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Objective To evaluate the association between arterial and venous Doppler waveforms and adverse perinatal outcome in severe intrauterine growth restriction. Design Fetuses between 26 and 32 weeks' gestation with ultrasonographically estimated fetal weight below the 5th centile were included in this prospective study. The last Doppler measurements of the umbilical artery, ductus venosus, umbilical vein and middle cerebral artery before delivery and adverse outcome parameters without gestational age independence were used for statistical analysis. Adverse outcome parameters were defined as the following: fetal demise or neonatal death in the first 30 days of life; 5-min Apgar score of < 7; intubation at birth; retinopathy of prematurity; respiratory distress syndrome; necrotizing enterocolitis; stay in neonatal intensive care unit of more than 60 days; intraventricular hemorrhage; periventricular leukomalacia. Results Nineteen fetuses fulfilled the inclusion criteria. Perinatal death, low 5-min Apgar values and necrotizing enterocolitis were gestational age-independent adverse outcome parameters. Abnormal Doppler velocimetry of the ductus venosus was the only significant parameter associated with perinatal death and low 5-min Apgar scores. None of the Doppler parameters predicted necrotizing enterocolitis. Conclusion Our data suggest that management of severely growth-restricted fetuses may be aided by the study of ductus venosus Doppler velocimetry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Problem: Recent evidence of growth hormone (GH) receptor expression in rat endometrium and human myometrium have focused our attention on the role of the GH in endometrial development. We tested the expression of GH in the human endometrium throughout the menstrual cycle and during pregnancy., Method of Study: Immunohistochemical study was performed on endometrial specimens of fertile women in different periods of the menstrual cycle and in decidua of pregnant women., Results: Glandular cells of the human endometrium were positive for GH in the mid and late luteal phase. Furthermore, the glandular cells of decidua showed intense staining for GH, while the stromal cells were negative. No immunostaining was expressed in the proliferative or early luteal phase. The intensity levels of staining for GH in decidual specimens were significantly higher than in glandular cells of secretory endometrium specimens (P < 0.01)., Conclusions: The glandular cells of the human endometrium express GH from the late luteal phase throughout pregnancy in the decidual tissue. We suppose that GH plays an important role in blastocyst implantation.

Problem: Tumor necrosis factor-alpha (TNFalpha) is produced by the endometrium, and it has been shown that this cytokine has cyclic variations through the menstrual cycle., Method of Study: In this study we assessed TNFalpha, estradiol and progesterone levels in the endometrium and serum of 21 patients with recent abnormal uterine bleeding (AUB). Eleven women showed histological diagnosis of endometrial hyperplasia, and ten women showed normal endometrium., Results: The TNFalpha value in the serum of patients with hyperplasia and in normal endometrium did not show significant differences (64.8 +/- 21.4 vs 77.6 +/- 14.8 pg). The amounts of TNFalpha released by hyperplastic endometrial tissue were significantly higher than in control patients (258.8 +/- 78.0 vs 140.6 +/- 79.8 pg/g; P < 0.001). Immunohistochemistry of hyperplastic endometria showed a stronger staining than normal ones. Serum E2 levels in patients with hyperplastic endometrium were 49.5 +/- 31.6 ng/mL, and in controls were 107.3 +/- 66.0 ng/mL. The levels of estradiol released by hyperplastic endometria were significantly lower than in normal endometria (152.7 +/- 60.0 vs 279.9 +/- 178.7 ng/g; P < 0.003)., Conclusions: Hyperplastic endometria produce higher amounts of TNFalpha with respect to controls. These findings may explain the frequent bleeding observed in the patients with endometrial hyperplasia, since TNFalpha promotes apoptosis and endometrial shedding.

