Incidence of pre-neoplastic and neoplastic lesions of the cervix before and after the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic had significant effects on healthcare systems worldwide, including the disruption of routine screening programs for cervical cancer. This study aimed to compare the incidence of cervical intra-epithelial neoplasia (CIN)2 and CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix before and after the COVID-19 pandemic. METHODS: A retrospective analysis was performed using archive data from the Policlinico di Bari, Unit of Gynecology and Obstetrics. The study included patients who tested positive for high-risk human papillomavirus (HPV) at the level I screening test (HPV test) and were subsequently referred to level II screening, which involves the Papanicolaou (Pap) test and colposcopic examination. We excluded individuals who did not comply with the recommended follow-up, patients with low-risk HPV infection, those with autoimmune diseases, oncologic diseases, or those undergoing immunosuppressive therapies. The time period spanned from January 2020 to December 2022. The incidence of CIN2/CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix was compared between the pre-screening period (2017-2019) and the post-screening period (2020-2022). RESULTS: The study comprised a cohort of 1558 consecutive European sexually active women with a median age of 34 years (range 25-65) who underwent colposcopic evaluation of the uterine cervix as a level II screening program. The comparison between the pre-screening and post-screening periods showed an increase in the incidence of CIN2/CIN3 lesions, rising from 23.9 to 63.3 per 100 000 (HR 2.62, 95% CI 1.64 to 4.20; p<0.001). Additionally, although there was an absolute increase in the incidence of cervical carcinoma and adenocarcinoma, the comparison did not reach statistical significance (squamous carcinoma: 2017-2019, 2.5 per 100 000; 2020-2022 3.4 per 100 000, p=0.72; adenocarcinoma: 2017-2019, 3.5 per 100 000; 2020-2022 7.6 per 100 000, p=0.24). CONCLUSION: This study showed a significant increase in the incidence rate of CIN2/CIN3 lesions after the COVID-19 pandemic. Our findings may be attributed to the temporary suspension of follow-up programs during the pandemic, although the study does not rule out direct effects of SARS-CoV-2 on the risk of pre-neoplastic and neoplastic conditions of the cervix.

Hormone replacement therapy in BRCA mutation carriers: how shall we do no harm?

Women with a BRCA mutation have an increased risk of developing breast and ovarian cancer. Bilateral salpingo-oophorectomy is the only effective strategy to reduce this risk. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended between the ages of 35 and 40 for women carriers of BRCA1 and between the ages of 40 and 45 for women carriers of BRCA1 and BRCA2 mutations. Most women undergo this procedure prior to their natural menopause subsequently developing an anticipated lack of hormones. This condition affects the quality of life and longevity, while it is more pronounced in women carrying a BRCA1 mutation compared to BRCA2 because they are likely to have surgery earlier. Hormone replacement therapy (HRT) is the only strategy able to significantly compensate for the loss of ovarian hormone production and counteract menopausal symptoms. There is strong evidence that short-term HRT use does not increase the risk of breast cancer among women with a BRCA1 mutation. Few data are available on BRCA2 mutation carriers. Therefore, BRCA mutation carriers require careful counseling about the outcomes of their RRSO, including menopausal symptoms and/or the fear associated with HRT use.

Prognostic factors in clear cell carcinoma of endometrium: analysis of 55 cases.

BACKGROUND AND AIM OF THE WORK: The purpose of this study was to evaluate the clinical and pathologic prognostic factors associated with survival in patients with clear cell carcinoma (CCC) of the endometrium. METHODS: A retrospective review of fifty-five patients with endometrial clear cell carcinoma were collected. RESULTS: The median overall and disease-free survivals were 40 and 20 months, respectively. A univariate analysis was performed with respect to stage of disease, age, lymph nodes status, myometrium invasion, lymph vascular space invasion and adjuvant therapy. Stage was found to be the only important prognostic factor related to survival. In fact, early stage had a median survival of 77 months compared to 34 months in the advanced disease (p<0.04). These differences remained significant after adjusting for single stage (stage III versus IV).    Conclusions: Endometrial CCC is a rare histotype. Advanced stage disease is considered a poor prognostic factor. Recurrences are high even in early stage. Randomized clinical trials are needed.

