Gianfranco Scarselli

Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions.

Leukemia inhibitory factor is essential for embryo implantation, and a shift from type 1 T-helper to type 2 T-helper response at the fetal–maternal interface may contribute to successful pregnancy. We show that LIF production is associated with type 2 T-helper cells, is upregulated by IL-4 and progesterone and is downregulated by IL-12, IFN-γ and IFN-α. We also show a decreased production of LIF, IL-4 and IL-10 by decidual T cells of women with unexplained recurrent abortions in comparison with that of women with normal gestation. The defective production of LIF and/or type 2 T-helper cytokines may contribute to the development of unexplained recurrent abortions.

Complex pelvic mass as a target of evaluation of vessel distribution by color Doppler sonography for the diagnosis of adnexal malignancies: results of a multicenter European study.

Objective. To compare the diagnostic accuracy of gray scale sonography and color Doppler imaging in the differential diagnosis of adnexal malignancies from benign complex pelvic masses in a multicenter prospective study. Methods. The study was performed as a collaborative work at 3 European university departments of obstetrics and gynecology. A total of 826 complex pelvic masses on which transvaginal sonography and evaluation of cancer antigen 125 plasma concentrations were performed before surgical exploration were included in the study. The scanning procedure was the same in the 3 institutions. An adnexal mass was first studied in gray scale sonography, and a probable histologic type was predicted. Second, solid excrescences or solid portions of the tumor were evaluated for vascular flow with color Doppler sonography (conventional or power). A mass was graded malignant if flow was shown within the excrescences or solid areas and benign if there was no flow. The overall agreement between the test result and the actual outcome was calculated by κ statistics. Results. Color Doppler evaluation was more accurate in the diagnosis of adnexal malignancies in comparison with gray scale sonography (κ = 0.82 and 0.65, respectively) because of significantly higher specificity (0.94 versus 0.84; P < .001). The evaluation of the cancer antigen 125 plasma concentration did not seem to increase the accuracy of either method. Conclusions. The evaluation of vessel distribution by color Doppler sonography in complex adnexal cysts seems to increase the diagnostic accuracy of gray scale sonography in the detection of adnexal malignancies in a large study population.

Preeclampsia in Lean Normotensive Normotolerant Pregnant Women Can Be Predicted by Simple Insulin Sensitivity Indexes

Certain similarities between preeclampsia and insulin resistance syndrome suggest a possible link between the 2 diseases. The aim of our study was to evaluate 3 insulin sensitivity (IS) indexes (fasting homeostasis model assessment IS [ISHOMA], quantitative insulin sensitivity check index [ISQUICKI], and oral glucose IS [OGIS]) early and late in pregnancy in a large number of normotensive pregnant women with a normal glucose tolerance and to test the ability of these indexes to predict the risk of subsequent preeclampsia. In all, 829 pregnant women were tested with a 75-g, 2-hour oral glucose load in 2 periods of pregnancy: early (16 to 20 weeks) and late (26 to 30 weeks). In early and late pregnancy, respectively, ISHOMA was 1.23±0.05 and 1.44±0.05 (P<0.01), ISQUICKI was 0.40±0.002 and 0.38±0.002 (P<0.01), and OGIS was 457±2.4 mL min−1 m−2 and 445±2.2 (P<0.001), all confirming the reduction in insulin sensitivity during pregnancy. Preeclampsia developed in 6.4% of the pregnant women and correlated positively with the 75th centile of ISHOMA (P=0.001), with a sensitivity of 79% in the early and 83% in the late period and a specificity of 97% in both. ISQUICKI <25th centile was also related with preeclampsia (P=0.001), with a sensitivity of 85% in the early and 88% in the late period and a specificity of 97% in both. Judging from our findings, ISHOMA and ISQUICKI are simple tests that can pinpoint impaired insulin sensitivity early in the pregnancy. Given their high sensitivity and specificity, these indexes could be useful in predicting the development of preeclampsia in early pregnancy, before the disease become clinically evident.

