{"paper_id":"69861f53-4a4e-43fb-a958-61ff455d1d62","body_text":"ENDOMETRIOSIS (PA STRA TTON, SECTION EDITOR)\nThe Role of the Endometriosis Fertility Index (EFI)\nand Endometriosis Scoring Systems in Predicting Infertility\nOutcomes\nAndrew S. Cook & G. David Adamson\nPublished online: 27 June 2013\n# Springer Science+Business Media New Y ork 2013\nAbstract Many aspects of endometriosis continue to make\nit an enigmatic medical condition nearly a century after its\nfirst description as a specific disease. The Endometriosis\nFertility Index (EFI) is the first validated scoring system that\nis predictive of nonassisted reproductive technologies preg-\nnancy following surgical evaluation when the patient has\nfunctional gametes and uterus. Pregnancy rates decrease\nsignificantly in patients wit h decreased ovarian reserve,\nwhich is especially a problem in older patients and also, as\nreflected in the EFI, decrease over time if pregnancy does not\noccur in the first year or two following surgery. Patient\nmanagement algorithms using this information to assist in\ndeciding when to continue nonassisted reproductive technol-\nogies vs. assisted reproductive technologies attempts at con-\nception are presented.\nKeywords Endometriosis . Fertility . Index . Scoring .\nPrediction\nIntroduction\nMany aspects of endometriosis continue to make it an enigmatic\nmedical condition nearly a centuryafter its first description as a\nspecific disease. Our suboptimal understanding of this disease\ncompromises many aspects of patient care and quality of life,\nresulting in inefficient care and increased direct and economic\ncosts of endometriosis.\nThe primary presenting symptoms of endometriosis\nare infertility and/or pain. These, along with many other\nsymptoms (e.g., fatigue), can combine to reduce quality\nof life, productivity, and even the ability to function with\nbasic daily tasks.\nSeveral basic issues need to be elucidated to facilitate\nmore efficient and effective care. These include improved\ndiagnosis and staging of endometriosis. A simple-to-use,\nsensitive and accurate, noninvasive diagnostic test is a crit-\nical component of providing improved and more timely care\nto women with endometriosis. Discussion of improved diag-\nnostic testing is beyond the scope of this chapter. This\nchapter is focused on recent clinical advances in the ability\nto predict endometriosis fertility outcomes.\nIn general, a scoring or staging system is ideally based on\nscientific data providing both meaningful and consistent re-\nsults that are easy for the health care provider to understand\nand utilize. It should provide a measure of the impact of the\ndisease on the patient ’s functionality, predict future fertility,\npredict degree of pain relief with any given treatment, and\nprovide an estimate of risk of recurrence of endometriosis.\nHistorically, none of the endometriosis staging systems\nwas able to predict the chance of conception following\ntreatment until the Endometriosis Fertility Index (EFI) was\npublished in October 2010. The EFI is predictive of\nnonassisted reproductive technologies pregnancy following\nsurgical evaluation.\nSince publication of the EFI, recent studies continue to\nprovide additional information about factors that are helpful\nto expand our understanding from which a comprehensive\nfertility treatment plan can be created. This paper will review\nthis information and present an evidence-based/linked fertil-\nity treatment algorithm.\nA. S. Cook\nVital Health Institute, 14830 Los Gatos Blvd.,\nSuite 300, Los Gatos, CA 95032, USA\ne-mail: acook@vitalhealth.com\nG. D. Adamson ( *)\nFertility Physicians of Northern California,\n540 University Ave., Suite 200, Palo Alto,\nCA 94301, USA\ne-mail: gdadamson@arcfertility.com\nCurr Obstet Gynecol Rep (2013) 2:186 –194\nDOI 10.1007/s13669-013-0051-x\n\nOvarian Reserve, Oocyte Quality, and Age\nFundamentally both a viable male and female gamete is\nrequired for conception. Decreased ovarian reserve (DOR)\nis reflective of a decreasing quantity and quality of oocytes,\nembryos at assisted reproductive technologies (ART), and\nresulting fertility. In fact, DOR is currently the second lead-\ning cause of infertility [1]. DOR can be a result of a variety of\nfactors but is most commonly seen with advanced maternal\nage. Age of the female partner is one of the most important\nfactors influencing fertility [ 2]. Women who are older than\n35 years and have not conceived in 6 months should undergo\nexpedited evaluation and treatment [ 3–5]. Because decreas-\ning quality of female gametes and ability to result in suc-\ncessful pregnancy is irreversible, its status dictates much of\nthe treatment algorithm for fertility patients. Historically,\nreproductive success often has been a result of repeated\nexposure rather than efficiency. Successful fertility treatment\noften is a combination of increasing monthly fecundity along\nwith repeated attempts at pregnancy. Unfortunately, couples\npresenting with infertility issues often are at an age where\nDOR is or will soon become a significant factor in their\ntreatment.