Expression, localization and control of activin A release from human umbilical vein endothelial cells.

Activin-A is a member of the TGFß superfamily found in maternal and umbilical cord blood throughout gestation. We investigated whether human umbilical vein endothelial cells (HUVEC) express activin-A in vivo and tested the effects of vasoactive (endothelin-1), pro-inflammatory (interferon-γ, interleukin-8) and anti-inflammatory (dexamethasone, urocortin) factors on activin-A release by isolated HUVEC in vitro. Activin ßA subunit protein and mRNA were strongly localized in the endothelial cells of umbilical veins and were also detectable in scattered cells of the cord connective tissue. Dimeric activin-A was detected in the HUVEC culture medium at picomolar concentrations. Activin-A release by HUVEC decreased after cell incubation with urocortin (p < 0.01), whereas no effect was observed with interleukin-8, interferon-γ, endothelin-1 or dexamethasone. In summary, activin-A is present in the human umbilical vein endothelium in vivo and is produced and released by isolated HUVEC. Activin-A secretion is inhibited in vitro by urocortin, a neuropeptide with predominantly anti-inflammatory action.

Ultrasound estimated fetal weight slightly below the median is associated with increased risk of spontaneous preterm birth.

BACKGROUND: This study investigates the possible relationship between ultrasound estimated fetal weight (EFW) at third trimester and the risk of preterm birth following spontaneous preterm labor in otherwise uncomplicated pregnancies. METHODS: We performed a nested case-control study including 281 cases of spontaneous preterm labor with preterm delivery in the third trimester and 3372 matched controls within a cohort of 6207 consecutive pregnant women. Pregnancies with fetal growth restriction (birth weight <10th centile of population-based normograms) or fetal anomalies were not included. EFW was calculated by using Hadlock's formula and converted to fetal gender adjusted multiples of median (MoM) for each gestational age. RESULTS: EFW correlated with birth weight (r = 0.959, p < 0.0001) and was lower in preterm than in control fetuses (p < 0.0001). The odds ratios (95% confidence intervals) for preterm birth for fetuses below 0.9 MoM, 0.85 MoM, 0.80 MoM, and 0.75 MoM of EFW were, respectively, 4.6 (3.6-5.9), 5.7 (4.3-7.5), 8.5 (5.9-12.1), and 11.2 (6.8-18.3). The independent relationship between preterm birth and lower EFW was confirmed in multivariate analysis with adjustment for potential confounders, such as maternal age, parity, and fetal gender. CONCLUSION: In asymptomatic women between 28 and 36 weeks of gestation, an EFW lower than 0.90 MoM increases by 4.6 times the risk of spontaneous preterm birth, and the risk increases proportionally to the degree of weight reduction.

Neuroendocrine aspects of placenta and pregnancy.

Placenta plays a central role in the regulation of physiological mechanisms of pregnancy, and in particular is the organ of communication between mother and fetus. This action is also related to its ability to produce hormones, growth factors and cytokines during the progression of pregnancy, and in response to stimuli such as stress and inflammation/infection. In the last years the understanding of the physiological and pathological functions of human placenta revealed the hypersecretion of hormones in presence of gestational diseases and raised the question whether this mechanism is cause of disorders of pregnancy, or part of an adaptive response of placenta to resolve adverse conditions. However, there are evidences indicating that changes of placental hormone secretion may have clinical usefulness, since they are measurable in biological fluids, and may be used as predictive markers or prognostic tools. Of particular interest is the role of corticotropin releasing hormone, urocortins and activins in the maintaining physiological pregnancy and in the pathogenesis of diseases (preterm birth and preeclampsia).

Serum activin A levels are lower in tubal than intrauterine spontaneously conceived pregnancies.