Maternal-Fetal Flow, Negative Events, and Preeclampsia: Role of ACE I/D Polymorphism

Abstract—The risk for an adverse pregnancy outcome is markedly higher in women with history of preeclampsia. This may stem from impaired placentation in early gestation and from high impedance to flow in uteroplacental circulation. The renin-angiotensin system is one of the mediators of the remodeling of spiral arteries throughout pregnancy. The D allele of the Insertion/Deletion (I/D) polymorphism in the ACE gene has been associated with higher ACE activity, accounting for 47% of the total phenotypic variance of serum enzyme levels. To investigate whether the ACE I/D polymorphism affects maternal uteroplacental and fetal umbilical circulation and the pregnancy outcome in women with a history of preeclampsia, 106 women underwent Doppler examination of uterine arteries resistance index and umbilical artery pulsatility index at the 16th, 20th, and 24th weeks of gestation and were genotyped for the I/D polymorphism. This study found a difference in genotype distribution (P =0.0002) and allele frequency (P <0.0001) between women with and those without preeclampsia recurrence and fetal growth restriction as well as an association (P =0.0007) between DD genotype and risk of recurrent preeclampsia or fetal growth restriction. At the 16th, 20th, and 24th weeks, uterine artery resistance indexes were significantly lower in II, higher in DD, and intermediate in ID genotype carriers, whereas the umbilical artery pulsatility index values were significantly higher in the DD group in comparison to ID and II genotypes. The current study shows that the ACE I/D polymorphism affects uteroplacental and umbilical flows and the recurrence of an adverse pregnancy outcome in women with history of preeclampsia.

Ovarian surgery for bilateral endometriomas influences age at menopause

BACKGROUND Questions remain as to whether surgical excision of ovarian endometriomas might cause damage to ovarian function. To test the hypothesis that ovarian surgery for endometrioma compromises ovarian function and accelerates ovarian failure. METHODS In a tertiary university Clinic, longitudinal prospective cohort study. Patients who underwent laparoscopy for endometriosis between March 1993 and November 2007 were assessed for inclusion in the study. A prospective follow-up at 3, 6 and 12 months then yearly was conducted. Evolution of menstrual pattern, symptoms and reproductive outcomes were investigated. RESULTS From over the 14-year period, 302 patients were included in the study. The mean age (±SD) of patients was 32.6 ± 5.6 years; the median duration of follow-up was 8.5 years (range 2-17 years). Menopause was documented in 43 women (14.3%) at a mean age of 45.3 ± 4.3 years (range 32-52 years). Women previously submitted to bilateral cystectomy were younger at menopause than those with monolateral endometrioma (42.1 ± 5.1 years versus 47.1 ± 3.5 years, P = 0.003). Premature ovarian failure (POF) was observed in 7 of 43 (16.3%) menopausal patients; the majority (4, 57.1%) after bilateral cystectomy. The relationship between the preoperative ovarian endometriomas total diameter and menopausal age was significant in case of surgery for bilateral endometriomas (R(2) = 0.754, P = 0.002). CONCLUSIONS Patients who had been operated on for bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at the time of surgery seems related to cyst diameter. In the case of unilateral ovarian endometrioma, the contralateral intact ovary might adequately compensate.

Ten-year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma: dNA aneuploidy identifies high-risk cases among the so-called 'low-risk' patients with well and moderately differentiated tumors.

To improve the outcome of endometrial cancer patients, a more accurate prognostic assessment is mandatory. The aims of the study were to evaluate the role of flow cytometric DNA ploidy as an independent prognostic factor in patients with endometrial cancer and to verify if ploidy was able to distinguish patients with different prognosis into homogeneous subgroups for grade of differentiation and stage.

Non-classic sHLA class I in human oocyte culture medium.

Soluble human leukocyte antigen (sHLA) class I molecules have been described in all human fluids. These molecules play a significant role in immune function. sHLA has been shown to produce tolerance and to induce apoptosis in cytotoxic alloreactive T cells. They are also present in the supernatant of many cultured cells. Similarly, non-classic HLA class I antigens in soluble form are present in human fluids. Among these, HLA-G is the most important because of its location in fetal tissue that suggests maternal immunological tolerance of the fetal semiallograft. In our present study we show that using two monoclonal antibodies, w6/32 and TP25.99, in the enzyme-linked immunosorbent assay allows the detection of non-classic sHLA class I molecules in the medium from human embryo cultures. The sample were collected from oocytes cultures. Oocyte donors were 11 women attending the in vitro fertilization program. The results showed a significant association (chi2 = 9.66, p = 0.002) between sHLA antigens and the oocyte cleavage rate measured 48 h after fertilization.

