External validation of the endometriosis fertility index (EFI) staging system for predicting non-ART pregnancy after endometriosis surgery

摘要

Study Questio: NCan the ability of the endometriosis fertility index (EFI) to predict non-assisted reproductive technology (ART) pregnancy after endometriosis surgery be confirmed by an external validation study? Summary Answer: The significant relationship between the EFI score and the time to non-ART pregnancy observed in our study represents an external validation of this scoring system.WHAT IS KNOWN AND WHAT THIS PAPER ADDSThe EFI was previously developed and tested prospectively in a single center, but up to now no external validation has been published. Our data provide validation of the EFI in an external fertility unit on a robust scientific basis, to identify couples with a good prognosis for spontaneous conception who can therefore defer ART treatment, regardless of their revised American Fertility Society (rAFS) endometriosis staging. Design: Retrospective cohort study where the EFI was calculated based on history and detailed surgical findings, and related to pregnancy outcome in 233 women attempting non-ART conception immediately after surgery; all data used for EFI calculation and analysis of reproductive outcome had been collected prospectively as part of another study.PARTICIPANTS AND SETTINGThe EFI score was calculated (score 0-10) for 233 women with all rAFS endometriosis stages (minimal-mild, n = 75; moderate-severe, n = 158) after endometriosis surgery (1 September 2006-30 September 2010) in a university hospital-based reproductive medicine unit with combined expertise in reproductive surgery and medically assisted reproduction. All participants attempted non-ART conception immediately after surgery by natural intercourse, ovulation induction with timed intercourse or intrauterine insemination (with or without ovulation induction or controlled ovarian stimulation).DATA ANALYSIS METHODAll analyses were performed for three different definitions of pregnancy [overall (any HCG 25 IU/l), clinical and ongoing 20 weeks]. Six groups were distinguished (EFI scores 1-3, 4, 5, 6, 7+8, 9+10), and Kaplan-Meier (K-M) estimates for cumulative pregnancy rate were calculated. Subjects were censored when they were lost to follow-up, had subsequent surgery for endometriosis, started ovarian suppression or underwent ART. As K-M estimates might overestimate the actual event rate, cumulative incidence estimates treating ART as competing event were also calculated. Cox regression analysis was used to assess the performance of EFI and constituting variables. Performance of the score (prediction, discrimination) was quantified with the following methods: mean squared error of prediction (Brier score), areas under the receiver-operating curve and global concordance index Cτ. Main Results and the Role of Chance: There was a highly significant relationship between the EFI and the time to non-ART pregnancy (cumulative overall pregnancy rate, P = 0.0004), with the K-M estimate of cumulative overall pregnancy rate at 12 months after surgery equal to 45.5% [95% confidence interval (CI) 39.47-49.87]-ranging from 16.67% (95% CI 5.01-47.65) for EFI scores 0-3, to 62.55% (95% CI 55.18-69.94) for EFI scores 9-10. For each increase of 1 point in the EFI score, the relative risk of becoming pregnant increased by 31% (95% CI 16-47%; i.e. hazard ratio 1.31). The 'least function score'-which assesses the tubal/ovarian function at conclusion of surgery-was found to be the most important contributor to the total EFI score among all the other variables (age, duration of infertility, prior pregnancy, AFS endometriosis lesion and total score).BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTIONThe EFI score had a moderate performance in the prediction of the pregnancy rate. Indeed, the decrease in prediction error was rather small, as shown by the decrease in Brier score from 0.213 to 0.198, and low estimates for R2 (13%) and C τ (0.629).GENERALIZABILITY TO OTHER POPULATIONSAs the EFI was validated externally in our own European population after