Augusto Ferrari

Myo-inositol in patients with polycystic ovary syndrome: A novel method for ovulation induction

Background. Polycystic ovary syndrome (PCOS) is often characterized by chronic oligo- or anovulation (usually manifested as oligo- or amenorrhea), and hyperandrogenism. In addition, 30–40% of PCOS women have impaired glucose tolerance, and a defect in the insulin signaling pathway (inositol-containing phosphoglycan mediators) seems to be implicated in the pathogenesis of insulin resistance. PCOS patients are subfertile as a consequence of such ovulatory disorders and often need drugs, such as clomiphene citrate or follicle-stimulating hormone, for ovulation induction, which increases the risk of multiple pregnancy and ovarian hyperstimulation syndrome. We hypothesized that the administration of an isoform of inositol (myo-inositol), belonging to the vitamin B complex, would improve the insulin-receptor activity, restoring normal ovulatory function. Materials and methods. Twenty-five PCOS women of childbearing age with oligo- or amenorrhea were enrolled in the study. Ovulatory disorder due to PCOS was apparently the only cause of infertility; no tubal defect or deficiency of male semen parameters was found. Myo-inositol combined with folic acid (Inofolic®) 2 g twice a day was administered continuously. During an observation period of 6 months, ovulatory activity was monitored with ultrasound scan and hormonal profile, and the numbers of spontaneous menstrual cycles and eventually pregnancies were assessed. Results. Twenty-two out of the 25 (88%) patients restored at least one spontaneous menstrual cycle during treatment, of whom 18 (72%) maintained normal ovulatory activity during the follow-up period. A total of 10 singleton pregnancies (40% of patients) were obtained. Nine clinical pregnancies were assessed with fetal heart beat at ultrasound scan. Two pregnancies evolved in spontaneous abortion. Conclusion. Myo-inositol is a simple and safe treatment that is capable of restoring spontaneous ovarian activity and consequently fertility in most patients with PCOS. This therapy did not cause multiple pregnancy.

No evidence of fetal DNA persistence in maternal plasma after pregnancy

Short- and long-term persistence of fetal DNA in maternal plasma has been investigated. Short-term persistence at very low concentration was detected in 47 out of 105 women within two days after delivery. Twelve out of 13 samples re-tested within three days scored negative. No long-term persistence was detected in 172 women who had previous sons or abortions. Molecular microchimerism due to circulating fetal DNA persisting from previous pregnancies should not hamper non-invasive plasma-based prenatal testing.

Fetal DNA detection in maternal plasma throughout gestation

The presence of fetal DNA in maternal plasma may represent a source of genetic material which can be obtained noninvasively. We wanted to assess whether fetal DNA is detectable in all pregnant women, to define the range and distribution of fetal DNA concentration at different gestational ages, to identify the optimal period to obtain a maternal blood sample yielding an adequate amount of fetal DNA for prenatal diagnosis, and to evaluate accuracy and predictive values of this approach. This information is crucial to develop safe and reliable non-invasive genetic testing in early pregnancy and monitoring of pregnancy complications in late gestation. Fetal DNA quantification in maternal plasma was carried out by real-time PCR on the SRY gene in male-bearing pregnancies to distinguish between maternal and fetal DNA. A cohort of 1,837 pregnant women was investigated. Fetal DNA could be detected from the sixth week and could be retrieved at any gestational week. No false-positive results were obtained in 163 women with previous embryo loss or previous male babies. Fetal DNA analysis performed blindly on a subset of 464 women displayed 99.4, 97.8 and 100% accuracy in fetal gender determination during the first, second, and third trimester of pregnancy, respectively. No SRY amplification was obtained in seven out of the 246 (2.8%) male-bearing pregnancies. Fetal DNA from maternal plasma seems to be an adequate and reliable source of genetic material for a noninvasive prenatal diagnostic approach.