\nThe ASRM recently has produced a document that ad-\ndresses the complexity of DOR [ 6]. Currently, there is no\nuniformly accepted definition of DOR, as the term may refer\nto three related but distinctly different outcomes: oocyte\nquality, oocyte quantity, or reproductive potential. The doc-\nument did not address endometriosis specifically, and it may\nbe that endometriosis patients have both similarities and\ndifferences with respect to the populations described in the\nstudies used to reach the summary and concluding state-\nments. This document summarized that available evidence\nconcerning the performance of ovarian reserve tests is very\nlimited by small sample sizes and performance of the studies\nsuch that the study results cannot easily be applied in clinical\npractice. A screening test itself can have very different out-\ncomes depending on sensitivity and specificity characteris-\ntics and cannot diagnose decreased ovarian reserve. Overall,\nfollicle stimulating hormone (FSH) is the most commonly\nused screening test for DOR, but antral follicle count (AFC)\nand anti-müllerian hormone (AMH) are promising predic-\ntors. Home tests of ovarian reserve have serious limitations\nand easily can provide false reassurance or unnecessary\nanxiety and concern.\nThe document concluded that there is insufficient evi-\ndence to recommend that any ovarian reserve test now avail-\nable should be used as the sole criterion for use of ART. The\nnumber of false-positive test results will increase when\nscreening tests for decreased ovarian reserve are used in\nlow-risk populations. (It is not known whether endometriosis\npatients are low risk or high risk, but those with prior ovarian\nsurgery are likely in higher-risk populations.) There is fair\nevidence to indicate that FSH has high specificity, but low\nsensitivity, when a high cutpoint value is used for predicting\npoor response to ovarian stimulation or failure to conceive.\nThere is fair evidence to refute the notion that ovarian re-\nsponse or pregnancy rates will be improved in cycles in\nwhich the FSH concentration is normal among women pre-\nviously exhibiting abnormally elevated values. There is fair\nevidence that the basal estradiol concentration helps in the\naccurate interpretation of basal FSH concentrations used to\nscreen for decreased ovarian reserve. There is reasonable\nevidence to suggest that a clomiphene citrate challenge test\nhas mildly increased sensitivity to detect decreased ovarian\nreserve compared with basal FSH concentration. There is\nmounting evidence to support the use of AMH as a screening\ntest for poor ovarian response, but more data are needed.\nThere is emerging evidence to suggest that a low AMH level\n(e.g., undetectable AMH) has high specificity as a screen for\npoor ovarian response but insufficient evidence to suggest its\nuse to screen for failure to conceive. There is fair evidence to\nsupport that a low antral follicle count (3 –10) has moderate\nto high specificity as a screening test for poor ovarian re-\nsponse and insufficient evidence to support the use of AFC\nas a screening test for failure to conceive. There is insuffi-\ncient evidence to indicate that the combined results of mul-\ntiple screening tests for diminished ovarian reserve are more\nuseful than that of each test alone.\nGiven our current knowledge, a woman with rAFS stage\nIII–IV endometriosis, especially those with a history of\nendometrioma, should probably undergo ovarian reserve\ntesting, even at a young age [ 7]. An argument also can be\nmade for interval evaluation of women in their early to mid\n30s who are delaying pregnancy until age 35 to 40 years [ 8].\nPerhaps future studies will provide data about when we can\npredict the end of an individual woman ’s optimal fertility\nwindow years in advance, but current studies do not allow\nthis. Patient outcome and the overall economic burden of\nfertility treatment would be significantly improved if patients\nhad the necessary information to pursue pregnancy proac-\ntively before entering into DOR.\nOther Potential Issues Contributing to Infertility\nIn the uterus, congenital abnormalities, myomas, adenomyosis,\npolyps, and adhesions can contribute to reduced fertility\ndepending on the severity of the condition. Unfortunately,\nwhile severe congenital abnormalities, especially those with a\nsmall uterine cavity, or a uterine septum, are thought to reduce\nfertility, good studies to predict the impact of such conditions\nare not available. Similarly, while large myomas distorting the\nuterine cavity likely reduce fertility, the size, number, location,\nand impact of intramural myomas are not clearly defined.\nSevere adenomyosis likely reduces fertility, but studies proving\nCurr Obstet Gynecol Rep (2013) 2:186 –194 187\n\nthis are lacking. Polyps can almost certainly be problematic,\nbut the size and location that impact pregnancy are un-\nknown. Minimal intrauterine adhesions may have some im-\npact on pregnancy, whereas moderate and severe adhesions\ncertainly reduce the ability to conceive and have a successful\npregnancy. Therefore, these l esions should likely be treated\nhysteroscopically in some patients who have endometriosis,\nbut patient selection and the degree of improved outcome\nare difficult to assess [ 9–12].