Galia Oron

Inflammatory bowel disease: risk factors for adverse pregnancy outcome and the impact of maternal weight gain.

Objective: To identify risk factors for adverse pregnancy outcome in women with inflammatory bowel disease (IBD) and to assess the effect of maternal pre-pregnancy weight and weight gain during pregnancy on pregnancy outcome. Methods: A retrospective, matched control study of all gravid women with IBD treated in a single tertiary center. Data were compared with healthy controls matched to by age, parity and pre-pregnancy BMI in a 3:1 ratio. Results: Overall, 300 women were enrolled, 75 women in the study group (28 with ulcerative colitis and 47 with Crohn’s disease) and 225 in the control group. The rates of preterm delivery and small for gestational age were higher in the study group (13.3 vs. 5.3% p = 0.02 and 6.7 vs. 0.9%, p = 0.004). The rate of cesarean section (36 vs. 19.1%; p = 0.002), NICU admission (10.7 vs. 4.0%, p = 0.03) and low 5-Min Apgar (4.0 vs. 0.4%, p = 0.02) were increased in the study group. Disease activity within 3 months of conception [OR 8.4 (1.3–16.3)] and maternal weight gain of less than 12 kg. [OR 3.6 (1.1–12.2)] were associated with adverse pregnancy outcome. Conclusion: Active disease at conception and inappropriate weight gain during pregnancy are associated with increased adverse pregnancy outcome in patients with IBD.

Serum-soluble CD40 ligand in normal pregnancy and in preeclampsia

OBJECTIVE: Soluble CD40 ligand is a transmembrane protein shed from activated platelets that is involved in the activation of endothelial cells. Findings that estradiol (E2) has an inhibitory effect on inflammation and platelet function and that serum E2 levels are low in women with preeclampsia prompted us to investigate the association between soluble CD40 ligand and serum E2 levels in normal pregnancy and in preeclampsia. METHODS: A case–control single-center design was used. The sample included 22 women with severe preeclampsia, 22 matched normotensive pregnant women, and 22 nonpregnant women. Enzyme immunoassay was used to measure soluble CD40 ligand. RESULTS: Significantly higher levels of soluble CD40 ligand were detected in the nonpregnant women (23,767 ± 15,637 pg/mL) and in the women with preeclampsia (21,025 ± 45,386 pg/mL) than in the normotensive pregnant women (8,292 ± 5,926 pg/mL) (P = .026). No significant correlation between soluble CD40 ligand levels and E2 levels was observed. CONCLUSION: The higher levels of soluble CD40 ligand detected in women with preeclampsia may indicate an exaggerated activation of platelets and endothelial cells. LEVEL OF EVIDENCE: II-2

Primary atherothrombotic occlusive vascular events in premenopausal women with history of adverse pregnancy outcome

OBJECTIVE To determine if adverse pregnancy outcomes are associated with atherothrombotic occlusive vascular disease (AOVD) in premenopausal women. DESIGN Retrospective matched case-control study. SETTING Tertiary, university-affiliated medical center. POPULATION Women aged less than 50 years treated for an AOVD (primary cerebrovascular, myocardial, or peripheral arterial ischemic event) from 1995 to 2004. METHOD The files were reviewed for classical risk factors for AOVD and complications of pregnancy (abortions, pregnancy-induced hypertension, preeclampsia, gestational diabetes, intrauterine growth restriction (IUGR), fetal loss and preterm delivery). Findings were compared with healthy women matched for age and body mass index. MAIN OUTCOME MEASURES Past pregnancy complications in premenopausal women with AOVD. RESULTS Of the 101 women with AOVD, 53 had a myocardial ischemic event, 33 a cerebrovascular event, and 15 a peripheral ischemic arterial event. On multivariate analysis, IUGR (OR 8.41, 95% CI 2.36-29.9, p=0.001) and more than one pregnancy complication (OR 13.7, 95% CI 1.56-120, p=0.02) were found to be independent significant variables associated with AOVD. CONCLUSION IUGR and composite pregnancy complications are independent significant variables associated with AOVD in premenopausal period. Pregnancy outcome might serve as a means to identify patients who may require increased medical surveillance and preventive measures for later vascular disease.

