Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol

d-chiroinositol (DCI) is a inositolphosphoglycan (IPG) involved in several cellular functions that control the glucose metabolism. DCI functions as second messenger in the insulin signaling pathway and it is considered an insulin sensitizer since deficiency in tissue availability of DCI were shown to cause insulin resistance (IR). Polycystic ovary syndrome (PCOS) is a pathological condition that is often accompanied with insulin resistance. DCI can positively affects several aspect of PCOS etiology decreasing the total and free testosterone, lowering blood pressure, improving the glucose metabolism and increasing the ovulation frequency. The purpose of this study was to evaluate the effects of DCI and insulin combined with gonadotrophins namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on key steroidogenic enzymes genes regulation, cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and cytochrome P450 side-chain cleavage (P450scc) in primary cultures of human granulosa cells (hGCs). We also investigated whether DCI, being an insulin-sensitizer would be able to counteract the expected stimulator activity of insulin on human granulosa cells (hGCs)

Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle-stimulating hormone starting dose in in vitro fertilisation cycles

To elaborate a nomogram based on markers of ovarian reserve for the calculation of the appropriate starting dose of follicle-stimulating hormone (FSH)

Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization

Since gonadotropins are the fundamental hormones that control ovarian activity, genetic polymorphisms may alter gonadal responsiveness to glycoproteins; hence they are important regulators of hormone activity at the target level. The establishment of the pool of primordial follicles takes place during fetal life and is mainly under genetic control. Consequently, single nucleotide polymorphisms (SNPs) in gonadotropins and their receptors do not seem to be associated with any significant modification in the endowment of nongrowing follicles in the ovary. Indeed, the age at menopause, a biological characteristic strongly related to ovarian reserve, as well as markers of functional ovarian reserve such as anti-Müllerian hormone and antral follicle count, are not different in women with different genetic variants. Conversely, some polymorphisms in FSH receptor (FSHR) seem to be associated with modifications in ovarian activity. In particular, studies suggest that the Ser680 genotype for FSHR is a factor of relative resistance to FSH stimulation resulting in slightly higher FSH serum levels, thus leading to a prolonged duration of the menstrual cycle. Moreover, some FSHR gene polymorphisms show a positive association with ovarian response to exogenous gonadotropin administration, hence exhibiting some potential for a pharmacogenetic estimation of the FSH dosage in controlled ovarian stimulation. The study of SNPs of the FSHR gene is an interesting field of research that could provide us with new information about the way each woman responds to exogenous gonadotropin administration during ovulation induction

Normal serum anti-Müllerian hormone levels in the general female population and the relationship with reproductive history

Objective: Anti-Müllerian hormone (AMH) has been evaluated by several groups as a potential novel clinical marker of ovarian reserve. Considering the wide use of AMH measurement in daily clinical practice and the large number of conditions in which it may be used, it is essential to establish reference values in the healthy female population. In this study we aim to calculate the age-by-age normal values of circulating AMH. In addition, we report on AMH levels in women according to BMI, smoking status and reproductive history. Study design: The study was performed at the Institute of Obstetrics and Gynecology, University of Modena, between January 2008 and December 2010. A total of 416 healthy women (aged 18-51) were recruited and serum AMH levels were measured for all of them. The centiles of AMH distribution were estimated with the CG-LMS method. The relationship between AMH levels and the womens' characteristics such as BMI, smoking status and reproductive history was analysed by using the uni- and multi-variable regression analysis and the Chi-square test. Results: Serum AMH concentrations show a progressive decline with female ageing. Age-related nomograms for the 5th, 25th, 50th, 75th, and 95th percentiles of AMH were produced. Mean AMH concentrations were not modified by smoking habit and BMI and were independent of parity of the women. Conclusion: In the present study, we established age-specific reference values for circulating AMH levels in the eumenorrheic female population. AMH measurement produces new information on ovarian pathophysiology and ovarian reserve and the establishment of reference values for AMH is the first step for a correct interpretation of the assay. © 2012 Elsevier Ireland Ltd

Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period

High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11\u2009IU for every year of age (1\u2009IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve

Individualization of the FSH starting dose in IVF/ICSI cycles using the antral follicle count

<p>Abstract</p> <p>Background</p> <p>The FSH starting dose is usually chosen according to women’s age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles.</p> <p>Methods</p> <p>This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model.</p> <p>Results</p> <p>A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively.</p> <p>Conclusions</p> <p>The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice.</p

Live birth rates in the different combinations of the Bologna criteria poor ovarian responders: a validation study

to compare the baseline characteristics and chance of live birth in the different categories of poor responders identified by the combinations of the Bologna criteria and establish whether these groups comprise a homogenous population