\nThe presence of hydrosalpinges makes pregnancy essen-\ntially impossible naturally, and salpingostomy carries preg-\nnancy rates of only 5 –30 %, with an average live birth rate\nprobably less than 20 %. Additionally, hydrosalpinges re-\nduce IVF pregnancy rates by approximately half. Therefore,\ntubal surgery for hydrosalpinges may occasionally be indi-\ncated in a favorable prognosis younger patient with limited\naccess to ART or for the patient undergoing ART who should\nhave salpingectomy or proximal tubal occlusion [ 13, 14].\nWith respect to the male, a normal semen analysis is one\nof the major factors to predict a better prognosis of concep-\ntion. The impact of only a fair semen analysis may be\nameliorated by attention to weight, medications, toxicants,\nheat, varicoceles, and other health factors. Intrauterine in-\nsemination may be of limited benefit in some patients.\nOverall, for severe male factor, IVF often is the only bio-\nlogic option, with donor insemination a potential alterna-\ntive. Men with semen abnormalities should be referred to an\nexpert in male infertility [ 15, 16]. Other factors can affect\nfemale fertility. Obesity is a major problem in many coun-\ntries, both developed and developing. The primary under-\nlying factor affecting fertility in obese women is ovulatory\ndysfunction [ 17, 18].\nCigarette smoking substantially affects fecundity and re-\nproduction. Reported effects include conception delay, ac-\ncelerated follicular depletion, a variety of effects on sperm\nparameters and increased miscarriage rates [ 19]. Other sys-\ntemic disease, such as diabetes mellitus or thyroid abnormal-\nities, should be managed appropriately.\nSurgery vs. ART for Endometriosis-Related Infertility\nThe highest pregnancy rates for women with endometriosis-\nrelated infertility are often achieved with a combination of\ntreatments utilizing both surgery and ART. This combined\ntreatment approach can provide significantly higher preg-\nnancy rates than either surgery or ART alone. Of the 825\npatients in a large study, 483 underwent surgery as the\nprimary option; 262 became pregnant (54.2 %). Of the\nsurgery patients who did not conceive, 144 underwent\nART, resulting in 56 pregnancies (30.4 %). The 318 com-\nbined total pregnancies from surgery and ART resulted in an\noverall pregnancy rate of 65.8 %. Sixty-eight of the 173\npatients undergoing ART as the first treatment option\nachieved pregnancy (32.2 %). Spontaneous pregnancy oc-\ncurred in 20 of the 169 patients (11.8 %) who received no\ntreatment. The mean time to pregnancy for the surgery pa-\ntients in this study was 11.2 months [ 20].\nMedical treatments are not indicated, either alone or fol-\nlowing surgery, for treatment of endometriosis-related infer-\ntility. The role and timing of surgery for infertility patients\nwith ovarian endometriomas is controversial. There is a deli-\ncate balance between the benefits of endometriomectomy,\nwhich have not been proven, and the possibility of causing\ndecreased ovarian reserve as a result of injury during removal\nof the endometrioma. ART as a primary treatment option is\ngenerally indicated in patients with decreased ovarian reserve\nand bilateral ovarian endometriomas. The presence of pelvic\npain, hydrosalpinges, and very large endometriomas may\nrequire surgery before ART. Patients who initially pursue\nART but are unsuccessful in achieving pregnancy should\nconsider undergoing surgery for treatment of their endometri-\nosis to improve their chance of conception spontaneously or\nwith the aid of additional ART. Generally, it is preferable to\nperform surgery first, if clinically indicated, and to perform\nART if pregnancy does not occur after 9–15 months. There are\nvery few patients for whom ART should be chosen as the first\ntreatment with a plan to follow with surgery if the ART is\nunsuccessful.\nThe Endometriosis Fertility Index Background\nAdamson and Pasta published the first validated and predic-\ntive endometriosis staging system in October 2010: the En-\ndometriosis Fertility Index (Fig. 1)[ 21]. The approach\nused to create this system was different than previous sys-\ntems. A comprehensive statistical analysis of prospectively\ncollected data from a large number of patients utilizing an\noutcome assessment for fertility revealed which variables\nwere predictive of pregnancy. This methodology was dis-\ntinctly different from the approach used in creation of previ-\nous endometriosis staging systems in which the authors\nmade assumptions of different variables usually based upon\nsurgical observations of various disease-related anatomic\nchanges.\nThe EFI was externally validated in a recent study [ 22].