{"paper_id":"b4f50cbe-f010-4a26-acfb-f8c864f023ef","body_text":"Endometriosis, Ovarian Reserve and Live Birth\nRate Following In Vitro Fertilization/\nIntracytoplasmic Sperm Injection\nEndometriose, reserva ovariana e taxa de nascidos vivos\napós FIV/ICSI\nMarcela Alencar Coelho Neto 1 Wellington de Paula Martins 1 Caroline Mantovani da Luz 1\nBruna Talita Gazeto Melo Jianini 1 Rui Alberto Ferriani 1 Paula Andrea Navarro 1\n1 Department of Obstetrics and Gynecology, Faculdade de Medicina\nde Ribeirão Preto, Universidade de São Paulo – USP, Ribeirão Preto,\nSP, Brasil\nRev Bras Ginecol Obstet 2016;38:218 –224.\nAddress for correspondence Paula Andrea Navarro, MD, PhD,\nDepartmento de Ginecologia e Obstetrícia, Faculdade de Medicina de\nRibeirão Preto, Hospital das Clínicas de Ribeirão Preto, Centro de\nReprodução Humana, Universidade de São Paulo, Avenida\nBandeirantes, 3.900, 8o andar, Ribeirão Preto, caixa postal: 14048-\n900, Ribeirão Preto, SP, Brazil (e-mail: pnavarro@fmrp.usp.br).\nKeywords\n► endometriosis\n► ovarian reserve\n► assisted reproduction\n► IVF\n► ICSI\nAbstract Purpose To evaluate whether women with endometriosis have different ovarian\nreserves and reproductive outcomes when compared with women without this\ndiagnosis undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/\nICSI), and to compare the reproductive outcomes between women with and without\nthe diagnosis considering the ovarian reserve assessed by antral follicle count (AFC).\nMethods This retrospective cohort study ev aluated all women who underwent IVF/\nICSI in a university hospital in Brazil between January 2011 and December 2012. All\npatients were followed up until a negative pregnancy test or until the end of the\npregnancy. The primary outcomes assessed were number of retrieved oocytes and live\nbirth. Women were divided into two groups a ccording to the diagnosis of endometri-\nosis, and each group was divided again into a group that had AFC /C20 6 (poor ovarian\nreserve) and another that had AFC /C21 7 (normal ovarian reserve). Continuous variables\nwith normal distribution were compared using unpaired t-test, and those without\nnormal distribution, using Mann-Whitney tes t. Binary data were compared using either\nFisher’s exact test or Chi-square ( /C31\n2)t e s t .T h es i g n ificance level was set as p < 0.05.\nResults 787 women underwent IVF/ICSI (241 of which had endometriosis). Although\nthe mean age has been similar between women with and without the diagnosis of\nendometriosis (33.8 /C6 4 versus 33.7 /C6 4 . 4y e a r s ,r e s p e c t i v e l y ) ,p o o ro v a r i a nr e s e r v e s\nwere much more common in women with endometriosis (39.8 versus 22.7%). The\nchance of achieving live birth was similar between women with the diagnosis of\nendometriosis and those without it (19.1 versus 22.5%), and also when considering\nonly women with a poor ovarian reserve (9.4 versus 8.9%) and only those with a normal\novarian reserve (25.5 versus 26.5%).\nreceived\nJanuary 5, 2016\naccepted\nMarch 30, 2016\npublished online\nMay 19, 2016\nDOI http://dx.doi.org/\n10.1055/s-0036-1584126.\nISSN 0100-7203.\nCopyright © 2016 by Thieme Publicações\nLtda, Rio de Janeiro, Brazil\nOriginal Article\nTHIEME\n218\n\n\nIntroduction\nSubfertility is the inability of achieving a pregnancy after one\nyear of regular, unprotected intercourse. 1 Approximately\n15% of women in reproductive age are considered subfer-\ntile.\n2–4 Assisted Reproduction Technologies (ARTs), particu-\nlarly in vitro fertilization (IVF) and intracytoplasmic sperm\ninjection (ICSI), are frequently used to help subfertile couples\nto conceive.\nEndometriosis is one of the most cited causes of subfer-\ntility, being much more common in subfertile (25 –40%) than\nin fertile woman (0.5 –5.0%).\n5 This disease is de fined by the\npresence of endometrial tissue outside the uterine cavity,\nand the mechanisms through which endometriosis impairs\nfertility are still unclear.