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Biomedical subjects

E Anteby

Publications and source records attributed to E Anteby.

At least 19 recordsLinked to original sources

GnRH agonist versus GnRH antagonist in ovarian stimulation: is the emperor naked?

OBJECTIVE: The aim of the study was to evaluate the influence of type of GnRH-analog used during controlled ovarian hyperstimulation (COH) on the outcome of in vitro fertilization (IVF) cycles. PATIENTS AND METHODS: All consecutive women aged < or = 35 years admitted to our IVF unit from January 2001 to December 2004 were enrolled in the study. Only patients undergoing up to their third IVF cycle attempt were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred, and clinical pregnancy rate were compared between women given GnRH-agonist or GnRH-antagonist during COH. RESULTS: Four hundred and eighty-seven consecutive IVF cycles were evaluated, 226 in the agonist group and 261 in the antagonist group. A clinical pregnancy was achieved in 93 patients in the agonist group (pregnancy rate 41.2% per cycle) and 66 patients in the antagonist grup (pregnancy rate 25.3%); this difference was statistically significant (p < 0.01). The agonist group also used significantly more gonadotropin ampoules, required longer stimulation, and had higher estradiol levels on the day of human chorionic gonadotropin administration. CONCLUSION: The midluteal long GhRH-agonist suppressive protocol should be the protocol of choice in young patients in their first three IVF cycle attempts.

Adult↗

Ocular manifestations in children born after in vitro fertilization.

OBJECTIVE: To report the ocular abnormalities found in children born after in vitro fertilization. METHODS: Forty-seven children (25 girls and 22 boys) born after an in vitro fertilization pregnancy (mean +/- SD birth weight, 2335 +/- 817 g; range, 924-4300 g) and referred for ophthalmic evaluation were included in the study. All underwent a thorough ocular examination. Obstetric history was gathered following a detailed questionnaire with the mothers. RESULTS: Of 70 eyes among nonverbal children, visual acuity was "normal for age" in 60 (86%), "fair" in 4 (6%), and "poor" in 6 (9%). Visual acuity in 24 eyes in verbal children ranged from 6/6 to no light perception, with 4 (17%) having poor vision. Cycloplegic refraction disclosed an emmetropia in 22 (27%), hypermetropia in 47 (57%), and myopia in 13 (16%) of the eyes. Anisometropia of more than 1.0 diopters was found in 8 children. Major ocular malformations were observed in 12 (26%) of the 47 children. These malformations included Coats disease, congenital cataract, congenital glaucoma, hypoplastic optic nerve head, idiopathic optic atrophy, coloboma with microphthalmos, and retinoblastoma. CONCLUSIONS: Ocular anomalies were frequently observed in this cohort of offspring born after in vitro fertilization. A diligent and prospective prenatal search for such malformations should unveil the real prevalence of ocular malformations in children born after in vitro fertilization.

Birth Weight↗

Expression of gelatinase B by trophoblast cells: down-regulation by progesterone.

OBJECTIVE: It is now accepted that gelatinase B (92 kd type IV collagenase) is involved in blastocyst implantation and trophoblast invasion. However, little is known about the regulation of this enzyme at the fetomaternal interface. Progesterone has been demonstrated to inhibit gelatinase B secretion from endometrial cells, myometrium, and cervical fibroblasts. Interestingly, the promotor of gelatinase B contains a progesterone-responsive element that may explain transcriptional activation of this metalloproteinase by progesterone. It may be hypothesized that progesterone secreted from trophoblast cells, representing the fetal part of the fetomaternal interface, may have a role in the regulation of gelatinase secretion and blastocyst implantation. STUDY DESIGN: To this end, use was made of first-trimester trophoblast cells obtained from first-trimester pregnancy terminations. The trophoblast cells were separated by trypsin degradation and fractionation on Percoll gradients. Metalloproteinase activity was measured by zymography, and the expression of the gelatinase B messenger ribonucleic acid was determined by the solution hybridization/ribonuclease protection assay. RESULTS: Primary cell cultures of trophoblasts from first trimesters of pregnancy constitutively elaborated two species of type IV collagenases (gelatinase A and B) as assessed on a gelatin matrix. Treatment with progesterone decreased the accumulation of a gelatinase B species in a dose-dependent fashion. Administration of a progesterone receptor antagonist onapristone (ZK-98.299) neutralized the progesterone inhibitory effect on the gelatinase B in a dose-dependent fashion, thus supporting the presumption that the progesterone effect is receptor mediated. Progesterone significantly attenuated the expression of gelatinase B by trophoblast cells, an effect that was neutralized by ZK-98.299. CONCLUSION: These observations provide strong indirect support for the participation of progesterone in the regulation of gelatinase B in trophoblast cells. It may be an important regulator of gelatinase production at the fetomaternal interface.