\nThe relationship between the EFI and non-ART pregnancy\nwas felt to be highly significant. The predictive accuracy and\ndiscriminative performance was moderate. Future studies\nmay find additional variables not currently included in the\nEFI that are predictive of pregnancy. Refinement of the EFI\nover time based on well-designed studies validating the\nbenefit of adding additional variables to the EFI may help\nfurther increase the accuracy and discriminative performance\nof this staging system.\n188 Curr Obstet Gynecol Rep (2013) 2:186 –194\n\nA study of 350 endometriosis associated infertility patients\nfollowing laparoscopic treatment confirmed the relationship\nbetween the Endometriosis F ertility Index and estimated\ncumulative pregnancy rates [23]. Y acoub et al. studied wheth-\ner the EFI is a good tool to predict pregnancy in patients with\nsurgically documented endometriosis followed by intrauterine\nCurr Obstet Gynecol Rep (2013) 2:186 –194 189\n\ninsemination (IUI) or in vitro fertilization (IVF) management\n[24 ]. Retrospective intention-to-treat analysis was\nperformed on 132 consecutive infertility patients with an\nisolated endometriosis diagnosis documented and treated\nby laparoscopy and then followed by ART management\n(IUI or IVF). Spontaneous or induced pregnancies obtained\nafter laparoscopy were recorded. Women were excluded if\nthey were older than age 40 years or had ovarian deficiency\nand those with other infertility factors: sperm abnormalities\nor tubal nonendometriosis-relat ed dysfunction. Fertility as\nreflected by cumulative birth rate was studied in relation to\nthe endometriosis stage (defined by rAFS score and EFI).\nComparison between differe nt stages was assessed using\nthe Kaplan –Meier survival method with a log-rank test.\nComparison of life-table curves according to EFI stages\nshows a significant association between the severity of\nendometriosis (different stages), infertility, and endome-\ntriosis and cumulative birth rate ( P=0.0005). However,\nthere was no significant association for the AFS score\n(P=0.48). The authors concluded that this study con-\nfirmed that the AFS score is not a good tool to predict\npregnancies and seemed to show that the EFI is a simple\nand reliable tool to predict pregnancy in patients with\nsurgically documented endometriosis followed by IUI or\nIVF management. The authors concluded, “In our opin-\nion, this score should be a main component in the choice\nof the postoperative ART management. Prospective stud-\nies are needed to confirm our data. ”\nClinical Role of the EFI to Predict Likelihood\nof Non-ART Pregnancy\nTo date, the EFI is the most scientifically based predictive\nstaging system for endometriosis-related fertility issues. It\nprovides very precise detailed information in a way that no\nprevious staging system has provided. The two issues that\nmost significantly impact the lives of women with endome-\ntriosis are those of fertility and pain. There has not been, nor\nis there, any current staging system for endometriosis-related\npain. A comprehensive endometriosis staging system would\nprovide predictive information for both future fertility and\npain relief. Development of an endometriosis pain staging\nsystem will most likely follow the approach used in devel-\nopment of the EFI. Postsurgical data outcome on more than\n700 endometriosis pelvic pain patients has been prospective-\nly collected during the past 10 years by one of the authors\n(AC). This large database is undergoing in-depth statistical\nanalysis with the hope of identifying predictive variables.\nIdeally this will provide the basis to predict both prognosis\nand risk of recurrence. If a pain staging system similar to the\nEndometriosis Fertility Index is developed, then ideally a\n“unified” endometriosis staging system would provide the\nbasis for treating both pelvic pain and infertility patients.\nEndometriosis can be one of the most complex and chal-\nlenging conditions that obstetrician/gynecologists encounter\nin their practice. Medically, it can be a chronic disease\ntranscending many medical specialties while often responding\npoorly to standard treatments. Stage III and IV endometriosis\n(rASRM classification system) and deep infiltrating endome-\ntriosis, as well as bowel and ureteral endometriosis, often\nresult in some of the most technically challenging surgeries\nencountered in surgery, and especially in gynecology. Referral\nto gynecologic surgeons with expertise in difficult endometri-\nosis cases is essential if patients are to receive the appropriate\ntreatment [25].\nWe present additional information and tables (Tables 1\nand 2) that may assist the physician, and possibly some\npatients, in understanding prognosis after diagnosis of endo-\nmetriosis at laparoscopy. These data can be used, if desired,\nin conjunction with the current EFI worksheet. The informa-\ntion contained in the EFI has been further analyzed to pro-\nvide summary information that may be helpful when com-\nmunicating with patients and referring physicians. This ad-\nditional information also is the basis for an algorithm and\nguidelines that may be helpful in treatment of endometriosis\nfertility patients (Table 3).