Colpocytological abnormalities in HIV infected and uninfected pregnant women: prevalence, persistence and progression.

In this retrospective case-control study, we analyse data of 48 HIV-positive pregnant patients, versus a control group of 99 HIV-negative pregnant women, followed as outpatients by our department from 2009 to 2014. The aims of the study were to investigate the prevalence, persistence and progression of cervical squamous intraepithelial lesions (SIL) in each group and to correlate colpo-cytological lesions to the socio-demographic and clinical-laboratory findings in the HIV + pregnant women. In our study we observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions. Pap smear and colposcopy should be part of routine care for HIV-infected pregnant women because these lesions behave aggressively in these patients. Success of prevention depends on massive access of patients to screening. HAART reduces viral load and maintains CD4 count and can affect progression of SIL. Multidisciplinary services on the same site appear to be one promising strategy to improve compliance in patients. Impact Statement What is already known on this subject: Our study provided novel information on a highly vulnerable population of young HIV + pregnant women. What the results of this study add: We observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions remarkable with colposcopy. We could consider these important risk factors to evaluate to establish an appropriate strategy of management for these patients. What the implications are of these findings for clinical practice and/or further research: Association of the risk between SIL presence and HIV and HPV infection also deserves additional investigation. We believe that Pap smears and colposcopies should be part of the routine care for HIV-infected women because these lesions behave particularly aggressively in these patients.

Chronic endometritis in patients with unexplained infertility: Prevalence and effects of antibiotic treatment on spontaneous conception.

PROBLEM: The correlations between chronic endometritis and unexplained infertility are unexplored. METHOD OF STUDY: We performed a retrospective study on consecutive patients referred to our hysteroscopy service due to unexplained infertility. All women underwent endometrial sampling with histological and cultural examinations. If chronic endometritis was diagnosed, patients received antibiotic therapy, and chronic endometritis resolution was subsequently ascertained by histological examination. We aimed to estimate chronic endometritis prevalence and the effects of antibiotic therapy on spontaneous conception during the year following hysteroscopy. RESULTS: A total number of 95 women were included. Pooled prevalence of chronic endometritis was 56.8%. Antibiotic therapy resulted in chronic endometritis resolution in 82.3% of patients, while in 17.6% disease was persistent. Women with cured chronic endometritis showed higher pregnancy rate and live birth rate in comparison with both women with persistent disease and women without chronic endometritis diagnosis (pregnancy rate = 76.3% vs 20% vs 9.5%, P < .0001; live birth rate = 65.8% vs 6.6% vs 4.8%, P < .0001). CONCLUSION: Chronic endometritis is highly prevalent in patients with unexplained infertility. Diagnosis and treatment of chronic endometritis improve spontaneous pregnancy rate and live birth rate in such patients.

Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy.

STUDY QUESTION: What is the prevalence of chronic endometritis (CE) in women with repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic treatment affect the reproductive outcome? SUMMARY ANSWER: Chronic endometritis, associated with infection with common bacteria or mycoplasma, is common in women complaining of RIF and antibiotic treatment significantly improves the reproductive outcome at a subsequent IVF cycle. WHAT IS KNOWN ALREADY: We have reported that CE is a frequent finding in women with repeated pregnancy loss and a significantly higher rate of successful pregnancies was achieved after adequate antibiotic treatment. Moreover, CE was identified in 30.3% of patients with repeated implantation failure at IVF and women diagnosed with CE had lower implantation rates (11.5%) after IVF cycles. In contrast, other authors reported that the clinical implication of CE should be considered minimal and that the reproductive outcome at IVF/ICSI cycles was not negatively affected by CE. STUDY DESIGN, SIZE, DURATION: A retrospective study was performed from January 2009 through June 2012 on 106 women with unexplained infertility and a history of RIF. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent hysteroscopy and endometrial sampling for histology and microbiological investigations. Women diagnosed with CE underwent antibiotic treatment and the effect of treatment was confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women had a further IVF attempt. The IVF outcomes were compared in women without signs of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment IVF attempt. MAIN RESULTS AND THE ROLE OF CHANCE: Seventy (66.0%) women were diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at hysteroscopy and histology, examinations were normal after appropriate antibiotic treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still present (Group 2). At IVF attempt after treatment, a significantly higher PR and LBR was reported in women from Group 1 compared with women from Group 2 (65.2 versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively). LIMITATIONS, REASONS FOR CAUTION: Possible biases related to retrospective studies and to preferential referral of patients with CE, and limited number of cases. WIDER IMPLICATIONS OF THE FINDINGS: A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt.

