Maurizio Nicola D'ALterio

Background: Adenomyosis is a prevalent gynaecological disorder whose pathogenesis remains incompletely understood. Congenital Müllerian anomalies provide an informative in vivo model, since obstructive and non‐obstructive variants impose spatially defined alterations of intrauterine pressure, myometrial architecture, and contractility. Objectives: To characterise adenomyosis localisation across Müllerian anomaly subtypes, assess concomitant endometriosis prevalence, and examine their topographic concordance with sites of uterine obstruction. Search Strategy: PubMed/MEDLINE, Embase and Scopus were searched from inception to October 2025 using MeSH/Emtree and free‐text terms for adenomyosis and congenital Müllerian anomalies, without date restrictions. Selection Criteria: Original case reports, case series, and observational studies in English explicitly describing the diagnostic modalities used for both conditions. Data Collection and Analysis: Two reviewers independently screened and extracted data; methodological quality was assessed with the Joanna Briggs Institute tools. Data were synthesised descriptively by malformation subtype, with case‐by‐case laterality analysis where individual patient‐level data were available. Main Results: Forty‐two studies (135 patients) were included. Unicornuate uterus predominated (102/135, 75.6%). Among patients with directly reported localisation and a non‐communicating functional rudimentary horn, adenomyosis involved the rudimentary horn in 10/12 cases (83.3%). In Robert's uterus, adenomyosis was ipsilateral to the blind hemicavity in 3/3 evaluable cases (100%). In Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, adenomyosis occurred in remnants lacking functional endometrium in 10/15 patients (66.7%). Concomitant endometriosis (43/134 evaluable patients, 32.1%) was most frequent in obstructive anomalies (Herlyn‐Werner‐Wunderlich syndrome (HWW) 3/5, 60.0%; Robert's uterus 2/4, 50.0%) and least frequent in septate uterus (0/2, 0%) and MRKH (2/15, 13.3%), localising ipsilateral to the obstruction in 9/10 (90.0%) reported obstructive cases. Conclusions: Adenomyosis preferentially involved structurally abnormal or obstructed uterine compartments. The endometriosis gradient was compatible with impaired menstrual efflux as a shared mechanical determinant. These findings derive from a low‐quality evidence base and should therefore be regarded as hypothesis‐generating. Prospective confirmation is required, although these findings may support increased clinical awareness in women with Müllerian anomalies, particularly obstructive variants.

To evaluate the clinical efficacy and safety of a once-daily oral fixed-dose combination of relugolix 40 mg, estradiol 1 mg, and norethisterone acetate 0.5 mg in women with symptomatic adenomyosis coexisting with uterine fibroids. This case series included six women with uterine fibroids and concomitant adenomyosis, diagnosed by transvaginal ultrasound according to MUSA criteria. All patients received continuous treatment for 12 months. Clinical outcomes included changes in dysmenorrhea and pelvic pain assessed by the Visual Analogue Scale (VAS), menstrual blood loss evaluated through the Pictorial Blood Assessment Chart (PBAC), and hemoglobin levels. Ultrasonographic assessment measured uterine volume and adenomyosis-related features before and after treatment. All patients achieved complete resolution of dysmenorrhea and chronic pelvic pain, with VAS scores reduced to zero. Menstrual bleeding ceased in all cases (PBAC = 0), and hemoglobin levels improved after 12 months. Ultrasound examination demonstrated a reduction in uterine volume ranging from 8.6% to 58.3%, along with partial regression of direct adenomyotic features. No adverse events or treatment discontinuations were reported during follow-up. Relugolix/estradiol/norethisterone acetate combination therapy was effective, well-tolerated, and associated with consistent clinical and sonographic improvement in women with adenomyosis and coexisting fibroids. Future larger-scale, controlled studies with extended follow-up are warranted to validate these findings.