\nAt least every year patients should be reassessed. In fact,\nmost patients in treatment should be assessed every 3 to\n6 months and ongoing management discussed and deter-\nmined based not only on prognosis but other clinical, social,\npsychological, financial, and other factors. Depending on her\nage and years of infertility, the patient will experience a\nreduced pregnancy rate over time for several reasons: more\nfertile patients tend to conceive earlier so the remaining\npopulation is less fertile (consistent with duration of infertil-\nity being a strong predictor of fecundity), the patient gets\nolder, and endometriosis may recur. It has been shown that\nfecundity is fairly constant after surgery for approximately\n12–15 months before it decreases and is generally very low\nafter 2 years [ 26]. This time factor in outcome is represented\nin the EFI by the flattening of the life table curve over time,\nrepresenting lower pregnancy rates as the patient goes longer\nwithout conceiving. This decrease has been presented in a\ntable that shows decreasing fecundity over time for all of the\nEFI scores (Table 3).\nThe monthly fecundity data provide a rational basis, cre-\nating a table with four levels of treatment groups: Level I has\nthe highest fecundity and Level IV has the lowest. These\nlevels can be used for making treatment recommendations\nfor patients, consistent with the idea that chances for preg-\nnancy decrease over time, and start from different baselines\ndepending on the EFI score. The treatment level and thus\ntreatment recommendations for any given EFI score can\nchange up to three levels over time.\n190 Curr Obstet Gynecol Rep (2013) 2:186 –194\n\nThe tables suggest that for Level I, with a monthly fecun-\ndity greater than 3 % (annual fecundity greater than 35 %), it\nis inappropriate to utilize invasive or expensive treatment\nimmediately. Indeed, pregnancy still has approximately a\n10–30 % chance occurring in the third year after diagnosis\nfor EFI score 6 and higher.\nFor patients with Level II, pregnancy rates are 25 –35 %\n(monthly fecundity 2 –3 %). By the third year, all EFI scores\nare Level III or IV , except for EFI score 7 patients, which\npersist at Level II (see discussion below). Therefore, non-\nART treatments of EFI score 6 or higher for up to 2 years\ncould be reasonable, but probably not for a third year (except\nEFI score 7).\nFor treatment Level III, chance of pregnancy is approx-\nimately 10–25 % (monthly fecundity 1 –2 %) and so it might\nbe reasonable to attempt non-ART treatment for a short\nperiod of time. Patients in Treatment Level IV have annual\nfecundity less than 10 % and ART should be utilized as\nsoon as possible, because very few pregnancies will occur\nwithout ART.\nTables 1 and 2 show that patients with an EFI score of 7 do\nnot experience the same decrease in pregnancy rates to a\nLevel III or IV as all other EFI scores. Interestingly, patients\nwith an EFI score of 7 are the only group to persist with\nLevel II treatment recommendations in year 3. The reasons\nfor the drop to Treatment Level I or II for EFI scores 0 –6 are\nprobably different than for EFI scores 8 –10. It seems rea-\nsonable that the low year 3 pregnancy rates for EFI scores of\n0–6 is a result of a reproductive system that has global issues\nand is generally not working well. Patients with an EFI score\nof 8 –10 show a higher initial pregnancy rate with a more\ndramatic decrease in pregnancy rates by year 3. This seems\nto reflect a reproductive system that overall is working fairly\nwell but includes a segment of patients with an unknown and\nundiagnosed contributing factor to their infertility, one that\noften is nullified with ART. Patients with an EFI score of 7\nseem to have a compromised but intact reproductive system\nthat provides a relatively consistent, albeit reduced, fecundi-\nty over time.\nFor all patients, controlled ovarian stimulation with clo-\nmiphene citrate should be used for 3 to 6 months before ART\nunless the patient is in Level IV where ART is generally the\nmost appropriate first line of treatment. COS should be used\nfor more than 3 months only in young patients responding\nwell to the medications. Recent studies have shown that,\ncompared with IVF, gonadotropins and IUI treatment do\nnot result in higher pregnancy rates, and also it takes longer\nto conceive, costs more money, and results in more multiple\npregnancies [ 27]. Therefore, gonadotropins and IUI gener-\nally should not be used but rather patients should go straight\nfrom clomiphene to ART.