The importance of the 'uterine factor' in recurrent pregnancy loss: a retrospective cohort study on women screened through 3D transvaginal ultrasound.

STUDY QUESTION: What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)? SUMMARY ANSWER: Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%. WHAT IS KNOWN ALREADY: ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria. MAIN RESULTS AND THE ROLE OF CHANCE: The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11-17%), 29 (7%; 95% CI: 5-9%), and 47 (11%; 95% CI: 8-14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3-7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2-5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2-6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3-6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19-27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3-7%). LIMITATIONS, REASONS FOR CAUTION: The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems. WIDER IMPLICATIONS OF THE FINDINGS: The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Clinical and ultrasound characteristics of vaginal lesions.

OBJECTIVE: Ultrasound examination represents the most important diagnostic method to preoperatively assess gynecological diseases. However, the ultrasound characteristics of vaginal pathologies are poorly investigated. The aim of this study was to describe the clinical and ultrasound characteristics of vaginal lesions detected at ultrasound. METHODS: This was a single center, prospective, observational study including patients with vaginal masses examined from January 2017 to May 2019. Morphologic sonographic characteristics of the lesions were described as unilocular, multilocular, unilocular-solid, multilocular-solid, and solid. For the analysis, patients were grouped into a 'malignant group', including patients with confirmed malignancy at final histology, and a 'benign group', including patients with a confirmed benign pathology at final histology and patients without a histological diagnosis but with a lesion that manifested no changes during follow-up. RESULTS: 44 patients were enrolled. 22 (50%) of 44 lesions were benign: 12 (54.5%) of these underwent ultrasound follow-up and did not show any changes at the 12 month follow-up whereas 10 (45.5%) lesions had surgical excision which confirmed the benign nature. The remaining 22 (50%) of 44 lesions underwent surgery because of suspicion of malignancy: histology confirmed a malignancy in 20 (90.9%) of 22 cases. Benign lesions were described as follow: 11/24 (45.8%) unilocular, 3/24 (12.5%) multilocular with two locules, and 10/24 (41.7%) solid lesions. Malignant lesions were solid in 19/20 (95%) cases and multilocular-solid in 1/20 (5%). Most benign lesions had a color score of 1-2 (20/24, 83.4%) while malignant lesions had a color score of 3-4 (18/20, 90%). CONCLUSION: A typical ultrasound image of a benign lesion was a unilocular cyst or hypoechoic solid mass with no or minimal vascularization on color Doppler examination. Malignant vaginal lesions were hypoechoic solid tumors with irregular margins and moderate/rich vascularization or multilocular-solid. Ultrasound should be used to supplement the clinician in the management of vaginal lesions.

Palliative electro-chemotherapy in elderly patients with vulvar cancer: A phase II trial.

OBJECTIVE: The primary endpoint of this trial was to assess clinical response (cCR) of squamocellular vulvar cancer (V-SCC) in elderly patients treated with electro-chemotherapy (ECT). Secondary endpoints were symptoms relief and local tumor control. METHODS: A phase II study was designed and elderly patients with V-SCC unfit for other treatments were treated. Response Evaluation Criteria in Solid Tumors (RECIST criteria) were applied to evaluate tumor response. Quality of life (QoL) was evaluated by visual analogue score (VAS) for pain and four items of vulvar cancer subscale (VCS), of functional assessment of vulvar cancer therapy (FACT-V) [16], before, one month after the procedure and during follow-up. RESULTS: Median age was 85 years (range 66-96 years). One month after treatment complete response was observed in 13 patients (52%), partial response in 7 (28%), stable disease in 3 (12%), and progressive disease in 2 (8%). Local tumor control at 1 and 6 months was 91% and 53%, respectively. Symptom free survival at 1 and 6 months was 78% and 40%, respectively, with significant reduction of pain (P < 0.01). One-year overall survival was 34%. CONCLUSIONS: Our study showed that ECT produces high response rate with significant reduction of pain and improvement of local symptoms.

Single or repeated gonadotropin-releasing hormone agonist treatment avoids hysterectomy in premenopausal women with large symptomatic fibroids with no effects on sexual function.

AIM: The aim of our study was to explore the effects on symptoms and female sexual function of the medical management with gonadotropin-releasing hormone agonist (GnRHa) in women of more than 45 years old compared to surgical management. METHODS: Women with symptomatic uterine fibroids were enrolled to participate to the present open-label study. We offered two different treatment options: medical with GnRHa for 6 months (group A) or hysterectomy (group B). The patients were reviewed in follow-up for 24 months. The impact of medical or surgical therapy on sexual life was evaluated. RESULTS: No significant differences were found in population characteristics between the two groups. GnRHa treatment was efficient in reducing symptoms in 88% of patients but 22% of patients needed adjunctive cycles of medical therapy. After 24 months, 16% of the patients did not complete the study. The failure percentage of the medical treatment was 12%. No severe side-effects were recorded, and eight patients had reached menopause. No significant differences were observed in the Female Sexual Function Index score in each domain between the medical and surgical groups, with total scores of 18.94 ± 10.16 and 22.00 ± 8.86, respectively (mean ± standard deviation), and the prevalence of dysfunction was 12% and 22%, respectively, similar to the general population of the same age. CONCLUSION: We found that medical therapy with GnRHa is a satisfactory alternative to surgery for fibroids in women of more than 45 years old.

