{"paper_id":"e8a8d32b-5a88-4d9b-b1f9-8648ce953e9c","body_text":"1\nV ol.45, No.1  1-11, 2020Acta Med Kindai Univ\nSignificance of surgery for infertile \npatients with endometrioma\nIsao Tsuji, Risa Fujishima, Nahoko Fujinami, Noriomi Matsumura\nDepartment of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, Japan\nAbstract\nBackground: The significance of cystectomy for \ninfertile patients with endometrioma remains con-\ntroversial.\nMethods: Between 1997 and 2013, 852 female pa-\ntients visited Kindai University Hospital and were \ntreated for infertility, and the significance of sur -\ngery for infertile patients with endometrioma was \nretrospectively analyzed in this study.\nResults: Among patients without endometrioma \n(N=740), patients with unilateral endometrioma \n(N=81), and patients with bilateral endometrioma \n(N=31), the proportion of patients with reduced \novarian reserve at the start of treatment was not \ndifferent in patients <35 years old (5.0% vs 8.0% \nvs 10.5%, p=0.41) but was significantly different \nin patients 35 to 39 years old (15.6% vs 29.6% vs \n45.5%, p=0.014). Among these three groups, the \ncumulative pregnancy rates in patients before sur -\ngery or in those who did not undergo surgery were \nsignificantly different in patients <35 years old \n(59.9% vs 27.3% vs 18.0%, p=0.008) and were not \ndifferent in patients 35 to 39 years old (45.3% vs \n38.0% vs 10.0%, p=0.93). Among the three groups, \nthe cumulative pregnancy rates of patients who \nunderwent surgery were not different in patients \n<35 years old (51.2% vs 45.2% vs 50.0%, p=0.71) \nbut were significantly different in patients 35 to 39 \nyears old (40.7% vs 31.3% vs 0%, p=0.025).\nConclusions: Surgery, including cystectomy, for \ninfertile patients with endometrioma improves \nfertility in patients <35 years old by correcting the \npelvic environment to the same extent as that in \npatients without endometrioma but may decrease \nfertility in 35- to 39-year-old patients by reducing \novarian reserve.\nKey   words : endometrioma, infertility, ovarian \nreserve, surgery, ART\nIntroduction\n    \nEndometriosis is defined as the presence of \nendometrium or endometrial-like tissue outside \nof the uterine cavity; this tissue grows and pro-\nliferates by estrogen and causes dysmenorrhea, \nchronic pelvic pain and infertility. Endometriosis \naffects 10% of women of reproductive age\n1 and \n20-50% of infertile patients. 2,3 Endometriosis can \ncause infertility by leading to abnormal pelvic \nanatomy, alterations in the pelvic environment, \ndisorders in sperm function, a decline in oocyte \nquality, and impaired implantation.\n4-6 Endometri-\nomas are ovarian endometriotic lesions observed \nin 17-44% of endometriosis patients.\n7 Endometri-\nomas can cause ovulation disorders, reduce ovar -\nian reserve, and decrease ovarian responsiveness \nto hyperstimulation.\n4,8 Surgery has been the main \ntreatment choice for infertile patients with endo-\nmetriomas, especially cystectomy, which is con-\nsidered the standard surgery due to a higher post-\noperative pregnancy rate and lower recurrence \nrate of endometrioma compared with electrocoag-\nulation and fenestration.\n9-11 In patients who do not \nundergo surgery for an endometrioma, there are \nvarious risks, such as the infection of endometri-\nomas during oocyte retrieval in assisted reproduc-\ntive technology (ART) treatment, follicular fluid \ncontamination with endometrioma content, ob-\nstetrical complications, including endometrioma \nReceived July 10, 2019; Accepted November 20, 2019\n\nI.Tsuji et al.\n2\nrupture, during the pregnancy period, and the ma-\nlignant transformation of endometriomas. 12 How-\never, whether cystectomy truly improves fertility \nis controversial.\n13 In some studies, surgical endo-\nmetrioma treatment, including cystectomy prior to \nART, did not alter reproductive outcomes\n14,15 , and \ncystectomy caused severe ovarian damage. 14,16,17  \nPrevious reports relating endometrioma and infer -\ntility treatment outcomes are mainly retrospective \nstudies,\n18-36  and many of these reports have the \nproblem of selection bias because of comparisons \nbased on treatment content, such as surgery group \nvs nonsurgery group, and inconsistent data that \nwere not examined according to age stratifica-\ntion. This study retrospectively examined whether \nanalyses based on the state of endometrioma in \nthe same treatment group exhibited a difference in \npregnancy rates when stratified by age.