[The role of vitamin D in assisted reproduction techniques].

Vitamin D or calcitriol, which was first identified back in 1920, has a key role in bone metabolism and mineralization, and in calcium and magnesium homeostasis. A nuclear receptor (VDR) mediates vitamin D actions in a lot of organs like bowel, bone, kidney, breast, gonads, pancreas, brain, cardiovascular and immune systems. In all these tissues the 1,25(OH)2D play a fundamental role in reduction of chronic pathologies, in modulation of cellular growth, neuromuscular, immune and inflammation actions. Vitamin D is important in reproduction physiology and in development gynecological and obstetric disorders like polycystic ovarian syndrome, endometriosis, myomatosis, gestational diabetes and preeclampsia. Over the last few years, vitamin D has been suggested to have a role in assisted reproduction techniques.

Effect of a new oral contraceptive with estradiol valerate/dienogest on carbohydrate metabolism.

BACKGROUND: Insulin resistance may be induced by both the estrogen and progestin component in hormonal contraception. When estrogen dose is reduced from 50 to 20 mcg, the extent of hyperinsulinemia decreases. Recently, the oral combination contraceptive (COC) containing estradiol valerate (E2V) in combination with dienogest (DNG) was developed in a new estrogen step-down, progesterone step-up dosing strategy (Qlaira, Bayer Healthcare Pharmaceuticals). This study was conducted to evaluate of the effect of a 3-month treatment with E2V/DNG on carbohydrate metabolism in women with polycystic ovarian syndrome (PCOS) and insulin resistance. STUDY DESIGN: Study consisted of subjects attending the gynecological clinic of Siena or Pisa, with PCOS and insulin resistance, and without contraindications for the use of COCs. PCOS females (n=20) aged 18 to 33 years were treated with a contraceptive formulation containing E2V/DNG for 3 months. Before treatment and during the third month of therapy, body mass index (BMI) measurement and an oral glucose tolerance test (OGTT) were performed. RESULTS: Median values of insulin after treatment were lower than median values before treatment. In particular, the median value of insulin at T0 was reduced by 54.6% (p<.001), and the mean difference between time 0 and 30 min was significantly reduced [42.96 (9.99) mU/mL vs 38.00 (15.10) mU/mL; p<.05]. Homeostasis model assessment of insulin resistance levels were significantly decreased following treatment. OGTT after treatment revealed median fasting glucose levels to be stable (p=.895) at T0. At T30, T60, T120 and T180 min, glucose median values were moderately reduced in comparison to median values before treatment. No significant difference was observed between median BMI values before [26 (4.8) kg/m(2)] and after treatment [26 (3.7) kg/m(2)]. CONCLUSIONS: Median insulin levels at T0 and the mean difference between time 0 and 30 of insulin following OGTT were significantly reduced than values before treatment with E2V/DNG for 3 months. Median BMI and glucose levels were not significantly modified. Natural estradiol and nonandrogenic progestogen in the Qlaira formulation could be recommended as an oral contraceptive in women with PCOS who are insulin resistant or who are overweight.

Present and future of recombinant gonadotropins in reproductive medicine.

Pharmacological ovarian stimulation has a major role in reproductive medicine and has been used in anovulatory patients and in the induction of multifollicular development required for the procedures of assisted reproductive techniques (ART). Currently, gonadotropins are the most important tools to proceed with ovarian stimulation for all purposes, including ART and anovulation disorders, like hypogonadotropic hypogonadism and hypothalamic hypophyseal dysfunction. Gonadotropin preparations derived from human urine have been used clinically since the early 1960s and the first urine-derived preparation containing only FSH (urofollitropin) became available in 1983. More recently, the application of recombinant DNA technology has resulted in the development of recombinant FSH produced in mammalian cells. In the last period, LH became available by recombinant DNA technology and is now a new option for protocols of ovarian stimulation. Treatment with gonadotropins has been shown to be effective in males affected by hypogonadotropic hypogonadism. This success has resulted in attempts to utilize FSH therapy in oligozoospermic men, aimed at obtaining a quantitative increase in sperm count. The purpose of this review was to examine the pharmacological aspects and different clinical applications of recombinant gonadotropins (FSH, LH, hCG) in the treatment of female infertility in all its aspects and their use also in the treatment of male infertility. This review will trace these events, from the past through to the present, and conclude with a glance towards the future.