Cells, Cultured↗

Congenital heart defects: natural course and in utero development.

BACKGROUND: Most congenital heart defects (CHDs) are diagnosed on targeted prenatal transvaginal (TVS) or transabdominal (TAS) ultrasonography during the early second trimester or at midgestation. Nevertheless, delayed diagnosis in some cardiac malformations still remains despite detailed echocardiographic examination. The present study was conducted to evaluate the evolution of fetal cardiac anomalies and assess their development in utero. METHODS AND RESULTS: We retrospectively reviewed 22,050 pregnant women who were divided into two groups: 6924 who had initial TVSs at 13 to 16 weeks' gestation, followed by TASs at 20 to 22 weeks, and 15,126 who had initial TASs at 20 to 22 weeks. Both groups were subsequently examined in their third trimester. All newborns were examined by certified pediatricians. CHD was diagnosed in 168 babies: 66 in group A and 102 in group B. In group A, 42 malformations (64%) were detected at the first TVS examination, and 11 (17%) were found during the subsequent TAS. Three additional anomalies (4%) were found during the third trimester, and 10 malformations (15%) were detected postnatally. In group B, 80 malformations (78%) were detected in the initial examination at midtrimester, and an additional 7 (7%) were found in the third trimester, whereas 15 (15%) were diagnosed postnatally. The 10 anomalies (group A, n=3; group B, n=7) that were detected only during the third trimester comprised aortic stenosis (n=2), cardiac rhabdomyoma (n=2), subaortic stenosis (n=1), tetralogy of Fallot (n= 1), aortic coarctation (n=1), sealed foramen ovale (n=1), ventricular septal defects (n=1), and hypertrophic cardiomyopathy (n=1). CONCLUSIONS: Although most fetal cardiac anomalies are detectable early in gestation, some may evolve in utero at different stages of pregnancy.

Adolescent↗

Transcriptional regulation of human placental corticotropin-releasing factor by prostaglandins and estradiol.

The mechanism of labor initiation in humans has not been completely elucidated. Prostaglandins, estrogens, and corticotropin-releasing factor (CRF) have all been shown to affect uterine myocytes and enhance uterine contractility. There are also indications that these uterine regulators have additional effects on other sites involved in labor and that they may act in concert or, perhaps, by regulating each other. Therefore, we evaluated the CRF promoter for transcriptional regulation by prostaglandins and estrogens. Human placental choriocarcinoma cell lines were transfected with CRF-luciferase reporter genes and treated with prostaglandins. Prostaglandin E2 (PGE2), but not prostaglandin F2alpha (PGF2alpha), stimulated CRF-luciferase expression in choriocarcinoma cell lines via a cAMP-dependent pathway. A combination of transfections and in vitro binding studies tested for potential regulation of CRF by estrogen receptor (ER). ER neither regulated the CRF promoter nor interacted with steroid response half-sites from the CRF promoter. Our results provide a molecular regulatory link between PGE2 and CRF, two compounds that enhance uterine contractile function. Combined with the stimulation of prostaglandin release by CRF, these data support a potentially important "feed-forward" regulatory loop involving CRF and PGE2 in parturition. In contrast, we found no evidence for direct effects of estrogens or PGF2alpha on CRF transcription.

Animals↗

Cytokine-mediated regulation of type IV collagenase expression and production in human trophoblast cells.

The invasive property of trophoblast cells is dependent on the activity of proteolytic enzymes of the metallo- and serine proteases family. Interleukin-1 (IL-1) was found to be involved in the regulation of these proteases in various systems, serving as an important modulator in trophoblast physiology (e.g. induction of hCG beta, cytokines, and others). Therefore, consideration is given in this report to the role of IL-1 in the regulation of metalloprotease activity in human trophoblasts. Human trophoblast cells were isolated from first trimester placentas by trypsin degradation and Percoll fractionation. Primary cell cultures of first trimester trophoblasts constitutively elaborated two species of collagenase type IV (92 and 72 kDa), as assessed in gelatin matrix. Treatment with IL-1 further augmented the 92-kDa type IV collagenase secretion in a dose-dependent manner. Furthermore, IL-1 significantly (P < 0.01) increased 92-kDa collagenase gene expression by trophoblast cells, as determined by solution hybridization/ribonuclease protection assay. Both the increase in gene expression and protein biosynthesis of the 92-kDa collagenase type IV were neutralized by the soluble IL-1 receptor, indirectly suggesting a receptor-mediated response. Interestingly, transforming growth factor-beta a putative modulator of IL-1 induced effects, was shown to induce the 92-kDa collagenase type IV secretion as well. These results provide indirect evidence supporting the idea that IL-1 and transforming growth factor-beta may play an intermediary role in trophoblast invasion at the feto-maternal interface by regulating trophoblast expression of 92-kDa type IV collagenase, a protease of prime importance in trophoblast invasion.