OBJECTIVE: To measure serum activin A levels together with progesterone and hCG, in women with overt clinical signs and symptoms of ectopic pregnancy (EP) and, in gestational age-matched intrauterine pregnancy (IUP). DESIGN: Retrospective case-control study. SETTING: Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy. POPULATION: The study group was composed by 30 women with an EP; the control group was composed by 30 women with a sonographic evidence of a single spontaneous IUP. METHODS: Clinical examination; transvaginal ultrasound scan; hCG, progesterone and activin-A measurements; laparoscopy; uterine curettage; histological examination. MAIN OUTCOME MEASURE: Pregnancy outcome; sensitivity and specificity of hCG, progesterone, and activin A for EP. RESULTS: Serum hCG levels did not differ significantly between tubal EP and IUP, while P concentrations were significantly (P < 0.001) lower in tubal EP than IUP. Serum levels of activin A were significantly (P < 0.0001) lower in tubal EP than in IUP and, at the cutoff 0.43 ng/mL achieved a sensitivity of 96.7% and a specificity of 100% for EP. CONCLUSION: Activin A secretion in EP is reduced and measurement of its serum levels may have the potential clinical advantage to signal the presence of EP.

Peripartum and postpartum outcomes in uncomplicated term pregnancy following ART: a retrospective cohort study from two Italian obstetric units.

STUDY QUESTION: Do singleton uncomplicated term pregnancies conceived by assisted reproductive technology (ART) have adverse peripartum and postpartum outcomes? SUMMARY ANSWER: Term pregnancies following ART, even if uncomplicated until birth, have a higher risk of retained placenta and postpartum hemorrhage (PPH). WHAT IS KNOWN ALREADY: There is consistent evidence that pregnancies following ART have higher incidence of complications during pregnancy. However, few studies specifically investigated birth outcomes in ART term pregnancies. STUDY DESIGN SIZE DURATION: A retrospective cohort study was conducted on 14 415 deliveries at two university tertiary care obstetric units. Clinical data were extracted by reviewing obstetric records of all deliveries from 1 January 2010 to 31 December 2014, in a standardized electronic database regarding the mother's health before and during pregnancy, complications during pregnancy and at birth, and neonatal outcome. PARTICIPANTS/MATERIALS SETTING METHODS: Following an accurate evaluation of exclusion criteria (multiparity, maternal pre-pregnancy diseases, prior uterine surgery, fetal malformations, intrauterine deaths, elective cesarean section and pregnancy complications), the group of uncomplicated singleton term pregnancies from autologous ART conception by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (n = 188) was compared with a maternal age and body mass index (BMI) matched group of spontaneous pregnancies (n = 1168). Cases of intrauterine insemination (IUI) (n = 14) and ovulation induction with timed intercourse (n = 18) were not included. Labor, delivery and postpartum outcomes were evaluated. Odds ratios (OR) were adjusted with multivariable logistic regression to maternal age, BMI, nationality and gestational age at birth. MAIN RESULTS AND THE ROLE OF CHANCE: The age of women in the final analysis ranged from 25 to 45 years, while BMI ranged from 17 to 34 kg/m2. Uncomplicated term pregnancies with ART conception had a higher risk of operative delivery (adjusted OR 1.40, 95% confidence interval (CI) 1.01-1.95), retained placenta (adjusted OR 2.63, 95% CI 1.31-5.26) and PPH (adjusted OR 2.86 95% CI 1.37-5.99). Conversely, ART conception did not increase the risk of induced labor (adjusted OR 1.18, 95% CI 0.85-1.65). However, patients that conceived by ART and underwent labor induction had a higher risk of failed induction compared with the control group (adjusted OR 2.53, 95% CI 1.23-5.21). Infants born after ART had a similar birthweight, Apgar score and arterial blood pH compared with spontaneously-conceived ones. LIMITATIONS REASONS FOR CAUTION: The database lacked specific information about causes of infertility, smoking habit, family income and details on ART (fresh versus frozen cycle, IVF versus ICSI), limiting, in part, our analysis of the results. However, only autologous IVF/ICSI pregnancies were included in order to prevent bias related to conception by oocyte/embryo donation. In vivo conception ART cases were excluded because they were too few to allow comparison with IVF/ICSI. Nevertheless, the inclusion of only uncomplicated pregnancies provides a highly homogeneous and still representative population sample. Study sample is representative of a well-resourced obstetric facility in a high-income country, limiting to some extent the generalizability of study results. WIDER IMPLICATIONS OF THE FINDINGS: Pregnancies conceived by autologous ART that proceed uncomplicated until term may require counseling about the risk of placental retention with PPH. STUDY FUNDING/COMPETING INTERESTS: The authors have no conflict of interest and funding to declare.

Fetal middle cerebral artery Doppler in late-term pregnancy: a predicting factor for failed induction of labor.

