The authors' accepted manuscript "Evaluation of Cervicovaginal Melatonin Levels in Relation to HPV Infections and the Development of High-Grade Squamous Intraepithelial Lesions" [Gynecol Obstet Invest. 2026; https://doi.org/10.1159/000550377] by Belma Gözde Özdemir, Osman Yıldırım, Şeyma Kılıç, Ahmet Bilgi, Fikret Akyürek and Çetin Çelik has been retracted by the Publisher and the Editors.After peer review, the accepted, unedited manuscript was published online as Early View. Before the final Version of Record was published, concerns were raised regarding the methodology. The authors were asked to comment on this and provided a revised manuscript. Review of the revised manuscript resulted in the Editors' decision to rescind their original, provisional acceptance decision and reject the revised manuscript. Consequently, the published author's accepted manuscript has been retracted.

Objectives: The objective of this study was to evaluate whether ultrasound-based #Enzian classification predicts pain profiles and response to hormonal therapy in patients with endometriosis. Endometriosis is a chronic inflammatory disease affecting 10% of reproductive-age women, often causing debilitating pelvic pain. Although #Enzian is validated for surgical planning, its predictive role in medical therapy remains unexplored. Design: A retrospective cohort study, including 89 premenopausal patients referred between 2018 and 2023, was conducted. Hormonal therapies included progestin-only pills (dienogest – POP-D or other progestins – POP-O), combined estrogen-progestin pills (dienogest – EP-D or other EP-O), or norethisterone acetate. Pain was assessed via a 0–10 VAS at baseline, ≥3 months, and ≥6 months. Participants/Materials, Setting, Methods: Patients had ultrasound-confirmed endometriosis and were hormone therapy-naïve for ≥6 months. Baseline evaluation included demographic data, reproductive history, prior surgeries, and six pain domains. #Enzian classification mapped lesion location and size (A: rectovaginal/vagina; B: uterosacral/parametria; C: rectum; FA: adenomyosis; FB: bladder; FU: ureter; FI: intestine above rectum; FO: extra pelvic; O: ovary; P: peritoneum; T: fallopian tubes/adhesions). Linear regression and linear mixed-effects models assessed associations between #Enzian compartments and pain trajectories. Results: Dysmenorrhea occurred in 86.5%, and dyspareunia occurred in 56.2%. Ovarian endometriomas (O) were present in 76.4%, deep infiltrating endometriosis (A, B, C) in 51.7%, and adenomyosis (FA) in 66.3%. POP-D was most effective in reducing ovulatory pain in ovarian (O), uterosacral/parametria (B), rectal (C), and tubal/adhesion (T) involvement, while EP-D was superior for dyspareunia in T. Chronic pelvic pain (CPP) remained refractory. Higher total #Enzian scores correlated with reduced therapy efficacy. Limitations: Retrospective design, single-center, small sample, use of aggregated pain scores, and incomplete follow-up may limit generalizability. Conclusion: Ultrasound-based #Enzian classification correlates with lesion distribution and predicts hormonal therapy efficacy. POP-D therapy is superior at lower #Enzian scores; CPP remains challenging. Findings support individualized medical management and warrant prospective validation including multidimensional pain and quality-of-life assessments.