\nObviously many factors are considered when counseling\nan infertile couple about their options and recommended\ncourse of treatment. Referral or ART does not have to pro-\nceed on a fixed schedule. Indeed, it does appear pregnancies\nwill continue to occur even after 1 –2 years, although at a\nlower monthly fecundity. Even a relatively low monthly\nfecundity will over time result in a significant number of\npregnancies. Some couples may wish to proceed with non-\nART pregnancy attempts over a long period of time or may\nnever opt for ART treatment. Table 3 outlines a treatment\nalgorithm, which provides the basis of general guideline\nTable 1 Estimated Fecundity\nRates during 1, 2, and 3 years by\nEFI score\nEFI score Monthly fecundity (%) Yearly fecundity (%)\nAll patients ( n=801) Y ear 1 Year 2 Y ear 3 Year 1 Y ear 2 Y ear 3\n0–3 0.8 0.0 0.0 9.9 0.0 0.0\n4 1.3 0.8 0.5 15.2 9.4 5.9\n5 1.9 1.7 0.5 22.8 20.7 5.6\n6 2.5 2.2 1.0 29.5 26.2 12.5\n7 3.1 2.7 2.3 37.4 32.6 27.5\n8 3.4 2.3 1.1 41.0 27.3 13.5\n9–10 4.7 3.0 0.9 56.4 35.6 10.7\nTable 2 Treatment levels and\nrecommendations Treatment level Monthly\nfecundity\nTreatment\nrecommendation\nI >3 % Attempt non-ART conception for at least 1 year\nII 2 –3 % Probable attempt non-ART conception, consider role of IVF\nIII 1 –2 % Probable IVF, refer to reproductive endocrinologist for fertility management\nIV <1 % Refer to ART center for IVF\nCurr Obstet Gynecol Rep (2013) 2:186 –194 191\n\nrecommendations for treatment of women with endometriosis-\nrelated fertility.\nThis analysis demonstrates additional ways to utilize the\nEFI for management of endometriosis patients. It is hoped\nthis additional information will maximize its clinical useful-\nness and as a result provide the best chance of positively\nimpacting the care provided to all endometriosis fertility\npatients (Table 4).\nPredicting Pregnancy Rate with ART in Endometriosis\nPatients\nThe peritoneal lesions of stage III endometriosis, ovarian\nendometriomas, and deep infiltrating endometriosis all have\nbeen reported to independently affect fertility and ART suc-\ncess rates [ 28, 29].\nThe role and potential benefit of surgery both alone and in\nconjunction with ART has been debated. Several studies of\nsurgical treatment alone have demonstrated a positive impact\non both Stage I –II and Stage III –IV endometriosis [21, 30,\n31]. Ballester et al. recently published their findings and\npresented a nomogram providing precise information about\nICSI-IVF success to be used as a guide for both couples and\npractitioners [32]. Clinical pregnancy rates for patients with\nand without deep infiltrating endometriosis were reported at\n58 % and 83 % respectively, but the study had many\nlimitations.\nDarai et al. evaluated the effect of colorectal resection of\nendometriosis on fertility [33]. The 52 patients were random-\nized to laparoscopic or open surgery. Laparoscopic surgery\nresulted in a lower incidence of adhesion formation. The\npregnancy rate of 39.3 % was similar to that of other studies.\nTwo thirds of spontaneous pregnancies in this study occurred\nin the first year and none occurred after 18 months. No\npatient older than age 35 years experienced spontaneous\npregnancy.\nConclusions\nA variety of endometriosis diagnostic tests, scoring systems,\nand treatment data outcome have been published recently.\nThis information provides a working basis for constructing a\nrational and systematic approach to evaluation and treatment\nof endometriosis-related infertility patients. Treatment con-\nsideration should include availability of time to conceive,\novarian reserve, and the possibility to conceive by non-ART\nmeans.\nThe first step in counseling an endometriosis patient with\npotential fertility issues is evaluation of ovarian reserve.\nEarly screening of ovarian reserve in younger women with\nadvanced invasive endometriosis may be indicated even\nbefore the actual time of wanting to conceive. Women with\na decreased ovarian reserve should consider ART as first-line\ntherapy. Other factors, such as quality of sperm and uterine\nstatus, also need to be assessed and considered.\nThe endometriosis fertility index (EFI) provides the basis\nfor predicting the pregnancy rate over 3 years and providing a\nsimple visual graph for education of the physician and patient.\nA treatment algorithm derived from these data is presented.\nInfertility patients in whom ART is a potential treatment\noption generally should have started ART by the time they\nare 36 or 37 years old. The length of time endometriosis-\nTable 3 EFI score and treatment level\nEFI score Treatment level\nAll patients ( n=801) Year 1 Year 2 Y ear 3\n0–3I V I V I V\n4 III IV IV\n5 III III IV\n6 II II III\n7 I II II\n8 I II III\n9–10 I I IV\nTable 4 Age-weighted endometriosis treatment algorithm\n1st year 2nd year 3rd year\nEFI score <34 35 –37 >37 EFI score <34 35 –37 >37 EFI score <34 35 –37 >37\n0–3 I VI V I V0 –3 I VI V I V0 –3I V I V I V\n4 III IV IV 4 IV IV IV 4 IV IV IV\n5 III IV IV 5 III IV IV 5 IV IV IV\n6 II III IV 6 II III IV 6 III IV IV\n7 I II III 7 II III IV 7 II III IV\n8 I II III 8 II III IV 8 III IV IV\n9–10 I II III 9 –10 I II III 9 –10 IV IV IV\n192 Curr Obstet Gynecol Rep (2013) 2:186 –194\n\nrelated fertility patients should attempt pregnancy by non-ART\nmethods following surgery for treatment of endometriosis can\nrange from zero months to 2–3 years in very young patients, as\nelucidated by the EFI. V ery few patients with access to IVF will\nwait much longer than a year. But for patients who do not have\naccess to IVF, the EFI can give a realistic assessment of\npregnancy rates for up to 3 years, after which very few preg-\nnancies occur in any patients regardless of EFI score.