Cervical pessary for preterm birth prevention after an episode of arrested preterm labor: a retrospective cohort study with targeted maximum likelihood estimation of the average treatment effect.

OBJECTIVE: To evaluate whether cervical pessary effectively reduces the preterm birth < 37 weeks rate in patients who have not delivered after an episode of arrested preterm labor. PATIENTS AND METHODS: Retrospective cohort study was conducted on singleton pregnant patients admitted to our institution between January 2016 and June 2021 for threatened preterm labor and who had a cervical length < 25 mm. Women in whom a cervical pessary was placed were considered as exposed, while women in whom expectant management was preferred were considered as unexposed. The primary outcome was the rate of preterm birth before 37 weeks. A targeted maximum likelihood estimation was used to estimate the average treatment effect of cervical pessary by adjusting for a-priori-defined confounders. RESULTS: A cervical pessary was placed in 152 (36.6%) patients (exposed), while the remaining 263 (63.4%) were managed expectantly (unexposed). The adjusted average treatment effect was -14% (-18 to -11%), -17% (-20 to -13%), and -16% (-20 to -12%) for preterm birth < 37 weeks, < 34 weeks, and < 32 weeks, respectively. The average treatment effect for adverse neonatal outcomes was -7% (-8 to -5%). No difference in gestational weeks at delivery between exposed and unexposed emerged when gestational age at first admission was > 30.1 gestational weeks. CONCLUSIONS: The positioning of a cervical pessary placement may be evaluated to reduce the risk of a subsequent preterm birth after an episode of arrested preterm labor in pregnant patients with onset of symptoms before 30 gestational weeks.

Atrophic endometrium in postmenopausal women referred to diagnostic hysteroscopy: a study to avoid unnecessary examinations.

OBJECTIVE: Any diagnostic workup should be based on appropriateness criteria. Diagnostic hysteroscopy is a procedure widely used in endometrial pathology. Its high outpatient feasibility frequently leads to misuse. However, it can cause discomfort and, albeit rarely, complications. The present study aimed to provide an estimate of unnecessary examinations based on variables associated with atrophic endometrium in postmenopausal women referred to diagnostic hysteroscopy. PATIENTS AND METHODS: One-hundred and sixty-six postmenopausal women undergoing hysteroscopy were retrospectively analyzed. All included women had a final histological reference standard. The sample was divided into women with atrophic endometrium vs. women with endocavitary lesions (benign/premalignant/malignant). Univariate and multivariate analysis was performed to assess those patient characteristics associated with atrophic endometrium. Furthermore, based on the likelihood ratios, a post-test probability analysis was performed to provide an estimate of atrophy according to the presence of specific variables. RESULTS: Sixty-one postmenopausal women (36.7%) undergoing diagnostic hysteroscopy showed atrophic endometrium at final histology. Multivariate analysis showed that the independent variables associated with atrophy were the absence of abnormal uterine bleeding [Odds Ratio (OR)=6.43, Confidence Intervals (CI) 2.087 to 19.822], and endometrial thickness (criterion < 7 mm) (OR=0.417, CI 0.300 to 0.578). In women showing both variables associated with negative endometrial outcome, post-test probability analysis resulted in an atrophic endometrium rate of 89.13%, from a pre-test probability of 36.7%. CONCLUSIONS: About 90% of asymptomatic postmenopausal women with endometrial thickness <7 mm resulted in an atrophic endometrium at hysteroscopy. Every gynecologist should know and consider these data before referring such women to further examinations. In these cases, diagnostic hysteroscopy is not cost-effective leading to a high number of false positives.

Sensitivity and specificity values of high-risk HPV DNA, p16/ki-67 and HPV mRNA in young women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL).

