Luca Giannella

Anti-Mullerian Hormone in Premenopausal Women and After Spontaneous or Surgically Induced Menopause

Objective: The objectives of this study were: (1) to determine anti-Mullerian hormone (AMH) levels in menopausal women, and (2) to confirm the source of AMH in cycling women and its disapperance after the removal of the source. Methods: An observational and prospective study was conducted. Results: A total of 47 women were recruited for the study. The study population consisted of the following groups of patients: (A) women of late reproductive age (n= 24; mean age ± SD, 44 ± 2.8 years); (B) menopausal women (n= 14; mean age, 56 ± 4 years); (C) regularly cycling women undergoing surgical menopause (n= 9; mean age, 43 ± 4 years). Blood samples were obtained from all patients. In patients undergoing surgery, blood samples were obtained before and after surgery. AMH was undetectable in 13 of 14 postmenopausal women, whereas it was undetectacle in only two of 24 women of late reproductive age. A significant negative correlation has been found between AMH and age or follicle-stimulating hormone (FSH) in women of late reproductive age. In women who were candidates for oophorectomy, samples were obtained 3-5 days after surgery. AMH was undetectable after the surgery in all women. Conclusions: We found that AMH levels decreased in women in the late reproductive period and that menopause and ovariectomy in regularly cycling women are associated to undetectable AMH in serum. These observations confirm that the ovary could be the only source of AMH in women and that it is a novel marker for ovarian aging.

Different concentrations of interleukins in the peritoneal fluid of women with endometriosis: relationships with lymphocyte subsets.

The present study explored the possible relationships between immune cell subsets and interleukin (IL)-12 or IL-13 levels in the peritoneal fluid of patients with and without endometriosis. Peritoneal fluid samples were obtained from 80 women while they were undergoing laparoscopy for pain, infertility, tubal ligation or reanastomosis. The American Fertility Society scoring system was used to determine the extension of endometriosis. The peritoneal fluid mononuclear cells were analyzed for immunophenotyping using cytometry, whereas peritoneal fluid concentrations of interleukins were measured using two ultrasensitive commercially available enzyme-linked immunosorbent assay kits. Significantly higher peritoneal fluid IL-12 levels were found in women with moderate or severe endometriosis (stages III and IV) than in healthy controls (p<0.01). Conversely, subjects with endometriosis showed remarkably lower peritoneal fluid IL-13 concentrations than controls, independent of the severity of the disease (p<0.05). Considering immune system effectors, patients with endometriosis presented a significantly higher peritoneal fluid CD8+/CD4+ratio when compared with healthy controls. Moreover, the number of peritoneal fluid CD8+and CD4+activated T cells was significantly lower in the former than in the latter group, independent of the endometriosis stage. Connections were observed between peritoneal fluid interleukins and peritoneal fluid T cells: both patients with endometriosis and controls presented an inverse correlation between peritoneal fluid activated T cells and IL-13 levels, and a direct correlation between peritoneal fluid T cells and IL-12 concentrations. These data seem to suggest that a reciprocal modulation exists between peritoneal fluid cytokines and T lymphocyte subsets in patients with endometriosis.

Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome

OBJECTIVE To investigate a possible correlation between interleukin-12 (IL-12) and IL-13 levels and lymphocyte subsets in the preovulatory follicles of patients with and without polycystic ovarian syndrome (PCOS). DESIGN Controlled clinical study. SETTING University hospital. PATIENT(S) Seventy-eight infertile women undergoing IVF-embryo transfer. INTERVENTION(S) The subjects underwent blood sampling, ovum retrieval, and embryo transfer. MAIN OUTCOME MEASURES Follicular fluid levels of T, androstenedione (A); IL-12, IL-13, activated T cells, T helper, and T-suppressor lymphocytes. RESULT(S) The level of IL-12 detected in follicular fluid (FF) was significantly lower in patients with PCOS than in normally ovulating women (mean: 1.47 +/- 0.3 pg/mL vs. 2.25 +/- 0.7 pg/mL, respectively); in contrast, FF IL-13 concentrations were significantly higher in the patients with PCOS than in the normally ovulating women (mean: 32.5 +/- 3.7 pg/mL vs. 19.6 +/- 2.5 pg/mL, respectively), as was the total number of activated T lymphocytes (11.5% +/- 1.5% vs. 4.8% +/- 0.4%). A significant correlation was observed between FF activated T-cell concentrations and FF IL-12, IL-13, T, and A levels. No significant differences were observed when these data were compared with embryological parameters. CONCLUSION(S) The present study shows significant differences in the correlation between FF IL-12 and IL-13 levels and T lymphocyte numbers in the subset of patients with PCOS as compared to normally ovulating women.