\nBased on this information, patients should undergo surgi-\ncal treatment of endometriosis, if clinically indicated, by age\n33 years to provide sufficient time for success in attaining\npregnancy by non-ART. This approach avoids beginning the\nART phase of fertility treatment, if needed, after the patient\nhas entered into a period of DOR.\nThe EFI score can be used to create non-ART endometri-\nosis treatment levels to help provide the patient and physi-\ncian with increased understanding of the patient ’s current\nfertility potential and the prognosis for non-ART conception.\nFurther research hopefully will help us to continue to im-\nprove the management of endometriosis infertility patients.\nCompliance with Ethics Guidelines\nConflict of Interest Andrew S. Cook declares that he has no conflict\nof interest.\nG. David Adamson is a consultant for Auxogyn and Sonoa\nHealthcare, has received honoraria from Best of ASRM/ESHRE and\nWomen’s Hospital of Texas, has received royalties from Cambridge\nUniversity Press, and holds stock or stock options with Advanced\nReproductive Care, Inc. and netMD.\nHuman and Animal Rights and Informed Consent This article\ndoes not contain any studies with human or animal subjects performed\nby any of the authors.\nReferences\nPapers of particular interest, published recently, have been\nhighlighted as:\n Of importance\n Of major importance\n1. Buyuk E, Seifer DB, Y ounger J, Grazi RV , Lieman H. Random anti-\nMüllerian hormone (AMH) is a predictor of ovarian response in\nwomen with elevated baseline early follicular follicle-stimulating\nhormone levels. Fertil Steril. 2011;95(7):2369 –72.\n2.  The FIGO Fertility Tool Box http://www.figo.org/news/resources/\nFIGO_Fertility_Tool_Box. p. 41. The FIGO Fertility Tool Box\nprovides a comprehensive overview of the management of infertility\nfor all levels of healthcare providers in any clinical setting .\n3. The Practice Committee of the American Society for Reproductive\nMedicine. American Society for Reproductive Medicine, Birming-\nham, Alabama. Age –related fertility decline: a committee opinion.\nFertil Steril. 2008;90:S154 –5.\n4. Leridon H. A new estimate of permanent sterility by age: sterility\ndefined as the inability to conceive. Popul Stud (Camb). 2008;62:15–24.\n5. Te V elde ER, Pearson PL. The variability of reproductive aging.\nHum Reprod Update. 2002;8:141 –54.\n6.  ASRM Practice Committee. Testing and interpreting measures of\novarian reserve: a committee opinion. Fertil Steril. 2012;98(6):1408–\n15. Assessment of ovarian reserve is a critical component of selecting\nthe appropriate treatment from among those options available for\nany given patient. This document is written by a committee of experts\nwho provide an unbiased overview of the complexity of ovarian\nreserve testing and how to interpret the results in the clinical setting.\n7. Shah DK. Diminished ovarian reserve and endometriosis: insult\nupon injury. Semin Reprod Med. 2013;31:144 –9.\n8. Shebl O, Ebner T, Sommergruber M, Sir A, et al. Anti müllerian\nhormone serum levels in women with endometriosis: a case –con-\ntrol study. Gynecol Endocrinol. 2009;25(11):713 –6.\n9. The FIGO Fertility Tool Box http://www.figo.org/news/resources/\nFIGO_Fertility_Tool_Box. p. 69.\n10. The Practice Committee of the American Society for Reproductive\nMedicine in collaboration with the Society of Reproductive Sur-\ngeons. American Society for Reproductive Medicine, Birmingham,\nAlabama. Myomas and reproductive function. Fertil Steril.\n2008;90:S125–30.\n11. V erkauf BS. Myomectomy for fertility enhancement and preserva-\ntion. Fertil Steril. 1992;58:1 –15.\n12. The Practice Committee of the American Society for Repro-\nductive Medicine. American Society for Reproductive Medi-\ncine, Birmingham, Alabama. Pathogenesis, consequences and\ncontrol of peritoneal adhesions in gynecologic surgery: a committee\nopinion. Fertil Steril. In press. https://www.asrm.org/uploadedFiles/\nASRM_Content/News_and_Publica tions/Practice_Guidelines/\nCommittee_Opinions/Adhesions_2013.pdfmembers.pdf. Accessed\nonline May 3, 2013.\n13. The FIGO Fertility Tool Box http://www.figo.org/news/resources/\nFIGO_Fertility_Tool_Box. pp. 55, 69.\n14.  The Practice Committee of the American Society for Reproduc-\ntive Medicine. American Society for Reproductive Medicine, Bir-\nmingham, Alabama. The role of tubal surgery in the era of assisted\nreproductive technology. Fertil Steril. 2012;97:539 –45. The devel-\nopment of assisted reproductive technologies has made many for-\nmerly performed reproductive surgeries either unnecessary or in-\nappropriate because of unfavorable effectiveness, cost, time to\npregnancy, risk, or other factors. Nevertheless, reproductive sur-\ngery is still a better option than ART for many patients because of\nsuperior outcomes and treatment of related problems, such as pain,\nespecially true for endometriosis. This comprehensive and bal-\nanced document written by experts assesses the contemporary role\nof tubal surgery.