Alessandra Tirelli

Age-specific nomogram for the decline in antral follicle count throughout the reproductive period

OBJECTIVE To investigate the relationship between antral follicle count (AFC) and chronological age and to establish normal values for AFC in women with regular menstrual cycles. DESIGN Cross-sectional study. SETTING University hospital. PATIENT(S) Four hundred fifteen premenopausal women were recruited for the study. Data from 362 patients were available for the statistical analysis. INTERVENTION(S) AFC was measured by transvaginal ultrasound examination. MAIN OUTCOME MEASURE(S) Estimating the relationship between AFC and age and developing the AFC nomogram. RESULT(S) The analysis showed a linear decline in AFC with age; for every year increase in age, the median AFC decreases by 0.4. The AFC corresponding to the 5th, 25th, 50th, 75th, and 95th centiles for each age have been calculated. CONCLUSION(S) A linear relationship of AFC to age was found. For the first time, a nomogram reporting normal and interquartile values for AFC, age by age, throughout the reproductive period has been provided. Until now, the interpretation of the measurement was mainly based on the individual experience of the operator, because no normative data were present. Therefore, the establishment of a nomogram of AFC values is the first step to counsel patients on a scientific basis.

Insulin sensitivity and lipid metabolism with oral contraceptives containing chlormadinone acetate or desogestrel: a randomized trial

BACKGROUND Second-generation and third-generation oral contraceptives containing 30 mcg or more of ethinylestradiol (EE) decrease insulin sensitivity (SI). In this study, we investigated whether SI is decreased by contraceptives containing lower doses EE or by progestins with antiandrogenic properties. STUDY DESIGN Twenty-eight young healthy women were randomly allocated to receive 20 mcg of EE and 150 mcg of desogestrel (DSG) (n=14) or 30 mcg of EE and 2 mg of chlormadinone acetate (CMA) (n=14) for 6 months. SI and glucose utilization independent of insulin (Sg) were investigated by the minimal model method. Lipid modifications were also analyzed. RESULTS SI decreased with EE/DSG (7.09+/-1.4 vs. 4.30+/-0.91; p=.04; n=12), but not with EE/CMA (5.79+/-0.93 vs. 6.79+/-1.1; p=.48; n=12). SI modifications observed in the two groups were significantly different (-2.79+/-1.15 vs. 1.0+/-1.38; p=.05). Sg did not vary with either treatment. The response of C-peptide to glucose increased, but significantly so only with EE/CMA (p=.01). The C-peptide/insulin response increased with both EE/DSG (p=.05) and EE/CMA (p=.04). High-density lipoprotein (HDL) cholesterol (p=.02) and triglycerides (p=.02 and p=.01) increased in both groups, but HDL/low-density lipoprotein cholesterol (p=.02), apoprotein A1 (Apo-A1) (p=.04) and Apo-A1/apoprotein B (p=.048) increased significantly only with EE/CMA. CONCLUSIONS The present study confirms that DSG, even when associated with low EE dose, decreases SI. By contrast, EE/CMA does not deteriorate SI and induces a favorable lipid profile.

Route of administration of contraceptives containing desogestrel/etonorgestrel and insulin sensitivity: a prospective randomized study.

BACKGROUND The study was conducted to investigate whether hormonal contraceptives administered via the oral and vaginal route exert a similar effect on insulin sensitivity (SI). STUDY DESIGN This is a prospective, randomized study performed in the University Hospital. Subjects were healthy lean young women, needing a hormonal contraceptive, randomly allocated to receive for 6 months (a) an oral contraceptive (OC) containing 30 mcg ethinylestradiol (EE)/150 mcg desogestrel (DSG) (high-estrogen group; n=12), (b) an OC containing 20 mcg EE/150 mcg DSG (low-estrogen group; n=12) and (c) a vaginal ring contraceptive releasing, per day, 15 mcg EE/120 mcg etonorgestrel, the active DSG metabolite (n=12). SI and glucose utilization independent of insulin (Sg) were evaluated by the minimal model method. Modifications of total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterol and triglycerides were also evaluated. RESULTS Sg did not vary with any treatment. SI decreased during OCs (5.74+/-0.49 vs. 3.86+/-0.44; p=.0005), independently of the high/low-estrogen dose. SI did not decrease during vaginal ring use (4.64+/-1.03 vs. 5.25+/-1.36; p=.57; p=.019 vs. oral). Total cholesterol and HDL cholesterol increased (p=.02) during OCs, independently of the dose. Triglycerides increased during both oral (p=.01) and vaginal (p=.032) contraceptive use. CONCLUSIONS The present data indicate that in contrast to OC use, vaginal contraception with the ring does not deteriorate SI. The vaginal ring may represent an appropriate choice for long-term contraception in women at risk for developing diabetes mellitus or metabolic syndrome.

Embryo quality and implantation rate in two different culture media: ISM1 versus Universal IVF Medium

OBJECTIVE To compare the outcome of two different culture media marketed by the MediCult AS Company (Jyllinge, Denmark)-Universal IVF Medium and ISM1 Medium culture-which, in addition to glucose, pyruvate, and energy-providing components, also contain amino acids, nucleotides, vitamins, and cholesterol. DESIGN Laboratory and retrospective clinical study. SETTING University teaching hospital. PATIENT(S) A total of 726 patients, undergoing IVF-intracytoplasmic sperm injection procedure, comparable in mean age range, oocyte retrieval, and infertility indication, were included in the study. Laboratory quality and standard procedures were maintained unaffected. INTERVENTION(S) Oocyte retrieval, different embryo culture media. MAIN OUTCOME MEASURE(S) Embryo quality, ongoing pregnancy, and implantation rate. RESULT(S) The frequency of good-quality embryos (79% vs. 74%) and the percentages of ongoing pregnancy (27.5% vs. 18%) and implantation rate (15% vs. 10%) were significantly higher in the group treated with ISM1 Medium rather than Universal IVF Medium. CONCLUSION(S) ISM1 Medium culture seems to improve the performance of embryonic growth and development, as well as increasing the percentage of pregnancy.