\n6 Pelvic adhesions and distortion of\npelvic anatomy are associated with subfertility, and are\nfrequently observed in moderate and severe cases of endo-\nmetriosis.\n7 However, the mechanism underlying minimal or\nmild endometriosis related to subfertility is unclear, and may\nbe related to impairment of oocyte development, embryo-\ngenesis and implantation.\n8–10 The ideal fertility treatment\nfor women with endometriosis is not well established yet,\nbut ART treatments are responsible for the highest success\nrates.11,12\nThe relationship between the presence and severity of\nendometriosis and the reproductive outcomes in women\nundergoing ART are controversial.13–15 The first meta-analysis\nevaluating this issue found that endometriosis reduces the\nchances of achieving pregnancy in IVF/ICSI cycles, and that\npatients with moderate to severe endometriosis (III/IV) have\neven worse results.\n14 The second review observed that only\nsevere endometriosis impairs implantation and clinical preg-\nnancy rates when compared with women without the dis-\nease.\n15 However, the latest and largest published review found\nmoderate quality evidence suggesting that endometriosis does\nnot affect the chance of achieving clinical pregnancy and live\nbirth when considering only the fresh transfer cycle.\n13 Fur-\nthermore, the same review suggests that patients with endo-\nmetriosis have a reduced ovarian reserve, once fewer oocytes\nare retrieved from women in this group. Since a poor ovarian\nreserve is associated with poor reproductive outcomes,\n16,17 it\nis possible that the differences in the ovarian reserve, and not\nendometriosis itself, might be the cause of the heterogeneity\nobserved in the studies published so far.\n13\nConclusions Women diagnosed with endometriosis are more likely to have a poor\novarian reserve; however, their chance of conceiving by IVF/ICSI is similar to the one\nobserved in patients without endometriosis and with a comparable ovarian reserve.\nResumo Objetivo Avaliar se mulheres com endometriose possuem diferenças quanto a\nreserva ovariana (RO) e a resultados de reprodução assistida quando comparadas a\nmulheres sem este diagnóstico submetidas IVF/ICSI ( in vitro fertilization/intracytoplas-\nmic sperm injection ), e comparar resultados reprodutivos entre mulheres com e sem o\ndiagnóstico, considerando a RO obtida pe la contagem de folículos antrais (CFA).\nMétodos Este estudo de coorte retrospectivo avaliou todas as mulheres submetidas à\nFIV/ICSI em uma universidade do Brasil nos anos de 2011 e 2012. Todas as pacientes\nforam seguidas até um teste negativo de gravidez ou até o final da gestação. Os\ndesfechos primários analisados foram o número do oócitos captados e nascidos vivos.\nAs mulheres foram divididas em 2 grupos de acordo com o diagnóstico de endome-\ntriose e subdivididas de acordo com a CFA /C20 6( b a i x aR O )e /C21 7 (RO normal). As\nvariáveis contínuas com distribuição normal foram comparadas pelo teste t não\npareado e sem distribuição normal pelo t este de Mann-Whitney. Os dados binários\nf o r a mc o m p a r a d o sp o ra m b o so st e s t e sQ u i - q u a d r a d o(/C31\n2)ee x a t od eF i s h e r .On í v e ld e\nsignificância foi de finido como p < 0,05.\nResultados 787 mulheres foram submetidas a IVF/ICSI (241 com endometriose).\nEmbora a média de idade tenha sido simila r entre as mulheres com e sem o diagnóstico\nde endometriose (33,8 /C6 4 versus 33,7 /C6 4.4 anos, respectivamente), a baixa RO é\nmuito mais comum em mulheres com endometriose (39,8 versus 22,7%). A chance de\nobter um nascido vivo foi similar entre as mulheres com e sem endometriose (19,1\nversus 22,5%), e também quando consideradas apenas as mulheres com baixa RO (9,4\nversus 8,9%), e apenas com RO normal (25,5 versus 26,5%).\nConclusões Mulheres diagnosticadas com endome triose são mais susceptíveis a ter\nbaixa RO; no entanto, suas chances de conceber por IVF/ICSI são similares às\nobservadas em pacientes sem endometriose e com uma RO comparável.