related disorders that arise from the cells of conception. They include gestational choriocarcinoma (CC), placental site trophoblastic tumor, and epithelioid trophoblastic tumor with these forms arising from a molar pregnancy, abortion, or a normal genetic pregnancy. Most cases of GTN are diagnosed when the serum hCG levels plateau or rise in patients being followed up after the diagnosis of hydatidiform mole but can also be suspected due to persistent vaginal bleeding after a normal pregnancy and delivery. Early diagnosis and treatment are pivotal for ensuring optimal outcomes and given the rarity of the disease, clinical management and treatment should be provided in specialized centers. Here, we present a rare case of a 31-year-old woman diagnosed with choriocarcinoma with pulmonary metastasis following an uncomplicated full-term pregnancy. After the suction evacuation and curettage, she underwent six cycles of chemotherapy with an excellent response, a fact that resulted in a subsequent pregnancy and birth without complications, occurring 18 months thereafter.

Inguinal Lymph Node Metastasis as Sole Manifestation of Ovarian / Fallopian Tube Cancer: a Review of the Literature.

Background: Ovarian/fallopian tube cancer is the deadliest gynecological malignancy. Most cases are diagnosed at an advanced stage, typically after the cancer has spread to the peritoneal cavity, or via lymphatic drainage. The presence of distant lymph node metastasis in the inguinal region is a rare manifestation of lymphatic metastasis. Since the 2014 FIGO staging revision, ovarian cancer patients with inguinal metastasis are classified as stage IVB. However, the clinical significance of such an upstaging remains under investigation. Materials and Methods: Both Scopus and PubMed / MEDLINE databases were utilized, by inputting the following combination of keywords: (Ovarian cancer OR Fallopian tube cancer) AND (Inguinal lymph node AND Metastasis) on June 31st, 2023. The time of publication and text availability were not considered when searching the databases and all relevant articles in English were initially accepted. Results: Twelve patients from equal number of case reports were included in our review. Mean age of diagnosis was 56,5 years old, with 3 out of 12 women to be premenopausal at the time of diagnosis. Regarding the histologic type, 67% (8 out of 12) of the cases were serous adenocarcinoma and 4 patients (33%) were diagnosed with fallopian tube malignancy. All patients, except one, were treated with primary cytoreductive surgery. In all patients optimal cytoreductive surgery was achieved. All patients, except one, received adjuvant chemotherapy. Regarding the disease-free survival, mean DFS is calculated approximately at 2 years (23,1 months). Conclusion: Inguinal lymph node metastases from ovarian / fallopian tube malignancy as initial site of metastasis is extremely rare. However, patients with inguinal masses should be investigated for ovarian / fallopian malignancy. Further investigation ought to be conducted to enlighten the pathway and the oncological significance of inguinal lymph node metastasis in ovarian cancer patients.

Detection of zeb1 Gene in Granulosa Cells in Women Undergoing IVF Treatment.

BACKGROUND: ZEB1 plays a role in epithelial-to-mesenchymal transition and acts as a repressor of E-cadherin, TGF-ß, and Wnt/ß-catenin. Since ZEB1 protein is expressed in estrogen-responsive tissues, and expression of the gene in the normal ovary and endometrium is positively correlated with high estrogen levels, we performed a direct analysis of granulosa cell samples to determine whether there are any significant changes in zeb1 expression during folliculogenesis. METHODS: ZEB1 expression levels were measured in the granulosa cells of 56 infertile women undergoing IVF treatment. RNA extraction from granulosa cells was performed along with reverse transcription quantitative polymerase chain reaction (RT-qPCR) with SYBR Green I to determine zeb1 gene expression levels. Statistical analysis was performed by using t-test, while possible correlations of the expression of ZEB1 protein with body mass index (BMI), age, number of oocytes, and oocyte maturation were investigated. RESULTS: Zeb1 gene expression levels correlate significantly with body mass index (BMI) and age, but not with oocyte number and oocyte maturation stage. Obese women demonstrate a higher expression level of zeb1 gene compared to normal and overweight women. Moreover, zeb1 gene is overexpressed in women aged 35-40 years old and is under-expressed in women >40 years old. CONCLUSIONS: ZEB1 expression should be further investigated as it may unveil new potential findings of the zeb1 gene's role in female fertility and its use as a biomarker in fertility workups.

