The value of measuring inhibin-A (a beta A dimer) with human chorionic gonadotrophin (total or the sub-units free a-hCG and free beta-hCG separately), alpha-fetoprotein (AFP), and unconjugated oestriol (uE3) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples from 77 Down's syndrome singleton pregnancies and 385 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the sample, supplemented by data from 970 white women with unaffected pregnancies. Inhibin-A was elevated in the serum of women with Down's syndrome pregnancies with a median of 1.79 multiples of the median (MOM). Using the four serum markers AFP, uE3, total hCG, and inhibin-A, in addition to maternal age, 70 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE3, and total hCG with maternal age). If the estimate of gestational age were based on an ultrasound scan examination, the detection rate would be 77 per cent [95 per cent confidence interval (CI) 69-85 per cent] using the four serum markers including inhibin-A, compared with 67 per cent with the triple test or 79 per cent (95 per cent CI 71-87 per cent) if marker values were adjusted for maternal weight. If the detection rate were kept at 70 per cent and the gestational age were estimated by an ultrasound scan examination, the four-marker test would reduce the false-positive rate from 6-1 per cent using the triple test to 2-9 per cent. The results were virtually the same if free beta-hCG was used instead of total hCG. The inhibin-A-based four-marker test is the most effective method of prenatal screening for Down's syndrome suitable for routine use. If the extra cost required to carry out the inhibin-A test were less than about [symbol: see text]3 per woman screened, the four-marker test including inhibin-A would be financially cost-effective.
yields an estimate of 204-8 affected pregnancies at the time of amnio-centesis (157.74 1-0.231). This is 32% less than the number at CVS ([302-204.8]/302). References 1 Macintosh MCM, Wald NJ, Chard T, Hansen J, Mikkelsen M, Therkelsen AJ, Petersen GB, Lundsteen C. The selective miscarriage of Down's syndrome from 10 weeks of pregnancy. Br J Obstet Gynaecoll995; 102: 798-801.
The suppression of ovulation in subordinate female marmosets was associated with suppressed pituitary LH secretion and reduced pituitary LH response to gonadotrophin-releasing hormone (GnRH). In subordinate females, basal plasma LH concentrations were commonly below 2 IU/l (n = 5) (maximum 10.7 IU/l). Plasma oestrogen concentrations were similarly low (maximum 0.62 nmol/l) and plasma progesterone concentrations of below 30 nmol/l confirmed the anovulatory condition. This infertility condition was rapidly reversed when subordinate females (n = 5) were removed from their social groups and housed singly, when plasma LH (maximum 140.0 IU/l) and oestrogen (maximum 7.84 nmol/l) concentrations increased preceding ovulation. Infertility was rapidly reimposed when these singly housed females were re-introduced to subordinate status in new social groups, when plasma LH concentrations fell to their previous low values within 4 days; no ovulation occurred thereafter. Plasma oestrogen levels also fell, but less dramatically. The luteal phases of three of the subordinate females were shortened following the re-instatement of subordinate status. The maximum LH response of subordinate females to the highest dose of GnRH (200 ng) was only 19.1 +/- 6.7 IU/l (mean +/- S.E.M.; n = 8): this contrasted with that in dominant females in either the follicular phase (40.0 +/- 13.3 IU/l; n = 6) or the luteal phase (126.7 +/- 24.9 IU/l; n = 10) of the ovarian cycle. These results suggest that the social suppression of fertility in subordinate female marmosets is mediated by impaired hypothalamic GnRH secretion. Such an immediate and precise behavioural control of LH secretion and ovulation is without equal in anthropoid primates.
Objective-To investigate maternal serum unconjugated oestriol (uE,) and human chorionic gonadotrophin (hCG) levels in twin pregnancies and to considcr the implications of the results for antenatal screening for Down's syndrome. Design-Measurement of maternal serum uE, and hCG levels from 15-22 weeks of gestation in twin and singleton pregnancies. Previously available maternal serum alpha-fetoprotein (AFP) levels were also presented. Setting-Stored serum samples collected from women receiving routine antenatal care in Oxford were used. Subjects-200 women with a twin pregnancy and, for each, three singleton control pregnancies matched for gestational age (same completed week of pregnancy) and duration of storage of the serum sample (same calendar quarter). Results-The median uE,, hCG and AFP levels in the twin pregnancies were respectively, 1.67 (95% CI 1.56-1.79), 1-84 (95% CI 164-2.07) and 2.13 (95% C1 1.97-2-31) multiples of the median (MOM) for singleton pregnancies at the samc gestational age. The variance of values for the threc serum markers (expressed in logarithms), and the correlation coefficients between any two, were similar in the twin and singleton pregnancies. Conclusion-In maternal serum screening programmes for Down's syndrome dividing uE,, hCG and AFP MOM values in twin pregnancies by the corresponding medians for twin pregnancies will, in expectation, yield a similar falsepositive rate in twin pregnancies as in singleton pregnancies.
Inhibin-A, principally the 31-kDa form, is present in peripheral blood throughout human gestation at concentrations up to 50 times greater than maximum values found during the spontaneous menstrual cycle (approximately 100 ng/l). The finding of highest serum values during the third trimester and of significant concentrations in term placenta firmly support a placental rather than luteal origin for this material.
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