PURPOSE: To study the role of fetal middle cerebral artery (MCA) Doppler evaluated prior to induction of labor in late-term pregnancies, in order to build an ultrasound-based predictive model for failed induction. MATERIALS AND METHODS: A prospective cohort study on 250 nulliparous women carrying singleton late-term pregnancies was conducted. Prior to induction, each patient underwent to an ultrasound evaluation for fetal MCA Doppler. Additional ultrasound parameters such as cervical length (CL), membranes thickness, amniotic fluid index, placental location, and estimated fetal weight (EFW) were collected. According to the type of response, women were divided into three groups: (A) responders within 24 h; (B) responders after 24 h, and (C) no responders. RESULTS: Women who failed to enter active labor showed significantly higher fetal MCA pulsatility index (PI), longer CL and higher EFW. The estimated probability of logistic regression model combining the three variables achieved a sensitivity of 94.2% and a specificity of 86.36% (AUC, 0.926; 95% CI, 0.884 - 0.956, p < .0001) using as decision probability value the cut off >0.1838. CONCLUSIONS: In late-term pregnancies, an ultrasound-based model including cervical length, MCA PI, and EFW achieved a good accuracy in predicting those women who are likely to fail induction of labor.

Preimplantation and prenatal diagnosis, wrongful birth and wrongful life: a global view of bioethical and legal controversies.

BACKGROUND: Prenatal diagnosis based on different technologies is increasingly used in developed countries and has become a common strategy in obstetric practice. The tests are crucial in enabling mothers to make informed decisions about the possibility of terminating pregnancy. They have generated numerous bioethical and legal controversies in the field of 'wrongful life' claims (action brought by or on behalf of a child against the mother or other people, claiming that he or she has to endure a not-worth-living existence) and 'wrongful birth' claims (action brought by the mother or parents against the physician for being burdened with an unwanted, often disabled child, which could have been avoided). OBJECTIVE AND RATIONALE: The possibility which exists nowadays to intervene actively by programming and deciding the phases linked to procreation and birth has raised several questions worldwide. The mother's right to self-determination could be an end but whether or not this right is absolute is debatable. Freedom could, with time, act as a barrier that obstructs intrusion into other people's lives and their personal choices. Therapeutic choices may be manageable in a liberal sense, and the sanctity of life can be inflected in a secular sense. These sensitive issues and the various points of view to be considered have motivated this review. SEARCH METHODS: Literature searches were conducted on relevant demographic, social science and medical science databases (SocINDEX, Econlit, PopLine, Medline, Embase and Current Contents) and via other sources. Searches focused on subjects related to bioethical and legal controversies in the field of preimplantation and prenatal diagnosis, wrongful birth and wrongful life. A review of the international state of law was carried out, focusing attention on the peculiar issue of wrongful life and investigating the different jurisdictional solutions of wrongful life claims in a comparative survey. OUTCOMES: Courts around the world are generally reluctant to acknowledge wrongful life claims due to their ethical and legal implications, such as existence as an injury, the right not to be born, the nature of the harm suffered and non-existence as an alternative to a disabled life. Most countries have rejected such actions while at the same time approving those for wrongful birth. Some countries, such as France with a law passed in March 2002, have definitively excluded Wrongful Life action. Only in the Netherlands and in three states of the USA (California, Washington and New Jersey) Wrongful Life actions are allowed. In other countries, such as Belgium, legislation is unclear because, despite a first decision of the Court allowing Wrongful Life action, the case is still in progress. There is a complete lack of case law regarding wrongful conception, wrongful birth and wrongful life in a few countries, such as Estonia. WIDER IMPLICATIONS: The themes of 'wrongful birth' and 'wrongful life' are charged with perplexing ethical dilemmas and raise delicate legal questions. These have met, in various countries and on certain occasions, with different solutions and have triggered ethical and juridical debate. The damage case scenarios result from a lack of information or diagnosis prior to the birth, which deprives the mother of the chance to terminate the pregnancy.

High maternal and fetal plasma urocortin levels in pregnancies complicated by hypertension.