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., Method: Tissue specimens of eutopic and ectopic endometria were obtained from eight patients with endometriosis at laparoscopy and from the endometria of 14 women without endometriosis as controls. They were tested for the expression of IGF-I and IGF-II by immunohistochemical analysis., Results: Immunohistochemical study for IGF-I in controls showed a more intense staining during the proliferative phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis a reduction in the staining was observed, whereas in epithelial cells of fibrotic peritoneal adhesions an intense immunostaining for IGF-I was observed. Immunohistochemical study of IGF-II in controls showed a more intense staining during secretory phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis, a reduction in the staining was observed, whereas in epithelial cells of fibrotic peritoneal adhesions an intense immunostaining for IGF-I was observed. Immunohistochemical study of IGF-II in controls showed a more intense staining during secretory phase both in stromal and epithelial cells. In eutopic endometria of women with endometriosis, a reduction in the staining was observed, whereas in epithelial cells of ovarian lesions and fibrotic peritoneal adhesions, no immunostaining for IGF-II was observed., Conclusions: In endometriosis there is an alteration of mechanisms regulating cell proliferation and differentiation.

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., Method: The study group of sixteen couples, in which the women were affected by an invasive mole or choriocarcinoma, and the control group of thirty normal fertile couples without history of spontaneous abortion or GTT were typed for class I and class II HLA antigen., Results: The results showed no differences in single HLA-A and B antigen frequency between GTT couples and controls. In HLA-DR, locus an increased frequency of DR-6 antigen was observed (p < 0.05). No differences were observed in the frequency of number of antigens shared. When considering the single locus no differences were found in the sharing of the antigens of the A and B locus, while the frequency of antigenic sharing for DR locus was significantly higher in GTT couples with respect to controls (p < 0.025). Furthermore a higher frequency of Bw35-DR5 antigenic combination was found in GTT partners than in controls (P < 0.02)., Conclusions: These data represent a confirmation of the existence of a MHC linked gene(s) influencing the GTT development.

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., Methods: HLA typing was performed for HLA-A, -B, and DR antigens in both partners of 75 couples with unexplained RSA, and compared with a control group of 30 fertile couples that never experienced abortion. A further 57 couples of this group were studied for their reproductive performance in a 3-year follow-up, and subdivided into three subgroups: 1) couples that achieved successful pregnancy during the follow-up, and subdivided into three subgroups: 1) couples that achieved successful pregnancy during the follow-up; 2) couples that experienced abortion and no livebirth during the follow-up; and 3) couples that experienced infertility during the follow-up., Results: There were no significant differences for antigen frequency in all the different HLA loci, and HLA antigen sharing between all the RSA couples and controls. Significant increase of sharing for HLA-DR locus was observed in the couples that aborted during the follow-up with respect to the couples that achieved livebirth and controls (P < 0.03 and P < 0.02 respectively), and significantly increased frequency of B44, DR5 antigen combination in the same comparison (P < 0.03). No significant differences were observed in terms of the interval between conceptions in couples without antigen sharing with respect to couples with 1, 2 or more antigens shared, and antigen sharing in Locus A, B or DR., Conclusions: The results suggest that gene(s) disadvantageous for reproduction may exist between the HLA-B and -DR chromosomal region which influences the pregnancy outcome in RSA couples, and that HLA-antigen sharing itself does not influence the outcome.

IgG anticardiolipin antibodies (ACL) have been shown to occur in a high proportion of women with repeated unexplained miscarriages. Forty-nine women with unexplained recurrent spontaneous abortions (RSA), previously assayed for the presence of ACL by an enzyme-linked immunoabsorbent assay, were typed for HLA-DR and DQ antigens by the classical microlymphocytotoxicity test. Twenty-five women were positive for ACL and 24 were negative. HLA-DR7 was found in 24.5% of 49 habitually aborting women vs. 28% of healthy controls; but the DR7 frequency was 40% in ACL positive patients vs. 8.3% in ACL negative patients (P = 0.011). These results show that in the Italian population an association between HLA-DR7 antigen and ACL is present in women with unexplained RSA, suggesting that HLA-DR genes might control the susceptibility to specific autoantibody production.