\nPalavras-chave\n► endometriose\n► reserva ovariana\n► reprodução\nassistida\n► fertilização in\nvirto\n► ICSI\nRev Bras Ginecol Obstet Vol. 38 No. 5/2016\nEndometriosis, Ovarian Reserve and Live Birth Rate Following IVF\\ICSI Coelho Neto et al. 219\n\n\nThus, the objective of this study was to evaluate whether\nwomen with endometriosis have different ovarian reserves\nand reproductive outcomes when compared with women\nwithout this diagnosis undergoing IVF/ICSI. We also com-\npared the reproductive outcomes between women with and\nwithout the diagnosis of endometriosis considering the\novarian reserve assessed by antral follicle count (AFC) evalu-\nated before the beginning of the controlled ovarian stimula-\ntion (COS) for FIV/ICSI.\nMethods\nThis retrospective cohort study included all women who under-\nwent IVF/ICSI at the fertility clinic of the university hospital of the\nRibeirão Preto Medical School, Universidade de São Paulo, Brazil,\nbetween January 2011 and December 2012. All data were\nobtained from medical records by one author. The study protocol\nwas approved by the Institutional Review Board, which waived\nthe requirement for additional informed consent due to the\nretrospective nature of the study.\nWomen were considered eligible if they had undergone\nIVF/ICSI between January 2011 and December 2012 at our\nfertility clinic. If women had undergone more than one cycle\nof COS during this period, only the data from the first cycle\nwith planned embryo transfer were included. All women\nwere followed up until a negative pregnancy test or the end\nof a pregnancy.\nIn or der to divide the women into groups, we assessed the\ndiagnosis of endometriosis made by laparoscopy and/or\nultrasound and the baseline AFC, performed before the\nbeginning of the treatment by transvaginal ultrasound using\na Voluson E8 Expert (GE Healthcare Austria GmbH & Co OG,\nZipf, Austria) operated by one of four well-trained sonolo-\ngists. Ultrasound is considered the first-line imaging method\nfor women with suspected pelvic endometriosis: although it\nfails to identify super ficial endometriosis, the method has an\nexcellent diagnostic accuracy for endometrioma and deep\ninfiltrating endometriosis.\n18–23\nThe unit of analysis of all parameters was the number of\nwomen. The primary endpoints of this study were the\nnumber of retrieved oocytes and the rates of live birth. The\nfollowing parameters were assessed: clinical pregnancy,\npresence of surplus frozen embryos, occurrence of embryo\ntransfer and oocyte retrieval, cancellation of the cycle due to\npoor response, number of oocytes retrieved, baseline AFC,\nbody mass index (BMI), age, and the protocol used for COS. In\ncases in which women did not undergo oocyte retrieval and\nembryo transfer, we considered that the number of both\noocytes retrieved and embryos transferred was zero; by\ndoing that, all women were included in the analysis. Further-\nmore, for 5.7% of women, AFC data was missing; so, for\nsubgrouping purposes, we considered that those patients\nhad an AFC /C21 7, and grouped them within the largest sub-\ngroup. All variables were obtained from the medical records.\nStatistical Analysis\nFirst, women were divided into two groups: those that had\nand those that did not have the diagnosis of endometriosis.\nFor a second analysis, women were further stratified into two\nsubgroups: AFC /C20 6a n dA F C /C21 7. This latter analysis was\nperformed to separate women with expected poor ovarian\nresponse according to the AFC cutoff values suggested in the\nBologna criteria. 24 The study size was determined by the\nprimary outcome number of oocytes retrieved. Considering a\ndifference of one oocyte retrieved as being clinically rele-\nvant,25 a standard deviation (SD) of 4.5 oocytes retrieved at\nour service, 26 a proportion of women with endometriosis to\nbe close to 30%, 13 significance level ¼ p < 0.05, we would\nneed 760 women to have a power of 80% to detect this\ndifference. A mean of 40 women are submitted to treatment\ncycle per month in our clinic. Considering that part of these\nwomen repeat the treatment in a short period of time, we\ncalculated that we would need to retrieve data from\n24 months in order to examine the estimated sample size.