Endometrial preparation with estradiol plus dienogest (Qlaira) for office hysteroscopic polypectomy: randomized pilot study.

STUDY OBJECTIVE: To estimate the effectiveness of Qlaira for endometrial preparation in women undergoing hysteroscopic polypectomy in the office setting. DESIGN: Randomized clinical pilot study (Canadian Task Force classification II-2). SETTING: Academic research environment. PATIENTS: Seventy-four cycling women undergoing hysteroscopic polypectomy (polyp size <1.5 cm). INTERVENTIONS: Women were randomized to be operated on during the proliferative phase (cycle day 5-7) of a spontaneous cycle (group A) or after 9 to 11 days of Qlaira intake (group B). Polypectomy was performed by using forceps and bipolar electrodes when required. MEASUREMENTS AND MAIN RESULTS: The quality of visualization of the uterine cavity during the procedure (visual analog score [VAS] 0-5, bad to optimal), total surgeon satisfaction (VAS 0-5, very difficult to easy to perform), and total patient satisfaction (VAS 0-5, severe pain to no pain) were compared. Endometrial thickness before and at the end of the procedure was significantly less in women in group B. Mean duration of interventions was shorter in group B than in group A. In addition, vision quality, and surgeon and patient satisfaction rates were significantly higher in women in group B. CONCLUSIONS: At 10 days before surgery, administration of Qlaira is effective for preparation of the endometrium for hysteroscopic polypectomy in the office setting. With preoperative administration of Qlaira, the surgical procedure can be performed more easily and faster, and both surgeon and patient satisfaction rates are improved.

Correspondence between hysteroscopic and histologic findings in women with chronic endometritis.

OBJECTIVE: To estimate if findings in women with chronic endometritis (CE) at fluid hysteroscopy correlate with the severity of inflammation at histology and to assess the possibility to score the severity of inflammation by fluid hysteroscopy. DESIGN: Controlled clinical study. SETTING: University hospital. POPULATION: A total of 211 outpatient women with a hysteroscopic diagnosis of CE and 30 control women without any such signs. METHODS: All patients underwent endometrial biopsy by means of a 3-mm Novak's curette connected to a 20-ml syringe without any anesthesia. MAIN OUTCOME MEASURES: Hysteroscopic records were reviewed and compared with histologic findings by using an arbitrary inflammation score (Grades 0-2, no inflammation to severe infiltration, nodules and glands disruption, respectively). RESULTS: A significant correlation between focal hyperemia and isolated micropolyps with Grade 1 inflammation and between generalized hyperemia, presence of diffuse micropolyps and polypoid endometrium with Grade 2 inflammation was found. Hysteroscopic and histologic grading showed good agreement (kappa index = 0.62). CONCLUSIONS: In women affected by CE the severity of histological alterations may be reliably evaluated by fluid hysteroscopy. This information may be clinically useful not only for giving a prognosis and as a basis for interpretation of patients' complaints, but also for monitoring treatment.

Reliability of narrow-band imaging (NBI) hysteroscopy: a comparative study.