Quantitative Analysis of Fetal DNA in Maternal Plasma in Pathological Conditions Associated with Placental Abnormalities

Abstract: An increased fetal DNA concentration in maternal plasma has been observed in placental pathological conditions associated with hypertension and preeclampsia. To confirm these data, we performed real‐time quantitative PCR on the SRY gene in a group of physiological and pathological male‐bearing pregnancies. In 78 physiological pregnancies, fetal DNA concentration in maternal plasma was 20.7, 13.4, 23.6, and 74.8 genome‐equivalents (g.e.)/mL during the first, second, and third trimesters and at term, respectively. In 10 preeclamptic women, fetal DNA concentration ranged from 59.3 to 615.2 g.e./mL (median: 332.9). In 7 women with preeclampsia and IUGR (intrauterine growth retardation), fetal DNA ranged from 96.5 to 859 g.e./mL (median: 146.8). In 4 women with IUGR and hypertension, fetal DNA ranged from 34 to 473.5 g.e./mL (median: 142.4). In 3 patients with IUGR, fetal DNA ranged from 168.6 to 519.7 g.e./mL (median: 308.1). In 2 patients with IUGR and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, fetal DNA concentration ranged from 105 to 394.1 g.e./mL (median: 249.7). Four women who developed preeclampsia some weeks later showed fetal DNA levels within the physiological range. These data suggest that increased fetal DNA concentrations might represent a valuable marker of placental abnormalities and suggest that this rise may precede clinical manifestation of preeclampsia by only a few weeks.

Pathologic findings in hysteroscopy before in vitro fertilization-embryo transfer (IVF-ET)

Background. The aim of this study was to evaluate hysteroscopy routinely performed prior to in vitro fertilization-embryo transfer (IVF-ET). Methods. We analyzed in a prospective study 300 patients who underwent hysteroscopy before the first IVF-ET cycle. We analyzed then in a retrospective manner 300 patients who did not perform hysteroscopy. Results. One-hundred-and-eighty (60%) hysteroscopies were normal but 120 (40%) revealed an unsuspected intrauterine abnormality. We did not find statistically significant differences between patients with normal or abnormal hysteroscopy in any characteristic. We found a statistically significant difference in pregnancy rate between women who performed hysteroscopy before IVF-ET cycle and in women who did not perform it. Conclusions. Hysteroscopy, as a routine examination, should be performed before the first IVF-ET cycle in all patients.

Risk Factors for Varicose Disease Before and During Pregnancy

Risk factors for varicose disease before and during pregnancy have been analyzed by use of data from a survey on venous disease in pregnancy conducted in 611 women (mean age thirty years, range fifteen to forty-seven) who consecutively delivered at the Obstetric-Gynecologic Clinic L. Mangiagalli of Milan between January and April, 1989. In total, 137 women (22%) reported varicose disease before the index pregnancy. The relative risk (RR) of varicose disease before the index pregnancy increased with age, being, as compared with women aged twenty-nine years or less, 1.6 in those aged thirty to thirty-four and 4.1 in those aged thirty-five years or more (χ2 1 trend 29.28, p < 0.001). Compared with nulliparae, women reporting a full-term pregnancy before the index pregnancy had an RR of venous disease of 1.2, and the risk increased to 3.8 in women reporting two or more births (χ2 1 trend 25.28, p < 0.001). A family history of varicose disease was associated with an RR of venous disease of 6.2 (95% confidence interval, CI, from 4.1 to 9.6). No relationship emerged between varicose disease and overweight. Of the 474 women who did not report venous disease before the index pregnancy, 132 (28%) developed venous disease during the index pregnancy. The risk of developing venous disease in pregnancy increased with age, being, as compared with women aged twenty-four years or less, 4.0 in those aged thirty-five years or more, and the trend in risk was statistically significant (χ2 1 trend 16.25, p < 0.001). To be secondiparae or more was associated with an increased risk of developing venous disease in pregnancy. Compared with primiparae, the estimated RR was 2.0 (95% CI 1.3 to 2.9) in women reported to have given birth to one child or more. Women who developed venous disease in pregnancy reported more frequently a family history of varicose disease than those who did not; the RR estimate was 5.8, (95% CI from 3.8 to 8.9).

Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms.

Aim:u2002 The aim of the present study was to assess the efficacy and safety of a standardized compound based on an extract of soy phytoestrogens, with high doses of isoflavones in the management of menopausal hot flushes.

Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome

Background.u2003Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism, acne and pattern alopecia, often characterised by ovulation disorders (usually manifested as oligo- or amenorrhea). In addition, 30–40% of women with PCOS have impaired glucose tolerance, and a defect in the insulin signalling pathway seems to be implicated in the pathogenesis of insulin resistance. For this reason, insulin-lowering medications represent novel approach in women with PCOS. The aim of this study was to evaluate the effects of myo-inositol (MYO), an isoform of inositol, belonging to the vitamin B complex, in the treatment of cutaneous disorders like hirsutism and acne. Methods.u2003Fifty patients with PCOS were enrolled in the study. BMI, LH, FSH, insulin, HOMA index, androstenedione, testosterone, free testosterone, hirsutism and acne were evaluated at the baseline and after receiving MYO therapy for 6 months. Results.u2003After 3 months of MYO administration, plasma LH, testosterone, free testosterone, insulin and HOMA index resulted significantly reduced; no significant changes were observed in plasma FSH and androstenedione levels. Both hirsutism and acne decreased after 6 months of therapy. Discussion.u2003MYO administration is a simple and safe treatment that ameliorates the metabolic profile of patients with PCOS, reducing hirsutism and acne.

IFN-γ Produced by Human Papilloma Virus-18 E6-Specific CD4+ T Cells Predicts the Clinical Outcome after Surgery in Patients with High-Grade Cervical Lesions

Cervical neoplastic lesions are associated with infection by high-risk human papilloma viruses (HPVs). HPV-16 and HPV-18 are the most common genotypes. It has been proposed that development of HPV-16-positive cervical lesions is associated with impaired CD4+ T cell immunity against early Ags. The aim of the study was to evaluate whether this impairment also applies to HPV-18. We investigated the presence and the quality of anti-HPV-18 E6 CD4+ T cell responses in the blood of 37 consecutive patients with high-grade cervical lesions, 25 normal donors, and 20 cord bloods. The immune infiltrate in the cervical lesions was also evaluated. The characteristics of the responses were correlated to the clinical outcome. We found that one or more HPV-18 E6 peptides, containing naturally processed epitopes, were able to induce a response in 40–50% of the patients, depending on the effector function tested. Importantly, these percentages rose to 80–100% when HPV-18-positive patients were considered. HPV-18 E6-specific CD4+ T cells produced mixed Th1/Th2 responses and statistical analysis of the cytokines produced revealed that the amount of IFN-γ released could predict infection persistence and/or disease relapse after surgery. Finally, we found that a higher number of infiltrating CD4+ and T-bet+ T cells in the lesions correlated with a favorable clinical outcome. Our results strongly suggest a relevant role for CD4+ T cells in the control of the HPV-18 compared with HPV-16 infections in patients with high-grade cervical lesions and identify an immunologic parameter potentially useful for patients’ stratification.

Isolated tubal torsion in pregnancy

Adnexal torsion is an uncommon cause of acute abdomen in pregnancy and isolated fallopian tube twisting accounts for a very small number of these cases. These conditions, either in pregnancy or in non-gestational circumstances, are known to be due to both genital and non-genital causes and, in most cases, predisposing factors can be identified. We reviewed the literature and retrieved only 19 cases of isolated fallopian tube torsion in pregnancy treated surgically from 1936 to today, including one recently published case from our experience. The clinical presentation was lower quadrant abdominal pain in all cases. The right side was involved in 90% of the cases. Tenderness was usually present but peritoneal irritation with guarding or rebound was exceptional. Symptoms were nausea and vomiting, scanty vaginal bleeding and dysuria. Signs suggestive of necrosis such as leucocytosis, increased CRP and mild hyperpyrexia were uncommon. Preoperative ultrasound evaluation was performed in eight patients and in all cases an adnexal cyst was detected on the ipsilateral side of the abdominal pain. The case we recently published was carefully investigated preoperatively by Doppler flow ultrasound techniques which allowed for a precise differential diagnosis with total adnexal torsion. This aspect has never been previously considered. The surgical approach showed acute isolated fallopian tube torsion in all the cases and a predisposing factor was identified in 75% of the patients. Foetal and maternal outcome were always excellent. In cases of acute abdomen in pregnancy, with detailed Doppler flow ultrasound evidence of normal ovaries and of a pelvic cyst, an isolated tubal-paratubal cyst torsion should be considered and appropriate ovary-sparing surgical treatment foreseen.