Reduced Pseudocholinesterase Activity in Patients With HELLP Syndrome

The authors previously reported a case of decreased pseudocholinesterase activity in a patient with HELLP syndrome. It was assumed that the reduced pseudocholinesterase activity in HELLP syndrome is associated with impaired liver function. The present study assesses the prevalence of low pseudocholinesterase in patients with HELLP syndrome. Serum pseudocholinesterase activity was determined with spectrophotometer in 15 patients with HELLP syndrome. Two control groups matched for gestational age were recruited: 15 healthy women with uncomplicated pregnancy and 15 women with severe preeclampsia without HELLP. The prevalence of reduced pseudocholinesterase activity lower than normal limit was 60.0% (9/15) in patients with HELLP syndrome, 33.3% (5/15) in patients with severe preeclampsia, and 6.6% (1/15) in women with normal pregnancy, respectively (P =.009). The pseudocholinesterase activity was found to correlate with serum alanine aminotransferase levels (r = 0.417, P = .006) and with serum aspartate aminotransferase levels (r = 0.462, P = .002). Considering the increased prevalence of reduced pseudocholinesterase activity in patients with HELLP syndrome, the authors suggest that whenever general anesthesia is applied in these patients, the anesthesiologist should be aware that the patient may show slow metabolic degradation of choline-ester drugs.

Pregnancy outcome after ICSI with thawed testicular sperm from men with non-obstructive azoospermia compared to ICSI with ejaculated sperm from men with severe oligoasthenoteratozoospermia and IVF with normal ejaculated sperm

Abstract The aim of the study was to evaluate the clinical pregnancy outcomes, fetal complications and malformation rate of intracytoplasmic injection of thawed cryopreseverd sperm extracted by testicular aspiration from men with non-obstructive azoospermia (NOA) compared with intracytoplasmic injection of fresh ejaculated sperm from men with severe oligoteratoasthenozoospermia (OTA) and standard in vitro fertilization using ejaculated sperm from normospermic men. The mean oocyte fertilization rate was significantly lowest for ICSI with testicular aspirated sperm (NOA group). However, there was no significant difference among the three groups in pregnancy outcomes, namely rates of spontaneous abortion, biochemical pregnancy, extrauterine pregnancy, singleton multifetal pregnancy, preterm delivery before 36 weeks’ gestation, maternal complications, transfer to the neonatal intensive care unit, intrauterine growth restriction or fetal malformations. These results suggest that despite some earlier findings that intracytoplasmic injection of aspirated sperm from men with NOA is associated with lower fertilization rates and embryo quality, the pregnancy and immediate neonatal outcomes may be unaffected.

Early first-trimester crown-rump length measurements in male and female singleton fetuses in IVF pregnancies

Objectives: The generally higher birth-weight of male newborns compared to female newborns is attributed mainly to intrauterine exposure to testosterone. We aimed to determine if crown-rump length (CRL) differs between male and female fetuses early in the first trimester. Methods: A retrospective cohort study of 333 women with nondiabetic singleton IVF pregnancies attending a single university-affiliated tertiary medical center in 2000–2007 who underwent CRL measurement before 50 days of pregnancy (date of measurement minus oocyte retrieval date plus 14 days). Data on pregnancy outcome, including fetal sex, were collected by routine follow-up telephone interview and combined with the delivery data. Results: There were 169 female and 164 male fetuses according to the reported fetal sex at delivery. Most of the CRL measurements (68.7%) were performed at an actual gestational age of 43–45 days. On linear regression analysis, male fetal sex was a significant (p = 0.011) predictor of larger CRL: CRL (mm) = –23.851 + GA (days) × 0.621 + 0.334 × Sex (F = 1, M = 2), R2 = 0.512, p <0.001. A general linear model, adjusted for gestational age (40–50 days), revealed that mean CRL was significantly higher in male than in female fetuses (4.58 ± 0.09 mm, [95% CI: 4.3–4.7] vs 4.24 ± 0.09 mm [4.0–4.4]; p < 0.001). Conclusions: Male fetuses are larger than female fetuses in the early first trimester. Given that gonadal differentiation has not yet occurred, still unidentified nonhormonal factors are apparently responsible for this difference.

Suggested algorithm for cytomegalovirus surveillance in low-risk pregnancies

Cytomegalovirus (CMV) is the most common cause of intrauterine infection, occurring in 0.2–2.2% of all neonates. The rare but serious neonatal manifestations have prompted widespread discussions of the use of CMV surveillance during pregnancy. This study describes a decision-analysis algorithm for a surveillance protocol to detect the maximal number of primary CMV infections in low-risk pregnancies. The steps of the protocol adhere to the routine antenatal follow-up schedule. All calculations were based on the most stringent data in the literature as applied to a theoretical cohort of 100,000 pregnant women in the general population. By the time of delivery, the protocol failed to detect only four potentially ill neonates in the study group. These cases may be diagnosed and treated postnatally. Incorporation of the protocol in antenatal follow-up can reduce diagnostic confusion, assist clinicians in timing invasive procedures, and potentially spare patients unnecessary terminations of pregnancy.