ANRIL rs4977574 Gene Polymorphism in Women with Recurrent Pregnancy Loss.

BACKGROUND: ANRIL rs4977574 gene polymorphism has been associated with arterial thrombosis and cardiovascular disease development. ANRIL rs4977574 gene polymorphism could also be associated with recurrent pregnancy loss (RPL) since there is increasing evidence in favor of a potential shared pathophysiological mechanism with cardiovascular disease, potentially through arterial thrombosis. This study's goal is to investigate the differences in ANRIL rs4977574 gene polymorphism between women with and without RPL, if any, as well as a potential association with the number of pregnancy losses. METHODS: DNA was isolated from peripheral blood samples, and the sequence containing the polymorphism of interest was amplified with PCR. Results were visualized under UV light following electrophoresis in 3% agarose gel with ethidium bromide. ANRIL rs4977574 (A>G) prevalence was compared between 56 women with and 69 without RPL. Results were adjusted for women's age and BMI, while a stratified analysis was performed according to number of pregnancy losses. RESULTS: Allele A was significantly more prevalent in the control group compared to RPL women [31 (44.9%) vs. 14 (25%), p = 0.021]. Although not reaching statistical significance, a gradually decreasing prevalence of allele A with an increasing number of pregnancy losses was observed [31 (44.9%) in control, eight (30.7%) with two, six (23.1%) with three, and 0 (0.0%) with four pregnancy losses, p = 0.078]. Results were also similar following adjustment. CONCLUSIONS: This is the first study that demonstrates an association between RPL presence and ANRIL rs4977574 gene polymorphism (lower prevalence of allele A), while a difference according to the number of pregnancy losses cannot be excluded.

Caesarean Scar Pregnancy: Single Dose of Intrasac Ultrasound-Guided Methotrexate Injection Seems to be a Safe Option for Treatment.

Objective: The purpose of the study was to assess the efficacy of local ultrasound-guided methotrexate injection in patients with caesarean section scar pregnancy, to chart the course of beta-human chorionic gonadotropin levels (HCG) after treatment, and to see if HCG levels are correlated with clinical presentation. Methods: Between May 2018 and January 2021, data were collected retrospectively from the Early Pregnancy Unit of a tertiary hospital. Results: Our clinic assessed 20 patients; one disputed terminating the pregnancy and was not included in the research. The remaining 19 patients, with a median age of 34 years, received intragestational sac methotrexate injection under ultrasound guidance. 7w3d was the median gestational age. These women had one to four previous caesarean sections, with a mean of 1.60±9. Patients with caesarean scar pregnancy most typically presented with spotting (42.1%), whereas 26.3% were asymptomatic. Except in cases of pain, the symptomatic women's HCG levels were lower than in the non-symptomatic women. The level of HCG in patients with pain was approximately double that of non-pain patients (p=0.2557). In our series, intragestational sac methotrexate injection was effective in 17/19 women, or 89.5% (95%CI: 75.7-100%). HCG levels were undetectable in 97.6±30 days on average (minimum: 42 days, maximum: 147 days). Conclusion: Caesarean scar pregnancy is a rare possibly fatal condition with no consensus on the optimal treatment. An experienced Early Pregnancy Unit member performing local methotrexate injections under ultrasound guidance is a feasible and successful strategy in clinically stable patients.

Evaluation of IOTA-ADNEX Model and Simple Rules for Identifying Adnexal Masses by Operators with Varying Levels of Expertise: A Single-Center Diagnostic Accuracy Study.

