Marco Bonomi’s research while affiliated with University of Milan and other places

To provide the latest scientific knowledge on the efficacy of inositols for improving reproductive disorders in women with and without polycystic ovary syndrome (PCOS) and to reach a consensus on their potential use through a Delphi-like process. A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes. A total of eight consensus statements were drafted. Myo-inositol (Myo) supplementation can be used to improve menses irregularities and anovulation in PCOS. Myo supplementation can be used in subfertile women with or without PCOS to reduce the dose of r-FSH for ovarian stimulation during IVF, but it should not be used to increase the clinical pregnancy rate or live birth rate. Myo supplementation can be used in the primary prevention of gestational diabetes mellitus (GDM), but should not be used to improve pregnancy outcomes in women with GDM. Myo can be preconceptionally added to folic acid in women with a previous neural tube defects (NTD)-complicated pregnancy to reduce the risk of NTDs in newborns. Myo can be used during pregnancy to reduce the risk of macrosomia and neonatal hypoglycemia in mothers at risk of GDM. This consensus statement provides recommendations aimed at guiding healthcare practitioners in the use of inositols for the treatment or prevention of female reproductive disorders. More evidence-based data are needed to definitively establish the usefulness of Myo, the appropriate dosage, and to support the use of D-chiro-inositol (DCI) or a definitive Myo/DCI ratio.

An Endo-European Reference Network (ERN) guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult, and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted and the evidence graded according to Grading of Recommendations, Assessment, Development and Evaluation system. When evidence was insufficient or lacking, conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on induction of puberty with FSH and hCG in hypogonadotrophic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommend that pubertal induction or sex hormone replacement to sustain puberty should be treated by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualized but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with a disorder of sex development or congenital pituitary deficiencies. Transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.

Objective: To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of CAH due to 21-hydroxylase deficiency. Design and methods: A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN. Results: Pdex treatment is currently provided by 36 % of the surveyed centres. The treatment is initiated by different specialties i.e. paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23 % stated to initiate therapy at 4 to 5 weeks post conception (wpc), 31 % at 6 wpc, and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/d is used. Dose distribution among the centres varies between once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72 % of the responding centres. Cases treated per country and year vary between 0.5 to 8.25. Registries for long-term follow-up are only available at 46 % of the centres that are using Pdex treatment. National registries are only available in Sweden and France. Conclusions: This study reveals a high international variability and discrepancy on the use of Pdex treatment across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence based guidelines on prenatal diagnostics, treatment and follow up of pregnancies at risk for CAH.