Bromocriptine inhibits proliferation in the endometrium from women with adenomyosis.

Objective: Bromocriptine treatment has been shown to reduce menstrual bleeding and pain in women with adenomyosis in a pilot clinical trial. The underlying mechanism contributing to the treatment effect is however unknown. The purpose of this study was to explore the effect of bromocriptine on the proliferation and migration properties of the endometrium in women with adenomyosis, by assessing cellular and molecular changes after six months of vaginal bromocriptine treatment. Methods: Endometrial specimens were collected during the proliferative phase from women with adenomyosis (n=6) before (baseline) and after six months of treatment with vaginal bromocriptine. Immunohistochemistry was used to determine changes in the protein expression of Ki67 in the endometrium of women with adenomyosis. Primary endometrial stromal cells isolated at baseline were expanded in vitro and exposed to different doses of bromocriptine to determine the optimal half-maximum inhibitory concentration (IC50) using CellTiter-Blue® Cell Viability Assay. Cell proliferation was assessed by bromodeoxyuridine ELISA assay and Ki67 gene expression was checked by real-time PCR. The migratory ability of endometrial stromal cells was determined by wound healing and transwell migration assays. Small RNA sequencing was applied on tissues collected from women with adenomyosis before and after bromocriptine treatment to identify differentially expressed microRNAs (miRNAs) after bromocriptine treatment. Bioinformatic methods were used for target gene prediction and the identification of biological pathways by enrichment procedures. Results: Vaginal bromocriptine treatment reduced the Ki67 protein expression in the endometrium of women with adenomyosis and did not change the prolactin mRNA expression and protein concentration of prolactin in endometrial tissues. Bromocriptine significantly inhibited the proliferative and migrative abilities of endometrial stromal cells derived from women with adenomyosis in vitro. Moreover, small RNA sequencing revealed 27 differentially expressed miRNAs between the endometrium of women with adenomyosis before and after six months of vaginal bromocriptine treatment. KEGG pathway analysis on targeted genes of 27 miRNAs showed that several signaling pathways associated with cell proliferation and apoptosis were enriched after bromocriptine treatment. Conclusion: Bromocriptine treatment exhibits an anti-proliferative effect in the endometrium of women with adenomyosis in vivo and in vitro. Bromocriptine might inhibit the proliferation of endometrial tissue in adenomyosis in part through the regulation of dysregulated microRNAs and proliferation-associated signaling pathways.

HPV genotype distribution and age correlation in a selected Italian population undergoing conization.

BACKGROUND: Detection and genotyping of human papillomavirus (HPV) has gained increasing importance in cervical cancer prevention and treatment of cervical intraepithelial neoplasia (CIN). This study aims to determine the HPV type distribution in cervical specimens obtained from women diagnosed with CIN. We evaluated in a selected Italian population the distribution of HPV genotypes. METHODS: Cervical samples were collected from women undergoing laser CO2 conization for high grade at Colposcopic Laser Surgery Unit of the Careggi University Hospital and at the Colposcopy Service of Local Health Unit Toscana Centro in Florence, Italy, between September 2014 and February 2017. HPV genotyping was performed using the LINEAR ARRAY® HPV Genotyping Test. RESULTS: Three hundred and six patients were enrolled. HPV infection was detected on 244 samples (79.7%). A different rate of mono- and poly-infections was observed, with higher poly-infection rates in younger women. Moreover, depending on different age groups (clustered in 5-years interval from 22 to 69 years old) significant different distribution of HPV was fund as genotype, phylogenetic type and cancer-related risk. CONCLUSIONS: Our results suggest that some physiological conditions (i.e. menopause), could influence selection and clearance of specific HPV genotypes. The results of this study represent the basis for supporting the HPV genotyping as clinical tool providing benefits in the management of women with high CIN grade.

High grade cervical intraepithelial neoplasia positive biopsy: the importance of accurate pre-operative workup.