Electrochemotherapy can be used as palliative treatment in patients with repeated loco-regional recurrence of squamous vulvar cancer: a preliminary study.

OBJECTIVE: Electrochemotherapy (ECT) is an attractive treatment for solid cutaneous tumours with a good response rate (55-92%). No studies have evaluated ECT performed in vulvar cancer. The aim of our study was to evaluate the safety, local tumour efficacy and relief of symptoms of ECT treatment in patients affected by recurrence of squamocellular vulvar cancer (V-SCC) unsuitable for standard treatments. METHODS: We enrolled nine patients with histological diagnosis of recurrence of V-SCC. Intravenous bleomycin was injected under general sedation after an accurate mapping of all lesions and ECT was performed. Patients were reviewed after one, three and six months. Response to therapy was evaluated using RECIST criteria and quality of life (QoL) was evaluated via questionnaires. RESULTS: The median age was 84 years (range 80-90 years). The main location of recurrences was the vulva (87.5%). Multiple lesions were present in 25% of cases. No peri-operative complications were observed. Response to therapy was complete in 62.5% of patients, partial in 12.5%, no change was observed in 12.5% and progression of disease in 12.5% of patients respectively. Evaluation of symptoms showed a significant reduction of pain, bleeding, odour (p < 0.04) and urinary discomfort (p < 0.04). We observed two relapses at four and seven months after treatment. After nine months fifty percent of patients were alive. CONCLUSIONS: Our preliminary study showed that ECT is a suitable procedure in elderly patients with loco-regional vulvar cancer relapses. ECT can be used as palliative therapy and the treatment relieves symptoms and improves QoL.

Systematic pelvic and aortic lymphadenectomy in advanced ovarian cancer patients at the time of interval debulking surgery: a double-institution case-control study.

BACKGROUND: The prognostic role of systematic lymphadenectomy remains unclear in advanced ovarian cancer (AOC). Only few retrospective case series have investigated the percentage of lymph node metastases after neoadjuvant chemotherapy. This multi-institutional case-control study analyzed the prognostic role of systematic lymphadenectomy in AOC patients at the time of interval debulking surgery (IDS). METHODS: From January 2005 to December 2010, the records of patients with AOC admitted to IDS at the Catholic University of Rome (n = 101, controls) and at the University of Bologna (n = 50, cases) were retrospectively analyzed. The cases, routinely submitted to systematic pelvic and aortic lymphadenectomy, were matched 1:2 with the controls, who did not routinely undergo lymphadenectomy. To correctly assess the prognostic role of lymphadenectomy, only patients with optimally debulked disease were included. Progression-free survival and overall survival were analyzed by a log-rank test. RESULTS: After an overall mean follow-up of 36 months (95% confidence interval 33-39), 35 and 63 recurrences (70.0 vs. 62.4%; p = NS) and 15 and 24 deaths due to disease (30 vs. 23.7%; p = NS) were observed in the case and controls, respectively. The 2-year progression-free survival rate was 36 versus 25% (p = 0.834), and the 2-year overall survival rate was 69 versus 88% (p = 0.777), in the case and controls, respectively. The median operating time was longer, and the percentage of patients requiring blood transfusions was higher in the cases than in the controls (225 vs. 210 min, p = 0.023, and 54 vs. 22.8%, p = 0.0001, respectively). CONCLUSIONS: Lymphadenectomy at the time of IDS could be omitted, at least in high-risk patients.

Clinical significance of microinvasion in borderline ovarian tumors and its impact on surgical management.