Combined oral contraceptives in women with menstrual migraine without aura.

OBJECTIVE: To compare the efficacy of two regimens (21 active pills + 7 placebo pills vs. 24 active pills + 4 placebo pills) of combined oral contraception (COC), both containing 20 µg of ethinyl E(2) and 3 mg of drospirenone, in improving the severity of pure menstrual migraine without aura. DESIGN: Prospective randomized study. SETTING: Patients attending the gynecology department of the University of Siena for consultation regarding an appropriate contraception. PATIENT(S): Women ages 20 to 35 years (n = 60) suffering from pure menstrual migraine without aura. INTERVENTION(S): Three months of contraceptive use (ethinyl E(2) 20 µg/drospirenone 3 mg) in two different regimens: group A received 21 active + 7 placebo pills whereas group B received 24 active + 4 placebo pills. MAIN OUTCOME MEASURE(S): Monthly evaluation of the duration and severity of patients' daily headache attacks. RESULT(S): Although both study groups demonstrated significant reduction in the intensity and duration of menstrual migraine, patients in group B (24/4 COC) reported a significant reduction in the intensity and a shorter duration of their menstrual migraine, compared with group A (21/7 COC). CONCLUSION(S): The 24/4 COC regimen is recommended as the preferred treatment for patients suffering from pure menstrual migraine without aura.

The role of inositol supplementation in patients with polycystic ovary syndrome, with insulin resistance, undergoing the low-dose gonadotropin ovulation induction regimen.

In an attempt to evaluate the role of inositol supplementation in insulin-resistant patients with polycystic ovary syndrome (PCOS), undergoing gonadotropin ovulation induction using the low-dose step-down regimen, we conducted a prospective longitudinal study comparing the stimulation characteristics of 15 patients treated with inositol, to a cohort, matched by age and body mass index (BMI), without inositol. Inositol nutritional supplementation produced very good clinical results with a significant reduction in cancellation rate (0 vs. 40%) and the consequent improvement in clinical pregnancy rate (PR) (33.3% vs. 13.3%).

Effect of oral contraceptives on markers of hyperandrogenism and SHBG in women with polycystic ovary syndrome.

BACKGROUND: This randomized study's aim was to compare the effect of four oral contraceptives (OCs) containing 30 mcg of ethinylestradiol (EE) and different progestogens [drospirenone, (DRSP), chlormadinone acetate (CMA), desogestrel (DSG), gestodene (GSD)] on biochemical and hormonal parameters of hyperandrogenism and sex hormone-binding globulin (SHBG) in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Forty women with PCOS (age 16-35 years) were recruited and randomly assigned to one of four treatment groups of 10 women each, treated, respectively, with 3 mg DRSP/30 mcg EE (Yasmin, Bayer Shering), 2 mg CMA/30 mcg EE (Belara, Grunenthal), 75 mcg GSD/30 mcg EE (Minulet, Wyeth Lederle) and 150 mcg DSG/30 mcg EE (Practil 21, Organon Italia). Blood samples were obtained on day 6-8 of the control cycle and day 6-8 of the third treatment cycle for assay of the following hormones: androsteredione (A), total testosterone (T), free T, SHBG, dehydroepiandrosterone sulphate (DHEAS). RESULTS: In all groups, mean concentrations of free T, total T and A dropped by 40-60%, and concentrations of DHEAS dropped by 20-50%. Formulations with DRSP and CMA caused a greater reduction of androgens and a progressive increase in serum concentrations of SHBG than those with DSG and GSD. CONCLUSIONS: Clinical studies need to be performed to determine effects of these OCs upon clinical signs of hyperandrogenism.