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.

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. METHODS: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. RESULTS: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. CONCLUSIONS: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

Impact of optimizing pre-analytical phase on the diagnosis of gestational diabetes and related outcomes.

OBJECTIVES: Pre-analytical plasma glucose (PG) sampling methodology may significantly affect gestational diabetes mellitus (GDM) incidence, but no studies directly examined the impact on perinatal outcomes. We compared the effect on oral glucose tolerance test (OGTT) results of using for blood sampling the traditional sodium fluoride (NaF) tubes, batched at controlled temperature, and the more effective citrate-buffered tubes, in terms of GDM diagnosis and related outcomes. METHODS: We evaluated 578 pregnant women performing OGTT between 24- and 28-weeks' gestation. Paired NaF and citrate blood samples were drawn and analyzed for PG. GDM diagnosis was made by applying the 'one-step' American Diabetes Association strategy. Data on perinatal outcomes were collected in a subset of 330 women who delivered in our hospital network. RESULTS: Using the standard NaF approach, 69 (11.9%) GDM women were detected. Using citrate PG values, 90 women were additionally identified as GDM, increasing the GDM prevalence to 27.5%. Perinatal outcomes were analyzed according to the different diagnostic allocation (NaF-diagnosed GDM, additional citrate-diagnosed GDM, and no GDM). NaF-diagnosed GDM showed a higher incidence of large for gestational age (LGA) (p=0.034), and of cesarean and preterm delivery (p<0.01) vs. no GDM. The only outcome remaining more frequent in the additional citrate diagnosed GDM when compared with no GDM group was LGA (17.2 vs. 6.8%, p=0.025). CONCLUSIONS: If a health care system plans to use citrate tubes for GDM diagnosis, considerations about clinical implications are mandatory by balancing higher sensitivity in detecting a poor glycemic control with effects on outcomes to avoid "overdiagnosis".

Effect of Dienogest therapy on the size of the endometrioma.

Studies have been published on the efficacy of Dienogest in the management of pain symptoms in endometriosis. Nonetheless, few data are available on the reducing effect on endometrioma's size. The aim of the study was to evaluate if Dienogest could determine significant changes in size, as well as in symptoms. In this prospective observational study, patients were enrolled with pain symptoms and at least one endometrioma diagnosed via TV-US. The volume of the endometrioma and pain symptoms was measured according to the LxDxWx0.5233 formula and VAS, respectively. Dienogest 2 mg was administered daily. Follow-up visits were scheduled after 6 and 12 months of treatment to assess changes in patients' symptoms and endometrioma's volume. Seventy patients were enrolled, 63 patients completed a 6-month treatment. The reduction of the mean volume after 6 months was 66.71%. Fifty-eight patients completed the 12 month-treatment. The reduction of the mean volume after 12 months was 76.19%. Dysmenorrhea showed a 74.05% reduction after 6 months and a 96.55% reduction after 12 months. Patients reported a reduction in dyspareunia and chronic pelvic pain of 42.71% and 48.91% after 6 months and 51.93% and 59.96% after 12 months, respectively. Dienogest leads to a statistically significant reduction of endometrioma's volume and pain symptoms.

Medical treatment of ovarian endometriomas: a prospective evaluation of the effect of dienogest on ovarian reserve, cyst diameter, and associated pain.

The aim of the present study was to evaluate the effect of medical treatment of ovarian endometriomas on cyst diameter, associated pain, and ovarian reserve as measured with antral follicle count (AFC) and anti-Mullerian hormone (AMH). In this prospective study, 32 patients with unilateral endometrioma associated with pelvic pain, underwent 6-month medical treatment with dienogest. Before treatment, and at the end of 6 months of treatment, patients underwent evaluation of endometrioma diameter and AFC at transvaginal ultrasonography, measurement of AMH, and evaluation of associated pain. Mean cyst diameter was 4.0 ± 1.3 cm at baseline, and 2.4 ± 1.2 cm after 6 months of treatment (p < .0001), for a reduction in diameter of 40% and a reduction in volume of 79%. Mean visual analog scale score at enrollment was 6.3 ± 2.0, with a significant improvement at 6 months (0.9 ± 1.0, p < .0001). AFC for the affected ovary improved from 4.2 ± 2.8 at baseline, to 8.6 ± 4.2 cm after 6 months (+105%; p < .0001). AMH did not change significantly from baseline (3.40 ± 2.32 ng/mL) to end of treatment (2.80 ± 1.90 ng/mL, -18%, p = .27). Medical treatment with dienogest significantly reduces endometrioma diameter and associated pain, whereas the ovarian reserve appears to be preserved, with a significant improvement of AFC and no significant change in AMH.