Background: Vitamin D deficiency during pregnancy has been linked to adverse maternal-fetal outcomes. However, it remains unclear whether standard supplementation mitigates risks equally in patients with differing baseline 25-hydroxyvitamin D [25(OH)D3] levels. Objectives: The objective of this study was to determine whether differences exist in obstetric outcomes and pregnancy-related disorders among patients with different levels of 25(OH)D3 in the first trimester who receive standard supplementation. Design: This retrospective comparative cohort study involves pregnant women aged 16–50 years who received prenatal care at a semiprivate hospital in Northeastern México between January 2022 and December 2024. Participants/Materials, Setting, Methods: Participants were grouped based on first-trimester serum 25(OH)D3 levels (≥30 ng/mL vs. <30 ng/mL), all receiving standard 25(OH)D3 supplementation (4,000 IU/day). For comparisons between groups, we performed independent samples t-tests or Mann-Whitney U tests for quantitative variables and chi-square tests for qualitative variables. A multivariate logistic regression analysis was conducted to identify predictors of adverse obstetric outcomes. Results: A total of 303 women (mean [standard deviation] age 29.3 [5.4] years) were analyzed, divided almost equally between first-trimester 25(OH)D3 deficient group (n = 151) and the sufficient group (n = 152), with similar baseline characteristics. Although insufficient 25(OH)D3 women reached sufficiency during the second and third trimesters, sufficient women maintained significantly higher serum 25(OH)D3 levels throughout pregnancy (p < 0.001) and had lower rates of preeclampsia (1.3% vs. 10.6%, p < 0.001), gestational diabetes (8.6% vs. 24.5%, p < 0.001), preterm labor (0% vs. 5.3%, p = 0.003), urinary tract infections (4.6% vs. 14.6%, p = 0.003), and bacterial vaginosis (3.9% vs. 13.2%, p = 0.004). Logistic regression confirmed first-trimester 25(OH)D3 sufficiency as independently protective against adverse outcomes (OR = 0.21, 95% CI: 0.10–0.43, p < 0.001). Conclusions: First-trimester 25(OH)D3 sufficiency was associated with reduced risk of obstetric complications, compared with women with insufficiency, even when the last achieved sufficiency in the second and third trimester. These findings highlight the importance of early screening and support the need for personalized supplementation strategies before conception to optimize maternal-fetal outcomes.

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 findings to biological conditions, and the heterogeneous etiology of RIF. Conclusions: Differences in formation of 17β-estradiol in the presence of two specific inhibitors of 17β-HSD1 and 7 between RIF patients and controls were found. Although 17β-HSD1, expressed at the fetal-maternal interface, has been associated with fertility, the potential role of 17β-HSD7 in human implantation has not been previously described. The observed differences between patients with RIF and controls warrant future research on the role of this main enzyme and its lesser-known 17β-HSD type in endometrial receptivity and implantation.

Plain Language SummaryThe etiology of low birth weight has been related to different factors, including maternal health status, nutritional intake during pregnancy, social-economic conditions, and environmental exposures. Recently, a major area of interest has been the role of maternal systemic inflammation and its impact on the pregnancy. In particular, different hematological markers, easily derived from routine blood tests, offer a novel perspective on the inflammation status. By integrating these different markers into a composite analysis, this research provides a new perspective of the multifaceted nature of maternal inflammation and its potential impact on fetal development as reflected in birth weight. This study highlighted a negative impact of a composite inflammatory index on fetal weight and head circumference at birth. This correlation suggests the potential application of the indirect inflammatory index in clinical setting. Further research is required to assess the relationship between these markers and their use in clinical practice, enhancing their routine clinical adoption.

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.

Objectives: The aim of the study was to evaluate current practices among gynecologists in managing large endometriomas before in vitro fertilization (IVF). Design: A cross-sectional online survey was conducted. Participants/Materials: The survey was distributed to an estimated 410 gynecologists, with 111 specialists completing the survey (response rate: 27.8%). Among respondents, 73% practiced in academic settings, and 61% had more than 15 years of clinical experience. Setting: Gynecologists involved in IVF treatments or endometrioma surgery were recruited via email through professional societies across multiple countries. Methods: An online survey consisting of 18 questions covering clinical experience, surgical thresholds, techniques, hormonal protocols, and timing of ovarian stimulation post-surgery was distributed through professional societies. Responses were collected anonymously and analyzed using SPSS version 29.0.2.0. Results: Laparoscopic cystectomy was the most common procedure (48.2%). The median threshold size for surgery was 50 mm (interquartile range [IQR] 40–60). Despite the same median threshold, surgeons performing laparoscopic surgery as their main clinical activity had a significantly different distribution of thresholds (IQR 40–60 vs. 47–89, p = 0.006), with a tendency to recommend surgery for smaller endometriomas. Techniques like CO2 laser ablation and plasma energy were less commonly used. Notably, 40.5% of participants indicated they would change their practice if a CO2 laser or plasma energy device were available in their surgical armamentarium. Most participants (67.9%) adjusted their strategy based on preoperative anti-Müllerian hormone levels. The average timing for IVF stimulation post-surgery was 6 weeks (IQR 4–8) with no difference across different experiences. Limitations: The survey-based design may introduce response bias and reflect only the opinions of those who chose to participate. Additionally, the study may not capture regional or institutional differences comprehensively. Conclusion: Managing large endometriomas before IVF involves balancing surgical benefits with risks to ovarian reserve. The survey highlights significant variability in practices, with a median surgical threshold size of 50 mm. Laparoscopic cystectomy, while common, is associated with ovarian tissue loss, whereas emerging techniques like CO2 laser ablation show promise in preserving ovarian reserve. The need for up-to-date evidence-based guidelines is essential to standardize practices and optimize outcomes for IVF patients.

