Alessandro Caruso

Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered β2‐glycoprotein I

OBJECTIVE To investigate the in vitro ability of antiphospholipid antibodies (aPL) to bind human trophoblast cells and to affect gonadotropin secretion and invasiveness. METHODS Antiphospholipid antibody IgG from women with recurrent miscarriages, beta2-glycoprotein I (beta2GPI)-independent IgG aPL human monoclonal antibody (mAb) (519), and IgM anti-beta2GPI human mAb (TMIG2) were investigated for their binding to trophoblasts cultured for various amounts of time, their ability to affect invasiveness of Matrigel-coated filters, and their release of human chorionic gonadotropin (hCG). RESULTS Polyclonal IgG aPL, as well as mAb 519 and TMIG2, bound to trophoblasts, the highest binding being found when cells displayed the greatest amount of syncytium formation. TM1G2 binding was found to be betaGPI dependent. Both polyclonal and monoclonal aPL, but not the controls, significantly reduced hCG release and Matrigel invasiveness. CONCLUSION These findings suggest that aPL recognition of both anionic PL and adhered beta2GPI on trophoblast cell structures might represent a potential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome.

Cardiopulmonary bypass in pregnancy

The cardiopathic patient can sustain acute heart failure during pregnancy. In such cases, if open heart operation is necessary to save the patients life, the fetus could be seriously compromised after exposure to cardiopulmonary bypass. From 1958 to 1992, 69 reports of cardiac operations during pregnancy with the aid of cardiopulmonary bypass have been published. Maternal mortality was 2.9%. Embryofetal mortality was 20.2%. Examining only the last 40 patients, maternal and embryofetal mortality were 0.0% and 12.5%, respectively. Embryofetal mortality was 24.0% when hypothermia was used, compared with 0.0% while operating in normothermia. Maternal mortality did not change. The use of hypothermia during cardiopulmonary bypass provoked uterine contractions in several patients. Hypothermia decreases O2 exchange through the placenta. Pump flow and mean arterial pressure during cardiopulmonary bypass seem to be the most important parameters that influence fetal oxygenation. We speculate that cardiac operation is not a contraindication to pregnancy prolongation.

Proteinuria and outcome of 444 pregnancies complicated by hypertension

The purpose of this study was to determine the role of proteinuria on pregnancy outcome in 444 hypertensive women with singleton pregnancies. The patients were divided into three hypertensive groups: 98 with chronic hypertension, 199 with nonproteinuric gestational hypertension, and 147 with proteinuric preeclampsia and chronic hypertension with superimposed proteinuric preeclampsia. The presence of increased proteinuria (greater than 0.3 gm/L) predicted an adverse pregnancy outcome. Furthermore, the majority of small-for-gestational-age infants occurred in the group with proteinuric preeclampsia (52%), whereas the rate of small-for-gestational-age infants was 18% and 12% in the group with nonproteinuric gestational hypertension and chronic hypertension, respectively. The group with chronic hypertension did not show any increased risk for fetal outcome. Perinatal mortality rate was extremely poor in the group with proteinuric preeclampsia at 129 per 1000, four times higher than those of the other two groups.

Recurrent spontaneous abortion and intrauterine fetal growth retardation as symptoms of coeliac disease

Women having recurrent miscarriages or intrauterine growth retardation could have subclinical coeliac disease, which can be detected by serological screening tests.

Impact of insulin and body mass index on metabolic and endocrine variables in polycystic ovary syndrome