Cells, Cultured↗

Characterization of intraperitoneal cytokines and nitrites in women with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess the potential involvement of cytokines and nitrites in the hyperpermeability characterizing the ovarian hyperstimulation syndrome (OHSS). DESIGN: A controlled clinical study comparing peritoneal fluid (PF) from patients with severe OHSS and from non-OHSS controls. SETTING: Women hospitalized with severe OHSS in three tertiary medical centers. PATIENTS: Twelve patients with severe OHSS necessitating paracentesis and 20 non-OHSS controls. INTERVENTIONS: The criteria for ultrasound-guided paracentesis were tense ascites, hydrothorax, hemoconcentration, or oliguria. MAIN OUTCOME MEASURES: Interleukin (IL) 1 beta IL-1 receptor agonist, IL-2, IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha) levels in PF were assayed by ELISA; nitrites were measured by the "Griess" reaction. Estradiol and P were determined by RIA. RESULTS: Ovarian hyperstimulation syndrome patients had significantly higher PF IL-6 (3,523 versus 30 pg/mL), TNF alpha (14 versus 4.2 pg/mL), and IL-8 (1,695 versus 900 pg/mL). In the serum, only IL-6 levels were significantly higher (375 versus 11 pg/mL). Conversely, nitrite levels were significantly lower in PF of OHSS patients (0.5 versus 34 nmol/mL). Interleukin 1 levels were higher and IL-1 receptor antagonist levels were lower in OHSS patients, suggesting potentially increased biologic potency of IL-1. CONCLUSION: These findings suggest that these substances could be involved in mediating the capillary hyperpermeability characterizing this syndrome.

Ascitic Fluid↗

Transvaginal ultrasonography at early pregnancy cannot be used alone for targeted organ ultrasonographic examination in a high-risk population.

OBJECTIVE: A study was performed to evaluate whether early second-trimester (13 to 16 weeks) transvaginal scan can be used alone for structure evaluation of the fetus or whether it should be followed by a transabdominal scan performed at 18 to 20 weeks of gestation. STUDY DESIGN: A total of 536 pregnant women at high risk for birth defects were examined by transvaginal ultrasonography at 13 to 16 weeks' gestation. This was followed by a transabdominal scan at 18 to 20 weeks of pregnancy. Aborted specimens were examined by a pediatric pathologist in terminated pregnancies, and newborn babies were examined by a pediatrician to detect congenital anomalies. RESULTS: Transvaginal ultrasonography performed at 13 to 16 weeks' gestation identified 42 structural anomalies. Of these, 24 pregnancies were terminated and one fetus died. The other 17 fetuses and the rest of the population underwent a second transabdominal survey at 18 to 20 weeks' gestation, which identified eight structural anomalies that were not diagnosed by the previous examination. In five cases the diagnosed anomaly disappeared. Together, the scans brought about the detection of 41 of 46 abnormal fetuses (89%). CONCLUSIONS: Because a significant number of birth defects (17.4%) was not detected by early second-trimester vaginal scan, we recommend that whenever early transvaginal ultrasonographic examination is performed it should be followed by a transabdominal scan at the most advanced stage of pregnancy at which an abortion is still feasible.

Adult↗

Interleukin-1 stimulates prostaglandin E production by human trophoblast cells from first and third trimesters.

