F. Scarpellini

Differential Expression of IGF-I and IGF-II in Eutopic and Ectopic Endometria of Women With Endometriosis and in Women Without Endometriosis

PROBLEM: Factors regulating the development, growth, and differentiation of endometrial cells of endometriotic lesions are poorly understood. To investigate the paracrine‐autocrine regulation of ectopic endometrial cell growth, the expression of IGF‐I and IGF‐II were studied.

Psychological stress and lipoperoxidation in miscarriage.

It is a common belief that emotional distress, like anxiety and frustrating experiences, can negatively influence reproductive life and pregnancy outcome. Basic research during the last few years has led to increased awareness of the role of psychological stress on the physiology and pathophysiology of pregnancy. Although a reliable system to measure stress and its biological effects is not available, a number of papers have been published; therefore, the real role played by emotional distress in reproductive life remains a debated issue. It has been suggested that serum lipoperoxide levels in pregnant women are directly influenced by psychological stress. Furthermore, increased serum lipoperoxide levels have been shown to be associated with pregnancy diseases like preeclampsia.* We have attempted to develop a model to study stress and its biological effects on early pregnancy, using lipoperoxidation activity as a biochemical marker. We reports the results of a preliminary study on normal healthy pregnant women and women with threatened abortion tested concurrently for lipoperoxidation activity and psychological distress.

Serum CA 125 and first trimester abortion

Objective: The study was carried out to assess the clinical value of serum CA 125 in association with serum β‐human chorionic gonadotropin (hCG) for predicting pregnancy outcome. Methods: One hundred spontaneous pregnancies, 52 non‐threatened pregnancies and 48 with threatened abortions, observed in the Department of Obstetrics and Gynecology at the University ‘La Sapienza’, Rome, Italy, were evaluated during the first trimester using ultrasound examination, CA 125 and β‐hCG titrations. Results: Threatened pregnancies had statistically significantly higher CA 125 serum values than non‐threatened pregnancies, especially those with a negative outcome (P < 0.01). The CA 125 levels in the threatened pregnancies were positively correlated with the tropho‐decidual hematoma volume (r = 0.839, P < 0.0001). The CA 125‐β‐hCG association showed a higher prognostic value (sensitivity 78.9%, specificity 96.5%) in assessing pregnancy outcome than CA 125 or β‐hCG alone (sensitivity 78.9% and 57.9%, respectively; specificity 75.8% and 86.2%, respectively). Conclusions: Our findings are in accordance with the hypothesis of a tropho‐decidual origin of this marker, suggesting its possible usefulness in the prognostic evaluation of first trimester threatened abortion.

Influence of Histocompatibility Antigens in Recurrent Spontaneous Abortion Couples and on Their Reproductive Performances

PROBLEM: To determine if human leukocyte antigens (HLA) play any role in the aetiology of recurrent spontaneous abortion (RSA), a substantial group of RSA couples were studied, and their reproductive performances in a 3‐year follow‐up recorded.

Serum Lipoperoxide Level Variations in Normal and Luteal Phase Defect Cycles

A luteal phase defect (LPD) is a clinical problem leading to infertility and is characterized by reduced progesterone levels during the luteal phase. Serum lipoperoxidation is an expression of cellular hypoxic damage occurring under all stress-oxidative conditions. Forty-eight consecutive infertility patients, according to the infertility class II of the WHO classification, underwent clinical observation. Twenty-five patients ovulated constantly with a normal luteal phase, while the other 23 had a LPD, hormonally and histologically assessed. The luteal phase was monitored biochemically by titration of progesterone, oestradiol, and serum lipid peroxides during the ovulatory period and 6-12 days after ovulation. The mean plasmatic concentration of oestradiol was not statistically different between the LPD and the normal-cycle groups, while a statistically significant difference was found for progesterone plasmatic concentrations between the LPD and the normal-cycle groups (p < 0.05); a greater statistical difference was also found in the mean serum lipoperoxide titration (p < 0.001). These findings suggest that serum lipoperoxidation titration may be a useful tool in the study of the interactions between hormonal milieu and sympathetic activity.

HLA antigen sharing in Italian couples in which women were affected by gestational trophoblastic tumors

PROBLEM: The development of gestational trophoblastic tumors (GTT), in which genetic factors are strongly involved, is a rare event. To test the possibility that gene(s) linked to the Major histocompatibility Complex (MHC) may have a role in both embryo growth and tumor development, the HLA typing was performed on patients affected by GTT and on their partners.

Doxycycline May Inhibit Postmenopausal Bone Damage

Postmenopausal calcium bone loss is one of the most common problems of public health. In recent years various therapeutic strategies have been proposed and tested to counteract this event. However, until now these treatments were principally based on stimulation of new bone synthesis and increased osteoblastic activity. Doxycycline, a semisynthetic tetracycline, has been found to block metalloproteinases, especially collagenase.1 Moreover, tetracyclines, including doxycycline, have been found to inhibit osteoclast-mediated bone resorption in culture.* Accordingly, we carried out a preliminary study to test our hypothesis that doxycycline, by inhibiting bone cell matrix metalloproteinases and bone resorption, could be beneficial in early postmenopausal women.

PreImplantation Factor in endometriosis: A potential role in inducing immune privilege for ectopic endometrium.

Endometriosis is a chronic inflammatory condition characterised by the growth of endometrial epithelial and stromal cells outside the uterine cavity. In addition to Sampson’s theory of retrograde menstruation, endometriosis pathogenesis is facilitated by a privileged inflammatory microenvironment, with T regulatory FoxP3+ expressing T cells (Tregs) being a significant factor. PreImplantation Factor (PIF) is a peptide essential for pregnancy recognition and development. An immune modulatory function of the synthetic PIF analog (sPIF) has been successfully confirmed in multiple animal models. We report that PIF is expressed in the epithelial ectopic cells in close proximity to FoxP3+ stromal cells. We provide evidence that PIF interacts with FoxP3+ cells and modulates cell viability, dependent on cell source and presence of inflammatory mediators. Our finding represent a novel PIF-based mechanism in endometriosis that has potential for novel therapeutics.

1141229409 Immunolocalization of IL-10 in endometrium of habitual abortion: new diagnostic tool?

Recently, the role of IL‐10, in controlling the response of the maternal immune system to the embryo has been highlighted. We studied the expression of IL‐10 by immunohistochemistry in human endometrium of patients with habitual abortions and in fertile controls. Endometria of 79 women affected by habitual abortion, without evidence of known abortive causes and sampled in the late secretory phase, were studied by immunohistochemistry for IL‐10 and CD‐56 expression. Monoclonal antibodies for these antigens were used on paraffin embedded tissues. Controls were endometria of 22 fertile women and 10 IVF pregnancies. HSCORE system was used for a semi‐quantitative assay. Stromal cells CD56 positive of secretory phase endometria and the decidua of pregnancies express IL‐10, whereas no expression was observed in proliferative phase samples. In the samples of habitual aborters, a statistical significant decrease of IL‐10 expression was shown. 29 of 79 patients showed a reduction in IL‐10 expression of more than 50%, relative to controls. IL‐10 is expressed in stromal cells of secretory phase and pregnancy, and markedly reduced in habitual aborters. Assessment of IL‐10 in secretory endometrium may be used in these patients to find Th2 impairment.