Background: Endometriosis is a chronic disease characterized by endometrial-like tissue outside the uterus. Superficial endometriosis (SE) is the most prevalent form, yet it remains underdiagnosed due to subtle clinical and imaging presentations. Traditionally, diagnosis relies on laparoscopy, which is relatively invasive and often contributes to diagnostic delay. With advancements in imaging techniques, especially transvaginal ultrasound (TVS), a reassessment of the diagnostic approach for SE is needed. This review updates the understanding of SE diagnostics and integrates both historical perspectives and contemporary clinical insights. Objectives: The review aimed to explore advancements in the diagnosis of SE, focusing on the growing role of TVS as a non-invasive diagnostic tool. Additionally, it seeks to highlight emerging diagnostic challenges and present new approaches to managing SE to offer updated recommendations for clinicians. Methods: A comprehensive literature search was conducted using PubMed, MEDLINE, and Google Scholar. The following keywords were used: “superficial endometriosis,” “diagnostic pathways,” “endometriosis diagnosis,” “superficial lesions,” “transvaginal ultrasound,” “laparoscopy,” “non-invasive imaging,” and “diagnostic accuracy.” Only English-language articles were included, focusing on original research, metanalyses, and clinical guidelines, offering historical and current perspectives. In addition to the literature review, contemporary insights were gathered from our clinical practice at a tertiary endometriosis clinic to offer real-world context to the literature findings. Outcome: The review highlights TVS as a promising non-invasive method for diagnosing SE. While SE has historically been diagnosed through laparoscopy, TVS is gaining recognition as a valuable tool for detecting SE lesions, particularly through the identification of key sonographic features such as hyperechoic foci and cystic spaces. These advancements help overcome the challenges posed by the variability of SE presentation on imaging. Emerging techniques, such as sonoPODography, further enhance SE diagnosis and offer the potential for broader clinical application. Despite challenges such as the need for operator expertise and variability in lesion presentation, the literature and clinical insights support the growing utility of TVS in diagnosing SE. Conclusions and Outlook: TVS has significant potential as a non-invasive diagnostic tool for SE. While limitations such as variability in sensitivity and the need for operator expertise remain, TVS can significantly reduce reliance on invasive methods like laparoscopy. Additionally, the review provides insights into managing cases, where TVS results are negative for SE. In such cases, clinicians must adopt a patient-centered approach that emphasizes symptom management, patient autonomy, and education about possible risks and treatment options. Rather than defaulting to a “watchful waiting” or a “one size fits all” strategy, it is essential to engage patients in shared decision-making, allowing them to make informed choices about further diagnostic or therapeutic interventions. This review underscores the importance of integrating TVS into routine diagnostic pathways for SE, improving early detection and enhancing patient care. Future research should focus on refining TVS techniques, establishing standardized diagnostic criteria, and exploring alternative diagnostic strategies for patients with negative imaging results. This approach has the potential to shift the paradigm of SE management, reducing diagnostic delays and empowering patients with a more proactive, informed approach to their care.

