DOI: 10.1111/1471-0528.

16107 Systematic review

www.bjog.org

Endometriosis fertility index for predicting non-

assisted reproductive technology pregnancy
after endometriosis surgery: a systematic review
and meta-analysis
S Vesali,a M Razavi,b M Rezaeinejad,c A Maleki-Hajiagha,d S Maroufizadeh,e M Sepidarkishf,g
a
Reproductive Epidemiology Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran b Pregnancy Health Research
Centre, Department of Obstetrics and Gynaecology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran c Department of
Obstetrics and Gynaecology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran d Research Development Centre,
Arash Women’s Hospital, Tehran University of Medical Sciences, Tehran, Iran e School of Nursing and Midwifery, Guilan University of Medical
Sciences, Rasht, Iran f Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran
g
Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
Correspondence: Dr M Sepidarkish, Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical
Sciences, Ganjafrooz Street, Babol 47176-47745, Iran. Email: Mahdi.sepidarkish@gmail.com

Accepted 13 January 2020. Published Online 19 February 2020.

Background Results of studies that have assessed the accuracy of
the endometriosis fertility index (EFI) for predicting non-assisted
reproductive technology (ART) pregnancy are inconsistent.
Objective We intended to evaluate the accuracy of EFI for the
prediction of non-ART pregnancy.
Search strategy Embase, Medline, Scopus and Web of Science
were searched up to 5 October 2019.
Selection criteria We included studies that used EFI to predict
non-ART pregnancy in women with surgically documented
endometriosis.
Data collection and analysis A total of 5547 studies were
identified, from which we included 17 studies on 4598 women in
the meta-analysis. Eight studies were classified as good quality,
and the rest were considered to be of fair quality. Only five
(29.41%) studies used appropriate approaches to account for
potential confounders. Pooled effect sizes with corresponding 95%
CI were calculated using random-effects model.
Main results The cumulative non-ART pregnancy rate at
36 months was 10% (95% CI: 3, 16%; P < 0.001) for women with
an EFI of 0–2, which significantly increased to 69% (95% CI: 58,
79%; P < 0.001) for women with an EFI of 9–10. Compared with
women with an EFI of 3–4 (18%, 95% CI: 12, 24%; P < 0.001), the
combined cumulative non-ART pregnancy rates were 44% (95% CI:
26, 63%; P < 0.001) for women with an EFT of 5–6 and 55% (95%
CI: 47, 64%; P < 0.001) for women with an EFI of 7–8. Paired
comparison by the chi-square test showed a significant difference
between all categories (P < 0.001). The odds ratio (OR) for EFI was
1.33 (95% CI: 1.17, 1.49, P < 0.001) and the summary area under
the curve (AUC) was 72% (95% CI: 65, 80%, P < 0.001).
Conclusion The current findings highlighted the good
performance of the EFI score in predicting the non-ART
pregnancy rate. However, these findings should be considered
with caution because of the substantial heterogeneity between
studies.
Keywords Endometriosis Fertility Index, meta-analysis,
pregnancy, systematic review.
Tweetable abstract Review findings show the merits of
Endometriosis Fertility Index as having a prognostic ability for
non-assisted reproductive technology pregnancy.
Linked article This article is commented on by C Tomassetti,
p. 810 in this issue. To view this mini commentary visit
https://doi.org/10.1111/1471-0528.16180.

Please cite this paper as: Vesali S, Razavi M, Rezaeinejad M, Maleki-Hajiagha A, Maroufizadeh S, Sepidarkish M. Endometriosis fertility index for predicting
non-assisted reproductive technology pregnancy after endometriosis surgery: a systematic review and meta-analysis. BJOG 2020;127:800–809.

endometrium-like tissue outside the uterus. The main

Introduction
Endometriosis is a common pelvic disease that affects 10–
15% of reproductive-age women.1 It is associated with an
inflammatory condition characterised by lesions of
symptoms of endometriosis are infertility and dysmenor-
rhoea. Among infertile women, 25–50% have endometrio-
sis, of whom 30–50% are infertile.2–5 In European and
American guidelines,6,7 the management of endometriosis-