OBJECTIVE: We evaluated maternal and fetal plasma levels and placental mRNA expression of urocortin, a placental vasoactive neuropeptide, in singleton pregnancies (n = 70) complicated by hypertensive disorders classified as gestational hypertension (n = 36), pre-eclampsia (n = 19), and pre-eclampsia complicated by intrauterine growth restriction (PE/IUGR, n = 15), and in 70 healthy normotensive singleton pregnancies. METHODS: Plasma levels were assayed by radioimmunoassay, fetal biometry by ultrasound scans, utero-placental and fetal perfusion by Doppler velocimetry, and placental urocortin mRNA expression by quantitative real time reverse transcriptase-polymerase chain reaction. The main outcome measures were the correlation of urocortin concentrations with patterns of the utero-placental and fetal circulation, and the early prediction of a poor neonatal outcome such as the occurrence of perinatal death and intraventricular hemorrhage. RESULTS: Maternal and fetal urocortin levels were significantly (both P < 0.001) higher in gestational hypertension, pre-eclampsia and PE/IUGR women than in controls, and correlated with Doppler velocimetry patterns. Fetal concentrations were significantly (P < 0.0001) higher than and significantly (P < 0.0001) correlated to maternal levels. Placental mRNA expression did not change. Ten out of 140 newborns had a poor neonatal outcome, with an overall prevalence of 7.14% (pretest probability). Using the receiver operator characteristics curve analysis cut-off values, the probability of a poor neonatal outcome was 66.7% when urocortin was used, and was 0% if levels were unaltered. CONCLUSIONS: Maternal and fetal urocortin levels are increased in hypertensive disorders of pregnancy. Since urocortin has vasoactive properties, the evidence of increased urocortin levels in hypertensive disorders may represent an adaptive fetal response.

Low-molecular-weight heparin improves the performance of uterine artery Doppler velocimetry to predict preeclampsia and small-for-gestational age infant in women with gestational hypertension.

This study investigated whether a short course of subcutaneous low-molecular-weight heparin (LMWH) might modify the performance of uterine artery Doppler to predict preeclampsia and small-for-gestational age (SGA) newborns in a high-risk population. A controlled, open-labeled study included 94 women with gestational hypertension and 30 healthy women enrolled at 24 to 26 weeks gestation. Doppler evaluation of uterine arteries resistance index (RI) was performed before and after a two-week course of LMWH (enoxaparin, 4000 IU/d, n = 56 hypertensive patients) or no treatment (n = 38 hypertensive women and 30 healthy controls). There was a significant decrease of uterine artery RI after LMWH (p < 0.001, paired Student's t-test), whereas the untreated hypertensive patients and the healthy control group showed no change between the two Doppler evaluations. The change induced by LMWH was restricted to women with normal outcome, whose RI decreased from (mean +/- standard error) 0.62 +/- 0.01 to 0.56 +/- 0.01 (p < 0.0001). By consequence, the second RI measurement, performed after LMWH administration, had fewer false positive results and higher positive likelihood ratios (LR+) to predict both preeclampsia (LR + 5.91) and SGA (LR + 4.69) compared with the first Doppler examination (LR + 1.97 and 2.22, respectively). Thus, LMWH improved the performance of uterine artery RI to predict preeclampsia and SGA in women with gestational hypertension.

Endocrinology of human parturition.

The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta. The "final common pathway" to delivery is composed by inflammatory and endocrine interactive paths that tip the balance in favor of coordinated uterine contractility and cervical dilation. These mechanisms involve a shift from progesterone to estrogen dominance, CRH action, increased sensitivity to oxytocin, gap junction formation, and increased prostaglandins activity. Complementary changes in the cervix involve a decrease in progesterone dominance and the actions of prostaglandins and relaxin, via connective tissue alterations, leading to cervical softening and dilation. Neuronal, hormonal, inflammatory and immune pathways participate in initiation of labor and the utero-placental unit plays a major role in the synthesis and release of parturition mediators.

Twin pregnancies after assisted reproductive technologies: the role of maternal age on pregnancy outcome.