Prostaglandins (PGs) play a major role during implantation and labor, and their level is regulated by various cytokines. Interleukin-1 (IL-1) is a known mediator of prostaglandin E (PGE) production in various cell types, including endothelial, amniotic, and endometrial cells; however, its role in the regulation of PGE production in the trophoblast cells is yet unknown. As IL-1 and PGE are both known to be synthesized in the human trophoblast cells, we examined the possibility that IL-1 regulates PG production in human trophoblast cells. To this end, use was made of first and third trimester trophoblast cells, obtained from first trimester terminations of pregnancies and elective cesarean sections. The trophoblast cells were separated by trypsin degradation and fractionation on Percoll gradients, and cultured for 18 h under serum-free conditions in the absence or presence of IL-1 (10 ng/mL). IL-1 induced a 5-fold increase in PGE production, a response that was cell density, time, and dose dependent. IL-1-induced PGE biosynthesis was prevented in the presence of either IL-1 receptor antagonist or the soluble IL-1 receptor, suggesting a receptor-mediated response. Significantly, de novo production of PGE by trophoblast cells in the absence of IL-1 was also markedly (50%) reduced by either the IL-1 receptor antagonist or the soluble IL-1 receptor, further supporting the notion that IL-1 is involved in PGE synthesis even under basal conditions. Transforming growth factor-beta 1, a putative modulator of the effects of IL-1, significantly attenuated IL-1-stimulated PGE production, supporting the possibility that transforming growth factor-beta 1 may serve as a regulator of the effects of IL-1 in trophoblast cells. These observations suggest a pivotal role of IL-1 in the regulation of PGE economy by trophoblast cells. As trophoblast cells are in intimate contact with maternal cells, understanding the regulation of PGE levels may explain crucial processes at the feto-maternal interface, including implantation of the developing blastocyst, immunosurveilance, and the initiation of labor.

Cell Count↗

Clinical relevance of gestational thrombocytopenia of < 100,000/microliters.

We identified 22 women with thrombocytopenia of < 100,000/microliters found incidentally during pregnancy and prospectively monitored their platelet count and clinical outcome for a minimum of 6 months postpartum. During the study period, four women became pregnant twice, accounting for a total of 26 pregnancies. The lowest platelet count during pregnancy was 65,600/microliters +/- 19,400 (mean +/- SD), and at delivery 84,500/microliters +/- 32,300 (P < 0.02). The thrombocytopenia was virtually asymptomatic in all patients during the pregnancy and delivery, whether vaginal or surgical. Neonatal platelet counts (n = 18) were normal (270,700/microliters +/- 69,900), and none of the newborns (n = 24) had a bleeding diathesis. Normalization of the platelet count (i.e., > 150,000/microliters) was documented in 18 patients within 1 month postpartum, in five within 3 months postpartum, and in two as late as 5 months after delivery. One woman did not recover from the thrombocytopenia and eventually developed other stigmata of an autoimmune disease. Long-term follow-up showed recurrence of thrombocytopenia in four patients: three in the context of a subsequent pregnancy and one who developed idiopathic thrombocytopenic purpura. Retrospective analysis of blood counts obtained from 12 previous pregnancies demonstrated thrombocytopenia of a similar degree to the index pregnancy. We conclude that gestational thrombocytopenia of < 100,000/microliters is clinically a benign phenomenon that can recur in subsequent pregnancies and is not accompanied by neonatal thrombocytopenia. In some cases, however, pregnancy-associated thrombocytopenia may be a manifestation of an autoimmune disease with its attendant implications for the neonate. Since the differential diagnosis between the two conditions may be difficult to establish when first encountered during pregnancy, a conservative approach emphasizing careful surveillance and guarded reassurance is justified as long as the platelet counts are > 50,000/microliters.

Adult↗

Monosomy 8q: prenatal diagnosis and autopsy findings.

The autopsy findings of a fetus with deletion of the long arm of chromosome 8 are described. Many of the features are similar to those of the tricho-rhino-phalangeal syndromes, types I and II, which are associated with deletions on chromosome 8q24. Other findings in this case, such as total absence of the corpus callosum and intestinal malrotation, have not been described in these syndromes. Genes involved in the development of the latter malformations may reside in adjacent regions on the long arm of chromosome 8. An elevated serum level of beta human chorionic gonadotropin (beta hCG) was found during pregnancy. This aberration should be included with other chromosomal disorders which may be detected by this test.

Abortion, Induced↗

Simultaneous detection of three common sexually transmitted agents by polymerase chain reaction.