800 ª 2020 Royal College of Obstetricians and Gynaecologists


associated infertility is based on the disease stage defined
according to the revised American Fertility Society score
(rAFS) or the American Society of Reproductive Medicine
classification.8,9 The rAFS classification is useful for
expressing the severity of endometriosis and has been used
to predict the recurrence potential of endometriosis after
surgery.10 However, this classification has limitations,
including failure to predict the postoperative pregnancy
rate and to account for the different types of endometriotic
lesions.11–15
For these reasons, Adamson and Pasta published the
first validated and predictive endometriosis staging system,
the endometriosis fertility index (EFI), in October 2010,
to estimate the natural conception rate after laparoscopic
surgery for endometriosis. It is a scoring system that
ranges from 0 to 10, from lowest to highest probability
of a natural pregnancy. The EFI staging system includes
historical factors of age, length of infertility, previous
pregnancy and surgical factors of the AFS total score, AFS
endometriosis lesions and the least function score as the
anatomical and functional result of the surgery on the
reproductive fallopian tubes, fimbriae and ovaries. Of
note, the rAFS score accounts for only 20% of the EFI
score, but the EFI includes all of the components of the
rAFS stage score.16 However, the EFI does not consider
whether the woman underwent in vitro fertilisation (IVF)
after surgery for endometriosis.17 The benefit of the EFI
score is to help practitioners choose between assisted
reproductive technology (ART) and non-ART manage-
ment after laparoscopic surgery.13 All studies conducted
on this new system reported that this scoring tool would
be able to meet most of the requirements for staging cri-
teria. The EFI score has been validated as clinically useful
among women with surgically documented endometriosis,
though its predictive value needs to be confirmed. There-
fore, the objective of this systematic review and meta-
analysis was to identify and determine the accuracy of the
EFI scores to predict non-ART pregnancy in women with
surgically documented endometriosis who attempted con-
ception.
Methods
Eligibility criteria
The present systematic review was conducted according to
the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) guidelines. This review included
relevant diagnostic epidemiological (case–control or two-
arm cohort) studies that used EFI to predict non-ART
pregnancies in women with surgically documented
endometriosis who attempted conception. We excluded the
following studies: (i) review articles; and (ii) case series,
ª 2020 Royal College of Obstetricians and Gynaecologists
Endometriosis fertility index for predicting pregnancy
case reports, editorials, or letters to the editor that did not
include original data; and (iii) lacked adequate information
to accurately calculate the test estimates. If there were
duplicate publications, we included the most complete ver-
sion or the paper with the highest number of participants.
The EFI is a clinical tool used to predict non-ART preg-
nancy after endometriosis surgery. Although it is the only
system that is predictive of fertility, EFI is not a staging
system. EFI has six levels and separately uses the 1985 rAFS
staging system total and endometriosis sub-total scores. EFI
scoring is based on history (50%), surgical findings after
surgery (30%) and rAFS scores (20%).
Search strategy
A comprehensive computerised search to identify all pub-
lished original articles on the subject was performed with
the use of Embase, Medline (by PubMed), Scopus and
Web of Science bibliographic databases (inception, October
2019). We also hand-searched the references and citation
lists of pertinent articles using Google Scholar. Moreover,
investigators and specialists in the field were consulted for
additional potential studies. We also checked review articles
published on endometriosis and their reference lists for
possible unpublished research on the topic and additional
relevant citations. No language restrictions were made to
be as sensitive as possible. The search details are listed in
the Supplementary material (Appendix S1).
Study selection and data extraction
Two of the authors (MS and SV) independently screened
the titles and abstracts of all potentially relevant citations
according to the predetermined inclusion and exclusion
criteria. Any citation identified by either of the review
authors was selected for full-text review. Discrepancies were
resolved through discussion between the review authors or
arbitration by a third review author (AM). Final inclusion
decisions were made based on an examination of the full
manuscripts. The following characteristics were extracted
from each article: authors, setting, the period in which the
study was performed, study design (prospective versus ret-
rospective cohort study), sample size, adjusted confounders
and data to calculate accuracy estimates.
Assessment of methodological quality
The included studies were critically appraised by two
review authors (MS and SV) using the Newcastle–Ottawa
Scale (NOS) for included studies, which is a validated tool
for observational studies. The NOS consists of three com-
ponents for quality: (i) selection of the study groups; (ii)
comparability of the groups; and (iii) ascertainment of the
outcome of interest. The NOS assigns a maximum of four
points for selection, two points for comparability and three
