Alice Benjamin

Live birth after vitrification of in vitro matured human oocytes

OBJECTIVE To report the first healthy live birth from immature oocytes retrieved in a natural menstrual cycle, followed by in vitro maturation (IVM) and cryopreservation of the oocytes by vitrification. DESIGN Case report. SETTING University-based tertiary medical center. PATIENT(S) A 27-year-old woman with tubal disease and polycystic ovaries. INTERVENTION(S) Immature oocytes were retrieved by transvaginal ultrasound guided follicle aspiration on day 13 of her natural menstrual cycle, matured in vitro and vitrified. The oocytes were thawed in a subsequent menstrual cycle, inseminated by intracytoplasmic sperm injection, and the resulting embryos transferred. MAIN OUTCOME MEASURE(S) Oocyte maturation and survival rates, pregnancy, and live birth. RESULT(S) One metaphase II and 18 germinal vesicle stage oocytes were collected; 16 out of 18 germinal vesicle oocytes matured, and a total of 17 oocytes were vitrified. After thawing, four IVM oocytes survived; three embryos were transferred. The woman went on to deliver a single healthy live baby at term. CONCLUSION(S) We provide proof-of-principle evidence that the novel fertility preservation strategy of immature oocyte retrieval, IVM, and vitrification of oocytes can lead to successful pregnancy and healthy live birth.

Obstetric admissions to the intensive care unit

OBJECTIVE To determine whether obstetric admissions to the intensive care unit (ICU) are useful quality-assurance indicators. METHODS We analyzed retrospectively obstetric ICU admissions at two tertiary care centers from 1991 to 1997. RESULTS The 131 obstetric admissions represented 0.3% of all deliveries. The majority (78%) of women were admitted to the ICU postpartum. Obstetric hemorrhage (26%) and hypertension (21%) were the two most common reasons for admission. Together with cardiac disease, respiratory disorders, and infection, they accounted for more than 80% of all admissions. Preexisting medical conditions were present in 38% of all admissions. The median Acute Physiology and Chronic Health Evaluation II score was 8.5. The predicted mortality rate for the group was 10.0%, and the actual mortality rate was 2.3%. CONCLUSION The most common precipitants of ICU admission were obstetric hemorrhage and uncontrolled hypertension. Improved management strategies for these problems may significantly reduce major maternal morbidity.

An international trial of antioxidants in the prevention of preeclampsia (INTAPP).

OBJECTIVE We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. STUDY DESIGN In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions. RESULTS Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes. CONCLUSION Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes.

A Common RET Variant Is Associated with Reduced Newborn Kidney Size and Function

Congenital nephron number varies five-fold among normal humans, and individuals at the lower end of this range may have an increased lifetime risk for essential hypertension or renal insufficiency; however, the mechanisms that determine nephron number are unknown. This study tested the hypothesis that common hypomorphic variants of the RET gene, which encodes a tyrosine kinase receptor critical for renal branching morphogenesis, might account for subtle renal hypoplasia in some normal newborns. A common single-nucleotide polymorphism (rs1800860 G/A) was identified within an exonic splicing enhancer in exon 7. The adenosine variant at mRNA position 1476 reduced affinity for spliceosome proteins, enhanced the likelihood of aberrant mRNA splicing, and diminished the level of functional transcript in human cells. In vivo, normal white newborns with an rs1800860(1476A) allele had kidney volumes 10% smaller and cord blood cystatin C levels 9% higher than those with the rs1800860(1476G) allele. These findings suggest that the RET(1476A) allele, in combination with other common polymorphic developmental genes, may account for subtle renal hypoplasia in a significant proportion of the white population. Whether this gene variant affects clinical outcomes requires further study.

A Common Variant of the PAX2 Gene Is Associated with Reduced Newborn Kidney Size

Congenital nephron number ranges widely in the human population. Suboptimal nephron number may be associated with increased risk for essential hypertension and susceptibility to renal injury, but the factors that set nephron number during kidney development are unknown. In renal-coloboma syndrome, renal hypoplasia and reduced nephron number are due to heterozygous mutations of the PAX2 gene. This study tested for an association between a common haplotype of the PAX2 gene and subtle renal hypoplasia in normal newborns. A PAX2 haplotype was identified to occur in 18.5% of the newborn cohort, which was significantly associated with a 10% reduction in newborn kidney volume adjusted for body surface area. This haplotype was also associated with reduced allele-specific PAX2 mRNA level in a human renal cell carcinoma cell line. Subtle renal hypoplasia in normal newborns may be partially due to a common variant of the PAX2 gene that reduces mRNA expression during kidney development.

Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality.

Summary: Valproate (VPA) is an effective, widely used antiepileptic drug. Unfortunately its use in pregnant women is associated with neural tube defects in the offspring. Although the etiology of neural tube defects is multifactorial, there is evidence that underlying genetic susceptibility plays a part. We describe two women taking moderate doses of VPA who repeatedly bore children with neural tube defects, despite folate supplementation. This suggests a pharmacogenetic susceptibility to the teratogenic effects of VPA.

Placental weight for gestational age and adverse perinatal outcomes.