Objectives The discrimination of ovarian lesions presents a significant problem in everyday clinical practice with ultrasonography appearing to be the most effective diagnostic technique. The aim of our study was to externally evaluate the performance of different diagnostic models when applied by examiners with various levels of experience. Methods This was a diagnostic accuracy study including women who were admitted for adnexal masses, between July 2018 and April 2021, to a Greek tertiary oncology center. Preoperatively sonographic data were evaluated by an expert gynecologist, a 6 th and a 1 st year gynecology resident, who applied the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR) and Assessment of Different NEoplasias in the adneXa (ADNEX) model to discriminate between benign and malignant ovarian tumors. The explant pathology report was used as the reference diagnosis. Kappa statistics were used for the investigation of the level of agreement between the examined systems and the raters. Results We included 66 women, 39 with benign and 27 with malignant ovarian tumors. ADNEX (with and without "CA-125") had high sensitivity (96-100%) when applied by all raters but a rather low specificity (36%) when applied by the 1st year resident. SR could not be applied in 6% to 17% of the cases. It had slightly lower sensitivity, higher specificity, and higher overall accuracy, especially when applied by the 1st year resident (61% vs. 92%), compared to ADNEX. Conclusion Both ADNEX and SR can be utilized for screening in non-oncology centers since they offer high sensitivity even when used by less experienced examiners. In the hands of inexperienced examiners, SR appears to be the best model for assessing ovarian lesions.

sFLT1, PlGF, the sFLT1/PlGF Ratio and Their Association with Pre-Eclampsia in Twin Pregnancies-A Review of the Literature.

Twin pregnancies demonstrate a 2-3-fold higher chance of developing PE compared to singletons, and recent evidence has demonstrated that the sFLT1/PIGF ratio is strongly associated with PE, adverse pregnancy outcomes, as well as imminent deliveries due to PE complications. The primary objective of this systematic review was to summarise the available data on the levels of sFLT1, PlGF and their ratios in twin pregnancies and to investigate their association with the development of PE, adverse pregnancy outcomes and the timing of the delivery. A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. sFLT1 levels and the sFLT1/PIGF ratio appeared higher in twins compared to singleton pregnancies, especially in the third trimester, while PlGF levels appeared higher up until the third trimester, with their values showing no difference or being even lower than in singletons thereafter. The sFLT1/PIGF ratio has been reported to be an independent marker of adverse outcomes related to pre-eclampsia and is associated with the mean time until delivery in an inverse manner. Further research is required in order to establish the optimal sFLT1/PIGF cut-off values and to stratify the risk of adverse outcomes in twin pregnancies.

Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications.

As the leading cause of neonatal morbidity and mortality, preterm birth is recognized as a major public health concern around the world. The purpose of this review is to analyze the connection between infections and premature birth. Spontaneous preterm birth is commonly associated with intrauterine infection/inflammation. The overproduction of prostaglandins caused by the inflammation associated with an infection could lead to uterine contractions, contributing to preterm delivery. Many pathogens, particularly Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Gardnerella vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Actinomyces, Candida spp., and Streptococcus spp. have been related with premature delivery, chorioamnionitis, and sepsis of the neonate. Further research regarding the prevention of preterm delivery is required in order to develop effective preventive methods with the aim of reducing neonatal morbidity.

External Validation of the Ovarian-Adnexal Reporting and Data System (O-RADS) Lexicon and the International Ovarian Tumor Analysis 2-Step Strategy to Stratify Ovarian Tumors Into O-RADS Risk Groups.