OBJECTIVE: The aims of this study were to evaluate the rate of recurrences in borderline ovarian tumors (BOTs) with microinvasion and to evaluate the possibility to enlarge fertility-sparing surgery in this group of patients. METHODS: Between 1985 and 2010, 209 patients with BOTs were retrospectively divided into 2 groups: group 1 consisted of 28 women with microinvasive BOTs; group 2 consisted of 181 with BOTs without microinvasion. All of the patients were submitted to surgical treatment: in group 1, 10 patients underwent cystectomy (CYS), 11 patients underwent monolateral salpingo-oophorectomy (MSO), and 7 patients underwent bilateral oophorectomy with or without total hysterectomy (BSO); in group 2, 34 patients underwent CYS, 58 patients underwent MSO, and 89 patients underwent BSO. Specific prognostic factors such as stage, surgical approach, intraoperative spillage, histology, exophytic tumor growth, and endosalpingiosis were analyzed. Tumor recurrence rate and overall and disease-free survivals were evaluated. RESULTS: After a mean follow-up of 53 months, relapses occurred in 21.4% of the cases in group 1 and in 12.7% of the cases in group 2 (P = 0.21). The prognostic factors had no significant differences in the 2 groups. Relapses after CYS, MSO, and BSO were observed in 30%, 27.3%, and 0%, respectively, in group 1 and in 29.4%, 12.1%, and 6.7%, respectively, in group 2. Progression-free survival was significantly longer in BOTs compared to microinvasive BOTs (P = 0.041), but overall survival did not differ. CONCLUSIONS: Although exploratory, our data suggest that BOTs with microinvasion present earlier relapses, but overall incidence of relapses and overall survival do not differ significantly from BOTs without microinvasion. Fertility-sparing surgery is feasible in this group of patients, but strict follow-up has to be suggested.

Complete Uterine Septum, Double Cervix and Vaginal Septum (U2b C2 V1): Hysteroscopic Management and Fertility Outcomes-A Systematic Review.

BACKGROUND: complete uterine septum, double cervix and vaginal septum is a rare complex Müllerian anomaly affecting patients' quality of life in terms of fertility and pelvic pain. The aim of our review is to gather the studies concerning the diagnosis and treatment this complex malformation and to describe the related fertility outcomes. METHODS: this study was conducted in 2022, according to the criteria of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the protocol was submitted to the International Prospective Register for Systematic Reviews (PROSPERO). PubMed, Scopus and Web of Science electronic databases were searched to find eligible articles. In total, 538 articles were identified through literature research. A total of ten articles satisfied the eligibility criteria and were included in the systematic review. RESULTS: 86 affected women were evaluated, and 71 of them were treated. Almost all patients included in our research presented with primary infertility or with a history of recurrent miscarriages; half of all patients also reported dyspareunia. After surgical treatment, 47 pregnancies were achieved: 41 live birth and ongoing pregnancies and six spontaneous miscarriages occurred; a significantly lower miscarriage rate was reported after surgical treatment. CONCLUSION: hysteroscopic treatment of U2b C2 V1 anomaly can be safely performed, leading to favorable fertility outcomes, measured as the achievement of pregnancy and a reduction in miscarriage rate.

The Role of Ultrasound in the Evaluation of Inguinal Lymph Nodes in Patients with Vulvar Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the efficacy of ultrasound in assessing the inguinal lymph nodes in patients with vulvar cancer. METHODS: A systematic review of published research up to October 2020 that compares the results of ultrasound to determine groin node status with histology was conducted. All study types that reported primary data on the role of ultrasound in the evaluation of groin lymph nodes in vulvar cancer were included in the systematic review. Data retrieved from the included studies were pooled in random-effects meta-analyses. RESULTS: After the screening and selection process, eight articles were deemed pertinent for inclusion in the systematic review and meta-analysis. The random-effects model showed a pooled Se of 0.85 (95% CI: 0.81-0.89), Sp of 0.86 (95% CI: 0.81-0.91), PPV of 0.65 (95% CI: 0.54-0.79) and NPV of 0.92 (95% CI: 0.91-0.94). There was a pooled LR+ and LR- of 6.44 (95% CI: 3.72-11.4) and 0.20 (95% CI: 0.14-0.27), respectively. The pooled accuracy was 0.85 (95% CI: 0.80-0.91). CONCLUSIONS: Although the studies had small sample sizes, this review represents the best summary of the data so far. Ultrasound has revealed high sensitivity and high negative predictive value in the assessment of nodal status in vulvar cancer.

Local α-tocopherol for acute and short-term vaginal toxicity prevention in patients treated with radiotherapy for gynecologic tumors.

INTRODUCTION: Data in literature about the use of adjuvant treatment to reduce acute adverse effects of radiotherapy on the pelvis are scant, with the exception of a few reports on the topical use of estrogen, which promotes proliferation of epithelium. MATERIALS AND METHODS: In this prospective trial, α-tocopherol acetate was topically administered to patients affected by endometrial and cervical cancer and undergoing radiation treatment to avoid acute vaginal complications. RESULTS: Vaginal application of α-tocopherol reduced vaginal toxicity and pain, although vaginal secretion was not significantly different in the 2 groups studied. The histological scoring system showed a significant reduction of inflammation, no difference in fibrosis, and an increase of acanthosis. CONCLUSIONS: The use of α-tocopherol as adjuvant treatment to reduce the acute adverse effects of radiotherapy on the vagina should be considered.