points for exposure or outcome.
801
 Vesali et al.
Primary outcome and statistical analysis
The primary outcome of this systematic review was non-
ART clinical pregnancy, which we defined as the develop-
ment of a gestational sac visualised by transvaginal ultra-
sonography after ovulation. The EFI score ranges from 0 to
10, with 0 representing the poorest prognosis and 10 the
best prognosis. Based on Adamson, the EFI score was strat-
ified into five categories: 0–2, 3–4, 5–6, 7–8 and 9–1016.
We calculated the combined non-ART pregnancies in the
EFI categories. Summary and individual estimates (propor-
tion of non-ART pregnancies) were presented graphically
with the 95% CIs by a forest plot based on the EFI cate-
gories. As none of the studies reported sensitivity and
specificity, we could not calculate accuracy indicators such
as summary receiver operating characteristic curves, posi-
tive predictive value, negative predictive value, positive or
negative likelihood ratios, and the diagnostic odds ratio for
a predefined reference standard outcome. Therefore, accu-
racy for EFI was determined by the available parameters of
the area under the curve (AUC) and adjusted odds ratio
(OR), with 95% CIs. The AUC and adjusted odds ratio for
predicting pregnancy were pooled using random-effects
models with the DerSimonian–Laird estimator. The results
of the included studies were tested for statistical hetero-
geneity by visual examination of both forest plots and
using the Higgins index (I2). I2 describes the percentage of
the variability in effect estimates that is due to heterogene-
ity rather than sampling error. Guidelines were categorised
as: might not be important (0–40%), moderate heterogene-
ity (30–60%), substantial heterogeneity (50–90%) and con-
siderable heterogeneity (75–100%). We used the chi-square
test to assess the heterogeneity of the results between differ-
ent studies. Statistical analyses were performed using the
STATA/SE 13 package (Stata Corporation, College Station,
TX, USA) for Windows.
Patient involvement
Because the meta-analysis used already published data,
there was no requirement for patient involvement.
Funding
No financial support was received for this study.
Results
Selection, characteristics and quality of studies
We found 5547 records. After the removal of the dupli-
cates, there were 2428 evaluable records. Of these, 51
abstracts remained for full-text assessment and 24 full
papers for evaluation. We excluded seven papers for vari-
ous reasons (see Supplementary material, Figure S1).
Therefore, 17 articles were assessed qualitatively and quan-
titatively in the current systematic review and meta-
802
analysis. Table S1 (see Supplementary material) sum-
marises the main characteristics of the studies included in
the systematic review. There were four prospective and 13
retrospective studies. Nine observational studies were car-
ried out in China18–26, three in France13,27,28 and one each
in the USA16, Belgium17, Italy29, Australia30 and Japan31.
Regarding language, two studies were in Chinese, and the
others were in English. Sample sizes ranged from 40 to
1097 women with endometriosis who underwent laparo-
scopic surgery. Table S2 (see Supplementary material)
shows the methodological quality of the included studies.
There were nine studies classified as good and seven were
of fair quality. Only five (27.77%) studies adopted appro-
priate approaches to account for potential confounders.
Most of the included studies had a moderate risk of selec-
tion bias. Only six studies selected their exposed and non-
exposed participants from the same community sample.
All cohort studies provided adequate criteria for the diag-
nosis of the outcomes of interest and provided a proper
description of how the outcomes were measured. All
studies were classified as no risk of ascertainment of expo-
sure.
Cumulative non-ART pregnancy based on EFI
categories
We identified eight published studies that reported the
cumulative non-ART pregnancy rate in five standard EFI
categories. The combined results of these studies that
included 3199 participants indicated that EFI had a direct
association with a cumulative natural pregnancy rate. The
cumulative non-ART pregnancy rate at 36 months was
10% (95% CI: 3, 16%; P < 0.001) for women with an EFI
of 0–2 and significantly increased to 69% (95% CI: 58,
79%; P < 0.001) for women with an EFI of 9–10. Com-
pared with women with an EFI of 3–4 (18%, 95% CI: 12,
24%; P < 0.001), the combined cumulative non-ART preg-
nancy rate was 44% (95% CI: 26, 63%; P < 0.001) for
women who had an EFI of 5–6 and 55% (95% CI: 47,
64%; P < 0.001) for the women with an EFI of 7–8. Paired
comparison by the chi-square test showed a significant dif-
ference between all categories (P < 0.001). The tests of
homogeneity (P < 0.10) and I2 statistics indicated consider-
able heterogeneity for the EFI categories of 5–6
(I2 = 96.74%, P < 0.001), 7–8 (I2 = 87.36%, P < 0.001)
and 9–10 (I2 = 90.39%, P < 0.001).There was no hetero-
geneity found for the EFI category of 0–2 (I2 = 0%,
P = 0.95) and non-significant heterogeneity for the EFI cat-
egory of 3–4 (I2 = 38.84%, P = 0.12). Figures 1–3 sum-
marise the combined cumulative non-ART pregnancy rates
with 95% CI, classified by EFI scores during a 36-month
follow up in eight studies. There was no evidence of publi-
cation bias (Egger’s regression intercept = 1.04, 95% CI:
7.08, 9.17; P = 0.755).
ª 2020 Royal College of Obstetricians and Gynaecologists
 Endometriosis fertility index for predicting pregnancy

