Quantitative DNA perturbations of p53 in endometriosis: analysis of American and Icelandic cases.

OBJECTIVE: To investigate quantitative aberrations involving p53 copy numbers in eutopic endometrial and endometriotic tissue from two populations. DESIGN: Comparative analysis of normal and diseased tissue. SETTING: Tissue specimens collected in Iceland and USA. PATIENT(S): Subjects with moderate/severe endometriosis (Iceland, n = 26; USA, n = 45). Paraffin-embedded tissue from 19 matched Icelandic cases and seven unaffected controls. American cases were fresh surgical tissue from 17 matched cases and 28 unaffected controls. DNA isolation and real-time polymerase chain reaction (PCR) with TaqMan assay were performed. MAIN OUTCOME MEASURE(S): The frequency of p53 loss and/or gain based on quantitative differences for copy numbers of p53 located on chromosome (17p) and GAPDH on a control locus (chromosome 12p). RESULT(S): Among American cases, significant p53 gain (n = 13) or loss (n = 4) was observed in 17 of 21 cases. In Icelandic cases this was not seen to the same degree. Mean normalized p53 values were 3.46 and 1.16 copies per reaction, respectively. Significant differences were observed between normalized p53 in the control blood and affected tissue for the American and Icelandic cases compared to standard GAPDH control but not in normal Icelandic and American endometrium. CONCLUSION(S): The results continue to support a role for nonrandom somatic p53 locus alterations in the pathogenesis of late or severe-stage endometriosis. Differences between Icelandic and American subjects have implications for generalization of genome-wide approaches.

Ganirelix acetate use in normal- and poor-prognosis patients and the impact of estradiol patterns.

OBJECTIVE: To evaluate cycle outcomes in patients with either poor or normal prognosis undergoing IVF treatment with a GnRH antagonist (ganirelix acetate) for LH suppression. DESIGN: Nonrandomized, noncontrolled, retrospective review. PATIENT(S): 204 patients, aged 23-41 years, undergoing IVF. INTERVENTION(S): Patients completed 225 consecutive cycles of IVF with a GnRH antagonist (Antagon; Organon, Roseland, NJ) for LH surge prevention. Sixty cycles were conducted in patients with a known poor prognosis, whereas 165 were conducted in patients with a normal IVF prognosis. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR), for the series as a whole and according to prognosis, and serum E2 patterns. RESULT(S): The PR per initiated cycle for the series as a whole was 33.3%. The pregnancy rate was 42.1% per ET for the entire series, with a cycle cancellation rate of 21%. When evaluated by prognosis, the poor-prognosis patients had PRs of 8.3% per attempt and 15% per transfer, whereas the normal-prognosis patients had PRs of 40% per attempt and 45% per transfer. Pregnancy rate did not vary by E2 pattern (drop, plateau, or rise). Oral contraceptive pretreatment was noted to be associated with high cancellation rates in the group of known poor responders, whereas for the group as a whole, cycle outcome was unaffected by the use of oral contraceptives. CONCLUSION(S): Use of GnRH antagonists in patients with an a priori poor IVF prognosis results in predictably poor outcomes. Patients without factors predicting poor outcome have acceptable PRs. The pattern of E2 rise immediately after initiation of GnRH antagonists does not predict cycle outcome. Oral contraceptives can be successfully used to schedule antagonist-based IVF cycles but might increase the risk of cycle cancellation in some patient populations.