\nWith that sample size, the power to detect an absolute 5%\ndecrease in live birth rates was 40%, and of detecting a\ndecrease of 10% in live birth rates was 90%.\nThe normality of distribution of continuous variables was\nanalyzed using the Kolmogorov-Smirnov test. Continuous\nvariables with normal distribution were summarized as\nmean /C6 SD and compared between the two groups using\nunpaired t-test. Continuous variables without normal distri-\nbution were summarized as median (interquartile range)\nand comparisons were made between the two groups using\nMann-Whitney test. Binary data were presented as ratio and\nproportion and compared between the two groups using\neither Fisher ’s exact test or Chi-square ( /C31\n2) test. The level of\nsignificance was de fined as p < 0.05. We also calculated the\nrelative risk (RR), the mean difference (MD) and their 95%\nconfidence interval (CI) for the studied outcomes. All statis-\ntical analysis were performed using SPSS (version 18.0, SPSS\nInc., Chicago, IL, USA).\nResults\nDuring the study period, 787 women underwent IVF/ICSI in our\nclinic; data were analyzed from all 787 cycles. All women were\nfollowed until a negative pregnancy test or the end of the\npregnancy, with reproductive outcomes analyzed in all cases.\nIn the analysis of the 787 women included, 241 (30.6%)\nwere diagnosed with endometriosis. The diagnosis of endo-\nmetriosis was performed by ultrasound in only 30 partic -\nipants (12.4%); by laparoscopy in 182 of them (75.5%); and by\nboth laparoscopy and ultrasound in 29 subjects (12.0%).\nConsidering the 546 women without the diagnosis of endo-\nmetriosis, 151 (26.7%) underwent laparoscopy with negative\nfindings for endometriosis, and 395 women presented no\nclinical or ultrasonographic suspicion of endometriosis, and,\ntherefore, did not undergo laparoscopy. In the subgroup with\na poor ovarian reserve (AFC /C20 6), 220 women were included,\nand of these, 96 (43.6%) had endometriosis. Among these\nwomen, the diagnosis of endometriosis was performed by\nultrasound in only 12 (12.5%) of them; by laparoscopy in 70\n(72.9%) of them; and by both laparoscopy and ultrasound in\n14 women (14.6%). In the subgroup without a poor ovarian\nreserve (AFC /C21 7), 567 women were included, and of these,\nRev Bras Ginecol Obstet Vol. 38 No. 5/2016\nEndometriosis, Ovarian Reserve and Live Birth Rate Following IVF\\ICSI Coelho Neto et al.220\n\n\n145 (25.6%) had endometriosis. Among these patients, the\ndiagnosis of endometriosis was performed by ultrasound in\nonly 18 (12.4%) of them; by laparoscopy in 112 (77.2%) of\nthem; and by both laparoscopy and ultrasound in 15\nwomen (10.3%).\nRegarding the type of COS, 68.1% (536 women) used\ngonadotropin-releasing hormone (GnRH) antagonist pro-\ntocol with standard exogenous gonadotropins (150 –\n300IU/day); 21.1% (166 women) used GnRH agonist pro-\ntocol with standard exogenous gonadotropins; and 10.8%\n(85 women) used clomiphene citrate with low-dose exog-\nenous gonadotropins ( < 150 UI/day). For final follicular\nmaturation, 93.9% (739 women) used urinary or recombi-\nnant human chorionic gonadotropin (hCG) for triggering,\nwhile 6.1% (48 women) used GnRH agonist. Oocytes were\nr e t r i e v e d3 4t o3 6h o u r sa f t e rt h et r i g g e r i n g .T h ed i s t r i -\nbution of COS protocols between the groups is described\nin\n►Tables 1 , 2 and 3.\nWhen considering all women, no signi ficant difference\nwas observed between the two groups regarding age, and\nBMI was slightly lower in the endometriosis group. Param-\neters of ovarian reserve and response to the treatment were\nworse among women with endometriosis: they had lower\nAFC, fewer oocytes retrieved, more cycles cancelled due to\npoor response, fewer women underwent oocyte retrieval/\nembryo transfer, and fewer had surplus frozen embryos.