Inhibition ratio (I.R.) and transformation index (T.I.): new indexes to compare the effectiveness and clinical behaviour of modern progestin-only pills (POP).

Progestin-only pills (POPs) have emerged as a crucial contraceptive option for women, particularly those contraindicated to oestrogens. This opinion paper introduces two new indices, the Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.), to evaluate and compare the efficacy and clinical behaviour of modern POPs. The I.R. quantifies the ratio between the progestin dosage in a POP and the minimum dose required to inhibit ovarian function, providing insights into contraceptive efficacy. The T.I., on the other hand, assesses its clinical impact by considering the ratio between the total progestin dose and the dose required to induce endometrial luteinising changes. Both indices thus offer valuable tools for comparing progestins even at significantly different dosages and regimens, providing information on clinical characteristics and drug effects. The newest formulations of POPs (Desogestrel 28 and Drospirenone 24 + 4) have demonstrated higher I.R. and T.I. in comparison to older versions, indicating significant improvements in contraceptive efficacy and clinical impact with better menstrual cycle control. We believe that using these indices will ensure a more informed and personalised choice of progestin not only for contraceptive purposes but also for therapeutic use in gynaecology. The future goal is to develop other progestins with even more advantageous I.R. and T.I., ensuring the best contraceptive efficacy with fewer side effects, even in women at risk (obese, etc.).

The Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.) are two new proposed indexes to evaluate and compare the efficacy and clinical behaviour of modern and future POPs.

Impact of human ovarian tissue manipulation on follicles: evidence of a potential first wave of follicle activation during fertility preservation procedures.

PURPOSE: The aim of this study was to investigate the impact of processing human ovarian tissue on follicle activation dynamics. METHODS: Fresh ovarian tissue was retrieved from 9 women undergoing laparoscopic surgery for benign conditions. Biopsies from each patient were divided into 3 fragments, the first of which was immediately fixed in the operating room (T0) and the second and third just after processing at 25 (T25) and (T90) 90 min. To evaluate follicle activation, markers of the PI3K and Hippo signaling pathways were immunolabeled at each time point, targeting phospho-Akt (p-Akt) by immunohistochemistry and yes-associated protein (YAP) cellular localization in the granulosa cell layer by immunofluorescence. RESULTS: Four hundred forty primordial follicles were evaluated for p-Akt and 420 for YAP. Significantly stronger p-Akt expression was observed at T25 (23.01 ± 13.45%; p=0.04) and T90 (38.99 ± 25.21%; p<0.001) than at T0 (2.72 ± 3.35%). A significant nucleus-to-cytoplasm shift in YAP was detected at T25 (1.21 ± 0.25; p=0.015 compared to T0 (0.95 ± 0.09), while T90 (1.10 ± 0.16) values were similar to T25. CONCLUSION: Our data prove that ovarian tissue manipulation significantly impacts follicle dynamics by stimulating the PI3K and Hippo signaling pathways involved in primordial follicle activation. Further experimental evidence must nevertheless be gathered to understand and gain control of follicle activation mechanisms in non-physiological conditions (like ovarian tissue manipulation), in order to optimize fertility preservation and restoration strategies.

COVID-19 susceptibility in endometriosis patients: A case control study.

PROBLEM: Starting from November 2019, the world has had to face a devastating pandemic caused by SARS-CoV-2. Various studies have identified potential risk factors facilitating the infection, however it has not been demonstrated whether endometriosis might represent one of them. The purpose of this study was to evaluate if patients with endometriosis had a higher risk of contracting COVID-19 infection and, in such case, whether they developed a more severe infection than the general population. Furthermore, this study evaluated the possible correlation with the stage of endometriosis, based on the r-ASRM score, and the potential worsening of the disease during the SARS-CoV-2 infection. METHOD OF STUDY: A case-control study was conducted from March 2020 to April 2021 at Macedonio Melloni Hospital, in Milan. A total of 401 women were recruited. The cases were 201 women with clinical or surgical diagnosis of endometriosis. The control group consisted of 200 women, without the disease. All women completed a self-administered questionnaire which evaluated their demographic and clinical characteristics, as well as a potential diagnosis of Covid-19. RESULTS: Comparison between the two groups showed that women with endometriosis had a higher frequency of COVID-19 than the control subjects (23% vs. 13.5%, P = .014), with a greater prevalence of fever (14.4% vs. 6%, P = .008) and myalgias or arthralgias (11.4% vs. 4.5%, P = .01). In multivariable logistic regression analyses, women with endometriosis had a higher risk of contracting SARS-CoV-2 infection (OR = 2.11, 95% IC: 1.20-3.80), regardless the stage of the disease. CONCLUSION: Endometriosis increases the susceptibility to COVID-19, and women who suffer from it should be considered as fragile patients, worthy of prior access to SARS-CoV-2 vaccination campaign.

Endometriosis and irritable bowel syndrome: a systematic review and meta-analysis.

PURPOSE: Irritable bowel disease and endometriosis are two common diseases characterized by chronic inflammation state and recurrent abdominal pain. As a consequence of sharing of symptoms and chronic inflammation, endometriosis and IBS may coexist and be misdiagnosed and this leads to delays in diagnosis, mismanagement, and unnecessary testing. In recent years, some studies have found higher risk of IBS in women with endometriosis, compared to women without endometriosis. To provide a general overview, we performed a systematic review and a meta-analysis on published data on this issue. METHODS: By a systematic literature search selection process, 11 studies were identified for the current study: 2 prospective and 2 retrospective cohort studies, 4 case-control studies, 1 cross-sectional study and 2 clinical series. RESULTS: When we meta-analysed data about the prevalence of IBS in women with endometriosis, the overall OR (95%CI), compared to women without endometriosis was 3.26 (1.97-5.39) with no statistically significant heterogeneity. All three studies considering the incidence of IBS in women with a previous diagnosis of endometriosis showed about twofold greater risk among women with endometriosis than women without. Likewise, in the random effects model of the meta-analysis, the overall OR of history of IBS in women with endometriosis was 3.10 (95% CI 2.06-4.67), with no heterogeneity between three studies considered. CONCLUSION: This meta-analysis provides epidemiological evidence of a link between endometriosis and IBS, highlighting two or more times higher risk of IBS in women with endometriosis compared to women without the condition.