OBJECTIVES: Our aim was to investigate whether advanced maternal age (≥40years) still impairs the outcome of twin pregnancies after assisted reproductive techniques (ART). STUDY DESIGN: The retrospective observational study evaluated 430 nulliparous dichorionic diamniotic twin pregnancies conceived with ART. The population was divided into women <40 years old (Group A, n=265) and ≥40 years old (Group B, n=165). RESULTS: Gestational diabetes mellitus and gestational hypertension/preeclampsia were significantly more frequent in nulliparous twin pregnancies after ART ≥40years compared to <40years (p=0.021 and p<0.001, respectively). In univariate analysis of twin pregnancies after ART, there was only a trend of higher incidence of total preterm birth (PB) rate within mother aged ≥40 years old (p=0.104). However, Group A showed higher rate of spontaneous preterm birth (SPB) <37 weeks, whereas Group B showed significantly higher rate of iatrogenic PB <37 weeks of gestation (p=0.023 and p=0.001, respectively). For delivery <32 weeks of gestation, the rate of SPB in Group A was significantly higher (p=0.002). A higher incidence of PB was observed in Group B after heterologous treatment (p<0.001). Despite this, the absolute prevalence of PB in the entire population is higher in Group A, both after autologous (22.5%) and heterologous (25%) ART treatment, than in Group B (10.1% vs 21.4%). CONCLUSIONS: Our data indicate that nulliparous twin pregnancies conceived with ART in mothers ≥40 years old did not show significantly higher incidence of PB, even if an increased rate of iatrogenic PB <37 weeks is showed.

Amniotic fluid S100B protein in mid-gestation and intrauterine fetal death.

Fetal death in the mid-trimester of pregnancy is unexplained and no reliable markers are available to identify at-risk women. We aimed to assess use of alpha fetoprotein and S100B concentrations in amniotic fluid as markers. We did a case-control study in 758 healthy women undergoing amniocentesis at mid-gestation, of whom 12 had a spontaneous intrauterine fetal death before 28 weeks, and 746 matched controls. Concentrations were corrected for gestational age by conversion to multiples of median (MoM) of healthy controls of the same gestational age. Concentrations of S100B, but not alpha fetoprotein, were significantly higher (p<0.0001) in women who later had spontaneous fetal death (median 4.431 MoM [95%CI 3.605-6.197]) than in controls (1.000 MoM [1.062-1.121]). Sensitivity, specificity, and positive and negative predictive values of S100B as a diagnostic test were 100%, suggesting that measurement of this protein at amniocentesis could be useful to identify at-risk women.

Factor II: C activity and uterine artery Doppler evaluation to improve the early prediction of pre-eclampsia on women with gestational hypertension.

OBJECTIVE: To evaluate whether the determination of maternal plasma Factor II:C (FII:C) and mean uterine artery resistance index may be useful to early predict pre-eclampsia in patients with gestational hypertension. DESIGN: Prospective study. SETTING: Consecutive enrollment in a public tertiary clinical care centre. PATIENTS: A total of 65 women with gestational hypertension at 24-26 weeks. INTERVENTION: Measurements of maternal plasma FII:C activity levels, ultrasonographic biometrical parameters and Doppler velocimetry of maternal uterine arteries. MAIN OUTCOME MEASURE(S): The probability of developing pre-eclampsia was the main outcome of the study and it was computed by combining the FII:C and the mean uterine artery resistance index cut-off points, chosen by receiver operating characteristic (ROC) curve analysis. RESULTS: F-II:C activity levels and mean uterine artery resistance index were significantly (both P < 0.01) higher in women who developed pre-eclampsia. A weak, but significant correlation (r = 0.3, P < 0.05) was found between these two parameters. FII:C activity levels at the cut-off value of 136.5% achieved a sensitivity of 61.1% and a specificity of 71.3%, while mean uterine artery resistance index (RI) at the cut-off value of 0.57 showed a sensitivity of 85.7% and a specificity of 90.2% in predicting the onset of pre-eclampsia. When both FII:C and mean uterine RI were over the cut-off points the positive predictive value was of 89%, with a 100% negative predictive value when both were below the cut-off points. CONCLUSION: F-II:C activity levels and mean uterine artery resistance index determination at mid trimester may improve the prediction of superimposed pre-eclampsia on women with early onset gestational hypertension.

Reduced maternal plasma urocortin concentrations and impaired uterine artery blood flow at human mid pregnancy.