\nNotwithstanding, there was no evidence of difference on\nlive birth rates and clinical pregnancy (\n►Table 1 ).\nWe also performed a subgroup analysis, stratifying women\ninto two subgroups: those with a poor ovarian reserve\n(AFC /C20 6) and those without a poor ovarian reserve (AFC/C21 7).\nThe proportion of women with AFC /C20 6 was signi ficantly\nhigher in participants with endometriosis: 39.8 versus 22.7%\n(►Table 1 ). Among women with a poor ovarian reserve, we\nobserved that those with endometriosis were signi ficantly\nyounger, with no difference on BMI. Unlike the previous\nanalysis, there was no difference in the parameters related\nto the response of the treatment between women with and\nwithout endometriosis: number of oocytes retrieved, number\nof cycles cancelled due to poor response, proportion of women\nundergoing oocyte retrieval and embryo transfer, proportion\nof women with surplus frozen embryos, live birth, and clinical\npregnancy. Notwithstanding, AFC was lower in the endome-\ntriosis group (\n►Table 2 ). In the subgroup of women without a\npoor ovarian reserve (AFC /C21 7), we did not observe any\ndifference in age, but women with endometriosis had a lower\nBMI. Women with endometriosis presented lower AFC and less\noocytes retrieved, while no difference was observed in the\nnumber of cycles cancelled due to poor response, the propor-\ntion of women undergoing oocyte retrieval and embryo\ntransfer, the proportion of women with surplus frozen\nembryos, live birth rates, and clinical pregnancy.\nTable 1 Evaluated parameters of all women undergoing IVF/ICSI d u r i n gt h es t u d yp e r i o dd i v i d e db a s e do nt h ed i a g n o s i so f\nendometriosis\nParameter Endometriosis Control\nMean SD N Mean SD N p/C3\nAge 34.4 4.3 241 34.5 4.5 546 0.7\nBMI 24.2 4.0 225 25.1 4.2 525 0.01\nMedian IQR N Median IQR N p/C3/C3\nAFC 8.0 4 –13 233 12.0 7 –20 509 < 0.001\nNumber of oocytes retrieved 4.0 2 –8 241 6.0 3 –10 546 < 0.001\n%n N %n N p/C3/C3/C3\nProportion of women with AFC /C20 6 39.8% 96 241 22.7% 124 546 < 0.001\nCycle cancelled - poor response 6.2% 15 241 2.7% 15 546 0.03\nUnderwent OR 92.5% 223 241 97.1% 530 546 0.007\nUnderwent ET 77.2% 186 241 83.2% 454 546 0.06\nWomen with surplus embryos 32.0% 77 241 42.1% 230 546 0.007\nClinical pregnancy 22.4% 54 241 27.5% 150 546 0.2\nLive birth 19.1% 46 241 22.5% 123 546 0.3\nCOS\nFSH þ Ant 63.1% 152 241 72.7% 397 546 0.01\nFSH þ Ago 22.8% 55 241 19.4% 106 546\nCC þ FSH þ Ant 14.1% 34 241 7.9% 43 546\nAbbreviations: AFC, antral follicle count; Ago, agonist protocol; Ant, antagonist protocol; BMI, body mass index; CC, clomiphene citrate; COS,\ncontrolled ovarian stimulation; ET, embryo trans fer; FSH, follicle-stimulating hormone; IQR, interquartile range; n, number of events; N, number of\nwoman analyzed; OR, oocyte retrieval; SD, standard deviation.\nNotes: /C3 p values calculated by unpairedt-test; /C3/C3 p values calculated by Mann-Whitney test;/C3/C3/C3 p values calculated by Fisher exact test or Chi-square (/C312) test.\nRev Bras Ginecol Obstet Vol. 38 No. 5/2016\nEndometriosis, Ovarian Reserve and Live Birth Rate Following IVF\\ICSI Coelho Neto et al. 221\n\n\nTable 3 Evaluated parameters of women undergoing IVF/ICSI during the study period without a poor ovarian reserve (AFC /C21 7)\ndivided based on the diagnosis of endometriosis\nParameter Endometriosis Control\nMean SD N Mean SD N p/C3\nAge 33.8 4.0 145 33.7 4.4 422 0.7\nBMI 24.2 3.8 135 25.4 4.2 406 0.01\nMedian IQR N Median IQR N p/C3/C3\nAFC 12.0 9.0 –17.5 137 15.0 10.0 –22.0 385 < 0.001\nNumber of oocytes retrieved 6.0 3.0 –10.0 145 7.0 4.75 –11.0 422 0.02\n%n N %n N p/C3/C3/C3\nCycle cancelled - poor response 2.8% 4 145 1.4% 6 422 0.3\nUnderwent OR 95.9% 139 145 98.3% 415 422 0.1\nUnderwent ET 84.8% 123 145 88.2% 372 422 0.3\nWomen with surplus embryos 43.4% 63 145 50.2% 212 422 0.2\nClinical pregnancy 29.7% 43 145 31.5% 133 422 0.8\nLive birth 25.5% 37 145 26.5% 112 422 0.9\nCOS\nFSH þ Ant 70.3% 102 145 73.7% 311 422 0.6\nFSH þ Ago 26.2% 38 145 22.0% 93 422\nCC þ FSH þ Ant 3.4% 5 145 4.3% 18 422\nAbbreviations: AFC, antral follicle count; Ago, agonist protocol; Ant, antagonist protocol; BMI, body mass index; CC, clomiphene citrate; COS,\ncontrolled ovarian stimulation; ET, embryo transfer; FSH, follicle-stimu lating hormone; IQR, interquartile range; n, number of events; N, number of\nwoman analyzed; OR, oocyte retrieval; SD, standard deviation.