Rectus abdominis muscle endometriosis: Case report and review of the literature

The abdominal wall is an uncommon site of extrapelvic endometriosis, which usually develops in a previous surgical scar and it should be considered in the differential diagnosis of any abdominal swelling. Endometriosis involving the rectus abdominis muscle is a very rare event and its rarity explains the incomplete nature of the reports in the literature. Up to the present, 18 cases with lesions contained entirely within the rectus abdominis muscle were clearly documented in medical literature with only four cases as a primary location. We report a case, which came to our observation, of primary endometriosis of the rectus abdominis muscle. The patient underwent only surgery without any medical treatment. Currently, the patient is in follow up for four years with no recovery of the disease. In our experience, surgery is the treatment of choice and it is decisive. We reviewed the literature and summarized all reported cases.

Changes in the cervical competence in preterm labour

Cervical competence is a key function in normal and abnormal labour. Remodelling of the cervical structure, by reorientation and changes in the integrity of collagen fibres by an alteration in the content of water, proteoglycans and hyaluronic acid, takes place before parturition. Such morphological changes have been associated with the activation of several biochemical pathways, sharing those of an apyretic, proinflammatory reaction, including the inducible isoform of the nitric oxide synthase (NOS). Nitric oxide (NO) is believed to be the final mediator in the mechanisms that allow ripening of the cervix. A reduction of NO activity in the uterus, together with its activation in the cervix, is hypothesised to be a facilitating factor in human parturition. The local application of NO donors in both animals and humans induces ultrastructural changes similar to those occurring during physiological cervical maturation. NO donors have proven to be clinically effective in facilitating first trimester dilation and curettage. Preliminary data also suggest that in women presenting with threatening preterm labour, there is increased activity of NO in the cervix, which is associated with shortening. A complex interaction between cytokines, prostaglandins (PGs) and NO is the key biochemical pathway accounting for the preterm ripening of the cervix.

Diagnostic accuracy of endometrial thickness for the detection of intra-uterine pathologies and appropriateness of performed hysteroscopies among asymptomatic postmenopausal women

OBJECTIVE To measure the diagnostic accuracy of endometrial thickness for the detection of intra-uterine pathologies among asymptomatic postmenopausal women, and to test the diagnostic accuracy and appropriateness of performed hysteroscopies. STUDY DESIGN Prospective study of 268 asymptomatic postmenopausal women with endometrial thickness ≥4 mm referred to diagnostic hysteroscopy. The diagnostic accuracy of various endometrial thickness cut-off values was tested. Histological and hysteroscopic results were compared to measure the diagnostic accuracy of outpatient hysteroscopies. RESULTS No endometrial thickness cut-off values had optimal diagnostic accuracy [positive likelihood ratio (LR+) >10 and negative likelihood ratio (LR-) <0.1]. The best endometrial thickness cut-off value for the detection of all intra-uterine pathologies was ≥8 mm (LR+ 10.05 and LR- 0.22). An endometrial thickness cut-off value ≥10 mm did not miss any cases of endometrial cancer. The success rate of diagnostic hysteroscopy was 89%, but 97% of these revealed a benign intra-uterine pathology. The diagnostic accuracy of hysteroscopy was optimal for all intra-uterine pathologies, except endometrial hyperplasia (LR- 0.52). CONCLUSION Using an endometrial thickness cut-off value ≥4 mm, only 3% of performed hysteroscopies were useful for the detection of pre-malignant or malignant lesions. Despite the finding that endometrial thickness did not show optimal diagnostic accuracy, using the best cut-off value (≥8 mm) may be helpful to decrease the number of false-positive results. No cases of endometrial cancer were diagnosed in asymptomatic postmenopausal women with endometrial thickness <10mm.

