Byrne, Dominic Lawrence; (1994) The feasibility of early amniocentesis for fetal karyotyping. Doctoral thesis (M.D.), UCL (University College London).

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Abstract

This thesis investigates the feasibility of amniocentesis in the first trimester of human pregnancy for the diagnosis of fetal karyotype. A cross sectional study of amniotic fluid from 125 pregnancies at 8–18 weeks' gestation, demonstrated an exponential increase in the total number of cells with gestation; however, the number of viable cells did not change significantly. A subsequent pilot study of amniocentesis in 56 women, prior to elective termination of pregnancy at 9–14 weeks' gestation, demonstrated culture success in all 39 cases where the fetal crown-rump length was >37mm, but in only 8 of the 17 (47%) where it was >37mm. In a randomised study a sample was successfully obtained at the first attempt in 320 of 324 (98.8%) cases of early amniocentesis and in 323 of 326 (99%) cases of chorion villus sampling; culture and chromosomal analysis was successful in 98.1% and 99.4% of these cases respectively. To limit the large proportion of amniotic fluid removed at early amniocentesis amnifiltration was developed. This is the filtration of amniotic fluid to trap free cells whilst the fluid is returned to the amniotic sac. A series of experiments involving 218 patients undergoing elective termination of pregnancy at 10-14 weeks' gestation established that (i), a cellulose acetate filter with 0.8 ?m pore size was the most efficient filter tested (ii) 20 mls amniotic fluid must be filtered to achieve the same number of clones in culture as early amniocentesis, (iii) filtered cells could be cultured and karyotyped in a similar time interval to early amniocentesis, (iv) amnifiltration was not associated with bacterial or viral contamination of the amniotic fluid and did not significantly change the urea, electrolytes, proteins and enzyme concentration . The safety and diagnostic accuracy of early amniocentesis remains to be determined by a randomised trial, but preliminary outcome results demonstrate comparable rates of livebirths following early amniocentesis and chorion villus sampling (92% versus 93.8%). However, fetal losses were higher following early amniocentesis than after chorion villus sampling (5.2% versus 1.2%).

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