\nNotes: /C3 p values calculated by unpairedt-test; /C3/C3 P values calculated by Mann-Whitney test;/C3/C3/C3 P values calculated by Fisher exact test or Chi-square (/C312) test.\nTable 2 Evaluated parameters of women undergoing IVF/ICSI during the study period with a poor ovarian reserve (AFC /C20 6)\ndivided based on the diagnosis of endometriosis\nParameter Endometriosis Control\nMean SD N Mean SD N p/C3\nAge 35.2 4.5 96 37.3 3.6 124 < 0.001\nBMI 24.2 4.4 90 24.4 4.2 119 0.8\nMedian IQR N Median IQR N p/C3/C3\nAFC 3.5 3.0 –5 . 09 65 . 0 3 . 3 –6.0 124 < 0.001\nNumber of oocytes retrieved 2.00 0.3 –4 . 89 63 . 0 1 . 0 –5.0 124 0.2\n%n N %n N p/C3/C3/C3\nCycle cancelled - poor response 11.5% 11 96 7.3% 9 124 0.4\nUnderwent OR 87.5% 84 96 92.7% 115 124 0.3\nUnderwent ET 65.6% 63 96 66.1% 82 124 1.0\nWomen with surplus embryos 14.6% 14 96 14.5% 18 124 1.0\nClinical pregnancy 11.5% 11 96 13.7% 17 124 0.7\nLive birth 9.4% 9 96 8.9% 11 124 1.0\nCOS\nFSH þ Ant 52.1% 50 96 69.4% 86 124 0.03\nFSH þ Ago 17.7% 17 96 10.5% 13 124\nCC þ FSH þ Ant 30.2% 29 96 20.2% 25 124\nAbbreviations: AFC, antral follicle count; Ago, agonist protocol; Ant, antagonist protocol; BMI, body mass index; CC, clomiphene citrate; COS,\ncontrolled ovarian stimulation; ET, embryo transfer; FSH, follicle-stimu lating hormone; IQR, interquartile range; n, number of events; N, number of\nwoman analyzed; OR, oocyte retrieval; SD, standard deviation.\nNotes:\n/C3 p values calculated by unpairedt-test; /C3/C3 p values calculated by Mann-Whitney test;/C3/C3/C3 p values calculated by Fisher exact test or Chi-square (/C312) test.\nRev Bras Ginecol Obstet Vol. 38 No. 5/2016\nEndometriosis, Ovarian Reserve and Live Birth Rate Following IVF\\ICSI Coelho Neto et al.222\n\n\nDiscussion\nThis study showed that although the mean age was similar\nbetween women with and without the diagnosis of endometri-\nosis, the proportion of participants with a poor ovarian reserve\nwas significantly higher among young women diagnosed with\nendometriosis. Furthermore, women with endometriosis had\nfewer oocytes retrieved. Among women with a decreased\nfunctional ovarian reserve, those with endometriosis were\nsignific a n t l yy o u n g e r .A l t h o u g ht h el i v eb i r t hr a t em i g h tb e\nconsidered slightly lower in women with endometriosis (19.1\nversus 22.5%) without significant difference, it was very similar\nwhen considering only women with a low ovarian reserve (9.4\nversus 8.9%) or a normal ovarian reserve (25.5 versus 26.5%).\nA recent review found moderate quality evidence suggest-\ning that endometriosis does not affect the chance of achieving\nlive birth and clinical pregnancy when considering the first\nembryo transfer,\n13 which is in agreement with our results.\nAdditionally, the same review observed that women with\nendometriosis have fewer oocytes retrieved, suggesting a\nreduced ovarian reserve, which is also in agreement with\nthe findings of the present study. However, some of the\nstudies published so far have observed signi ficantly worse\nresults in women with endometriosis.\n27–29 We believe that\nthe difference among studies might be explained by the\nreduced ovarian reserve associated with endometriosis, as\nthis reduction is related to poor assisted reproduction out-\ncomes.