Original Article Received: May 13, 2014 Accepted after revision: August 6, 2014 Published online: January 27, 2015

Gynecol Obstet Invest 2015;79:113–118 DOI: 10.1159/000366443

External Validation of the Endometriosis Fertility Index (EFI) for Predicting Spontaneous Pregnancy after Surgery: Further Considerations on Its Validity Elisabetta Garavaglia a Luca Pagliardini a Iacopo Tandoi b Cristina Sigismondi b Paola Viganò a Stefano Ferrari a Massimo Candiani b   





Obstetrics and Gynecology Unit and b Vita-Salute University, Milano, IRCCS San Raffaele Scientific Institute, Milano, Italy  


Key Words Endometriosis · Fertility · Score · Assisted reproduction technology

Abstract Background/Aims: The revised American Society for Reproductive Medicine classification of endometriosis has a limited predictive value for pregnancy after surgery. A tool for predicting spontaneous pregnancy or pregnancy following assisted reproduction technology (ART) represents a clinical need. This study aimed to (i) provide an external validation of the EFI score in predicting pregnancy in infertile Italian endometriosis women; (ii) evaluate the predictive value of EFI score on ART outcome for patients who previously attempted to spontaneously conceive after surgery. Methods: In 104 women with endometriosis, EFI score was calculated based on a prospective database data. Cumulative pregnancy rates curves were calculated using Kaplan-Meier (K-M) product limit estimate and log-rank test was used to evaluate differences between EFI groups. A receiver operating characteristic (ROC) curve was plotted for EFI as a predictor of ART outcome. Results: Differences in time to non-ART

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pregnancy for the six EFI groups were statistically significant (log-rank, p = 1.4 × 10–4). The area under the curve (AUC) for EFI as ART outcome predictor was 0.75 (95% CI 0.61–0.89, p = 6.2 × 10–3), while the best cut-point for pregnancy was 5.5. Conclusion: The EFI score is a reliable scoring system to predict non-ART and ART pregnancy outcome after surgery for endometriosis. © 2015 S. Karger AG, Basel


The role of surgery in the management of infertile women with endometriosis is currently a matter of debate. Indeed, while the growing popularity and widespread diffusion of operative laparoscopy has resulted in an increase of surgical procedures in women with endometriosis, the current management modalities have been introduced in the standard practice based mainly on uncontrolled studies especially for moderate to severe disease [1–4]. The decisions at the basis of the surgical excision are mostly derived from clinical guidelines and expert opinions rather than on statistical prediction models Dr. Paola Viganò Obstetrics and Gynecology Unit Scientific Institute San Raffaele Via Olgettina, 60, IT–20132 Milano (Italy) E-Mail vigano.paola @ hsr.it

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Gynecol Obstet Invest 2015;79:113–118 DOI: 10.1159/000366443

gated. This with the general purpose to meet the clinical need to identify a valuable tool to be used to counsel infertile endometriosis patients receiving reproductive surgery about the various postoperative pregnancy options that could be of use to them.

Materials and Methods Study Population: Patient Selection From September 1st 2008 onward, data on anamnesis, surgical findings and postoperative short- and long-term outcomes, particularly fertility outcome, of patients affected by endometriosis and operated at the Gynecological division of San Raffaele Hospital, Italy were collected prospectively in a database. Indication to surgery was proposed to infertile young women with signs suggestive of endometriosis at physical examination and ultrasound or symptomatic women with signs suggestive of endometriosis at physical examination and ultrasound, not responsive to medical therapy. The hospital represents a tertiary referral center for endometriosis and reproductive surgery. The laparoscopic approach was the first choice surgical approach. Concerning the postoperative management, in case of operated women with at least a unilaterally normal tubal function and a male partner with a normal sperm analysis, spontaneous conception was recommended for 12 months. After 12 months of failed spontaneous conception or immediately after the intervention in case of possible compromised ovum pick-up, bilateral and several tubal disorders or major sperm disorders ART was suggested. The primary outcome was to calculate the cumulative nonART pregnancy rate after surgery for endometriosis, thus validating the EFI score. The secondary outcome was to evaluate the predictive value of EFI score on pregnancy outcome of cumulative ART cycles for patients who previously attempted to obtain a spontaneous pregnancy after surgery. All women undergoing a surgical intervention routinely provide informed consent for their clinical data and anonymised records to be used for research purposes in general. Local Institutional Review Board approvals for the use of clinical data for research studies were obtained. Statistical Analysis The EFI was calculated as previously reported, with EFI scores ranging from 0 for the poorest prognosis to 10 for the best prognosis. Analysis was then conducted using the same six EFI groups (group 1: EFI scores 0–3; group 2: EFI score 4; group 3: EFI score 5; group 4: EFI score 6; group 5: EFI scores 7–8; group 6: EFI scores 9–10) reported by Adamson and Pasta (2010) in order to enhance comparability [7]. Cumulative pregnancy rate curves for the 24 months subsequent to surgery were calculated using Kaplan-Meier (K-M) product limit estimate and presented as percentage ± SE. The event was considered clinical pregnancy defined as the ultrasound evidence of an intrauterine gestational sac with viable fetus [10]. For this analysis, subjects were censored when they were lost to follow-up, had subsequent surgery for recurrent endometriosis, started ovarian suppression medication or underwent ART. Log-rank test was used to test for significant