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

BackgroundThe 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.MethodsThis 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.ResultsA 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.ConclusionsThe 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.

Levonorgestrel administration in emergency contraception: bleeding pattern and pituitary-ovarian function.

BACKGROUND This study was conducted to evaluate the effects of levonorgestrel administration for emergency contraception (EC) on bleeding pattern and pituitary-ovarian function. STUDY DESIGN In 69 women with a reported stable menstrual cycle length of 24-34 days, we investigated bleeding patterns following EC administration in the follicular (n=26), periovulatory (n=14) and luteal (n=29) phase. In a subgroup of 8 women, hormonal evaluation and ultrasonography were performed. RESULTS EC taken in the follicular, but not in the periovulatory or luteal phase, significantly shortened cycle length by 10.9+/-1 days. The subsequent cycle was not affected. EC taken in the late preovulatory phase, prior to the gonadotrophin surge, suppressed ovulation (n=7), while ovulation was not blocked when EC was given during an ongoing luteinizing hormone (LH) pulse (n=1). CONCLUSIONS Our data indicate that EC given before the onset of the luteinizing hormone (LH) surge inhibits ovulation and hastens the end of the current menstrual cycle. Subsequently, the length of the following menstrual cycle returned as prior to treatment. By contrast, levonorgestrel administered after the expected ovulation has no effect on menstrual cycle length.

Influence of an oral contraceptive containing drospirenone on insulin sensitivity of healthy women

OBJECTIVES Oral contraceptives (OCs) containing androgenic second and third generation progestins decrease insulin sensitivity (SI). In this study we investigated whether an oral contraceptive containing the anti-androgenic progestin drospirenone (DRSP) still alters SI. Lipid modifications were investigated as well. STUDY DESIGN Eleven young healthy women were allocated to receive for 6 months ethinyl-estradiol (EE) 30μg plus DRSP (3mg). SI and glucose utilization independent of insulin (Sg) was investigated by the minimal model method. Lipid modifications were also analyzed. RESULTS SI did not vary during EE/DRSP (from 3.72±2.62 to 3.29±2.93; p=0.73). Similarly, values of Sg did not vary (from 0.03±0.02 to 0.032±0.014; p=0.87). An increase was observed in HDL cholesterol (9.4±9.8mg/dl; p=0.05) and triglycerides (46.9±75.1mg/dl; p=0.046), with no modification in LDL cholesterol (-4.64±1.704mg/dl; p=0.6). CONCLUSIONS EE/DRSP does not deteriorate SI. These results are reassuring for the long-term use of this association.

Hormonal and ultrasound markers of ovarian function in a woman with a balanced 1;11 translocation.

OBJECTIVE To present a case of a poor responder woman with a rare balanced autosomal translocation. DESIGN Case report. SETTING Infertility center in a university teaching hospital. PATIENT(S) A 34-year-old white woman with primary infertility. INTERVENTION(S) Laboratory and ultrasound evaluation, karyotype analysis, ovarian stimulation with gonadotropins. MAIN OUTCOME MEASURE(S) Markers of ovarian reserve and ovarian response to gonadotropin stimulation. RESULT(S) The patient was a carrier of a balanced translocation (1;11) (q23;p11.2). The hormone ovarian reserve markers (FSH, anti-Mullerian hormone, inhibin B) were within the normal range. The antral follicle count (AFC) was measured twice and only in one occasion did it reach the lower limit of the normal range. Furthermore, the patient had regular menstrual cycles. However, ovarian response to the administration of a maximal dose FSH was extremely poor. CONCLUSION(S) Patients with balanced autosomal translocations should be counseled regarding their increased risk for poor response even if markers of ovarian reserve are in the range of normality.

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

Backgroundd-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).MethodsThe study was conducted on primary cultures of hGCs. Gene expression was evaluated by RT-qPCR method. Statistical analysis was performed applying student t-test, as appropriate (P < 0.05) set for statistical significance.ResultsDCI is able to reduce the gene expression of CYP19A1, P450scc and insulin-like growth factor 1 receptor (IGF-1R) in dose–response manner. The presence of DCI impaired the increased expression of steroidogenic enzyme genes generated by the insulin treatment in gonadotrophin-stimulated hGCs.ConclusionsInsulin acts as co-gonadotrophin increasing the expression of steroidogenic enzymes genes in gonadotrophin-stimulated granulosa cells. DCI is an insulin-sensitizer that counteracts this action by reducing the expression of the genes CYP19A1, P450scc and IGF-1R. The ability of DCI to modulate in vitro ovarian activity of insulin could in part explain its beneficial effect when used as treatment for conditions associated to insulin resistance.

La contraccezione d’emergenza oggi

La velocita con cui oggi si modificano i modelli di riferimento adolescenziali, in relazione alla trasformazione cui e soggetta la comunicazione, fa da sfondo alla scoperta della sessualita. La salute sessuale richiede, da parte degli esperti, un’attenzione costante a tali cambiamenti. Dunque, l’educazione sessuale rappresenta lo strumento d’elezione per favorire il benessere individuale e di coppia, fornendo gli strumenti per elaborare le contraddizioni esistenti tra accesso alla sessualita e conoscenza.