STUDY QUESTION: Are endometriotic lesions affecting bilateral organs or anatomical structures distributed symmetrically on both sides of the body? SUMMARY ANSWER: The left-sided preponderance of pelvic endometriotic lesions, and the right-sided dominance of thoracic and inguinal lesions, suggest that endometriotic lesions exhibit a non-random, asymmetric lateral distribution. WHAT IS KNOWN ALREADY: Evaluating the anatomical distribution of endometriotic lesions may elucidate the underlying pathogenic mechanism(s) of the disease. If the coelomic metaplasia or embryonic cell remnant theory is correct, a symmetrical right-left pattern would be expected. Conversely, retrograde menstruation would likely result in asymmetrical distribution, influenced by gravity, peritoneal fluid circulation, and anatomical niches. STUDY DESIGN, SIZE, DURATION: This systematic review with meta-analysis included full-length, English-language articles published up to 10 June 2024. Literature searches were performed in PubMed/Medline and Embase databases with the keyword ‘endometriosis’, ‘lateral’, ‘distribution’, ‘right’, ‘left’, and ‘asymmetry’. PARTICIPANTS/MATERIALS, SETTING, METHODS: The review focused on anatomical structures commonly affected by endometriosis with surgically defined right or left laterality: ovaries, uterosacral ligaments, colon, ureters, inguinal regions, and hemithorax (diaphragm, pleura, lungs). Case reports were excluded. Risk of bias was assessed using ROBINS-I for non-randomized studies and a dedicated tool for case series. Meta-analyses of proportions were conducted in R. Heterogeneity was quantified using the I2 statistic. Funnel plots for publication bias and Egger tests were performed using Stata. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6356 articles screened, 154 met the inclusion criteria. A statistically significant left-sided preponderance was observed for ovarian (58%; 95% CI: 57–60%; P < 0.001), uterosacral ligament (56%; 95% CI: 54–59%; P < 0.001), ureteral (71%; 95% CI: 67–76%; P < 0.001), and bowel (72%; 95% CI: 64–79%; P < 0.001) lesions, whereas thoracic (98%; 95% CI: 96–100%; P < 0.001) and inguinal (92%; 95% CI: 83–98%; P < 0.001) lesions were predominantly right-sided. These findings were confirmed in the sensitivity analyses. Egger’s test indicated a possible small study effect only for ovarian lesions (P = 0.012). LIMITATIONS, REASONS FOR CAUTION: The preponderance of retrospective studies, the variability in surgical procedures, and the potential difficulties in accurately distinguishing unilateral from bilateral lesions may have influenced the magnitude of the estimated difference. However, the large patient cohorts, geographical diversity, and consistent asymmetry across lesion types strengthen the results’ validity and generalizability. WIDER IMPLICATIONS OF THE FINDINGS: The pattern of endometriotic lesion distribution, including the opposite asymmetry observed in the pelvis and upper abdomen/thorax, can be explained by factors influencing dissemination and implantation of refluxed endometrial cells. However, it cannot be explained as well by the coelomic metaplasia or embryonic cell remnant theories. This may have important clinical implications, providing a pathogenic basis for secondary prevention strategies. STUDY FUNDING/COMPETING INTEREST(S): The open access facility of this paper was funded by the Italian Ministry of Health, Current research IRCCS Ca’ Granda Ospedale Maggiore Policlinico. P.V. is a member of the Editorial Board of Human Reproduction Open, Journal of Obstetrics and Gynaecology Canada, and International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters in UpToDate. All other authors declare no conflicts of interest. REGISTRATION NUMBER: CRD42024511356 (PROSPERO).

Background: Pelvic organ prolapse (POP) affects up to 50% of postmenopausal women, negatively impacting sexual function and quality of life. While surgery remains the primary treatment, increasing attention has been given to perioperative vaginal oestrogen therapy and its potential impact on surgical outcomes.Objectives: This systematic review aims to evaluate the latest evidence on the role of vaginal oestrogen therapy in perioperative management and its impact on surgical outcomes in postmenopausal women with POP.Search Strategy: A systematic literature search was performed across PubMed, MEDLINE, ClinicalTrials.gov and Embase from inception to December 31, 2024. No geographic restrictions were imposed and only peer‐reviewed English‐language studies were included.Selection Criteria: Only prospective, randomised controlled trials (RCT) examining perioperative vaginal oestrogen therapy in postmenopausal women undergoing POP surgery were included.Data Collection and Analysis: Study identification and data extraction were independently performed by two and three authors, respectively. The Cochrane Collaboration's tool was used to assess bias, with disagreements resolved by a fourth reviewer.Main Results: Ten studies involving 709 patients were analysed. Vaginal oestrogen therapy showed a positive effect on Vaginal Maturation Index (VMI), vaginal thickness and surgeon's perception of tissue quality. It also appeared to reduce postoperative urinary tract infections (UTIs) and antibiotic use. However, no significant impact on sexual function, surgical ease, rates of surgical failure or POP recurrence was observed.Conclusions: Despite potential benefits in enhancing vaginal tissue quality and reducing UTIs and antibiotic use, current evidence is limited. Further standardised trials are needed for more definitive conclusions.