Garavaglia/Pagliardini/Tandoi/ Sigismondi/Viganò/Ferrari/Candiani

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[5]. As a matter of fact, surgical removal of the lesions may be ineffective. Indeed, surgery may not surmount all the local biomolecular alterations associated with the endometriosis-related chronic inflammation and it may not adequately repair some of the detrimental effects of the disease. Importantly, the existence of valid alternatives to surgery such as Assisted Reproduction Techniques (ART) complicates further the scenario [6]. In this context, one of the major issues is represented by the lack of valid tools that allow the possibility to predict effectively the clinical outcomes of the surgical treatment in terms of fertility potential. This complicates the clinical decision also after surgery in relation to the opportunity of deferring or not ART treatment. Given this scenario, in 2010 Adamson and Pasta proposed the endometriosis fertility index (EFI) as a novel scoring system able to predict spontaneous conception after endometriosis surgery [7]. EFI combines the evaluation of conception-related factors such as age, duration of infertility and gravidity history with a detailed functional score of fallopian tubes, fimbriae of fallopian tubes and ovaries calculating the least-function scores, and the severity of the disease. The result is a 10-point scale in which half of the points have its source in historical factors and half in surgical factors. After its establishing, testing and internal validation in an American population, the system has been validated externally in  populations of infertile endometriosis patients in Belgium [8] and in China [9]. According to the external validation in Belgium, a highly significant relationship could be found between EFI and the time to spontaneous conception with an estimation of cumulative pregnancy rate at 12 months after surgery equal to 45.5% ranging from 16.6% for EFI scores from 0 to 3 to 62.5% for EFI scores from 9 to 10. Among all the factors considered, the least-function score was the most important contributor to the EFI score. On the other hand, the general performance of the score in terms of predictive accuracy and discriminative ability resulted in a moderate value [8]. According to the Chinese study, the cumulative pregnancy rate at 36 months after surgery ranged from 8.3% for EFI scores from 0 to 3 to 60.9% for EFI scores from 8 to 10 [9]. On this basis, this study aimed firstly to provide a further external validation of the EFI score in predicting spontaneous pregnancy in a population of infertile Italian women with endometriosis. Moreover, the validity of the EFI score in predicting pregnancy outcome of cumulative ART cycles for patients who previously attempted to obtain a spontaneous pregnancy after surgery was investi-

Patients were selected from the database of operated patients for any stage of endometriosis, from January 1st 2010 to January 1st 2013, in order to have at least one year of follow-up to be able to report on fertility outcome. The patients suffering from endometriosis who desired to become pregnant after the surgery were 121 in number. The patients who tried to become pregnant with ART after the surgery without a period of spontaneous childbearing were excluded from analysis. Therefore, 104 patients were eligible for EFI validation analysis. The EFI score was calculated for these patients based on the data containing information about general, surgical and particularly fertility/infertility history. The basic characteristics of women included in the study group are summarized in table 1. The median EFI score was 7 and the distribution for the EFI scores of the population studied is shown in figure 1. Cumulative spontaneous clinical pregnancy rate calculated using K-M estimates for all the patients was 35.7 ± 5.1% and 44.6 ± 6.5% at 12 and 24 months, respectively. Figure 2 shows cumulative pregnancy rates as a function of EFI. Differences in time to non-ART pregnancy for the six EFI groups was highly statistically significant (logrank p = 1.4 × 10-4). Cumulative pregnancy rates with relative standard errors at 12 and 24 months are summarized in table  2. It is interesting to note that only 19.9% of the total pregnancies estimated was achieved in the second year and that no spontaneous pregnancies were  reported for patients with an EFI score less or equal to 4. The subjects who tried to conceive spontaneously (mean months of childbearing 11.2 ± 0.85) and then underwent ART procedures (n = 44) were then analyzed in order to evaluate if EFI was also a good predictor of the ART outcomes. Since ART outcome is not a time-dependent event [11], ROC curve analysis was used to analyze these data (fig. 3). The area under the curve (AUC) for Endometriosis Fertility Index in Predicting ART and Non-ART Pregnancy















Endometriosis fertility index score

Fig. 1. Distribution of patients according to their endometriosis

fertility index score.

Table 1. Characteristics of the women included in the study. Vari-

ables marked with an asterisk are used to calculate the EFI score n/total (%) unless shown otherwise Age at surgery, mean ± SD ≤35 years* 36–39 years* ≥40 years* At least one previous therapeutic surgery for endometriosis At least one previous failed IUI cycle At least one previous failed ART cycle Duration of infertility (months) median (min–max) >3 years* ≤3 years* Prior pregnancy No* Yes* Least function score High score (7–8)* Moderate score (4–6)* Low score (1–3)* AFS endometriosis lesion score

External validation of the endometriosis fertility index (EFI) for predicting spontaneous pregnancy after surgery: further considerations on its validity.

The revised American Society for Reproductive Medicine classification of endometriosis has a limited predictive value for pregnancy after surgery. A t...
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