Background: No conceptually new drugs for the safe and successful cure of endometriosis are likely to become available soon. Hormonal modulation of ovarian function and suppression of menstruation remain the pillars of disease control. However, existing drugs may be used following novel modalities to limit the consequences of endometriosis progression. Objectives: The aims of this review were to propose a pharmacological approach aimed at limiting the potential detrimental effects of the recent dramatic increase in postmenarcheal repetitive ovulatory menses and to define the type of hormones and the routes of administration that can be used to maximize safety and tolerability in the medical treatment of endometriosis. Methods: For this narrative review, we selected the best quality evidence, prioritizing RCTs, systematic reviews, meta-analyses, network meta-analyses, and international guidelines, preferably published in the last decade. Outcome: Medical treatment of endometriosis should be included into all aspects of prevention. Very-low-dose combined oral contraceptives can be used for years to counteract the increased risk of ovarian cancer observed in patients with endometriosis. This primary prevention measure saves lives and can effectively integrate targeted risk-reducing surgery. Secondary pharmacological prevention, based on a working diagnosis of early onset adenomyosis-endometriosis selectively in adolescents with severe dysmenorrhea and heavy menstrual bleeding, can potentially impede the development of advanced disease forms, and reduce the need for management of complications due to a delay in diagnosis and treatment. Tertiary prevention, i.e., medical therapy of established disease, is based initially on the safest available estrogen-progestogen combinations and progestogen monotherapies. Whenever possible, ethinyl estradiol and cyproterone acetate should be avoided because of thromboembolic and meningioma risks, respectively. Estradiol can be administered transdermally. Switching to gonadotropin-releasing hormone agonists and antagonists should not be delayed when the first-line agents fail. Conclusions and Outlook: Two-thirds of symptomatic endometriosis patients can be managed satisfactorily for many years using, with the right modality, the existing safe, effective, and well-tolerated medications. Despite the constant plea for new drugs, this already appears to be an excellent clinical outcome, unsurpassed when managing other human chronic inflammatory diseases. Cohort studies are needed to verify whether turning off the recurrent inflammation caused by repeated ovulation and menstruation could also affect the risk of systemic conditions associated with endometriosis.

Objective: The objective of this meta-analysis was to conduct a comprehensive assessment of the therapeutic effectiveness and safety profile of the combination of immune checkpoint inhibitors (ICIs) with either chemotherapy or tyrosine kinase inhibitors (TKIs) in the treatment of advanced-stage endometrial cancer (EC). Methods: This meta-analysis conducted a thorough literature search across PubMed, Cochrane Library, Embase, and Web of Science databases from their earliest records up to November 18, 2023, identifying qualified randomized controlled trials (RCTs), cohort studies, and single-arm trials for inclusion in the analysis. The meta-analysis were performed to quantify and analyzed the evidence from the existing literature, focusing on outcomes including the objective response rate (ORR), disease control rate (DCR), duration of response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Results: A total of 13 studies were included. In terms of ICI combined with chemotherapy, the single-arm trials showed that ICI combined with chemotherapy was effective in improving the ORR, but the overall rate of AE was higher. The results based on RCT suggested that ICI combined with chemotherapy resulted in a longer PFS of 12–24 months and OS of 18 months compared to the control group in advanced EC. In terms of ICI combined with TKI, the pooled ORR was 39.0%, the pooled DCR was 79.9%, the pooled OS rate was 50.4%, and the pooled overall AE rate was 95.8%, the pooled grade ≥3 AE rate was 73.8%, the pooled median progression-free survival was 6.126 months, and pooled OS was 15.099 months in advanced EC. Conclusions: The integrative therapeutic approach combining ICIs with chemotherapy or TKIs demonstrates notable clinical efficacy in advanced EC, which can prolong the survival and help disease control. Nevertheless, it is imperative for clinicians to be vigilant regarding the potential for adverse reactions to emerge. In addition, more RCTs are needed to solidify this study’s efficacy and safety further.