Early pregnancy ultrasound measurements and prediction of first trimester pregnancy loss: A logistic model.

Our objective was to prospectively validate the use of gestational sac (GS), yolk sac (YS) diameter, crown-rump length (CRL), and embryonal heart rate (HR) dimensions to identify early pregnancy loss. This was a prospective cohort study of first trimester pregnancies. GS and YS diameter, CRL, and HR measurements were serially obtained in singleton and twin pregnancies from 6 through 10 weeks' gestation. Non-parametric tests and logistic regression models were used for comparisons of distributions and testing of associations. A total of 252 patients were included, of which 199 were singleton pregnancies, 51 were twins, and 2 were triplets (304 total fetuses). Fifty-two patients had 61 losses. We built nomograms with the changes of the parameters evaluated in ongoing, as well as in pregnancy loss. In the pregnancies which failed, all the parameters showed significant changes, with different temporal onsets: GS and YS were the first to become abnormal, deviating from normality as early as 6 weeks' gestation (OR 0.01, 95% CI 0.0-0.09, and OR 3.36, 95% CI 1.53-7.34, respectively), followed by changes in HR, and CRL, which became evident at 7 and 8 weeks (OR 0.96, 95% CI 0.92-1.0, and OR 0.59, 95% CI 0.48-0.73, respectively). Our observations showed that, after 5 complete weeks' gestation, a small GS and a large YS reliably predicted pregnancy loss. The YS reliably identified the occurrence of a miscarriage at least 7 days prior its occurrence. CRL and HR became abnormal at a later time in pregnancy and closer to the event. These findings have important implications for patient counseling and care planning, as well as a potential bearing on cost effectiveness within early pregnancy care.

Pilot study establishing a nomogram of yolk sac growth during the first trimester of pregnancy.

AIM: The yolk sac (YS) has been reported as a reliable predictor of adverse pregnancy outcomes, however, it has always been evaluated cross-sectionally with a single ultrasound per patient. We sought to validate the use of YS dimensions in serial ultrasounds throughout the first 10 weeks of singleton and multiple gestations. METHODS: This was a prospective cohort study where YS diameters were serially obtained with 2D ultrasound in singleton and multiple gestations from 5 to 11 weeks. Nonparametric test were used for comparisons with P < 0.05 indicating significance. RESULTS: One hundred ninety-three patients were included, 42 twins (3 monochorionic and 39 dichorionic), 2 triplets (monochorionic twins plus a singleton) and 148 singleton pregnancies (238 total fetuses). There was no difference in YS dimensions in singleton versus multiple pregnancies. Starting at 5 weeks' gestation, the YS increased 0.4 mm (95% CI 0.3-0.5 mm) per week until 10 weeks' gestation. Forty-five fetuses were lost in the first trimester. The risk of pregnancy loss was higher with a large YS until 8 weeks (P ≤ 0.001), while after 8 weeks it was higher with a small YS (P < 0.005). CONCLUSION: We established a nomogram of YS development during the first 10 weeks of pregnancy. The YS reliably detected pregnancies that ended in loss as early as 6 weeks' gestation. The YS was either smaller or larger than in ongoing pregnancies. While all pregnancies with large YS were lost within 10 weeks, those with smaller YS were lost beyond the first 10 weeks.

Diagnosis of Placental Position by Early First-Trimester Ultrasound: A Pilot Study.

OBJECTIVE: Conventional wisdom is that placental location cannot be identified before 8 weeks' gestation when the placenta first becomes hyperechogenic on ultrasound. We sought to evaluate whether placental location could be reliably diagnosed between 5 and 6 weeks' gestation. MATERIALS AND METHODS: This was a retrospective analysis of prospectively acquired data. Early placental location was diagnosed by evaluation of the embryonal and yolk sac position inside the gestational sac on transvaginal ultrasound. Placental position was described as anterior, posterior, fundal, or lateral. Early and mid-pregnancy placental locations were compared and coded as being the same, having migrated to an adjacent surface, or being on an opposite surface. RESULTS: A total of 111 patients met study criteria, providing 141 placental locations, comprising 85 singleton and reduced pregnancies and 28 dichorionic twin pregnancies. The most common placental location was anterior in both singleton and twin/triplet pregnancies. Placental location at the mid-pregnancy ultrasound was consistent with early pregnancy location in 100% of cases, with 79.5% (112/141) being on the same surface and 20.5% (29/141) having expanded onto an adjacent surface. Placental location was not associated with pregnancy outcome, although our study may have been underpowered to detect a significant difference. CONCLUSIONS: Placental location diagnosed at 5 to 6 weeks' gestation is consistent with the location on mid-pregnancy ultrasound. Excluding the presence of an ectopic, cornual, or cesarean section scar and uterine subseptation pregnancy in early first trimester would allow a more effective tailoring of pregnancy follow-up.

Serum Anti-Müllerian hormone (AMH) in mothers with polycystic ovary syndrome (PCOS) and their term fetuses.

We sought to determine serum AMH levels in the maternal circulation, and the umbilical artery and vein, in normal women and women with PCOS, and their neonates at time of delivery. This represents a cross-sectional study of 57 pregnant patients who presented to the labor and delivery suite and subsequently delivered. We obtained maternal, as well as fetal blood from both, umbilical artery and vein. We measured serum concentrations of estradiol, AMH, testosterone and FSH. A total of 30 patients delivered a female and 27 a male neonate. Of them, 18/30 and 18/27 had a diagnosis of PCOS by NIH criteria. Mean age, BMI, weight gain in pregnancy, and gestational age did not differ between the two groups of mothers. AMH serum levels were statistically higher in women with PCOS (p < 0.005) and in their fetuses, independently of gender. Testosterone was higher in women with PCOS (p < 0.001), but there was no PCOS-related difference in their fetuses. FSH levels were significantly lower in PCOS than non-PCOS mothers carrying a male (p = 0.022), but not a female, fetus. AMH was positively correlated with maternal serum testosterone (p = 0.001) and negatively with fetal serum FSH (p < 0.026). In PCOS pregnancies, AMH was negatively correlated with maternal BMI (p = 0.019), menstrual cycle length (p = 0.035), and fetal uterine vein FSH (p = 0.021). In conclusion, at time of delivery, fetuses of women with PCOS had higher AMH levels and similar testosterone levels compared to fetuses from non-PCOS mothers, irrespective of gender. Our results may help explaining developmental differences in offspring of PCOS women.

Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14).

In this study, we identified and characterized an N-ethyl-N-nitrosourea (ENU) induced mutation in Usp14 (nmf375) that leads to adult-onset neurological disease. The nmf375 mutation causes aberrant splicing of Usp14 mRNA, resulting in a 95% reduction in USP14. We previously showed that loss of USP14 in ataxia (ax (J)) mice results in reduced ubiquitin levels, motor endplate disease, Purkinje cell axonal dystrophy and decreased hippocampal paired pulse facilitation (PPF) during the first 4-6 weeks of life, and early postnatal lethality by two months of age. Although the loss of USP14 is comparable between the nmf375 and ax (J) mice, the nmf375 mice did not exhibit these ax (J) developmental abnormalities. However, by 12 weeks of age the nmf375 mutants present with ubiquitin depletion and motor endplate disease, indicating a continual role for USP14-mediated regulation of ubiquitin pools and neuromuscular junction (NMJ) structure in adult mice. The observation that motor endplate disease was only seen after ubiquitin depletion suggests that the preservation of NMJ structure requires the stable maintenance of synaptic ubiquitin pools. Differences in genetic background were shown to affect ubiquitin expression and dramatically alter the phenotypes caused by USP14 deficiency.