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

Abstract

Can 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? 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. The 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. 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. The 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). All 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 C(τ). 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). The 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). As the EFI was validated externally in our own European population after initial testing by Adamson and Pasta (Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril 2010;94:1609-1615) in an American population, it appears that the EFI can be used clinically to counsel infertile endometriosis patients receiving reproductive surgery in specialized centers about their post-operative conception options. This research was supported by funds obtained via the Clinical Research Fund of the University Hospitals Leuven, Belgium, via the Ferring Chair in Reproductive Medicine and Surgery, and the Serono Chair in Reproductive Medicine granted to the Leuven University Fertility Center. The authors have no conflicts of interest to declare.