Cesare Battaglia

The role of color doppler imaging in the diagnosis of polycystic ovary syndrome

OBJECTIVE Our purpose was to evaluate whether intraovarian and uterine blood flow variations are associated with clinical, ultrasonographic, and endocrine polycystic ovary syndrome findings. STUDY DESIGN Thirty-two hirsute, oligomenorrheic patients and 18 volunteer women underwent in the early follicular phase ultrasonographic evaluation of ovarian volume, echodensity, and follicle number; transvaginal color Doppler measurement of the uterine and intraovarian vessel variations; and radioimmunologic dosage of luteinizing hormone, follicle-stimulating hormone, estradiol, progesterone, testosterone, androstenedione, and other hormonal compartments. RESULTS In the patients with polycystic ovary syndrome (increased luteinizing hormone/follicle-stimulating hormone ratio, elevated androstenedione levels, high number of subcapsular follicles by ultrasonography-augmented ovarian volume and echodensity) (n = 22) we observed, at Doppler analysis, significantly elevated uterine artery pulsatility index values associated with a typical low resistance index of stromal ovary vascularization. The pulsatility index was positively correlated with the luteinizing hormone/follicle-stimulating hormone ratio, and the resistance index was negatively correlated. The elevated uterine artery resistance was correlated with androstenedione levels. CONCLUSION Doppler analysis can be a valuable additional tool for the diagnosis of polycystic ovary syndrome.

Maternal hyperoxygenation in the treatment of intrauterine growth retardation

OBJECTIVE In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated. STUDY DESIGN Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and untreated (n = 19) groups. Doppler analysis of the fetal circulation was performed on the arrival to the hospital, after 12 hours, and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery. RESULTS Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women. The Doppler variations were associated with complementary modifications in fetal blood gas. These differences resulted in a significant modification in perinatal mortality with an incidence of 29% and 68% (p less than 0.01) in treated and untreated groups, respectively. CONCLUSION Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation.

Perifollicular Doppler flow and follicular fluid vascular endothelial growth factor concentrations in poor responders

OBJECTIVE To prospectively evaluate follicular fluid levels of vascular endothelial growth factor in women undergoing IVF cycles and to investigate the correlation of these levels with ovarian response to gonadotropins and with uterine or ovarian Doppler findings. DESIGN Prospective study. SETTING University hospital. PATIENT(S) 41 patients undergoing ART were divided into two groups according to response to ovarian stimulation protocols: poor responders (n = 18) and normoresponders (n = 23). INTERVENTION(S) Doppler analysis of perifollicular arteries and assay of follicular fluid vascular endothelial growth factor. MAIN OUTCOME MEASURE(S) During ovarian stimulation, patients underwent hormonal (E2), ultrasonographic (follicular number and diameter, endometrial thickness) and Doppler (uterine and perifollicular arteries) evaluation. Serum and follicular fluid concentrations of vascular endothelial growth factor were assayed in each female patient. RESULT(S) Compared with poor responders, more oocytes were collected and more embryos were transferred but follicular fluid levels of vascular endothelial growth factor levels were lower in normoresponders. Follicular fluid levels of vascular endothelial growth factor were inversely correlated with number of oocytes retrieved. Poor responders had significantly higher uterine and perifollicular Doppler flow resistances. The pregnancy rate per cycle was significantly higher in normoresponders (26%) than poor responders (6%). CONCLUSION(S) Elevated follicular fluid levels of vascular endothelial growth factor concentrations are associated with poor ovarian response and a very low pregnancy rate.

Doppler ultrasound studies of the uterine arteries in spontaneous and IVF stimulated ovarian cycles

The changes of uterine artery blood flow in women were studied throughout normal and in vitro fertilization (IVF) stimulated cycles. The obtained data showed that uterine blood flow variations are correlated to spontaneous or induced hormonal changes. Furthermore, Doppler investigation may be very important in predicting the pregnant state at a very early stage in patients enrolled in an IVF program.

A comparative, randomized study of three different progesterone support of the luteal phase following IVF/ET program

The use of luteal phase support has been demonstrated in patients undergoing IVF/ET in cycles stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists. However, it is still not clear which is the most suitable kind of supplementation. This study was designed to compare the absorption and the efficacy of three different luteal support. We randomly administered progesterone i.m. (50 mg/day), human chorionic gonadotrophin (hCG) (2000 IU every three days), progesterone vaginal cream (100 mg/day) or nothing (controls) to 176 women treated for assisted procreation. We were not able to show any statistical differences for the percentage of pregnancy rate between groups. The serum progestrerone (P) and 17-ß-estradiol (E2) and E2/P ratio levels of the luteal phase were compared with the control not supplemented group. All the treatments were able to increase significantly the luteal P values versus controls (p<0.01). Moreover, vaginal cream and natural P im significantly decreased E2/P ratio (p<0.05). Serum P levels were more steady with P vaginal cream than im injection. Vaginal cream for better bioavailability and acceptance appear the most suitable and comfortable method for luteal phase support.