OBJECTIVE: The aim of the study was to evaluate the sensitivity and specificity values of high-risk HPV DNA test, p16/ki-67, and HPV mRNA in histologically high-grade cervical intraepithelial lesions (CIN2-CIN3) in women aged 21-24 years with diagnosis of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) at pap smear. PATIENTS AND METHODS: 342 patients between 21-24 years old, attending spontaneously our clinics, 118 with ASCUS and 224 with LSIL, were enrolled in the study. All patients underwent colposcopy and biopsies were performed in the areas with major changes. All patients were tested at the same time for p16/ki-67, high-risk HPV DNA and HPV mRNA. RESULTS: Nineteen out of 118 women with ASCUS showed a high-grade cervical intraepithelial lesion, 11 out of 118 (9.32%) CIN2, and 8 out of 118 (6.78%) CIN3. The sensitivity of high-risk HPV DNA was 99.9%, and the specificity 23.2%; p16/ki-67 pointed out a sensitivity of 90.9%, and a specificity of 81.8%; HPV mRNA showed a sensitivity of 81.8%, and specificity of 87.9% in CIN2 lesions. In CIN3 lesions, the sensitivity of high-risk HPV DNA was 99.9%, while the specificity was 19.1%; p16/ki-67 showed a sensitivity of 99.9%, and a specificity of 73.7%; HPV mRNA relived a sensitivity of 87.5%, and a specificity of 80.8%. In women with LSIL, a total of 42/224 (18.75%) of CIN2 were found at the histopathological examination, while 17/224 (7.59%) women presented a CIN3. No case of invasive cancer was identified. High-risk HPV DNA was positive in 190/224 (84.8%), p16/ki-67 in 119/224 (53.1%), and HPV mRNA in 104/224 (46.4%). In women with CIN2, the sensitivity of high-risk HPV DNA was of 92.8%, and the specificity 17.5%, the sensitivity of p16/ki-67 was 95.2%, and specificity 61.8%. HPV mRNA showed a sensitivity of 88.8% and a specificity of 87.8%. In women with CIN3, the sensitivity of high-risk HPV DNA was 88.2%, and the specificity 29.7%; p16/ki-67 pointed out a sensitivity of 94.1%, and a specificity of 49%; HPV mRNA showed a sensitivity of 88.2% and a specificity of 80.6. CONCLUSIONS: Taking into account the high rate of spontaneous regression of high-grade lesions in young women, these tests, in particular, the HPV mRNA test, used as a triage test for ASCUS or LSIL, can modify follow-up triage strategy. In fact, this biomarker, due to its high specificity, could lead to a cytology repetition instead of an immediate colposcopy, avoiding over diagnosis and potential overtreatment in this category of women.

Vaginal natural oxygenation device (VNOD) for concomitant administration of hyaluronic acid and topical hyperbaric oxygen to treat vulvo-vaginal atrophy: a pilot study.

OBJECTIVE: This is a pilot study to evaluate the effectiveness of concomitant administration of hyaluronic acid and topical hyperbaric oxygen therapy (THOT) by a specifically designed medical device (vaginal natural oxygenation device, VNOD) in improving the symptomatology of postmenopausal patients with vulvo-vaginal atrophy (VVA). PATIENTS AND METHODS: Women with diagnosis of severe VVA from September 2017 to May 2018 were included. Five biweekly administration of THOT and concomitant of hyaluronic acid were performed with a specifically designed medical device. In each occasion, the intensity of patient's symptoms (well-being such as absence of dyspareunia, vaginal dryness, vulvar and/or vaginal itching; vaginal burning; presence of fluid) was determined with a graduated scale from 1 to 6 and the vaginal elasticity and the vaginal wall epithelium appearance were also determined with a graduated scale from 1 to 5. The change in all parameters from baseline to end of therapy was evaluated. RESULTS: Twenty-five patients were considered for the final analysis. A significant improvement in well-being (0.3 vs. 5.1, p < 0.001), vaginal burning (0.2 vs. 5.1, p < 0.001), presence of fluid (0.6 vs. 4.9, p < 0.001), vaginal epithelium appearance (1.8 vs. 4.7, p < 0.001), and vaginal elasticity (1.1 vs. 3.8, p < 0.001) was observed between the first and the last therapy session. All the patients reported a recovery of their sexuality at the end of the five treatment sessions. CONCLUSIONS: In this pilot study, the use of VNOD seems to be a valid treatment of VVA, resulting in a completely natural type of therapy well accepted by patients with immediate therapeutic effects and without side effects; these findings must be confirmed in a well-designed randomized controlled trial.

