Aneuploidy in human granulosa lutein cells obtained from gonadotrophin-stimulated follicles and its relation to intrafollicular hormone concentrations

Proliferation of granulosa cells is inversely related to differentiation an d hormone production. The purpose of this study was to evaluate the intrafo llicular and serum steroid concentrations and to compare these results to g ranulosa cell proliferation as measured by DNA flow cytometry, Human granul osa lutein cells in follicular fluid of in-vitro fertilization (IVF) patien ts were investigated with regard to ploidy, percentage of S-phase cells and proliferation index (PI: percentage of cells in the S- and G(2)/M-phase). The study was originally designed to indicate an additional marker for the outcome of IVF treatment by DNA flow cytometric measurements of granulosa l utein cells, Follicular fluids of 160 follicles (45 patients) were evaluate d; 45.6% (n = 73) of the follicles showed aneuploid granulosa lutein cells and 5.6% (n = 9) of the follicles contained multiploid granulosa cells, def ined as at least two aneuploid populations of cells with different DNA indi ces. A total of 48.8% (n = 78) of the follicles had only diploid cells. Thu s >50% of the investigated follicles showed aneuploidy, In all, 73% (33 of 45) of patients had at least one follicle containing aneuploid granulosa lu tein cells. The PI of the aneuploid cell populations significantly exceeded that of the diploid cell populations (median: aneuploid: 15.5; diploid: 7. 4; P < 0.0001). The intrafollicular concentrations of testosterone, progest erone and dehydroepiandrosterone sulphate (DHEA-S) were significantly lower in follicles with aneuploid granulosa cell populations, Luteinizing hormon e concentration was significantly higher in follicles with aneuploid granul osa cells. Intrafollicular concentrations of oestradiol, follicle stimulati ng hormone and the serum concentrations of all steroid hormones did not sho w any significant correlation to ploidy, Although aneuploidy has been repor ted for oocytes (in similar to 17% of the oocytes), no study, to our knowle dge, has observed such a high incidence of aneuploidy in granulosa lutein c ells after gonadotrophin stimulation. Except for aneuploidy found in tissue s with some characteristics of neoplastic growth (colon adenoma, borderline tumours, endometriosis with atypic cells, etc.), it is unique for non-mali gnant human cells, The correlation with intrafollicular steroid concentrati ons points to a possible pathophysiological or physiological relevance of t hese findings. However, it was impossible to correlate the outcome of IVF w ith DNA flow cytometry results.