\n15. The FIGO Fertility Tool Box http://www.figo.org/news/resources/\nFIGO_Fertility_Tool_Box. p. 44.\n16. ASRM and SMRU. The Practice Committee of the American\nSociety for Reproductive Medicine in collaboration with the Soci-\nety for Male Reproduction and Urology. American Society for\nReproductive Medicine. Birmingham, Alabama. Evaluation of the\nazoospermic male. Fertil Steril. 2008;90:S74 –7.\n17. The Practice Committee of the American Society for Reproductive\nMedicine. American Society for Reproductive Medicine, Birming-\nham, Alabama. Obesity and reproduction: an education bulletin.\nFertil Steril. 2008;90:S121 –4.\n18. van der Steeg JW, Steures P , Eijkemans MJ, Habbema JD, Hompes\nPG, Burggraaff JM, et al. Obesity affects spontaneous pregnancy\nchances in subfertile, ovulatory women. Hum Reprod. 2008;23:324–8.\n19. The Practice Committee of the American Society for Reproductive\nMedicine. American Society for Reproductive Medicine, Birming-\nham, Alabama. Smoking and infertility. Fertil Steril. 2008;90:S254–9.\n20.  Barri PN, Coroleu B, Tur R, Barri-Soldevila PN, Rodr ıguez I.\nEndometriosis-associated infertility: surgery and IVF, a comprehen-\nsive therapeutic approach. Reprod BioMed Online. 2010;21:179–85.\nCurr Obstet Gynecol Rep (2013) 2:186 –194 193\n\nThis study provides additional information regarding important fac-\ntors that affect pregnancy rates that need to be considered in man-\nagement decisions for endometriosis patients with infertility.\n21.  Adamson GD, Pasta DJ. Endometriosis fertility index: the new,\nvalidated endometriosis staging system. Fertil Steril. 2010;94:1609–\n15. The Endometriosis Fertility Index (EFI) is the first validated\nendometriosis staging system that predicts non-ART pregnancy rates\nfollowing the surgical diagnosis and treatment of endometriosis. This\ntool is easy to use by physicians and helps patients understand and\nparticipate in clinical decision making to decide how long to pursue\nnon-ART attempts at conception before moving on to ART.\n22. Tomassetti1, B. Geysenbergh, C. Meuleman, D. Timmerman, S.\nFieuw, S and T. D’Hooghe External validation of the endometriosis\nfertility index (EFI) staging system for predicting non-ART preg-\nnancy after endometriosis surgery. Hum Reprod. 2012;0(0):1 –9.\n23. Wei DM, Y u Q, Sun AJ, Tian QJ, et al. Relationship between\nendometriosis fertility index and pregnancies after laparoscopic\nsurgery in endometriosis-associated infertility. Zhonghua Fu Chan\nKe Za Zhi. 2011;46(11):806 –8.\n24. Y acoub A, Ferdinus C, Mourtialon P , et al. Is Endometriosis Fer-\ntility Index a good tool to predict pregnancy in patients with\nsurgical documented endometriosis followed by ART Manage-\nment? World Congress Endometriosis, Montpelier, France. Clinical\nFree Oral Communication S#10-4. 7 September 2011.\n25. D ’Hooghe T, Hummelshoj L. Multi-disciplinary centres/networks\nof excellence for endometriosis management and research: a pro-\nposal. Hum Reprod. 2006;21(11):2743 –8. Epub 2006 Sep 18.\n26. Adamson GD, Hurd SJ, Pasta DJ, Rodriguez BD. Laparoscopic\nendometriosis treatment: is it better? Fertil Steril. 1993;59:35 –44.\n27.  Reindollar RH, Regan MM, Neuman PJ, et al. A randomized\nclinical trial to evaluate optimal treatment for unexplained infertil-\nity: the Fast Track and Standard Treatment (FASTT) Trial. Fertil\nSteril. 2010;94:888 –99. This excellent, large, randomized trial\nprovided evidence on which to base decisions regarding the dura-\ntion and type of controlled ovarian stimulation before ART\ntreatment.\n28. V ercellini P , Barbara G, Buggio L, Frattaruolo MP , et al. Effect of\npatient selection on estimate of reproductive success after surgery\nfor rectovaginal endometriosis: literature review. Reprod BioMed\nOnline. 2012;24:389–95.\n29. Douay-Hauser N, Y azbeck C, Walker F, Luton D, et al. Infertile\nwomen with deep and intraperitoneal endometriosis: comparison of\nfertility outcome according to the extent of surgery. J Minim Inva-\nsive Gynecol. 2011;18:622 –8.\n30. Adamson GD, Pasta DJ. Surgical treatment of endometriosis-\nassociated infertility: meta-analysis compared with survival analy-\nsis. Am J Obstet Gynecol. 1994;171:1488 –504. discussion 504 –5.\n31. Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile\nwomen with minimal or mild endometriosis. Canadian Collabora-\ntive Group on Endometriosis. N Engl J Med. 1997;337:217 –22.\n32. Ballester M, Oppenheimer A, d ’Argent M, Touboul C, et al. No-\nmogram to predict pregnancy rate after ICSI IVF cycle in patients\nwith endometriosis. Hum Reprod. 2012;27(2):451 –6. doi:10.1093/\nhumrep/der392. Epub 2011 Nov 23.\n33. Darai E, Lesieur B, Dubernard G, Rouzier R, et al. Fertility after\ncolorectal resection for endometriosis: results of a prospective\nstudy comparing laparoscopy with open surgery. Fertil Steril.\n2011;95:1903–8.\n194 Curr Obstet Gynecol Rep (2013) 2:186 –194","source_license":"CC0","license_restricted":false}