OBJECTIVE: To evaluate the usefulness of narrow-band imaging (NBI) technology for improving the diagnostic reliability of hysteroscopy. DESIGN: Prospective controlled clinical study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENT(S): Three hundred ninety-five outpatient women undergoing diagnostic hysteroscopy were enrolled. INTERVENTION(S): All patients underwent fluid minihysteroscopy with white light (WL) and NBI exploration with endometrial eye-directed biopsy. MAIN OUTCOME MEASURE(S): Hysteroscopic findings with WL and NBI were compared with histology, which was considered the gold standard. RESULT(S): Overall, the number of correct diagnoses with NBI was significantly higher than with WL. For differentiating normal from abnormal endometrial histopathology, the use of NBI showed a significantly higher specificity (0.93 vs. 0.78) and negative predictive value (0.92 vs. 0.81); NBI hysteroscopy significantly improved the sensitivity for the diagnosis of proliferative endometrium (0.93 vs. 0.78), chronic endometritis (0.88 vs. 0.70), low-risk hyperplasia (0.88 vs. 0.70), and high-risk hyperplasia (0.60 vs. 0.40). CONCLUSION(S): The use of NBI improved the reliability of diagnostic hysteroscopy. The high specificity and the low number of false negatives may reduce the number of unnecessary biopsies or of those performed in wrong areas. Moreover, compared with WL observation, NBI hysteroscopy showed significantly higher sensitivity for the detection of chronic endometritis and low-risk and high-risk hyperplasia.

Risk of long-term pelvic recurrences after fluid minihysteroscopy in women with endometrial carcinoma: a controlled randomized study.

OBJECTIVE: Concerns exist about the risk of endometrial cancer cells spreading into the peritoneal cavity after fluid minihysteroscopy. The aim of our study was to evaluate the 5-year incidence of pelvic recurrences in women affected by early-stage endometrial carcinoma (stage IA or IB) who did or did not undergo preoperative hysteroscopy with low pressure (<70 mm Hg) saline uterine distention. METHODS: A total of 140 women were randomized into two groups of 70 women who underwent or did not undergo diagnostic fluid minihysteroscopy before surgical staging. Women were followed up every 6 months for at least 5 years. Diagnosis of pelvic recurrence was based on a positive result at clinical examination and/or at vaginal cytology and/or at magnetic resonance imaging/positron emission tomography scan. Univariate analysis of disease-free survival was performed with the Kaplan-Meier method and survival curves were compared using the long-rank test. RESULTS: No difference in peritoneal cytology was observed between the two groups (5.7% and 8.5% of cases in the hysteroscopy and control group, respectively). After a mean duration of follow-up of 62 months, 2 (2.85%) pelvic recurrences in the hysteroscopy group and 3 (4.28%) in the control group were found. No significant difference was found between the two groups when the recurrence rate was compared. Overall survival rates and disease-free survival projected by Kaplan-Meier curves were not significantly different for the two groups. CONCLUSIONS: Preoperative low-pressure fluid minihysteroscopy does not increase the risk of intraperitoneal transport of endometrial carcinoma cells during the examination or the risk of pelvic recurrence at the 5-year follow-up. It does not seem to modify the recurrence rate, disease-free survival, and overall survival, although multicenter randomized trials and long-term follow-up are required to evaluate the overall oncologic outcomes of this procedure.

Correlates of HIV-1 shedding in cervicovaginal secretions and effects of antiretroviral therapies.

OBJECTIVES: To evaluate the determinants of HIV-1 RNA shedding in cervicovaginal secretions and the effects of antiretroviral therapy in a group of infected women. METHODS: A total of 122 women from whom paired peripheral blood and cervicovaginal lavage samples were available were enrolled in the study. HIV-1 RNA was quantified in the plasma and cell-free fraction of cervicovaginal lavages by the nucleic acid sequence-based amplification assay (lower limit of detection 80 copies/ml). RESULTS: Seventy-one per cent of the women had detectable viral load in the cervicovaginal lavage and this appeared to be correlated to plasma viral load and to the degree of immunodeficiency as expressed by the absolute number of CD4 cells. Antiretroviral-treated patients had a lower risk of shedding the virus in the genital tract, but this association was limited to patients treated with highly active antiretroviral therapy (HAART). However, in 25% of women with undetectable plasma viral load, a genital shedding of the virus was demonstrated. CONCLUSION: Plasma viral load may fail as a marker of infectivity of genital secretions. HAART treatment seems to be more efficacious in suppressing viral shedding at the genital level. The female genital tract represents a distinct compartment for HIV-1 replication/evolution.