A Risk-Scoring Model for the Prediction of Endometrial Cancer among Symptomatic Postmenopausal Women with Endometrial Thickness > 4 mm

Objective. To develop and test a risk-scoring model for the prediction of endometrial cancer among symptomatic postmenopausal women at risk of intrauterine malignancy. Methods. We prospectively studied 624 postmenopausal women with vaginal bleeding and endometrial thickness > 4 mm undergoing diagnostic hysteroscopy. Patient characteristics and endometrial assessment of women with or without endometrial cancer were compared. Then, a risk-scoring model, including the best predictors of endometrial cancer, was tested. Univariate, multivariate, and ROC curve analysis were performed. Finally, a split-sampling internal validation was also performed. Results. The best predictors of endometrial cancer were recurrent vaginal bleeding (odds ratio (OR) = 2.96), the presence of hypertension (OR = 2.01) endometrial thickness > 8 mm (OR = 1.31), and age > 65 years (OR = 1.11). These variables were used to create a risk-scoring model (RHEA risk-model) for the prediction of intrauterine malignancy, with an area under the curve of 0.878 (95% CI 0.842 to 0.908; P < 0.0001). At the best cut-off value (score ≥ 4), sensitivity and specificity were 87.5% and 80.1%, respectively. Conclusion. Among symptomatic postmenopausal women with endometrial thickness > 4 mm, a risk-scoring model including patient characteristics and endometrial thickness showed a moderate diagnostic accuracy in discriminating women with or without endometrial cancer. Based on this model, a decision algorithm was developed for the management of such a population.

Nitric oxide metabolite levels and assessment of cervical length in the prediction of preterm delivery among women undergoing symptomatic preterm labor

To evaluate the diagnostic accuracy of measuring cervical length (CL) in combination with cervical and plasma nitric oxide metabolite (NOx) levels to identify women undergoing preterm labor (PTL) who will deliver preterm.

High-grade CIN on cervical biopsy and predictors of the subsequent cone histology results in women undergoing immediate conization

OBJECTIVE To identify the clinical/colposcopic variables that associate with low-grade/negative cone histology in screening-age women undergoing conization for high-grade cervical intraepithelial neoplasia (CIN). The follow-up outcomes of study participants were also compared. STUDY DESIGN In this retrospective cohort study, 585 consecutive screening-age women who underwent immediate conization for CIN2-3 were divided according to cone histology (CIN2+ versus ≤CIN1) and assessed in relation to clinical/colposcopic variables by univariate and multivariate analyses. RESULTS Low-grade [adjusted odds ratio (AOR)=52.67, 95% confidence interval (CI) 22.49-123.34] or normal (AOR=9.81, 95% CI 2.38-40.44) colposcopic impression and CIN2 on cervical biopsy (AOR=19.59, 95% CI 6.62-57.92) associated with CIN1/negative cone histology. Multivariate analysis also showed that Eastern European ethnicity (AOR=0.13, 95% CI 0.03-0.52) and high-risk-Human Papillomavirus (hr-HPV)-positivity (AOR=0.38, 95% CI 0.17-0.87), associated with CIN2+ cone histology. Overall, there were no significant differences between the two groups in terms of high-grade recurrence during the 2-year follow-up. Conversely, a higher rate of high-grade recurrence was present in CIN2-3 (positive cone margins) than in CIN1/negative cone histology (21.9% versus 7.4%, P=0.008, respectively). CONCLUSION The presence of CIN2 on cervical biopsy and a low-grade colposcopic impression were predictive of a minor cone histology, unless the subject was of East European ethnicity or was positive for hr-HPV test. Given the follow-up outcomes, the same women need to perform a close monitoring. However, positive cone margins in women with CIN2-3 cone histology seem to define a population at greater risk of high-grade recurrence.

Pedunculated Angiomyofibroblastoma of the Vulva: Case Report and Review of the Literature

Angiomyofibroblastoma (AMFB) is a rare benign mesenchymal tumour that occurs almost exclusively in the vulvovaginal region of women but can also occur occasionally in the inguinoscrotal region of men. It is a well-circumscribed lesion that clinically is often thought to represent a Bartholins gland cyst and usually does not form a pedunculated mass. To our knowledge, only five cases of vulvar AMFB with pedunculated mass have been reported in the English literature and all cases involving the labia majora and middle-aged women. We report the first case of pedunculated AMFB of the vulva occurring in a young woman of 21 years old and involving the left labia minora. After excluding the most common diseases, pedunculated AMFB should be part of differential diagnosis in the workup of any pedunculated vulvar mass even in young women with a lesion involving the labia minora. We reviewed the literature and summarized all reported cases.