A %
Study ES (95% CI) Weight Proportion

Adamson (2010) 0.11 (0.01, 0.35) 19.20 2/18

Zeng (2014) 0.08 (0.00, 0.38) 16.55 1/12

Boujenah (2015) 0.50 (0.01, 0.99) 0.84 1/2

Jinling (2015) 0.20 (0.01, 0.72) 3.29 1/5

Li-qing (2017) 0.07 (0.00, 0.34) 22.24 1/14

Maheux-Lacroix (2017) 0.11 (0.00, 0.48) 9.60 1/9

Jing-jing (2018) 0.07 (0.00, 0.34) 22.24 1/14

Zhang (2018) 0.14 (0.00, 0.58) 6.02 1/7

Overall (I2 = 0.00%, P = 0.95) 0.10 (0.03, 0.16) 100.00

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Proportion

B %
Study ES (95% CI) Weight Proportion

Adamson (2010) 0.24 (0.15, 0.36) 17.75 17/71

Zeng (2014) 0.33 (0.12, 0.62) 5.39 5/15

Boujenah (2015) 0.05 (0.00, 0.25) 18.40 1/20

Jinling (2015) 0.22 (0.03, 0.60) 4.32 2/9

Li-qing (2017) 0.24 (0.13, 0.40) 13.78 11/45

Maheux-Lacroix (2017) 0.20 (0.07, 0.41) 10.33 5/25

Jing-jing (2018) 0.15 (0.04, 0.34) 12.73 4/27

Zhang (2018) 0.18 (0.09, 0.31) 17.30 10/55

Overall (I2 = 38.84%, P = 0.12) 0.18 (0.12, 0.24) 100.00

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Proportion
Figure 1. Forest plot displaying the cumulative non-ART pregnancy with 95% CIs, classified by EFI scores during a 36-month follow up; (A) EFI score
0–2, (B) EFI score 3–4. ART, assisted reproductive technology; EFI, endometriosis fertility index; ES, effect size.

EFI for prediction of natural pregnancy EFI for prediction of non-ART pregnancy varied between
We retrieved eight studies that had a total of 2082 patients 64% (95% CI: 56, 72%) and 85% (95% CI: 79, 91%).
in which the AUC with 95% CI was reported. The AUC of Meta-analysis revealed a pooled AUC of 71% (95% CI: 65,

ª 2020 Royal College of Obstetricians and Gynaecologists 803

 Vesali et al.