BACKGROUND: In cervical cancer screening programs, women with abnormal cytology and confirmation by biopsy are referred for colposcopy for histological evaluation. METHODS: We characterized the presence and the genotype of HPV by Linear Array HPV genotyping assay in cytological samples collected from about 400 women undergoing conization, with reported high CIN grade after biopsy. RESULTS: The most prevalent genotype was HPV 16, with an increasing presence depending on the severity of the CIN and with the highest incidence in the 26-35 age range. In the group of younger women (<25) we found the highest percentage of CIN3 (39.3%) and the lowest of CIN1 (17.9%). An increase of CIN1 with increasing age was observed. A different distribution of HPV presence was observed depending on CIN grade (P<0.001): CIN1 HPV negative samples were 46.3%, CIN2: 5.8% and CIN3: 1.4%. Interesting, in the analyzed cohort, we observed the presence of 30% of CIN1. Moreover, within CIN1, 85% of them were associated to negative HPV detection, this observation suggested that the detection of HPV presence may be useful to identify low CIN grade that should be reconsidered for surgical treatment. CONCLUSIONS: These findings suggest implementing the protocol for the management of women with high risk precancer lesions, with a further HPV test before surgical treatment. The evaluation of HPV presence and genotype before conization might represent a useful tool in reducing or postpone the conization treatment.

Prevalence of Infertility Among Patients With Isthmocele and Fertility Outcome After Isthmocele Surgical Treatment: A Retrospective Study.

Background: An isthmocele is a diverticulum on the anterior wall of the uterine isthmus at the site of a cesarean delivery scar. We evaluated the prevalence of infertility among patients with isthmocele, the resolution of symptoms, and infertility outcomes after hysteroscopic isthmoplasty. Methods: We conducted a retrospective study of 35 consecutive patients with symptomatic isthmocele between 2010 and 2015 at Hospital Piero Palagi in Florence, Italy. Patients with symptomatic isthmocele had postmenstrual abnormal uterine bleeding, sovrapubic pain, and infertility. Results: The study population was divided into Group A - Fertile Patients (n=19) and Group B - Infertile Patients (n=16) according to the prevalence of infertility after the diagnosis of isthmocele. Group B was subdivided into Group B1 (became pregnant, n=9) and B2 (did not become pregnant, n=7) according to infertility resolution after isthmocele treatment. We found statistically significant differences between Groups A and B regarding the number of cesarean sections (P=0.0205), the grade of isthmocele (P=0.0421), and body mass index (P=0.0001). In the subgroup analysis, we found statistically significant differences between Groups B1 and B2 for age (P=0.0151), grade of isthmocele (P=0.0361), and cervical dilatation (P=0.0293). Conclusion: We identified a subgroup of patients at higher risk of being infertile after the diagnosis of isthmocele and a subgroup of patients who could benefit the most in terms of fertility after minimally invasive hysteroscopic surgery.

Spontaneous Resolution of an Acquired Uterine Arteriovenous Malformation in an Elderly Primigravida.

BACKGROUND Uterine arteriovenous malformation (AVM) is an uncommon lesion characterized by an abnormal connection between arterial and venous circulation that can be congenital or acquired. Acquired uterine AVMs are generally traumatic and follow delivery, abortion, curettage, or uterine surgery. CASE REPORT A 45-year-old female who was gravida 1 para 0 presented to our hospital with severe vaginal bleeding. Two weeks before, the patient underwent therapeutic abortion. At admission, a transvaginal ultrasound showed an unclear intrauterine lesion that spread out to the myometrium. Color Doppler evaluation demonstrated an elevated color score. Beta human chorionic gonadotropin (beta-hCG) levels were measured at admission and daily repeated, with a progressive decrease of values up to a negative level. A pelvic magnetic resonance imaging described an area of tubular and tortuous structures involving the myometrium. A computed tomography angiography confirmed the presence of a lesion infiltrating the endometrium and myometrium containing arteriovenous structures with a highly enhanced effect. Despite these findings, the patient was clinically stable. A diagnosis of uterine AVM was made and, after accurate counselling with the patient, she was discharged and underwent "watch and wait" management. After 35 days, the patient had a follow-up ultrasound that showed a complete resolution of the uterine lesion. CONCLUSIONS AVM should be considered in the presence of heavy and sudden vaginal bleeding in a patient with risk factors for acquired AVM. A color Doppler ultrasound scan should be performed as the first approach and an expectant management should be taken into account especially with a patient of childbearing age and hemodynamic instability.

Epidemiology and Risk Factors of Uterine Fibroids.

Risk factors, both modifiable and non-modifiable, are associated with the development of fibroids. These include age, race, endogenous and exogenous hormonal factors, obesity, uterine infection, and lifestyle (diet, caffeine and alcohol consumption, physical activity, stress, and smoking). Some of the epidemiological data were conflicting; consequently, further studies are needed to better understand the factors that influence fibroid prevalence.