Francesco Branconi

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.

Lack of Histocompatibility Leukocyte Antigen-G expression in early embryos is not related to germinal defects or impairment of interleukin-10 production by embryos

The expression of Histocompatibility Leukocyte Antigen (HLA)-G molecules is a mandatory prerequisite for the development of pregnancy but no hypotheses have yet been advanced regarding the lack of HLA-G modulation expression in a percentage of early embryos obtained by in vitro fertilization (IVF). One possible hypothetical model assumes that the absence of regulation of HLA-G or impaired interleukin (IL)-10 secretion could be related to germinal defects. We investigated the presence of soluble HLA-G antigens in supernatants of single embryo cultures from couples admitted to a second fertilization procedure; these couples showed a complete absence of HLA-G modulation in the first cycles embryo supernatants (0/31). The results obtained in the second IVF cycle showed embryo supernatants positive for HLA-G (14/40), suggesting that the previous lack of antigen modulation is independent of germinal defects. Furthermore, since it has been reported that oocytes and early embryos can secrete IL-10, an anti-inflammatory cytokine produced by type 2 helper T cells that induces upregulation of HLA-G expression in monocytes and trophoblasts, we investigated the levels of IL-10 and soluble HLA-G in 40 embryo culture supernatants from 21 IVF cycles. No associations were observed between the presence of IL-10 and the production and concentrations of soluble HLA-G, or between IL-10 levels and pregnancy outcome. These results indicate that the lack of HLA-G production in early embryos is not related to germinal defects or to impairment in embryo IL-10 secretion but could be ascribed to possible uncorrected fertilization processes.

Chorion villosum does not express progesterone and estrogen receptors during the first trimester of pregnancy.

First-trimester chorion villosum plays the key role in the development of human placenta and secretes a large number of hormones and hormone-related substances. To test whether progesterone and estrogen could have regulatory effects on first-trimester chorion villosum functions, we investigated the presence of progesterone receptor (PR) and estrogen receptor (ER) in 47 chorion villosum samples from patients who underwent abortion during the first trimester of pregnancy. The study was carried out using immunohistochemical methods. No ER and PR positivity was evidenced in the 47 chorion villosum samples examined. The possibility that progesterone and estrogen play a role in the regulation of chorion villosum functions should therefore be excluded.

Maternal serum CA 125 levels in first trimester abortion

OBJECTIVE To assess the source of maternal serum CA 125 during the first trimester of pregnancy. STUDY DESIGN CA 125 was measured in stored samples from nonviable pregnancies of 8-13 weeks gestation. The study group comprised 19 women with vaginal bleeding and 13 non-bleeders. Only patients in whom chromosome analysis of the products of conception demonstrated a normal caryotype were included. CA 125 levels were expressed in multiples of the median (MoM) for normal pregnancies of the same gestational age. RESULTS Median MoM values of CA 125 were significantly higher in women with vaginal bleeding (1.81 MoM) as compared both to non-bleeders (0.82 MoM; p < 0.01-Mann-Whitney U-test) and to the normal pregnancies (1.01 MoM; p < 0.05). No significant difference was found between non-bleeding women and controls. CONCLUSIONS The present study indicates that in non-viable pregnancies with euploid fetuses an increase in maternal serum CA 125 levels was found only in presence of decidual disruption associated to vaginal bleeding. These findings are compatible with a prevalent decidual source of this antigen.

Decidual Progesterone and Estrogen Receptors in the First Trimester of Pregnancy

Receptor content of human decidua in early pregnancy (weeks 6-12) was investigated. Fifty-three tissue samples were obtained from voluntary patients undergoing abortion and whose gestational age range from 6 to 12 weeks. Blood samples were drawn at the time of operation in order to measure circulating estradiol (E) and progesterone (P) concentrations. Tissue samples underwent first histological confirmation and then were analyzed for receptor content by immunohistochemistry (IH) and by the conventional ligand binding technique (LBA). Estrogen receptors (ER) appeared to be always undetectable by IH (53 samples). LBA measured a significant amount of ER (> 10 fmol/mg) in two samples, borderline values (3-10 fmol/mg) in 6 and no binding in the other three. No relation was apparent between PR levels and either gestational age or blood P concentration. ER were possibly downregulated by the high E levels, and their synthesis inhibited by the high P levels.