A %
Study ES (95% CI) Weight Proportion

Adamson (2010) 0.50 (0.43, 0.57) 12.90 109/219

Zeng (2014) 0.47 (0.31, 0.64) 11.95 18/38

Boujenah (2015) 0.35 (0.25, 0.46) 12.61 30/85

Jinling (2015) 0.21 (0.09, 0.38) 12.24 7/34

Li-qing (2017) 0.94 (0.81, 0.99) 12.84 34/36

Maheux-Lacroix (2017) 0.34 (0.24, 0.45) 12.61 28/83

Jing-jing (2018) 0.43 (0.27, 0.61) 11.94 16/37

Zhang (2018) 0.28 (0.22, 0.35) 12.92 55/194

Overall (I2 = 96.74%, P = 0.00) 0.44 (0.26, 0.63) 100.00

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Proportion

%
B
Study ES (95% CI) Weight Proportion

Adamson (2010) 0.67 (0.61, 0.72) 14.33 214/320

Zeng (2014) 0.48 (0.35, 0.60) 11.36 31/65

Boujenah (2015) 0.42 (0.34, 0.50) 13.47 70/167

Jinling (2015) 0.48 (0.36, 0.60) 11.68 35/73

Li-qing (2017) 0.63 (0.53, 0.72) 12.74 67/107

Maheux-Lacroix (2017) 0.60 (0.47, 0.71) 11.74 43/72

Jing-jing (2018) 0.72 (0.55, 0.86) 10.19 26/36

Zhang (2018) 0.47 (0.42, 0.52) 14.49 211/450

Overall (I2 = 87.36%, P = 0.00) 0.55 (0.47, 0.64) 100.00

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Proportion

Figure 2. Forest plot displaying the cumulative non-ART pregnancy with 95% CIs, classified by EFI scores during a 36-month follow up; (A) EFI score
5–6, (B) EFI score 7–8. ART, assisted reproductive technology; EFI, endometriosis fertility index; ES, effect size.

804 ª 2020 Royal College of Obstetricians and Gynaecologists

 Endometriosis fertility index for predicting pregnancy

%
Study ES (95%
ES (95% CI)
CI) Weight
Weight Proportion

Adamson (2010) 0.75 (0.68,

0.75 (0.68, 0.81)
0.81) 13.89
13.89 130/173

Zeng (2014) 0.65 (0.45,

0.65 (0.45, 0.81)
0.81) 10.74
10.74 20/31

Boujenah (2015) 0.57 (0.45,

0.57 (0.45, 0.68)
0.68) 12.65
12.65 44/77

Jinling (2015) 0.54 (0.41,

0.54 (0.41, 0.67)
0.67) 12.19
12.19 33/61

Li-qing (2017) 0.79 (0.60,

0.79 (0.60, 0.92)
0.92) 11.45
11.45 23/29

Maheux-Lacroix (2017) 0.64 (0.47,

0.64 (0.47, 0.79)
0.79) 11.35
11.35 25/39

Jing-jing (2018) 0.94 (0.80,

0.94 (0.80, 0.99)
0.99) 13.54
13.54 32/34

Zhang (2018) 0.58 (0.53,

0.58 (0.53, 0.63)
0.63) 14.19
14.19 228/391

Overall (I2 = 90.39%, P = 0.00) 0.69 (0.58,

0.69 (0.58, 0.79)
0.79) 100.00
100.00

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Proportion

Figure 3. Forest plot displaying the cumulative non-ART pregnancy with 95% CIs during a 36-month follow up for EFI score 9–10. ART, assisted
reproductive technology; EFI, endometriosis fertility index; ES, effect size.

80%; P < 0.001; Figure 4A). Studies were substantially
heterogeneous, with a small proportion of studies that were
outliers (v2 38.53, P < 0.001, inconsistency I2 = 79.2%).
There was no evidence of publication bias (Egger’s regres-
sion intercept = 0.60, 95% CI: 3.12, 4.33; P = 0.713). Fig-
ure 4(B) shows a forest plot of the pooled OR of EFI on
non-ART pregnancy. There were six studies with 1094 par-
ticipants that reported an with 95% CI. Meta-analysis
revealed a pooled OR of 1.33 (95% CI: 1.17, 1.49;
P < 0.001). There was non-significant heterogeneity
between studies (P = 0.178, I2 = 34.5%).
Sensitivity analysis
Sensitivity analysis showed that the pooled estimate of the
AUC did not vary considerably with the omission of any
one study; in particular, the exclusion of the study by Jing-
jing et al., which accounted for about 13.97% of all weights
in the meta-analysis, resulting in a pooled AUC of 66.12%
(95% CI: 63.69, 68.56%). The exclusion of the studies with
fair methodological quality did not impact the combined
effect size (AUC= 0.72, 95% CI: 0.62, 0.81%). We found
that the pooled estimate of the OR did not vary consider-
ably with the omission of any one study. The omission of
the study by Jing-jing et al. resulted in a pooled OR of
1.31% (95% CI: 1.18, 1.44%)25. The exclusion of the
studies with fair methodological quality did not affect the
combined effect size (OR= 1.29, 95% CI: 1.16, 1.42).
Discussion
Main findings
To the best of our knowledge, this is the first systematic
review and meta-analysis to report and provide evidence of
non-ART pregnancy prediction after endometriosis surgery
using EFI. The findings of the present study emphasised
the merits of the EFI as having a prognostic ability for
non-ART pregnancy. This new staging system predicts
pregnancy rates in women with surgically confirmed
endometriosis who attempt non-ART pregnancy (natural
intercourse or intrauterine insemination).16,17
Strengths and limitations of the study
The strengths of the study are the inclusion of studies from
a large number of countries (eight countries), which
allowed a much greater possibility of drawing generalisable
conclusions; the large number of studies (18 studies of
4797 women), which enabled a much greater possibility of
drawing precise conclusions; and inclusion of only cohort
studies, which could provide stronger evidence than other
observational studies and enable us to reach a more

ª 2020 Royal College of Obstetricians and Gynaecologists 805

 Vesali et al.

