Progesterone, inhibin, and hCG multiple marker strategy to differentiate viable from nonviable pregnancies

OBJECTIVE: To determine whether a combination of serum and urine biomarkers drawn from symptomatic pregnant women will help early differentiation of viable from nonviable pregnancies. METHODS: We conducted a prospective cohort study of 220 women who presented in the first trimester of pregnancy with complaints of pain, cramping, bleeding, or spotting. Serum samples for progesterone, inhibin A, and hCG, and urine beta-core hCG, were collected at presentation. To evaluate whether those biomarkers could predict viable and nonviable outcomes in pregnancy, we used likelihood ratios to compare operating characteristics of single and multiple biomarker strategies. RESULTS: Of 220 pregnancies studied, 98 were viable and 122 nonviable. Among single biomarkers, progesterone alone appears to have the greatest utility (area under the receiver operator characteristic curve = 0.923). Among dual-biomarker strategies, progesterone plus hCG and progesterone plus inhibin A improved specificity but not sensitivity. At 95% sensitivity, the combination of progesterone and hCG improved specificity from 0.29 to 0.66 (improvement = 0.37 [95% confidence interval 0.23, 0.52]). A triple-biomarker combination did not show substantial improvement over the dual-biomarker strategy. Also, combinations that used urine beta-core hCG did not improve diagnostic accuracy. CONCLUSION: Serum progesterone appeared to be the single most specific biomarker for distinguishing viable from nonviable pregnancies. When a dual-biomarker strategy was applied, combining serum progesterone with hCG, specificity improved significantly, which suggests that a multiple biomarker strategy might help distinguish viable from nonviable pregnancies in early gestation.     

Obstructive sleep apnea is associated with alterations in markers of fetoplacental wellbeing

Background: Obstructive sleep apnea (OSA) has been associated with adverse fetal outcomes in some studies. Second trimester Down syndrome screening markers reflect fetal and fetoplacental wellbeing. We aimed to compare markers of fetal and feto-placental wellbeing in women with OSA and low risk controls.

Methods: A retrospective case-control study of pregnant women with OSA and available second trimester markers was performed. Controls were screened for sleep disordered breathing (SDB) at the time of delivery using a questionnaire. Women at low risk for OSA were selected. Marker levels were adjusted for gestational age and race and reported as multiples of median and later adjusted for body mass index (BMI).

Results: Twenty-four OSA cases and 166 controls were identified. Women with OSA had a higher mean BMI when compared to controls (37.1?±?12.7 versus 24.1?±?5.1, p?=?0.03). Estriol (uE3) multiples of the median (MoM) levels were lower in women with OSA compared to controls, even after adjusting for BMI, 0.74 (interquartile range (IQR) 0.45) versus 1.06 (IQR 0.38), respectively, p?=?0.026. Once adjusted for BMI, alpha feto-protein (AFP) MoM levels were no longer significantly different in women with OSA compared to controls.

Conclusion: OSA is associated with reduced serum uE3 levels, independently of BMI, possibly indicating fetal distress.     

The influence of depression, body mass index, and smoking on serum inhibin B levels in late reproductive-aged women

CONTEXT: Women experiencing depression have difficult psychosocial functioning, and recent data suggest an earlier onset of menopause. Understanding the biological mechanism for the impairment of reproductive function associated with depression is important. OBJECTIVE: The objective of the study was to determine whether a lifetime history of depression is associated with reduced ovarian reserve as reflected in serum levels of the granulosa cell product, inhibin B. DESIGN: Residual serum samples from a subset of patients in the Harvard Study of Cycles and Moods were collected. SETTING: Patients were recruited from seven Boston-area communities. PATIENTS: Women with or without a history of major depression, based on structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were enrolled. A subset of patients who had provided an early follicular phase blood specimen at study enrollment and two or more other samples over the first 18-month period of follow-up were included. Intervention: There were no interventions. MAIN OUTCOME MEASURE: Serum inhibin B levels were measured. RESULTS: Serum FSH levels were higher in women with a history of depression, whereas inhibin B levels did not differ between groups. Body mass index and age were significantly and inversely related to serum inhibin B levels. Smoking history was noted, for the first time, to have a significant negative association with inhibin B levels. CONCLUSIONS: Smoking has a direct negative effect on ovarian reserve, as suggested by decreased serum inhibin B levels. In contrast, effects of depression on the reproductive axis may occur at the level of the pituitary and/or hypothalamus rather than at the gonadal level, as suggested by increased serum FSH levels.     

First- and second-trimester Down syndrome screening markers in pregnancies achieved through assisted reproductive technologies (ART): a FASTER trial study

OBJECTIVE: To determine whether first- and second-trimester Down syndrome screening markers and screen-positive rates are altered in pregnancies conceived using assisted reproductive technologies (ARTs). METHODS: ART pregnancies in the multicenter FASTER trial were identified. Marker levels were evaluated for five types of ART: in vitro fertilization with ovulation induction (IVF-OI), IVF with OI and egg donation (IVF-OI-ED), IVF with ED (IVF-ED), and intrauterine insemination with OI (IUI-OI) or without OI (IUI). Each group was compared to non-ART controls using Mann-Whitney U analysis. RESULTS: First-trimester marker levels were not significantly different between ART and control pregnancies, with the exception of reduced PAPP-A levels in the IUI-OI group. In contrast, second-trimester inhibin A levels were increased in all ART pregnancies, estriol was reduced and human chorionic gonadotropin (hCG) was increased in IVF and IUI pregnancies without ED, and alpha-fetoprotein (AFP) was increased in ED pregnancies. Second-trimester screen-positive rates were significantly higher than expected for ART pregnancies, except when ED was used. CONCLUSIONS: These data show that ART significantly impacts second-, but not first-, trimester markers and screen-positive rates. The type of adjustment needed in second-trimester screening depends on the particular type of ART used.