Importance: Correct diagnosis of ovarian cancer results in better prognosis. Adnexal lesions can be stratified into the Ovarian-Adnexal Reporting and Data System (O-RADS) risk of malignancy categories with either the O-RADS lexicon, proposed by the American College of Radiology, or the International Ovarian Tumor Analysis (IOTA) 2-step strategy. Objective: To investigate the diagnostic performance of the O-RADS lexicon and the IOTA 2-step strategy. Design, Setting, and Participants: Retrospective external diagnostic validation study based on interim data of IOTA5, a prospective international multicenter cohort study, in 36 oncology referral centers or other types of centers. A total of 8519 consecutive adult patients presenting with an adnexal mass between January 1, 2012, and March 1, 2015, and treated either with surgery or conservatively were included in this diagnostic study. Twenty-five patients were excluded for withdrawal of consent, 2777 were excluded from 19 centers that did not meet predefined data quality criteria, and 812 were excluded because they were already in follow-up at recruitment. The analysis included 4905 patients with a newly detected adnexal mass in 17 centers that met predefined data quality criteria. Data were analyzed from January 31 to March 1, 2022. Exposures: Stratification into O-RADS categories (malignancy risk <1%, 1% to <10%, 10% to <50%, and ≥50%). For the IOTA 2-step strategy, the stratification is based on the individual risk of malignancy calculated with the IOTA 2-step strategy. Main Outcomes and Measures: Observed prevalence of malignancy in each O-RADS risk category, as well as sensitivity and specificity. The reference standard was the status of the tumor at inclusion, determined by histology or clinical and ultrasonographic follow-up for 1 year. Multiple imputation was used for uncertain outcomes owing to inconclusive follow-up information. Results: Median age of the 4905 patients was 48 years (IQR, 36-62 years). Data on race and ethnicity were not collected. A total of 3441 tumors (70%) were benign, 978 (20%) were malignant, and 486 (10%) had uncertain classification. Using the O-RADS lexicon resulted in 1.1% (24 of 2196) observed prevalence of malignancy in O-RADS 2, 4% (34 of 857) in O-RADS 3, 27% (246 of 904) in O-RADS 4, and 78% (732 of 939) in O-RADS 5; the corresponding results for the IOTA 2-step strategy were 0.9% (18 of 1984), 4% (58 of 1304), 30% (206 of 690), and 82% (756 of 927). At the 10% risk threshold (O-RADS 4-5), the O-RADS lexicon had 92% sensitivity (95% CI, 87%-96%) and 80% specificity (95% CI, 74%-85%), and the IOTA 2-step strategy had 91% sensitivity (95% CI, 84%-95%) and 85% specificity (95% CI, 80%-88%). Conclusions and Relevance: The findings of this external diagnostic validation study suggest that both the O-RADS lexicon and the IOTA 2-step strategy can be used to stratify patients into risk groups. However, the observed malignancy rate in O-RADS 2 was not clearly below 1%.

p16/Ki-67 Dual Staining Is a Reliable Biomarker for Risk Stratification for Patients With Borderline/Mild Cytology in Cervical Cancer Screening.

BACKGROUND/AIM: To evaluate p16/Ki-67 dual-staining performance for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the management of women with minor cervical abnormalities. PATIENTS AND METHODS: All 759 enrolled patients were tested for cytology, high-risk human papillomavirus (HR-HPV) and dual p16/Ki-67 staining. RESULTS: Positivity rates for HR-HPV and dual staining increased as dysplasia was worsened from non-CIN (37.6% and 0%) to CIN1 (62.5% and 1.6%) and CIN2+ (98.7% and 97.3%), respectively. HPV18 and HPV16 exhibited the highest odds ratios (53.16 and 11.31) in the CIN2+ group. Both p16/Ki-67 dual staining and HR-HPV presented similar sensitivities (97.3% and 98.7%, respectively) for CIN2+ detection. Dual staining specificity, however, was 99.3%, significantly higher compared to HR-HPV testing (52.2%). The utility of dual staining was evaluated in different screening strategies and appeared to reduce the number of colposcopies required for the detection of CIN2+ cases. CONCLUSION: p16/Ki-67 dual-staining cytology is a surrogate triage biomarker in cytology-based screening programs, with high performance for efficient risk stratification of women with mild cervical abnormalities.

Prolapse of a large pedunculated uterine myoma.

We report a rare case of a large prolapsed pedunculated uterine myoma measuring 15 cm in its greater diameter. In order to make a surgical procedure safe and feasible, appropriate clinical predictors should be taken into account and pre- and intraoperative preparations be available to the surgeon's armamentarium.