A
Study %
ID ES (95% CI) Weight

Tingting (2013) 0.71 (0.60, 0.82) 12.59

Ning (2014) 0.71 (0.59, 0.82) 12.07

Garavaglia (2015) 0.75 (0.61, 0.89) 10.64

Xiaohong (2015) 0.68 (0.53, 0.83) 9.82

Hobo (2017) 0.71 (0.58, 0.85) 10.76

Jing-jing (2018) 0.85 (0.79, 0.91) 15.62

Kim (2018) 0.71 (0.59, 0.83) 11.56

Zhang (2018) 0.65 (0.62, 0.68) 16.95

Overall (I2 = 80.9%, P = 0.000) 0.72 (0.65, 0.80) 100.00

NOTE: Weights are from random effects analysis

–0.914 0 0.914

Study %
ID ES (95% CI) Weight

Tomassetti (2013) 1.31 (1.16, 1.47) 35.66

Boujenah (2017) 1.62 (1.24, 2.15) 9.89

Boujenah (2017) 1.17 (0.98, 1.38) 28.99

Hobo (2017) 1.36 (1.08, 1.71) 17.34

Jing-jing (2018) 5.73 (2.57, 12.76) 0.10

Kim (2018) 1.57 (1.13, 2.17) 8.03

Overall (I2 = 34.5%, P = 0.178) 1.33 (1.17, 1.49) 100.00

NOTE: Weights are from random effects analysis

–12.8 0 12.8

Figure 4. Forest plot displaying the individual and pooled accuracy indices of EFI scores for predicting non-ART pregnancy; (A) AUC, (B) OR. ART,
assisted reproductive technology; AUC, area under a curve; EFI, endometriosis fertility index; ES, effect size; OR, odds ratio.