Impact of endometriosis on in vitro fertilization and embryo transfer cycles in young women: a stage-dependent interference

Objective. Endometriosis is a frequent indication for in vitro fertilization and embryo transfer (IVF‐ET). Its influence on IVF‐ET cycles remains controversial. We evaluated the impact of the severity of endometriosis on IVF‐ET cycles in young women. Design. Retrospective cohort study. Setting. Academic tertiary referral centre. Sample and Methods. In a retrospective cohort analysis, 164 IVF‐ET cycles in 148 women with endometriosis‐associated infertility were analyzed. Eighty cycles performed during the same period on 72 consecutive women with tubal infertility were considered as controls. All patients were younger than 35 years old. Main Outcome Measures. Response to controlled ovarian hyperstimulation (COH), number of oocytes retrieved, fertilization, implantation and pregnancy rate (PR). Results. Clinical PR was lower in the group with endometriosis (all stages) in comparison with the tubal factor group. Higher total gonadotropin requirements, lower response to COH and lower oocyte yield were also found in the endometriosis group. Stage‐stratified analysis showed a lower fertilization rate in stage I–II (52.6% stage I–II, 70.5% stage III–IV and 71.9% tubal factor). In stage III–IV endometriosis there was a higher cycle cancellation rate, a reduced response to COH and a lower PR compared with both the stage I–II and the tubal infertility groups (PR 9.7, 25 and 26.1%, respectively). Conclusions. Stage III–IV was strongly associated with poor IVF outcome. A decreased fertilization rate in stage I–II might be a cause of subfertility in these women, owing to a hostile environment caused by the disease.

The efficacy and safety of continuous intravenous administration of remifentanil for birth pain relief: an open study of 205 parturients.

In an observational study, we prospectively evaluated the efficacy and safety of remifentanil in 205 parturients. Remifentanil was administered as a continuous infusion. The initial infusion of 0.025 &mgr;g · kg−1 · min−1 was increased in a stepwise manner to a maximum dose of 0.15 &mgr;g · kg−1 · min−1. Maternal pain, other maternal and fetal variables, side effects, and satisfaction were recorded. The mean (±sd) visual analog score before the start of the infusion was 9.4 ± 1.2 cm and decreased to 5.1 ± 0.4 cm after 5 min and 3.6 ± 1.5 cm after 30 min. The maternal side effects were minimal and no fetal or neonatal side effects were noted.

Method of delivery and intraventricular haemorrhage in extremely preterm infants

Objectives. It has been reported that caesarean delivery (CD) protects against intraventricular haemorrhage (IVH) in the extremely preterm infant, but it is not known whether this effect involve the more severe grades of IVH. Thus, our aim was to confirm the correlation between the occurrence of IVH and the mode of delivery, and to evaluate this correlation for each grade of IVH. Methods. All infants with gestational age (GA) ≤ 28 weeks admitted to the neonatal intensive care unit of a tertiary hospital were studied for each grade IVH and major complications rate. Results. We found that vaginally born infants had a higher rate of each grade of IVH, but the increase was statistically significant only for grade 3 IVH (18% vs. 2%, p < 0.0001) and all grades IVH (45% vs. 20%, p < 0.0001). Multivariate analysis demonstrated that CD (RR: 0.42, 95% CI 0.28–0.63), birth weight ≥ 800 g (RR: 0.48, 95% CI 0.32–0.73), 27–28 weeks of GA (RR: 0.38, 95% CI 0.25–0.60) and antenatal steroids (0.66, 95% CI 0.22–0.46) decrease independently the risk of developing IVH. Conclusions. Our study demonstrates that CD decreases the risk of developing IVH in extremely preterm infants including the most severe grades of IVH.