M. Salvatori

Doppler, ultrasonographic and endocrinological environment with regard to the number of small subcapsular follicles in polycystic ovary syndrome

The aim of this study was to evaluate how, in patients with polycystic ovary syndrome, the number of small subcapsular follicles correlates with uterine and ovarian blood flow and with specific hormonal parameters. At an ultrasonographic evaluation, 30 patients with polycystic ovary syndrome showed 5-10 (group I; n = 14) or > 10 (group II; n = 16) small follicles. These patients underwent ultrasonographic (ovarian volume and stroma echodensity; number, diameter and distribution of follicles) and color Doppler (uterine and intraovarian vessels) analyses, and hormonal assay. In group II, significantly lower pulsatility index values than in group I were observed in the ovarian stromal arteries. The Ferriman-Gallwey score, plasma androstenedione level and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio results were significantly higher in group II than in group I. Androstenedione plasma levels correlated with the number of small follicles. Furthermore, the LH/FSH ratio correlated with both the number of small follicles and the stromal artery pulsatility index. The combined assessment of ovarian morphology by transvaginal ultrasound and color Doppler may provide insight into the pathological state of polycystic ovary syndrome.

Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome

OBJECTIVE To investigate a possible correlation between interleukin-12 (IL-12) and IL-13 levels and lymphocyte subsets in the preovulatory follicles of patients with and without polycystic ovarian syndrome (PCOS). DESIGN Controlled clinical study. SETTING University hospital. PATIENT(S) Seventy-eight infertile women undergoing IVF-embryo transfer. INTERVENTION(S) The subjects underwent blood sampling, ovum retrieval, and embryo transfer. MAIN OUTCOME MEASURES Follicular fluid levels of T, androstenedione (A); IL-12, IL-13, activated T cells, T helper, and T-suppressor lymphocytes. RESULT(S) The level of IL-12 detected in follicular fluid (FF) was significantly lower in patients with PCOS than in normally ovulating women (mean: 1.47 +/- 0.3 pg/mL vs. 2.25 +/- 0.7 pg/mL, respectively); in contrast, FF IL-13 concentrations were significantly higher in the patients with PCOS than in the normally ovulating women (mean: 32.5 +/- 3.7 pg/mL vs. 19.6 +/- 2.5 pg/mL, respectively), as was the total number of activated T lymphocytes (11.5% +/- 1.5% vs. 4.8% +/- 0.4%). A significant correlation was observed between FF activated T-cell concentrations and FF IL-12, IL-13, T, and A levels. No significant differences were observed when these data were compared with embryological parameters. CONCLUSION(S) The present study shows significant differences in the correlation between FF IL-12 and IL-13 levels and T lymphocyte numbers in the subset of patients with PCOS as compared to normally ovulating women.

Color Doppler analysis in oligo-and amenorrheic women with polycystic ovary syndrome

The objective of this study was to determine whether amenorrheic women have more severe blood flow variations and clinical-endocrinological patterns in comparison with oligomenorrheic polycystic ovary syndrome (PCOS) patients. Twenty oligomenorrheic women (cycle length > 35 days; Group I), and 20 amenorrheic women (no vaginal bleeding for at least 6 months; Group II) were submitted to ultrasonographic evaluation of ovarian volume, follicle distribution, number and diameter, color Doppler analysis of uterine and intraovarian blood flow, hormonal assay of different compartments, and plasma evaluation of lipid profile. The number of subcapsular small-sized follicles, and the ovarian volume, androstenedione and luteinizing hormone (LH) plasma levels, and the LH/follicle-stimulating hormone (FSH) ratio were significantly higher in the amenorrheic group compared with the oligomenorrheic patients. Furthermore, significantly lower high-density lipoprotein (HDL) and HDL/total cholesterol ratio were observed in Group II compared with Group I. In addition, in Group II, higher resistance in the uterine arteries and lower impedance to blood flow in the intraovarian arteries have been shown. The assessment of ovarian morphology by transvaginal ultrasound and Doppler flow analysis of both intraovarian and uterine arteries in patients with PCOS may provide an insight into the pathological state and the degree of progression of the disease.

Steroid-protein interaction in human placenta

Human placenta produces a large variety of bioactive substances with endocrine and neural competence: pituitary and gonadal hormones, hypothalamic-like releasing or inhibiting hormones, growth factors, cytokines and neuropeptides. The most recent findings indicate that locally produced hormones regulate the secretion of other placental hormones supporting a paracrine/autocrine regulation. In placental endocrinology, a particular relevance is played by steroid hormones. In fact, a specific gonadotropin-releasing hormone (GnRH)-human chorionic gonadotropin (hCG) regulation of placental steroidogenesis has been proposed as a placental internal regulatory system acting on steroids production from human placenta. In addition, activin and inhibin have been proposed as further regulatory substances of the synthesis and secretion of steroids; the addition of activin A to placental culture augments GnRH, hCG and progesterone, and this effect can be significantly reduced by the addition of inhibins. Finally, a steroid-steroid interaction is suggested by the evidence that placental estrogen has a positive role in the regulation of progesterone biosynthesis. Other steroid-protein interactions have been observed in human placenta. In fact, recent data indicate that progesterone inhibits placental corticotropin-releasing factor (CRF) and estrogens act on placental conversion of cortisol to cortisone, activating cortisol secretion by the fetal adrenal and enhancing fetal adrenal function with advancing gestation.

