Exposure of rat pituitary cell cultures to charcoal-extracted porcine follicular fluid (pFF) inhibits gonadotropin-releasing hormone (GnRH) stimulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in a dose-dependent manner. The inhibition of GnRH-stimulated gonadotropin secretion (gonadotropin surge-inhibiting factor [GnSIF] activity) by pituitary cells in vitro requires up to 24-48 h preexposure to pFF. One microliter of pFF inhibits approximately 50% of the GnRH-stimulated LH release and is defined as 1 unit of GnSIF activity. Basal LH secretion is unaltered under these conditions. GnSIF activity is distinct from that of inhibin, which selectively suppresses basal release of FSH but not LH. A partially purified preparation of inhibin contains less than 1% as much GnSIF activity as inhibin activity. GnSIF activity is resistant to moderate heat treatment (60 degrees C for 60 min) and is fully recovered after acetone precipitation. Chromatography of pFF on heparin/Sepharose affinity matrix effectively separates inhibin from GnSIF. Whereas inhibin has a high affinity for heparin, GnSIF activity does not associate with this affinity matrix and is recovered in the column void volume. In summary, we have developed an in vitro bioassay for the detection of GnSIF activity in pFF. Moreover GnSIF activity seemingly derives from a molecular entity distinct from inhibin, having different physicochemical characteristics and differential effects on pituitary gonadotropin secretion.

Before chorionic villus sampling at 10–13 weeks' gestation, 453 women had the crown–rump length and nuchal translucency (NT) measured with transabdominal ultrasound. There were 19 aneuploid pregnancies (ten cases of trisomy 21, six of trisomy 18, one of 47+marker, one 47,%, and one 45,X mosaic). Average NT was 1·7 mm (range 0–5 mm), correlating with the crown–rump length, but not maternal age. A static cut‐off of 2·5 mm gave a false‐positive rate of 1·3 per cent for crown–rump length between 30 and 35 mm, rising to 13 per cent in fetuses with a crown–rump length between 50 and 65 mm. This gave an overall false‐positive rate of 5·5 per cent for a detection rate of 30 per cent for trisomy 21. Applying a dynamic action limit (95th centile), the false‐positive rate remained at 5 per cent irrespective of the crown–rump length, detecting 30 per cent of trisomy 21 and 36·8 per cent of all aneuploidies. Raising the action limit to the 97·5th centile halved the false‐positive rate (2·5 per cent), with no change in trisomy 21 detection and only a slight decrease in aneuploidy detection (31·6 per cent). Aneuploid fetuses showed normal first‐trimester growth. NT increases with gestational age, making a dynamic action limit necessary to decrease the false‐positive rate, while maintaining aneuploidy detection rates. Aneuploidy does not cause significant first‐trimester growth retardation, enabling normal ranges for NT with crown–rump length to apply.

No abstract