To assess the differential impact of the insulin secretory pattern and obesity on the endocrinometabolic features of the polycystic ovary syndrome (PCOS), we studied 110 PCOS women. Patients underwent a gonadotropin-releasing hormone (GnRH) test, an oral glucose tolerance test (OGTT), and basal evaluation of hormonal and biochemical parameters. Basal androgens and lipids, basal and stimulated gonadotropins, insulin, and glucose levels were measured. Patients were classified into four groups according to the body mass index (BMI) and insulin secretion: normoinsulinemic-lean ([NL] n = 24), normoinsulinemic obese ([NO] n = 24), hyperinsulinemic lean ([HL] n = 17), hyperinsulinemic obese ([HO] n = 45). HL patients showed a higher luteinizing hormone (LH) area under curve (AUC) after GnRH stimulus compared with NL patients (HL v NL, 4,285 +/- 348 v 3,377 +/- 314 IU/L x 120 min, P < .05), whereas we failed to find a statistically significant difference in a similar comparison among obese subjects (HO v NO, 3,606 +/- 302 v 3,129 +/- 602 IU/L x 120 min). A trend toward increased plasma testosterone and decreased sex hormone-binding globulin (SHBG) was found in relation to hyperinsulinemia and obesity, thus resulting in a higher free androgen index (FAI) in groups HL and NO versus NL (HL, 5.54 +/- 0.51; NO, 5.64 +/- 0.49; NL, 4.13 +/- 0.33; P < .05 and P < .01, respectively). The presence of both exaggerated insulin secretion and obesity resulted in a synergistic additive effect on the FAI in the HO group (6.81 +/- 0.34). Concerning the lipoprotein lipid profile, the NL group showed lower plasma triglyceride levels compared with the other three groups, whereas no significant differences were found for nonesterified fatty acid (NEFA) concentrations. Higher low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein cholesterol (VLDL-C) and lower high-density lipoprotein cholesterol (HDL-C) levels were found in the obese groups compared with the lean counterparts, whereas the same parameters did not significantly differ in a comparison between normoinsulinemic and hyperinsulinemic groups. In conclusion, our data suggest an important role of hyperinsulinemia in the LH response to a GnRH stimulus and an independent and synergistic additive effect of obesity and hyperinsulinemia on the FAI in PCOS.

Vaginal microbial flora and outcome of pregnancy

BackgroundThe vaginal microflora of a healthy asymptomatic woman consists of a wide variety of anaerobic and aerobic bacterial genera and species dominated by the facultative, microaerophilic, anaerobic genus Lactobacillus. The activity of Lactobacillus is essential to protect women from genital infections and to maintain the natural healthy balance of the vaginal flora. Increasing evidence associates abnormalities in vaginal flora during pregnancy with preterm labor and delivery with potential neonatal sequelae due to prematurity and poor perinatal outcome. Although this phenomenon is relatively common, even in populations of women at low risk for adverse events, the pathogenetic mechanism that leads to complications in pregnancy is still poorly understood.ObjectiveThis review summarizes the current knowledge and uncertainties in defining alterations of vaginal flora in non-pregnant adult women and during pregnancy, and, in particular, investigates the issue of bacterial vaginosis and aerobic vaginitis. This could help specialists to identify women amenable to treatment during pregnancy leading to the possibility to reduce the preterm birth rate, preterm premature rupture of membranes, chorioamnionitis, neonatal, puerperal and maternal–fetal infectious diseases.ConclusionsVaginal ecosystem study with the detection of pathogens is a key instrument in the prevention of preterm delivery, pPROM, chorioamnionitis, neonatal, puerperal and maternal-fetal infections.

The duration of hypertension in the puerperium of preeclamptic women: Relationship with renal impairment and week of delivery

OBJECTIVE The purpose of the study was to determine whether the duration of hypertension in the puerperium of preeclamptic women was related to certain clinical features of disease severity. STUDY DESIGN We studied 269 singleton pregnancies divided into two groups: 159 with gestational hypertension and 110 with preeclampsia. The normalization time of blood pressure in puerperium was estimated as the interval between the delivery day and the first day when each of two to four self-measurements per day of diastolic blood pressure was observed to be < or = 80 mm Hg for at least 3 consecutive days. RESULTS Normalization time was shorter in gestational hypertension than in preeclampsia (6 +/- 5.5 [means +/- SD] vs 16 +/- 9.5, respectively, p < 0.0001). Normalization time of gestational hypertension showed a significant correlation with uric acid (r = 0.20, p < 0.025); normalization time of preeclampsia displayed significant correlations with the week of delivery (r = -0.34, p < 0.005), uric acid (r = 0.34, p < 0.025), and urea nitrogen (r = 0.29, p < 0.025), respectively. After stratification by parity, in both groups the correlations of normalization time with renal data were observed only among multiparous women, whereas in preeclampsia the link of normalization time with the week of delivery remained highly significant in both subgroups. CONCLUSIONS The differences observed between gestational hypertension and preeclampsia suggest that distinct mechanisms or a different maternal answer to the same mechanism(s), in maintaining high blood pressure in puerperium, are present in the two groups. Normalization time might reflect the recovery time of the endothelial damage in preeclampsia.