806 ª 2020 Royal College of Obstetricians and Gynaecologists


confident conclusion about the prognostic value of EFI in
non-ART pregnancy. Finally, the results from the quality
appraisal demonstrated that the methodological quality of
the included studies was generally good.
However, this systematic review and meta-analysis has
several limitations that need to be addressed. First, the
majority of studies included in this review did not ade-
quately report or present well-known measures of diag-
nostic indices alongside AUC, which made it difficult to
conduct the meta-analysis. It was not possible to pool
indicators such as sensitivity, specificity, positive predictive
value, negative predictive value, positive or negative likeli-
hood ratios, and the diagnostic odds ratio. Researchers,
who intend to conduct future studies in this field, should
present at the very minimum sensitivity and specificity
results to enable future comparisons. Furthermore, the
OR may not provide an objective or reliable measure of
diagnosis. Second, a number of the included studies
selected the exposed and non-exposed participants at the
beginning of the study. Results from these studies are
often criticised for being vulnerable to influences by selec-
tion bias because of the selection of appropriate non-ex-
posed participants. Selecting the appropriate group of
non-exposed participants can be one of the most chal-
lenging aspects of these studies. An important principle is
that the distribution of potential confounding variables
should be the same among exposed and non-exposed par-
ticipants; in other words, both groups should stem from
the same source population. Considering the nature of
the question, we have based this systematic review on the
data from observational studies, which are at higher risk
of confounding factors compared with randomised con-
trolled trials. The included studies in this meta-analysis
did not control for the same confounder variables. Several
studies did not control the effect of confounders. These
findings should be considered with caution because of the
substantial heterogeneity between studies.
Interpretation
In contrast, the existing rAFS system has substantial limita-
tions. This scoring system has arbitrary point scores, and
there are wide score ranges within the categories.14 There is
potential for observer error because of numerous morpho-
logical presentations, some subtle and microscopic, the
timing of the laparoscopy, and whether the staging is per-
formed at laparoscopy or laparotomy. This can affect the
accuracy of both the documentation and identification of
endometriomas.32,33 Limited reproducibility of the staging
has been reported with correlations of 0.38 for intraob-
server restaging and 0.52 for interobserver restaging.34 The
rAFS system does not provide any information about mor-
phological lesion type or age-related evolution, nor any
associations with hormones, pain, depth of lesions and the
ª 2020 Royal College of Obstetricians and Gynaecologists
Endometriosis fertility index for predicting pregnancy
possible appearance and disappearance of lesions.35 There
is a poor correlation between the extent of disease and pel-
vic pain.36 As well, rAFS stages correlate poorly with infer-
tility.37 EFI has been suggested to have greater predictive
power than rAFS for a successful pregnancy with or with-
out ART in women with endometriosis.8 It has been con-
firmed that the higher the EFI score, the higher the
probability of achieving a non-ART pregnancy or sponta-
neous pregnancy.13,30 So, natural conception is the first
choice for women with an EFI score of 6–10, whereas the
benefit of ART is greater for women with a low EFI score
in terms of non-ART pregnancy rates. Data from the litera-
ture could encourage natural conception or ART for
women with an EFI score of 4–5 according to their preg-
nancy desire and socio-economic status. In particular,
women with an EFI score of 0–3 should be informed about
the low possibility of non-ART pregnancy and ART should
be strongly advised.17,26,27 As suggested by Adamson and Li
et al., women with poor prognosis for non-ART pregnancy
or spontaneous pregnancy based on the EFI score could be
advised for IVF with embryo transfer earlier to prevent
treatment delays and optimise their chances for preg-
nancy.37,38 The non-ART pregnancy rate could be associ-
ated with duration before attempting ART. All previous
external validations of the EFI have shown a slower preg-
nancy rate after 9–12 postoperative months.16,17,27 How-
ever, guidelines and data such as the Cochrane review,39
did not focus on the duration between surgical treatment
for endometriosis and the establishment of the first preg-
nancy.40 As reported previously, the combined approach of
surgery and ART is an effective strategy to enhance the
pregnancy rate rather than surgery or ART alone13,41,42 and
it is associated with a higher non-ART pregnancy rate.13,43
EFI may be taken into consideration as a predictive factor
for a spontaneous second pregnancy for fertility manage-
ment.44 This finding was supported by the present meta-
analysis in which the pooled cumulative natural pregnancy
rate at 36 months was 9% for women with an EFI of 0–2
and increased to 17% for women with an EFI of 3–4. After
36 months of follow up, the pooled cumulative natural
pregnancy rate for women with an EFI of 9–10 was higher
than that of women with EFI of 5–6 and EFI of 7–8.
According to the present findings, the odds of natural preg-
nancy significantly increased in women with unit increases
in EFI. In the present meta-analysis, the pooled AUC of
EFI for prediction of non-ART pregnancy was equal to
0.71. This suggested that the EFI score had a greater ability
to predict non-ART pregnancy. Wang et al. conducted a
diagnostic accuracy study to compare the predictive value
of the EFI with that of the rAFS classification for IVF out-
comes in women with endometriosis. Regarding receiver
operating characteristics curve of pregnancy in fresh IVF
cycles for the EFI score and rAFS classification subsection,
807
 Vesali et al.
they found that the AUC of the EFI score (AUC 0.64) was
larger than that of the rAFS classification (AUC 0.44).10
This suggested that the EFI score had a greater ability to
predict clinical pregnancy rate than rAFS.
Conclusion
In this study, we observed that the EFI score could success-
fully predict the non-ART pregnancy rate after laparoscopy.
In conclusion, women with a high EFI score had a higher
chance of a non-ART pregnancy compared with women
with a low EFI score. However, these findings should be
considered with caution because of the substantial hetero-
geneity between studies.
Disclosure of interests
None. Completed disclosure of interests forms are available
to view online as supporting information.
Contribution to authorship
SV and MS formulated the idea for conducting the sys-
tematic review, performed the meta-analysis and wrote
the initial draft; MR, MR and SM performed literature
searches, study selection, data extraction and risk of bias
assessment; AM-H solved disagreements regarding study
selection and risk of bias assessment, and critically
revised the article.
Details of ethics approval
Ethics approval was not required for this research.
Funding
No financial support was received for this study.
Acknowledgments
None.
Supporting Information
Additional supporting information may be found online in
the Supporting Information section at the end of the
article.
Figure S1. Flow diagram of study inclusion.
Table S1. The study characteristics.
Table S2. Results of the critical appraisal of the included
studies.
Appendix S1. Search strategy. &
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