Vascular Risk in Young Women With Polycystic Ovary and Polycystic Ovary Syndrome

OBJECTIVE: To estimate if young polycystic ovary syndrome (PCOS) patients have subclinical risks of vascular disease compared with eumenorrheic polycystic ovary (PCO) women and healthy controls. METHODS: Twenty-eight PCOS patients, 17 eumenorrheic PCO women, and 15 healthy eumenorrheic volunteers underwent medical examination; blood measurement of nitrites/nitrates, biochemical and hormonal parameters; uteroovarian ultrasonographic analysis and color Doppler evaluation of uterine, stromal ovarian, and ophthalmic arteries; brachial artery flow–mediated vasodilatation; 24-hour ambulatory blood pressure monitoring. An oral glucose tolerance test was performed to analyze glucose, insulin, and C-peptide. RESULTS: Doppler analysis revealed a significantly higher uterine pulsatility index in the PCOS group compared with controls. The lowest vascular resistances in the ovaries were found in PCOS and PCO compared with controls. The ophthalmic artery back pressure was significantly higher in women with PCOS than in controls. The brachial artery diameter, at baseline, was similar in all the participants. After the reactive hyperemia, a greater vasodilatation was observed in controls and PCO patients in comparison with PCOS women. Total cholesterol, triglycerides, and the atherogenic plasma index were significantly higher in PCOS than PCO and controls. Leukocytes and homocysteine were slightly higher in PCOS. The nitrites/nitrates plasma levels were lower in PCOS and PCO patients compared with controls. The insulin and C-peptide plasma values were higher in PCOS patients than controls. In PCOS patients the different estimates of insulin sensitivity and pancreatic β-cell function were higher compared with PCO and controls. CONCLUSION: Polycystic ovary syndrome is a condition associated with an increased vascular risk. LEVEL OF EVIDENCE: II

Menstrual Cycle‐Related Morphometric and Vascular Modifications of the Clitoris

INTRODUCTION The evaluation of clitoral anatomy and function is of paramount importance to understand the physiology and pathology of clitoral function. AIM To prospectively evaluate the clitoral volumetric and vascular modifications during the menstrual cycle, and analyze their relationship with circulating hormones and nitric oxide levels. METHODS Thirty healthy eumenorrheic women were studied in different phases of the menstrual cycle (day 3, 10, 14, 20, and 27). They were submitted to ultrasonographic (US) and Doppler analyses, and to hormonal and biochemical evaluations. MAIN OUTCOME MEASURES Transvaginal US evaluation of uterus, ovaries, and clitoris; Doppler analysis of uterine and dorsal clitoral arteries; and measurement of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, androstenedione, testosterone, and nitrites/nitrates concentration. Sex hormone binding globulin was assayed, and free androgen index was calculated. RESULTS During the menstrual cycle, FSH, LH, and estradiol changed as expected, whereas androgens did not show any significant change. The US assessment of the clitoral body volume evidenced a progressive increase with significant modifications during the periovulatory phase, after which it remained stable until day 20. Subsequently, the clitoral body volume decreased into the premenstrual phase (day 27), reaching values similar to those observed on cycle day 3. A comparable trend was observed in the nitrite/nitrate circulating values. The uterine and clitoral arteries presented significant modifications with reduced resistances in the periovulatory period. Estradiol levels resulted positively correlated with the clitoral body volume and inversely correlated with the dorsal clitoral artery pulsatility index (PI). Furthermore, the dorsal clitoral artery PI was inversely and significantly correlated with the nitrite/nitrate circulating values and the clitoral body volume. CONCLUSIONS Clitoral anatomic and vascular modifications are observable during the normal menstrual cycle.