A Randomized Controlled Trial on the Efficacy and Safety of Low-Dose hCG in a Short Protocol with GnRH Agonist and Ovarian Stimulation with Recombinant FSH (rFSH) During the Follicular Phase in Infertile Women Undergoing ART.

Τhis study aims to investigate whether the addition of low-dose hCG throughout stimulation in infertile women undergoing IVF improves IVF outcome parameters. This is a prospective, multicenter, randomized, double-blind, placebo-controlled, Phase IIIb clinical study, conducted in three university IVF units. We studied whether the addition of 100 IU hCG/day to a short GnRH agonist IVF protocol from the onset of the follicular phase (group 1, n=40) or placebo (group 2, n=41) had any impact on the number of high-quality transferred embryos at day 2 and clinical pregnancy rates. The comparison encompassed descriptive statistics, and univariate and multivariate analyses. Concerning the primary outcomes, we found no differences in both the number of high-quality embryos (≥2) at day 3 [21/40 (52.5%) vs. 14/41 (34.2%), p=0.095] and clinical pregnancy rates [10/40 (25%) vs. 10/41 (24.4%), p=0.949], respectively. Similarly, there were no differences concerning the secondary outcomes preset for this trial. According to the results of the multivariate logistic regression analysis, no significant associations were noted for primary outcomes (clinical pregnancy: adjusted OR=0.89, 95% CI: 0.29-2.75; (≥2 excellent quality embryos at day 3: adjusted OR=0.54, 95% CI: 0.21-1.42, with group 1 set as reference category); similarly, no differences were noted with respect to secondary outcomes, except from the increased odds of ≥2 poor-quality embryos at day 3 occurring in group 2 (adjusted OR= 11.69, 95%CI: 1.29-106.19). The addition of low-dose hCG to a short GnRH agonist protocol for IVF does not improve the number of top-quality embryos and clinical pregnancy rates.

Treatment of Cervical Pregnancy with Ultrasound-Guided Intragestational Injection of Methotrexate: A Case Report.

This study is aimed at describing a noninvasive conservative strategy to the treatment of cervical pregnancy and highlighting the success of ultrasound-guided therapeutic techniques. A 43-year-old woman with a history of one previous cesarean section presented in our unit with vaginal spotting and a positive urine pregnancy test. She was diagnosed with a cervical pregnancy, and she was successfully treated conservatively with the administration of intragestational sac methotrexate under ultrasound guidance. Cervical pregnancy is a rare form of ectopic pregnancy that results from conceptus implantation in the cervical canal. The main concern is the associated life-threatening hemorrhage and subsequent need for urgent hysterectomy. The evolution of ultrasound over the past decades has enabled early diagnosis and has shifted the management from a radical surgical approach towards a stepwise conservative therapeutic approach, when possible.

Wandering Spleen: A Rare Case of an Adnexal Lesion.

The wandering spleen (WS) is a rare condition in which the spleen is not found in its usual location in the left hypochondrium but is positioned in the lower abdomen or the pelvis. This is a case of a 21-year-old woman who presented with chronic, intermittent, and subtle pain in the left lower quadrant of her abdomen. After clinical examination and ultrasound evaluation, an adnexal lesion was detected in the left lumbar area, and no splenic tissue was found in the left hypochondrium. The wandering spleen should be included in the differential diagnosis when encountering a patient with non-typical or acute abdominal pain. Accurate diagnostic evaluation can be performed with low-cost imaging modalities such as Doppler ultrasound.

Abdominal wall endometrioma: An insidious cause of delayed diagnosis.

An extremely rare extrapelvic position of endometriosis with a precise incidence of 0.07%-0.47%, leading usually to delayed and false diagnosis. Differential diagnosis should include that rare condition while ultrasonography remains a pivotal tool to unravel that enigma, especially in women with no specific symptoms and surgeries in the past.

Cloacal type defect of the anal canal following an obstetric anal sphincter trauma.

Neglected severe obstetric anal sphincter injuries may result in fecal incontinence. It is of paramount importance to identify such injuries at the time of vaginal delivery and have appropriate surgical training for optimal anatomical restoration of the perineal structures.