Is dienogest the best medical treatment for ovarian endometriomas? Results of a multicentric case control study.

Ovarian endometriomas are common manifestations of endometriosis. Surgical excision has been shown to potentially decrease ovarian reserves. In this prospective study, we included 81 patients with ovarian endometriosis. 40 were treated with 2 mg of dienogest daily (DNG) and 41 were treated with cyclic oral estro-progestins (ethinyl estradiol 30 mcg [EE] plus dienogest 2 mg) (DNG + EE). Aim of the study was the effect of the treatment on the size of the endometriotic cysts. Further, in the symptomatic patients, follow-up included an evaluation of chronic pain before and during treatment. Both treatments were able to significantly decrease the pain in symptomatic patients with no statistical differences. The mean visual analog scale score at enrollment was 65 ± 14 and 70 ± 18, and there was significant improvement (19 ± 15, p < .001, DNG; 18 ± 12, p < .001, DNG + EE). The size of the endometrioma cysts were significantly reduced in the DNG group. The mean cyst diameter was 52 ± 22 mm at baseline and 32 ± 12 mm after six months of treatment (p < .001), yielding a 75% volume reduction in DNG group. The decrease in the size of endometrioma cysts observed in the women treated with only progestin could be noteworthy, as it may reduce the negative impacts on the affected ovary and avoid surgery.

Epigenome Wide Association and Stochastic Epigenetic Mutation Analysis on Cord Blood of Preterm Birth.

Preterm birth (PTB) can be defined as the endpoint of a complex process that could be influenced by maternal and environmental factors. Epigenetics recently emerged as an interesting field of investigation since it represents an important mechanism of regulation. This study evaluates epigenetic impact of preterm birth on DNA methylation. Genome-wide DNAm was measured using the Illumina 450K array in cord blood samples obtained from 72 full term and 18 preterm newborns. Lymphocyte composition was calculated based on specific epigenetic markers that are present on the 450k array. Differential methylation analysis was performed both at site and region level; moreover, stochastic epigenetic mutations (SEMs) were also evaluated. The study showed significant differences in blood cell composition between the two groups. Moreover, after multiple testing correction, statistically significant differences in DNA methylation levels emerged between the two groups both at site and region levels. Results obtained were compared to those reported by previous EWAS, leading to a list of more consistent genes associated with PTB. Finally, the SEMs analysis revealed that the burden of SEMs resulted significantly higher in the preterm group. In conclusion, PTB resulted associated to specific epigenetic signatures that involve immune system. Moreover, SEMs analysis revealed an increased epigenetic drift at birth in the preterm group.

Mediterranean diet and outcomes of assisted reproduction: an Italian cohort study.

BACKGROUND: Detrimental lifestyle habits have been indicated as potential causes of reduced fertility. Recently studies have suggested an association between healthy diets and increased live birth rates after assisted reproduction techniques. However, the issue remains under debate, and evidence is still accumulating. OBJECTIVE: The objective of the study was to study the relationship between a Mediterranean diet and outcomes of assisted reproduction techniques in subfertile couples in an Italian population. STUDY DESIGN: This was a prospective cohort study, conducted in an Italian fertility clinic. Couples undergoing in vitro fertilization were interviewed on the day of oocyte retrieval to obtain information on personal and health history, lifestyle habits, and diet. Adherence to a Mediterranean diet was evaluated using a Mediterranean diet score. Relative risks and 95% confidence intervals for embryo transfer, clinical pregnancy, and live birth were calculated. Potential confounders were included in the equation model. RESULTS: Among 474 women (mean age, 36.6 years, range, 27-45), 414 (87.3%) performed embryo transfer, 150 (31.6%) had clinical pregnancies, and 117 (24.7%) had live births. In a model including the potential confounders (age, leisure physical activity, body mass index, smoking, daily calorie intake, and previous failed in vitro fertilization cycles), findings showed that the Mediterranean diet score was not significantly associated with in vitro fertilization outcomes. Adjusted analyses were performed in strata of age, previous assisted reproduction technique cycles, and reasons for infertility, with consistent findings. The only exception was observed in women >35 years old with an intermediate Mediterranean diet score, who showed a lower risk of not achieving clinical pregnancy (adjusted relative risk, 0.84, 95% confidence interval, 0.71-1.00, P = .049). CONCLUSION: No clear association was observed between adherence to a Mediterranean diet and successful in vitro fertilization.