Background: Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age, characterized by a broad spectrum of clinical, metabolic, and ultrasound findings. Over time, ultrasound has evolved into a cornerstone for diagnosing polycystic ovarian morphology (PCOM), thanks to advances in probe technology, 3D imaging, and novel stromal markers. The recent incorporation of artificial intelligence (AI) further enhances diagnostic precision by reducing operator-related variability. Methods: We conducted a narrative review of English-language articles in PubMed and Embase using the keywords “PCOS”, “polycystic ovary syndrome”, “ultrasound”, “3D ultrasound”, and “ovarian stroma”. Studies on diagnostic criteria, imaging modalities, stromal assessment, and machine-learning algorithms were prioritized. Additional references were identified via citation screening. Results: Conventional 2D ultrasound remains essential in clinical practice, with follicle number per ovary (FNPO) and ovarian volume (OV) functioning as primary diagnostic criteria. However, sensitivity and specificity values vary significantly depending on probe frequency, cut-off thresholds (≥12, ≥20, or ≥25 follicles), and patient characteristics (e.g., adolescence, obesity). Three-dimensional (3D) ultrasound and Doppler techniques refine PCOS diagnosis by enabling automated follicle measurements, stromal/ovarian area ratio assessments, and evaluation of vascular indices correlating strongly with hyperandrogenism. Meanwhile, AI-driven ultrasound analysis has emerged as a promising tool for minimizing observer bias and validating advanced metrics (e.g., SA/OA ratio) that may overcome traditional limitations of stroma-based criteria. Conclusions: The continual evolution of ultrasound, encompassing higher probe frequencies, 3D enhancements, and now AI-assisted algorithms, has expanded our ability to characterize PCOM accurately. Nevertheless, challenges such as operator dependency and inter-observer variability persist despite standardized protocols; the integration of AI holds promise in further enhancing diagnostic accuracy. Future directions should focus on robust AI training datasets, multicenter validation, and age-/BMI-specific cut-offs to optimize the balance between sensitivity and specificity, ultimately facilitating earlier and more precise PCOS diagnoses.

Introduction: The COVID-19 pandemic has substantially impacted the management of chronic conditions, particularly endometriosis. This study aims to analyze the effects of the pandemic on the quality of life among women with endometriosis under the care of an academic referral center in Italy. Methods: Conducted from June to October 2020, this observational study utilized an online survey to assess various health dimensions. The participants included women with a confirmed diagnosis of endometriosis whose clinic appointments were cancelled, and new ones were difficult to schedule due to COVID-19 pandemic restrictions. The online questionnaire comprised 117 questions designed to evaluate chronic pelvic pain, quality of life, and psychological impacts using validated scales such as SF-12, HADS, EHP-5, and PSQI. Results: A total of 105 participants completed the online questionnaire. It was found that pandemic-related disruptions in healthcare services exacerbated symptoms of endometriosis, increased pain levels, and heightened psychological distress among participants. Specifically, 23.8% of patients reported increased pain due to delays in medical consultations and treatments caused by the pandemic. Results indicated significant correlations between higher levels of anxiety, depression, and deteriorated physical and mental health. The analysis revealed that pandemic-related stress and disruptions in routine care were significant predictors of worsened symptoms and overall health status in patients with endometriosis. Conclusion: The study underscores the need for integrated care approaches that address both the physical and psychosocial aspects of endometriosis, especially during healthcare crises. Enhanced support and resources are essential to mitigate the impact of such disruptions on chronic disease management and improve the quality of life for those affected.

Background: Hysteroscopy currently represents the gold standard for the diagnosis and treatment of intrauterine pathologies. Recent technological progress has enabled the integration of diagnostic and operative time, leading to the “see and treat” approach. Diode laser technology is emerging as one of the most innovative and intriguing techniques in this context. Methods: A comprehensive search of the literature was carried out on the main databases. Only original studies reporting the treatment of intrauterine pathologies using diode laser were deemed eligible for inclusion in this systematic review (PROSPERO ID: CRD42023485452). Results: Eight studies were included in the qualitative analysis for a total of 474 patients undergoing laser hysteroscopic surgery. Eighty-three patients had female genital tract abnormalities, 63 had submucosal leiomyomas, 327 had endometrial polyps, and one patient had a scar pregnancy. Except for leiomyomas, whose technique already included two surgical times at the beginning, only seven patients required a second surgical step. Cumulative rates of intraoperative and postoperative complications of 2.7% and 0.6%, respectively, were reported. Conclusions: Diode laser through “see and treat” hysteroscopy appears to be a safe and effective method. However, additional studies with larger sample sizes and improved designs are needed to consolidate the evidence currently available in the literature.

Background: Endometriosis affects women of reproductive age, and its pathogenesis is still unclear. Typically, it overlaps other similar medical and surgical conditions, determining a delay in early diagnosis. Metabolomics allows studying metabolic changes in different physiological or pathological states to discover new potential biomarkers. We used the gas chromatography–mass spectrometer (GC–MS) to explore metabolic alterations in endometriosis to better understand its pathophysiology and find new biomarkers. Methods: Twenty-two serum samples of patients with symptomatic endometriosis and ten without it were collected and subjected to GC–MS analysis. Multivariate and univariate statistical analyses were performed, followed by pathway analysis. Results: Partial least squares discriminant analysis was performed to determine the differences between the two groups (p = 0.003). Threonic acid, 3-hydroxybutyric acid, and proline increased significantly in endometriosis patients, while alanine and valine decreased. ROC curves were built to test the diagnostic power of metabolites. The pathway analysis identified the synthesis and degradation of ketone bodies and the biosynthesis of phenylalanine, tyrosine, and tryptophan as the most altered pathways. Conclusions: The metabolomic approach identifies metabolic alterations in women with endometriosis. These findings may improve our understanding of the pathophysiological mechanisms of disease and the discovery of new biomarkers.