Trend of decreasing length of cervical cone excision during the last 20 years.

OBJECTIVE: The aim of the present investigation was to evaluate the cervical conizations performed in the last 20 years in a single institution, with a particular interest in analyzing the trend of the length of cone excisions. PATIENTS AND METHODS: A retrospective cohort study of women who underwent a CO2-laser cervical conization between January 1996 and December 2015. Cytological abnormalities on referral pap smear, colposcopic findings and pertinent clinical and socio-demographic characteristics of each woman were collected. In particular, the length of cone specimen was evaluated, taking into account all the factors potentially influencing the length of excision. RESULTS: A total of 1270 women who underwent cervical conization from January 1996 to December 2015 were included in the analysis. A mean cone length of 15.1 ± 5.7 mm was reported, and we observed a significant decrease in the length of cone excisions over the whole study period. Age (rpartial = 0.1543, p < 0.0001), see & treat procedure (rpartial = -0.1945, p < 0.0001) and grade II colposcopic findings (rpartial = 0.1540, p < 0.0001) were significantly associated with the length of cone excision on multivariate analysis. CONCLUSIONS: In the last 20 years, a significant decrease in the length of cone excision was observed. In our opinion, this can be due to the acquired awareness by the gynecologists of the potential disadvantages of wide cone excision in term of adverse obstetric outcomes in future pregnancies.

Predictors of malignancy in endometrial polyps: a multi-institutional cohort study.

PURPOSE OF INVESTIGATION: The risk of endometrial cancer in women with endometrial polyps (EPs) has been reported to vary between 0.3% and 4.8%. There is a lack of data about the management of asymptomatic women with incidental diagnosis of EPs. In the present study the authors correlated demographic and clinical characteristics with histopathological features of the EPs hysteroscopically removed. MATERIALS AND METHODS: An observational multi-institutional cohort study was conducted from February 2010 to December 2012 to identify all the premenopausal and postmenopausal women consecutively undergoing hysteroscopic polypectomy. The data of women were reviewed and clinical features were related to histopathologic results. RESULTS: The patients recruited were 813. The mean age was 52.5 years (range 22-87). The results showed a correlation between older age, high body mass index (BMI) and obesity, postmenopausal state, abnormal uterine bleeding (AUB), hypertension, and risk of malignant EPs. On multivariable analysis, the correlation remained only for age (OR 1.08, 95% CI 1.03 - 1.14) and AUB (OR 3.53, 95% CI 1.87 - 6.65). CONCLUSION: Older patients in postmenopausal status with AUB, a high BMI, and hypertension are at higher risk for premalignant and malignant polyps. In these patients a surgical approach should be used, consisting in hysteroscopical removing of the polyp.

Risk of recurrent menorrhagia after hydrothermoablation: role of GnRH analogues neoadjuvant treatment in long-term successful rate.

OBJECTIVE: To evaluate the long-term effectiveness of presurgical therapy with GnRH analogues in patients who underwenthydrothermal endometrial ablation (HTA) for menorrhagia and assess the relationship between sonographically measured myometrium thickness and pelvic pain. MATERIALS AND METHODS: A prospective randomized control study comparing 15 women (Group A) with presurgical subcutaneous triptorelin depot injection before HTA with controls (Group B, n = 15). Inclusion criteria were: recurrent menorrhagia, uterus length < 12 cm, no previous hormonal therapy for at least six month, and family plan completed. Student's t test was applied, as appropriate, to compare continuous variables. Proportion were compared with chi-squared. RESULTS: After 12 months of follow-up, Group A showed a significantly lower (0% vs 20%; p = 0.03) failure rate after hydrothermoablation than the Group B and a generally higher successful rate at 24 and 48 months. The discomfort, evaluated with VAS, showed a mean value of 47.6 +/- 15.9 +/- SD); 96.7% of women reported a mild-moderate postoperative pain. No perioperative and late complications were recorded. CONCLUSIONS: Presurgical treatment with GnRH analogues seems to improve long-term efficacy of HTA. Perioperative pelvic pain seems to not be affected by myometrium thickness.