\n16 A recent and large observational study 16 examined\ndata from more than 140,000 women with a single diagnosis\nof infertility; those with more than one cause were excluded\nfrom the analysis. Since this study considered that a reduced\novarian reserve was one of the causes of infertility, women\nwith both endometriosis and a reduced ovarian reserve were\nnot analyzed. This interesting study observed that couples\nwith only endometriosis have live birth rates (43.0%) very\nsimilar to those observed in couples with only male factor\n(42.7%), with only ovulatory dysfunction (44.1%), and those\nwith unexplained infertility (42%); however, all of these rates\nwere much higher than those observed in couples in which\nthe woman had a reduced ovarian reserve and no other cause\nof subfertility was detected (18.9%).\n16 Since women with\nendometriosis are more likely to have a reduced ovarian\nreserve, there is a reasonable chance to observe worse repro-\nductive outcomes in women with endometriosis by including\nall women without controlling for this confounding factor.\nAnother very important observation is that among women\nwith a decreased ovarian reserve, those with endometriosis are\nyounger. Since age and ovarian reserve are the most important\nfactors for the treatment ’ss u c c e s s ,\n16,30 when balancing risks\nand benefits, women with suspected endometriosis might be at\nan increased risk of facing a reduced ovarian reserve at an earlier\nage. The costs and psychological harms of an early fertility\ntreatment should be weighed against the risk of a reduced\no v a r i a nr e s e r v ea n d ,t h e r e f o r e ,w o r s er e p r o d u c t i v eo u t c o m e s\nfor both natural conception and subsequent assisted reproduc -\ntive techniques, caused by the delay in treatment on behalf of a\nmore precise diagnosis or intervention for endometriosis.\nAnother interesting point is that women with endometriosis\nare more likely to have endometrioma, which interferes more\nwith the AFC than with the number of oocytes retrieved and the\nchances of conceiving.\n30,31\nAs this is a retrospective study, we had to rely on data\nfrom our medical records. Antral follicle count data was\nmissing in 3% of the women with endometriosis and in 6% of\nthe controls; therefore, for the subgroup analysis we as-\nsumed that all missing AFC were /C21 7. This source of bias\ncould be overcome by a prospective study. Another issue is\nthat not all women underwent a laparoscopy for the\ndiagnosis of endometriosis. If on one hand it could be a\nsource of bias because some participants lacked a precise\ndiagnostic evaluation, on the other hand it improves gen-\neralization, since not every woman undergoes laparoscopy\npreviously to IVF/ICSI.\nThe generalization of the findings described is limited\nbecause this is a retrospective observational study; however,\nit should encourage the development of new research evalu-\nating reproductive outcomes in patients diagnosed with\nendometriosis taking into account their ovarian reserve.\nIn conclusion, among women undergoing IVF/ICSI, those\nwith endometriosis are more likely to have a poor ovarian\nreserve. However, women diagnosed with endometriosis\nhave similar chances of conceiving when compared with\nother women with a similar ovarian reserve.\nAcknowledgments\nThe authors are grateful to Universidade de São Paulo\n(USP), the Foundation for Support in Teaching, Research\nand Assistance (Faepa), and the Brazilian National Council\nfor Research and Development (CNPq) for their financial\nsupport.\nReferences\n1 Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl\nG. De finition and prevalence of subfertility and infertility. Hum\nReprod 2005;20(5):1144 –1147\n2 Bushnik T, Cook JL, Yuzpe AA, Tough S, Collins J. Estimating the\nprevalence of infertility in Canada. Hum Reprod 2012;27(3):\n738–746\n3 Thoma ME, McLain AC, Louis JF, et al. Prevalence of infertility in\nthe United States as estimated by the current duration approach\nand a traditional constructed approach. Fertil Steril 2013;99(5):\n1324–1331.e1\n4 Bhattacharya S, Porter M, Amalraj E, et al. 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