Control of Vascular Reactivity in Pregnancy Induced Hypertension

To evaluate the possibility that vascular reactivity in umbilical artery is different in normal and pre-eclamptic condition, we assessed an “in vitro study” on strips of umbilical arteries removed at the end of normal and pre-eclamptic pregnancy. We studied the reactivity of those arteries to prostaglandin A1 and prostaglandin F2α-The dose-response analysis to prostaglandins on normal umbilical arteries were between 10−7 and 10−4; in contrast, the results obtained on arteries removed at the end of pre-eclamptic pregnancies were not consistent. In this group a tendency to two different distributions seemed to occur and was related to different clinical features of pre-eclampsia, namely the early and the late onset of the disease. Our results suggest that the various clinical pictures of pre-eclampsia correlate with different conditions of vascular reactivity.

CA125 in Culture Medium of Preimplantation Embryo

The first stage of the implantation is the adhesion of the embryonic pole of the blastocyst to the decidua. Such a phenomenon has been demonstrated to be dependent on the presence of glycoproteic compounds, produced partly by the decidua and partly by the embryo. CA125 is an antigenic determinant associated to a glycoprotein expressed by various embryonic tissues. The objective of our research has been to measure the production of CA125 by the embryo in the initial phase of its development. Patients were recruited from our in vitro fertilization program. The culture medium used for the oocytes and for the embryos was collected and CA125 levels were measured. The results indicate that there is not a statistically significative difference between the values of CA125 measured in the mediums where a pronucleus or an embryo was present and the negative controls. From our data, therefore, it can be concluded that CA125 expression begins later in the human embryonic development than 8-cells-stage embryo.

P36.05: Twin–twin transfusion syndrome: a case of hydrops of the recipient after massive amnioreduction in the third trimester

Structural or karyotypic discordance in monozygotic twins has important implications for prenatal diagnosis and management, particularly when considering selective fetocide of the affected cotwin. Here we present the ultrasound and cytogenetic findings of monozygotic twins discordant for phenotype and genotype. A 39year-old woman was referred at 15 weeks’ gestation owing to a twin pregnancy with a structurally abnormal co-twin. She had conceived naturally, without any assisted reproductive treatment. Ultrasound revealed a normal male fetus and an abnormal female co-twin with cystic hygroma and hydrops fetalis. We performed a chorionicity scan and presumed a monochorionicity on the basis of sonographic findings, which included a thin dividing membrane, positive ‘T sign’ and single placenta. In addition, a previous ultrasound procedure had shown a single gestational sac at 6 weeks’ gestation. However, the discordant gender was puzzling. Therefore, we decided to perform cytogenetic studies to determine the chorionicity, which is a critical factor in the contemplation of selective fetocide in a twin pregnancy. We conducted genetic amniocentesis for each of the amnionic cavities. Cytogenetic analysis revealed a 46, XY karyotype in the amniocytes of the normal fetus and a 45, X karyotype in the amniocytes of the abnormal co-twin. Molecular analysis of polymorphic small tandem repeat markers by quantitative fluorescent PCR confirmed the presence of monozygotic twins. Considering the high probability of spontaneous death in the abnormal co-twin and the risks associated with selective fetocide, the pregnancy was terminated at 17 weeks’ gestation. Postmortem findings confirmed the prenatal sonographic findings, and the placenta was monochorionic-diamnionic. This case demonstrates that prenatal sonographic determination of the zygosity of twins can be as important as cytogenetic studies in the diagnosis and management of a twin pregnancy with discordant structural anomalies.