OBJECTIVE: Human papillomaviruses, herpes simplex viruses, and Chlamydia trachomatis are very common infections of the genital tract. The purpose of our study was to develop a polymerase chain reaction-based assay for the simultaneous detection of these organisms from a single genital swab. STUDY DESIGN: To prove the technical feasibility of a simultaneous polymerase chain reaction assay for these organisms, a mixture of deoxyribonucleic acids extracted from cells infected by these three agents was amplified in the same tube with three different sets of primers corresponding to specific regions of the human papillomavirus genome, the herpes simplex virus 1 and 2 genomes, and the Chlamydia trachomatis plasmid, respectively. Then genital swabs from patients with suspected infection by one or more of these agents were assayed by polymerase chain reaction for the presence of herpes simplex virus, human papillomavirus, and Chlamydia trachomatis independently and simultaneously. Most of the samples were analyzed in parallel by other methods: herpes simplex virus by culture., Chlamydia trachomatis by culture and antigen staining, and human papillomavirus by the filter in situ hybridization method. RESULTS: Analysis of the polymerase chain reaction products amplified from the deoxyribonucleic acid mixture revealed three bands corresponding to the respective amplified region of each microorganism. A total of 391 genital swabs were assayed independently by polymerase chain reaction for the presence of herpes simplex virus (113 samples), human papillomavirus (200 samples), and Chlamydia trachomatis (78 genital swabs and four urethral swabs). Forty-nine were herpes simplex virus positive (47 by culture), 45 were human papillomavirus positive (43 by filter in situ hybridization), and one sample was positive for Chlamydia trachomatis, both by polymerase chain reaction and by culture. Ninety-two of the 391 samples were analyzed simultaneously by polymerase chain reaction for the presence of the three agents. The correlation between the results obtained independently and simultaneously was of the order of 100%: 29 were positive for herpes simplex virus, 16 were positive for human papillomavirus, and one was positive for Chlamydia trachomatis, in one sample we could detect both human papillomavirus and herpes simplex virus. CONCLUSIONS: The polymerase chain reaction simultaneous assay is a quick and efficient way of detecting herpes simplex virus, human papillomavirus, and Chlamydia trachomatis from a single genital swab. This method can greatly simplify the diagnostic procedures in the laboratory.

Base Sequence↗

Developmental regulation of the expression of 72 and 92 kd type IV collagenases in human trophoblasts: a possible mechanism for control of trophoblast invasion.

OBJECTIVE: During early pregnancy fetal cytotrophoblast cells invade the uterus and penetrate the basement membrane, a property that is characteristic of malignant cells. However, unlike tumor invasion, trophoblast invasion of the uterus is under strict control. This control limits invasion, so that it primarily remains confined to the endometrial aspect of the myometrium and continues only until midgestation. The invasive properties of the trophoblast cells are made possible by the activity of proteolytic enzymes that belong to the metalloproteinases and serine proteinases. Type IV collagenase (metalloproteinase) is considered crucial in the extracellular matrix remodeling that takes place during the invasion process. In this study we set out to characterize the invasive properties of trophoblast cells at different stages of pregnancy. STUDY DESIGN: Human trophoblast cells were isolated from first- and third-trimester placentas by trypsin digestion and Percoll fractionation and were then cultured under serum-free conditions. The invasive ability of trophoblast cells was determined by the in vitro invasion assay, in which the ability of cells to penetrate an artificial basement membrane was examined. Metalloproteinase activity was measured by zymography, and the expression of messenger ribonucleic acid transcripts of 72 and 92 kd type IV collagenases was examined by reverse transcriptase polymerase chain reaction. RESULTS: First-trimester trophoblasts were 3.5 time more invasive in vitro than were third-trimester trophoblast cells (p < 0.005). Although first-trimester trophoblasts secreted both species of type IV collagenase, 72 and 92 kd, in large amounts, third-trimester cells secreted the 92 kd and only minimal amounts of 72 kd type IV collagenase. Moreover, first-trimester trophoblasts secreted significantly more (p < 0.05) 92 kd type IV collagenase than did third-trimester trophoblast. The messenger ribonucleic acid transcript expression of 72 and 92 kd type IV collagenases correlated with the activity of these enzymes secreted by first- and third-trimester trophoblasts. CONCLUSION: The described high in situ invasive capacity of first-trimester trophoblast might be explained by the increased expression and production of 72 kd type IV collagenase and the higher expression of 92 kd type IV collagenase by first-trimester trophoblast cells.

Base Sequence↗

[Adverse effects of tamoxifen on the female genital tract].

Tamoxifen is an established adjuvant therapy for breast cancer. It exerts both estrogenic agonist and antagonist effects on target tissues. Since the use of tamoxifen is expanding, it is expected that more women will suffer from its side-effects. 3 women aged 48, 48, and 65, respectively, who were treated with tamoxifen, were referred for evaluation of possible side-effects. They had, respectively, endometrial hyperplasia, a unique sonographic appearance of the endometrium resembling neoplasia, and an ovarian cyst.

Aged↗