Uterine and cerebral vascularization in postmenopausal women treated with hormone-replacement therapy

The effects of hormone-replacement therapy on the Doppler flow parameters of the ophthalmic artery in postmenopausal women were studied and compared with those registered at the level of the internal carotid and uterine arteries. Fifty-seven postmenopausal patients were submitted to continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate. During the estrogen phase of hormone-replacement therapy all patients underwent (at 1, 3 and 6 months after the beginning of hormone-replacement therapy) transvaginal ultrasonographic evaluation of the pelvic organs and of endometrial thickness. On the same day, they underwent color Doppler analysis of the blood flow impedance of the uterine, internal carotid and ophthalmic arteries. Estradiol plasma concentrations were assayed on the day that ultrasonographic and Doppler examinations took place. The pulsatility index of all the arteries improved, from baseline values, during the therapy and attained stable values compared to those after the first month of treatment. Furthermore, at the level of the internal carotid and ophthalmic arteries, a significant increase of the peak systolic blood flow velocity (Vmax) was observed over the 6 months of therapy. Doppler studies of the ophthalmic artery are capable of affording specific and precise pathophysiologic information to assess peripheral intracranial blood flow variations. Furthermore, such studies may be useful in monitoring hormone-replacement therapy effects on cerebral perfusion.

Successful induction of ovulation using highly purified follicle-stimulating hormone in a woman with Kallmann’s syndrome

OBJECTIVE To describe a woman with Kallmanns syndrome who was treated successfully with highly purified FSH to achieve ovulation induction and pregnancy. DESIGN Case report. SETTING University hospital. PATIENT(S) A 32-year-old woman with Kallmanns syndrome who had been treated with oral contraceptives to prime secondary sex characteristics and genital organs since the age of 16 years. INTERVENTION(S) Highly purified FSH was administered intramuscularly for a total dose of 3,825 IU. MAIN OUTCOME MEASURE(S) Follicle number and diameter. RESULT(S) Three follicles with a diameter of > 1.7 cm and an endometrial thickness of 8 mm were observed. A clinical pregnancy, which subsequently was spontaneously aborted, was obtained. CONCLUSION(S) In primed patients with Kallmanns syndrome, highly purified FSH may be a useful alternative to pulsatile GnRH or menopausal gonadotropins to achieve ovulation induction and pregnancy.

Color Doppler and hormone replacement therapy: The role of thromboxane and plasma viscosity

The aim of the study was to evaluate the plasma thromboxane and plasma viscosity in relation with Doppler flow parameters in postmenopausal patients treated with hormone replacement therapy. Thirty-two postmenopausal (follicle-stimulating hormone > 40 IU/l and estradiol < 100 pmol/l) women (mean age +/- SD, 54.7 +/- 2.9 years) participated in the study and were submitted to continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every second month. Doppler resistances at the level of the uterine and internal carotid arteries, thromboxane plasma levels and plasma viscosity were analyzed in basal condition and after 1, 3 and 6 months. During hormone supplementation, the pulsatility index significantly decreased at the level of the analyzed arteries. Similarly, plasma thromboxane levels and plasma viscosity were significantly reduced. Significant correlations were found between thromboxane plasma concentrations, plasma viscosity and uterine artery resistances. Thus hormone replacement therapy seems to be responsible for both direct and indirect modifications at the level of the vessel wall physiology.

Allergic reaction to a highly purified urinary follicle stimulating hormone preparation in controlled ovarian hyperstimulation for in vitro fertilization

We report a case of general hypersensitivity-like allergic reactions to intramuscular injections of highly purified urinary follicle stimulating hormone (uFSH-HP) successfully managed by using intramuscular recombinant FSH (rFSH). The patient underwent a first cycle of in vitro fertilization (IVF) and controlled ovarian hyperstimulation (COH) was achieved with a combination of gonadotropin releasing hormone against (GnRH-a) and uFSH-HP. Because, after oocyte recovery, no fertilization occurred, the couple subsequently entered an intracytoplasmic sperm injection (ICSI) program. During the COH, the woman developed general hypersensitivity-like allergic reactions with itching, redness and swelling. Although there was regular follicular growth, the allergic symptoms worsened and, on day 8 of COH, the stimulation cycle was suspended. A few months later, the patient entered a new ICSI cycle. COH was achieved by using a combination of GnRH-a and rFSH. The cycle was completed and the patient did not report any allergic reaction. To avoid allergic reaction to the protein components of the urine-derived FSH preparations, the use of rFSH is suggested in those patients who present local and/or general hypersensitivity-like allergic reactions.