Polycystic ovary syndrome and cardiovascular risk in young patients treated with drospirenone-ethinylestradiol or contraceptive vaginal ring. A prospective, randomized, pilot study

OBJECTIVE To compare the effects of a pill containing drospirenone with those of a combined contraceptive vaginal ring on the lipid and carbohydrate metabolism and on the surrogate markers of arterial function. SETTING Bologna University School of Medicine. PATIENT(S) Thirty-seven women with polycystic ovary syndrome (PCOS) were randomly submitted to drospirenone+ethinylestradiol (group I; n=19) or combined contraceptive vaginal ring (group II; n=18) therapy. The duration of the study was 6 months. INTERVENTION(S) The effect of treatments was assessed after 6 months of therapy. MAIN OUTCOME MEASURE(S) Utero-ovarian ultrasound analysis and color Doppler evaluation of uterine and stromal ovarian arteries. In addition, analysis of brachial artery flow-mediated vasodilatation and 24-hour ambulatory blood pressure monitoring were performed. Fasting blood samples were drawn for testing biochemical and hormonal parameters and nitrites/nitrates. RESULT(S) Both treatments improved hirsutism, hyperandrogenemia, and ultrasound and color Doppler ovarian parameters. Both drospirenone+ethinylestradiol or contraceptive vaginal ring induced a slight but significant increase of diurnal and 24-hour blood pressure. Although both therapies worsened the lipid profile, the oral pill administration was associated with a more evident increase of circulating triglycerides. The 6-month treatment with the vaginal ring significantly improved the area under the curve for glucose, insulin, and C-peptide, whereas the drospirenone+ethinylestradiol pill induced an increase in the insulinogenic index and homeostatic model assessment estimate for insulin resistance values. CONCLUSION(S) Vaginal hormonal contraception appears to be preferable to oral ethinylestradiol + drospirenone administration in hyperinsulinemic patients with PCOS.

PCOS, sexuality, and clitoral vascularisation: a pilot study

INTRODUCTION In polycystic ovarian syndrome (PCOS) women, the changes in body appearance (mainly obesity and hirsutism) may influence the feminine identity of the patients with consequent depression and sexual disturbances. AIM To evaluate if lean PCOS patients present an increased incidence of depression and sexual dysfunction in comparison with controls and if clitoral volume and vascularization are influenced by circulating androgens levels. METHODS 25 lean PCOS women (Group I) and 18 healthy nonhirsute volunteers (Group II) were submitted, on day 3-5 of the cycle, to ultrasonographic and Doppler analyses, and to hormonal and biochemical evaluations. MAIN OUTCOME MEASURES Utero-ovarian and clitoral ultrasonographic analysis, and color Doppler evaluation of the uterine, stromal ovarian, and dorsal clitoral arteries. Hormonal and nitrites/nitrates plasma concentrations were analyzed. Each woman filled in the 2-factor Italian McCoy female questionnaire (MFSQ) and the Becks Depression Inventory questionnaire (BDI). RESULTS Androgens resulted, as expected, more elevated in PCOS patients than in controls. However, the ultrasonographic (US) assessment of the clitoral body volume evidenced no significant differences between PCOS (0.72+/-0.41 mL) and control (0.62+/-0.20 mL) patients. The resistances registered at the level of the dorsal clitoral artery did not show any difference between Group I (PI=1.55+/-0.40) and Group II (PI=1.79+/-0.38). The 2-factor Italian MFSQ and the BDI did not show any difference between PCOS women and controls. CONCLUSIONS In PCOS women, probably, the moderate hirsutism and hyperandrogenism do not induce the sense of loss of feminine identity and have no impact on sexual self-worth and sexual satisfaction.

Biochemical aspects of hormonal contraception: effects on bone metabolism.

Both trabecular and cortical bone mineral content reduction physiologically occur during the premenopausal period and, overall, at the time of menopause. It is related to plasma estrogen fall. Several studies have examined the relationship between bone density and oral contraceptives (OCs), but their results disagree. The different results may be due to the small number of patients investigated, the different OC formulations, and to the multifactorial nature of the bone loss phenomenon. Furthermore, the use of different techniques and different sites for measuring the bone density may limit the interpretation and reproducibility of the reported findings. Our previous studies evidenced that: (1) in premenopausal (40-45 years) women (n = 26), OCs, over a period of 2 years, do not induce any change either in bone mineral density or in bone metabolism biochemical markers (osteocalcin, alkaline phosphatase, urinary hydroxyproline/creatinine ratio; and (2) independent from the therapy length, the premenopausal use of OCs does not modify the bone mineral loss in postmenopausal patients (n = 40). The present study compared, over a period of 36 months, in perimenopausal (46-53 years; follicle stimulating hormone < or = 35 mU/ml; estradiol < 50 pg/ml) women, the effect of OCs (n = 8) on bone metabolism. The results were compared with those of a matched control group (n = 9). In the treated group, a slight, though not significant, bone mass improvement was observed during the entire therapy period, whereas, in the control group, a continued and progressive bone mass loss was observed and a significant decrease was shown at the end of the observational period. Our data suggest that OCs have no significant effects on bone metabolism in women during their childbearing years. However, OCs may be beneficial in inhibiting bone reabsorption in pre- and postmenopause. Furthermore, the pill, also in virtue of its contraceptive effect, would be the first presidium in hormone therapy in the premenopause.