OBJECTIVE: Urocortin is a placental neuropeptide belonging to the family of corticotropin-releasing factors (CRFs), playing a role in the uteroplacental blood flow regulation through the binding to specific CRF receptors. Since CRF receptors are expressed in the uterine vascular bed of pregnant rats, and because urocortin has a relaxant effect on uterine vasculature, we evaluated mid-gestation plasma urocortin levels in women with impaired blood flow through uterine arteries. METHODS: Maternal plasma urocortin was assayed by specific radioimmunoassay and uterine artery resistance index (RI) by Doppler evaluation at 22-24 weeks' gestation in 57 healthy pregnant women, of which 29 showed a monolateral or bilateral uterine artery notch. Statistical analysis was performed by one-way analysis of variance (ANOVA), followed by post-hoc Tukey test for multiple comparison and Pearson correlation coefficient test. RESULTS: The mean uterine artery RI was significantly (P <.001) higher in women with a notch than healthy controls. Mean +/- SEM maternal plasma urocortin levels were significantly (P <.001) lower in women with unilateral (52.03 +/- 3.25 pg/mL) or bilateral (47.01 +/- 4.16 pg/mL) uterine artery notch than in healthy control pregnant women (84.01 +/- 3.5 pg/mL). While no difference was found in urocortin levels between patients with unilateral or bilateral uterine artery notch, urocortin concentrations inversely correlated with the mean RI (Pearson r = -0.7318; 95% confidence interval -0.8334 to -0.5822; P <.0001). CONCLUSIONS: The present findings suggest that reduced levels of circulating urocortin are associated with increased uterine artery resistances and support the hypothesis that urocortin may regulate uterine artery tone at mid gestation.

Urocortin 2 role in placental and myometrial inflammatory mechanisms at parturition.

The purpose of the study was to investigate urocortin (Ucn)2 involvement in placental and myometrial inflammatory pathways associated with parturition by evaluating: 1) Ucn2 and its receptor, CRH-receptor type 2 (CRH-R2), expression in laboring/nonlaboring human gestational tissues and in mouse utero-placental tissues approaching delivery; and 2) Ucn2 effect on myometrial contractility and on the expression of inflammatory mediators (prostaglandin F2α receptor and cytokines) and regulation of Ucn2 by TNF-α in cultured myometrial cell line. Placenta (n = 16), fetal membranes (n = 16), and myometrium (n = 22) were obtained from healthy pregnant women delivering at term by vaginal/elective caesarean delivery and from timed-pregnant mice on days 16-19. Expression of Ucn2/CRH-R2 in human/mouse tissues and inflammatory mediators in myometrial cell lines were measured by RT-PCR or ELISA, mouse Ucn2/CRH-R2 protein localization by immunohistochemistry. Ucn2 but not CRH-R2 was up-regulated (P < .05) in all human tissues in labor (compared with before labor) and increased significantly (P < .01) in mouse placenta approaching delivery. Ucn2 was up-regulated by TNF-α via nuclear factor-κB (NF-kB) in myometrium cell lines (P < .05 or P < .01 on the basis of treatment doses) and increased proinflammatory mediators and prostaglandin F (PGF2α) receptor expression (P < .05) via CRH-R2, without a direct effect on contractility. Placental and myometrial Ucn2 may play a role in the endocrine-inflammatory processes of parturition, representing a potential target for treating inflammation-induced obstetric complications.

The search for thrombophilic gene mutations in women with gestational hypertension does not help in predicting poor pregnancy outcome.