OBJECTIVE: The fetoplacental ratio has been used conventionally to study the contribution of the placenta to fetal growth restriction. However, this measure is problematic because a normal fetoplacental ratio can reflect birth weight and placental weight that are both normal, both low, or both high. The objective of this study was to examine the independent association between placental weight for gestational age and perinatal mortality or serious neonatal morbidity. METHODS: A sex- and gestational age–specific placental weight z score was calculated for a cohort of 87,600 singleton births at the Royal Victoria Hospital in Montreal, Canada, 1978–2007. The relationship between placental weight z score and adverse perinatal outcomes (stillbirth, neonatal death, 5-minute Apgar score lower than 7, seizures, or respiratory morbidity) was examined using logistic regression. Multivariable models examined whether the relationship was independent of birth weight and other pregnancy risk factors. RESULTS: After controlling for birth weight, fetuses with a low placental weight z score were at significantly increased risk of stillbirth (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4–2.6, percent population attributable risk 17.8%). In contrast, adverse neonatal outcomes were significantly more likely among those with high placental weight z scores (OR 1.4, 95% CI 1.2–1.7, percent population attributable risk 5% for any serious neonatal morbidity). Similar trends were observed after further adjusting for pregnancy risk factors. CONCLUSION: Placental weight for gestational age is an independent risk factor for adverse perinatal outcomes, above and beyond the known association with birth weight. The mechanisms behind the opposing effects of placental weight z score on risk of stillbirth compared with adverse neonatal outcomes require further elucidation. LEVEL OF EVIDENCE: III

Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study.

OBJECTIVE We sought to evaluate the association between inherited thrombophilia and preeclampsia. STUDY DESIGN From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia and selected 443 control subjects who did not have preeclampsia or nonproteinuric gestational hypertension. Blood samples were tested for DNA polymorphisms affecting thrombophilia (factor V Leiden mutation, prothrombin G20210A mutation, methylenetetrahydrofolate reductase C677T polymorphism), homocysteine, and folate levels, and placentae underwent pathological evaluation. RESULTS Thrombophilia was present in 14% of patients and 21% of control subjects (adjusted logistic regression odds ratio, 0.6; 95% confidence interval, 0.3-1.3). Placental underperfusion was present in 63% of patients vs 46% of control subjects (P < .001) and was more frequent in women with folate levels in the lowest quartile (P = .04), but was not associated with thrombophilia. CONCLUSION We did not find evidence to support an association between inherited thrombophilia and increased risk of preeclampsia. Placental underperfusion is associated with preeclampsia, but this does not appear to be consequent to thrombophilia.

Caesarean section and phaeochromocytoma resection in a patient with Von Hippel Lindau disease

This report describes the anaesthetic management of a women with a term gestation, Von Hippel Lindau disease (VHLD), and a phaeochromocytoma, scheduled for a combined phaeochromocytoma resection and Caesarean section. Von Hippel Lindau disease is characterized by diffuse haemangioblastomas of the central nervous system (CNS) and viscera. It is also associated with phaeochromocytomas and renal cell carcinomas. Patients frequently have asymptomatic spinal cord and intracranial pathology. The patient and her fetus presented a challenge because of the anaesthetic restrictions imposed by VHLD, and her pregnancy. She was also at risk of developing malignant hypertension from the phaeochromocytoma. The patient was not a candidate for regional anaesthesia because of the possibility of spinal cord haemangioblastomas. She had received adrenergic blockade with phentolamine (total 30 mg a day) and propranolol (total 40 mg a day) since the 27th wk of gestation in order to control hypertension secondary to the phaeochromocytoma. General anaesthesia was administered with aggressive management of hypertension with adrenergic blockers (labetalol 1.0 mg · kg−1 and esmolol 0.75 mg · kg−1) and sodium nitroprusside 1.5 μg · kg−1 (total). Before delivery of the baby, opioids, which could have resulted in a fetus with CNS depression, were avoided. After delivery, opioids (sufentanil 0.4 ng · kg−1 hr−1) were used to limit the use of inhalational anaesthesia which may contribute to uterine atony. Postoperative pain was managed with an intravenous narcotic infusion. Both patients had uneventful postoperative courses.RésuméCette observation décrit la conduite anesthésique chez une parturiente à terme souffrant de la maladie de Von Hippel Lindau (MVHL) associée a un phéochromocytome, programmée pour une césarienne et une résection simultanée de phéochromocytome. La maladie de Von Hippel Lindau est caractérisée par une hémangioblastomatose diffuse du système nerveux central et des viscères. Elle s’accompagne souvent de phéochrocytomes et de cellules carcinomateuses rénales. Les pathologies spinale et intracrânienne sont souvent silencieuses. La MVHL et la grossesse rendent plus complexe la conduite anesthésique. Au phéochromocytome se greffe aussi un risque d’hypertension maligne. La possibility d’hémangioblastose spinale fait de la malade une mauvaise candidate pour la régionale. A partir de la 27ième semaine de gestation, l’hypertension secondaire au phéochromocytome est contrôlée par une médication antiadrénergique de phentolamine (30 mg par jour) et de propanolol (40 mg par jour). Pendant l’anesthésie générale, avec le même objectif on administre des bloqueurs adrénergiques (labétalol 1,0 mg · kg−1 et esmolol 0,75 mg · kg−1) avec du nitroprussiate de soude 1,5 μ · kg−1 (dose totale). Avant la naissance, les opiacés sont évités dans le but de prévenir la dépression foetale. Après la naissance, du sufentanil 0,4 μ · kg−1 · h−1 permet de limiter la concentration d’inhalatoire pour prévenir l’atonie utérine. La douleur postopératoire est traitée avec une perfusion morphinique. La mère et l’enfant récupèrent sans complications.

Obstetrical factors related to nuchal cord

Background. To investigate the intrapartum factors related to umbilical cord nuchal loops (nuchal cord) with particular reference to shoulder dystocia.