Human growth hormone enhances progesterone production by human luteal cells in vitro: evidence of a synergistic effect with human chorionic gonadotropin

OBJECTIVE To examine the possible direct effect of human growth hormone (hGH) on basal and human chorionic gonadodotropin (hCG)-stimulated progesterone (P) production by cultured human luteal cells. DESIGN Cultures of human luteal cells from early and midluteal phase. SETTING All corpora lutea were obtained from the Obstetrics and Gynecology Department of the Catholic University, a public care center. PATIENTS, PARTICIPANTS Twelve nonpregnant women between 35 and 47 years of age underwent surgery for various nonendocrine disorders such as leiomyomatosis. INTERVENTIONS Corpora lutea were obtained at the time of hysterectomy. MAIN OUTCOME MEASURE Luteal cells were incubated with or without hCG and/or hGH at different concentrations. RESULTS Human growth hormone neither at 250 nor at 500 ng/mL increased basal P production, whereas from 1,000 ng/mL P concentration in media was significantly increased (P less than 0.05). The concomitant treatment with uneffective doses of hCG (6 and 12 ng/mL) and hGH (250 and 500 ng/mL) enhanced P production similarly to that obtained with the highest doses of hGH (1,000 ng/mL or more) or hCG (25 to 50 ng/mL) alone. CONCLUSIONS These results indicate a direct effect of hGH on the luteal steroidogenesis in vitro.

Growth hormone induces in vitro maturation of follicle- and cumulus-enclosed rat oocytes

The aim of this study was to assess the possible role of growth hormone (GH) on rat oocyte maturation. This effect was analyzed in follicle-enclosed, cumulus-enclosed and denuded oocytes obtained from immature pregnant mares serum gonadotropin (PMSG)-treated rats. The addition of GH to the cultures significantly accelerated maturation in both follicle- and cumulus-enclosed oocytes while no effect was seen on denuded oocytes maturation. Also, GH accelerated meiotic maturation in follicle-enclosed oocytes from immature untreated rats. The GH action was not mediated by lactogenic receptors since prolactin (Prl) did not affect the maturation process while it was mediated by insulin growth factor-I (IGF-I) as suggested by the block of GH action observed in the presence of antibodies anti-IGF-I. Finally, no GH effect was found when dbcAMP was added to the cultures. Our results demonstrate that GH is capable of inducing maturation in oocytes from both primed and unprimed rats. Since the presence of physiological levels of GH in the ovary is now well established, the present data strongly suggest a potential relevance of GH in the reproductive biology.

Antiphospholipid antibodies as cause of pregnancy loss

Antiphospholipid antibodies detected by lupus anticoagulant, anticardiolipin or anti-beta2 glycoprotein I assays were associated with fetal loss. Rather than being diagnostic tools only, antiphospholipid antibodies are thought to be pathogenic. The strongest demonstration of their pathogenic role lies in the ability to induce fetal resorptions - the experimental equivalents of the human fetal losses - when passively infused in pregnant naive animals. However, still debated is how the antibodies might induce the obstetrical manifestations. Thrombotic events at the placental levels might be related to endothelial cell activation, inhibition of protein C/S system and fibrinolysis as well as to Annexin V displacement. However, the thrombophilic state apparently cannot explain all the miscarriages and a direct antibody-mediated damage on the trophoblast has been suggested. During differentiation to syncytium, trophoblasts express cell membrane anionic phospholipids that can bind beta2 glycoprotein I, the main cationic phospholipid binding protein recognized by the antiphospholipid antibodies. Adhered b2-glycoprotein I might be recognized by the antibodies that, once bound, strongly interfere with in vitro trophoblast cell maturation so resulting in a defective placentation. These mechanisms have been suggested to play a role in early fetal loss, while thrombotic events would be responsible for miscarriages late in the pregnancy.