OBJECTIVE: To evaluate whether genetic thrombophilic mutations, biochemical and biophysical indices help to predict pregnancy outcome in women with gestational hypertension. DESIGN AND METHODS: A group of 59 women with gestational hypertension were prospectively tested between 24 and 26 weeks of gestation for: (i) DNA analysis to search for gene mutations of Factor V Leiden, prothrombin, methylenetetrahydrofolate reductase and plasminogen activator inhibitor type 1 (PAI-I) polymorphism; (ii) maternal serum concentrations of homocysteine and PAI-1, activated protein resistance and Factor II:C activity levels; (iii) mean uterine arterial resistance index (RI) by Doppler velocimetry; and (iv) history of hypertensive disorders in relatives (the mother and/or the father). Pregnancy outcome was evaluated, and considered 'poor' when patients developed severe pre-eclampsia, haemolysis-elevated liver enzymes-low platelets (HELLP) syndrome, fetal growth restriction (FGR), thromboembolic complications and disseminated intravascular coagulopathy (DIC). RESULTS: Eighteen women had a poor pregnancy outcome (11 with severe pre-eclampsia, of whom two had superimposed FGR; three with full HELLP syndrome, of whom one had DIC; four with FGR) and delivered, by emergency Caesarean section, neonates with a significantly lower mean gestational age (P < 0.0001) and birthweight (P < 0.0001). History of hypertensive disorders was significantly (P < 0.001) more common in the women group with poor (11 of 18) than normal (10 of 41) outcome. In addition, patients with a poor pregnancy outcome did not have a higher incidence of gene polymorphisms incidence, but significantly (P < 0.01) higher Factor II:C activity levels and significantly (P < 0.0001) higher mean uterine arterial RI than women with normal pregnancy outcome. CONCLUSIONS: Only Factor II:C activity levels, uterine arterial Doppler and a history of familial hypertension are useful in predicting poor pregnancy outcome in gestational hypertension.

Pregnancy and delivery after right common carotid artery endarterectomy.

BACKGROUND: Carotid artery atherosclerosis and essential hypercholesterolemia can add a predisposing risk factor for coagulation in pregnancy. Careful management of anticoagulation during labor, delivery, and puerperium is called for in such a case. CASE: A 41-year-old woman, gravida 2, para 1, with a previous endarterectomy at the right common carotid artery because of atherosclerotic plaques, underwent anticoagulation studies and prophylactic antithrombotic therapy. Low-molecular-weight heparin was administrated during pregnancy and puerperium. She successfully delivered by cesarean at 36 weeks of gestation. CONCLUSION: Low-molecular-weight heparin treatment is an effective and safe therapy in pregnancy. The healthy course of therapy, delivery, and puerperium reported here is a reference that may support women with a similar history.

Transvaginal ultrasonography in women receiving emergency contraception.

OBJECTIVE: To determine whether transvaginal ultrasonography improves evaluation of conception time in women seeking emergency contraception. DESIGN: Prospective study. SETTING: Obstetrics and Gynecology Department, Siena University, Siena, Italy. PATIENT(S): One hundred sixty-three women seeking postcoital contraception. MAIN OUTCOME MEASURE(S): Data on menstrual history and time of unprotected intercourse were recorded. Ultrasonographic variables evaluated were ovarian follicle or corpus luteum diameter, endometrial echopattern and thickness, and peritoneal fluid volume. Expected pregnancy rates were calculated according to the probability of conception as estimated from Dixon's table of data, based solely on anamnestic data, or from endometrial or ovarian findings on transvaginal ultrasonography. RESULT(S): According to the menstrual history (cut-off level < 0.03) we expected to find 7.6 pregnancies (7.9 in the high-risk group and 0.31 in the low-risk group). According to transvaginal ultrasonography (at the same cut-off), we expected 11.2 pregnancies (0.3 in the low-risk group and 10.9 in the high-risk group). No more than 7 pregnancies were observed, all of which occurred in the high-risk group as determined by transvaginal ultrasonography. In contrast, on the basis of anamnestic data, 4 of 7 pregnancies were in the high-risk group and 3 of 7 were in the low-risk group. CONCLUSION(S): Transvaginal ultrasonography allows timely definition of the fertile period and is a reliable method of computing the day of ovulation. It improves therapeutic options by allowing treatment of only women at high risk of conception.

Maternal serum inhibin A levels may predict pregnancy outcome in women with threatened abortion.

Determination of maternal serum inhibin A in women with threatened abortion may be helpful in predicting the failure of pregnancies.

A danazol-loaded intrauterine device decreases dysmenorrhea, pelvic pain, and dyspareunia associated with endometriosis.

A danazol-loaded intrauterine device (IUD) containing 300-400 mg of danazol was inserted for 6 months in a group of women (n = 18) (median age 36.6 years; age range: 30 to 46 years) with a histologic diagnosis of endometriosis, referred for recurrent pelvic pain. Dysmenorrhea, dyspareunia, and pelvic pain significantly decreased after the first month, with a persistent effect during the 6 months of IUD insertion. These results show that a danazol-loaded IUD is an effective conservative therapy for patients with endometriosis-related pelvic pain.