Vasoactive intestinal peptide and its receptors in human ovarian cortical follicles.

Background Ovarian cryopreservation is one option for fertility preservation in patients with cancer. The danger of reseeding malignancies could be eliminated by in vitro maturation of primordial follicles from the frozen-thawed tissue. However, the development of this system is hindered by uncertainties regarding factors that activate primordial follicles. Neuronal growth factors such as vasoactive intestinal peptide (VIP) play important roles in early mammalian folliculogenesis. There are no data on the expression of VIP and its vasoactive intestinal peptide pituitary adenylate cyclase 1 and 2 receptors (VPAC1-R and VPAC2-R) in human preantral follicles. Methodology/Principal Findings Tissue samples from 14 human fetal ovaries and 40 ovaries from girls/women were prepared to test for the expression of VIP, VPAC1-R, and VPAC2-R on the protein (immunohistochemisty) and mRNA (reverse transcription polymerase chain reaction) levels. Immunohistochemistry staining was mostly weak, especially in fetal samples. The VIP protein was identified in oocytes and granulosa cells (GCs) in the fetal samples from 22 gestational weeks (GW) onwards. In girls/women, VIP follicular staining (oocytes and GCs) was identified in 45% of samples. VPAC1-R protein was identified in follicles in all fetal samples from 22GW onwards and in 63% of the samples from girls/women (GC staining only in 40%). VPAC2-R protein was identified in follicles in 33% of fetal samples and 47% of the samples from girls/women. The mRNA transcripts for VIP, VPAC1-R, and VPAC2-R were identified in ovarian extracts from fetuses and women. Conclusions VIP and its two receptors are expressed in human ovarian preantral follicles. However, their weak staining suggests they have limited roles in early follicular growth. To elucidate if VIP activates human primordial follicles, it should be added to the culture medium.

Fertility Treatment Outcomes After Follicle Tracking With Standard 2-Dimensional Sonography Versus 3-Dimensional Sonography-Based Automated Volume Count: Prospective Study

The use of sonography‐based Automated Volume Count (SonoAVC; GE Healthcare, Kretz, Zipf, Austria) leads to substantially lower intraobserver and interobserver variability with a considerable advantage in time gain for both the physician and patient. It offers the possibility of continuous training and standardization of follicular monitoring. Manual and automated follicular measurements during in vitro fertilization (IVF) are reported to be comparable during gonadotropin‐releasing hormone (GnRH) agonist treatment. The aim of our study was to evaluate the effect of follicle tracking with 3‐dimensional (3D) SonoAVC on treatment outcomes in GnRH antagonist IVF cycles.

Contribution of the addition of anti-β2-glycoprotein to the classification of antiphospholipid syndrome in predicting adverse pregnancy outcome.

Objectives. Anti-β2 glycoprotein 1 (a-β2GP1) was added to the criteria for antiphospholipid syndrome (APS) in 2005. However, its clinical significance with respect to complications of pregnancy is not well established. The aim of this study was to evaluate the association of laboratory findings of a-β2GP1 with events of thromboembolism or obstetric complications (pregnancy loss, placental dysfunction, intrauterine growth restriction, preeclampsia, fetal death, and preterm delivery) in women with clinical and laboratory evidence of APS. Methods. A retrospective cohort design was used. Ninety-one patients (total 394 pregnancies) referred to a tertiary medical center for evaluation of clinical features consistent with APS were divided into three groups: group A (n = 34), two positive tests for anticardiolipin (ACL) or lupus anticoagulant (LAC), in accordance with original APS classification (1998); group B (n = 18), two positive tests for a-β2GP1, in accordance with the revised APS criteria; and group C (n = 39), only one positive test for ACL or LAC. Results. Of the 52 women with APS (group A or B), 36 had primary disease, and 16 had secondary disease. On comparison of the groups, group B was characterized by a significantly higher rate of complicated pregnancy (83.3%) than groups A (47.1%) and C (76.9%), P = 0.007, and a higher rate of fetal loss (72.2%) than groups A + C (28.8%, P = 0.001). Conclusions. The findings suggest that the revised APS criteria are preferable to the original classification for the prediction of complicated pregnancy.