\nMaterials and Methods\nPatients and study design\nBetween 1997 and 2013, 852 patients visited \nKindai University Hospital with the desire to be-\ncome pregnant and were subsequently followed \nfor at least 6 months. The clinical diagnosis of \nendometriosis was made by the presence of sub-\njective symptoms, such as dysmenorrhea, pain \nduring internal examination, or endometrioma \nby MRI. Ovarian function was assessed by base-\nline concentrations of FSH and AMH. The base-\nline concentration of FSH was measured with an \nelectrochemiluminescence immunoassay (Rosch \nDiagnostics KK). The concentration of AMH \nwas measured with a chemiluminescent enzyme \nimmunoassay (Beckman Coulter, Inc.). Baseline \nconcentrations of FSH ≥10 mIU/ml\n37 and AMH <2 \nng/ml 38 were defined as a reduced ovarian reserve. \nSince AMH was adapted as an infertility test at \nour hospital in 2011, the evaluation of ovarian re-\nserve by AMH is limited to cases after 2011. Sur -\ngery was performed for patients who did not be-\ncome pregnant following conservative infertility \ntreatment, and ART was recommended for those \nwho did not become spontaneously pregnant after \nsurgery. Cystectomy was performed for endome-\ntriomas. Other infertility factors were treated as \nfollows: tubal occlusion was treated by fallopo-\nscopic tuboplasty; peritubal and/or perifimbrial \nadhesions were lysed; hydrosalpinx was treated \nby salpingostomy or salpingectomy; endometrio-\nsis was treated by bipolar coagulation; and ade-\nnomyosis was treated by extirpation. The current \nstudy was retrospective. All study protocols were \napproved by the Kindai University Faculty of \nMedicine Ethics Committee (Approval number: \n31-025). Informed consent was obtained from all \npatients.\nStatistics\nStatistical analysis was performed using StatMateV \n(ATMS, Tokyo). The chi-square test, log rank test and \nKruskal-Wallis test were applied to obtain multiple \ngroup comparisons. Statistically significant differences \nwere defined as p < 0.05.\nResults\nPatient background\nThe mean age of the patients at the start of the \ninfertility treatment was 32.5±4.5 years (19–46 \nyears), and the mean duration of infertility was \n3.8 ± 5.8 years (0.5–15 years). A total of 546 pa-\ntients (64.1%) had primary infertility, and 306 \npatients (35.9%) had secondary infertility. A total \nof 112 (13.1%) patients had endometrioma and \nwere stratified according to the presence or ab-\nsence of surgery and ART (Fig 1). Twenty-sev-\nen patients underwent ART treatment, including \n6 patients (22%) before surgery and 21 patients \n(78%) after surgery. The mean size of the endo-\nmetriomas was 4.5±2.3 cm (1-11 cm). Eighty-one \npatients (72.3%) had unilateral endometriomas, \nand 31 patients (27.7%) had bilateral endometri-\nomas. There were no differences in the findings \nat surgery between unilateral and bilateral endo-\nmetriomas. Regarding other infertility factors, \n260 patients (30.5%) had an ovulatory factor, 209 \npatients (24.5%) had a tubal factor, 92 patients \n(10.8%) had a male factor, and 25 patients (2.9%) \nhad adenomyosis.\nPatient characteristics other than ovarian function \nwere examined for all age groups according to the \npresence or absence of endometrioma (Table 1). As \na result, pregnancy history (p=0.003), tubal factor \ninfertility (p=0.001), and adenomyosis (p=0.005) \nwere significantly higher in the patient group with \nendometrioma (N=112) compared to the patient \ngroup without endometrioma (N=740).\nDifferences in infertility treatment outcomes \nbased on the clinical diagnosis of endometriosis\nDifferences in infertility treatment outcomes \nwhen diagnosed with clinical endometriosis or \nendometrioma were examined. The patients were \nclassified into three groups: patients without \n\nSurgery and endometrioma\n3\nsuspected endometriosis (N=482), patients with \nsuspected endometriosis and without endometri-\noma (N=258), and patients with endometrioma \n(N=112). The cumulative pregnancy rates for pa-\ntients <35 years old and for those between 35 and \n39 years old were significantly different among \nthe three groups, and the rates in the group with \nendometrioma were lower (<35 years old; 65.4% \nvs 62.7% vs 51.1%, p=0.015, Fig 2a. 35-39 years \nold; 49.6% vs 52.3% vs 30.0%, p=0.034, Fig 2b). \nThe cumulative pregnancy rates for patients ≥40 \nyears old were not different among the three \ngroups (23.1% vs 22.6% vs 20.0%, p= 0.65, Fig 2c).\nTo evaluate the accuracy of the clinical diagno-\nsis of endometriosis, the pre- and postoperative \ndiagnoses were compared among patients who un-\nderwent surgery. The proportion of patients diag-\nnosed with endometriosis after surgery was 32.9% \n(47/143 patients) in the patient group without sus-\npected endometriosis and 53% (53/100 patients) \nTable 1.    The analysis of factors other than ovarian function.\nEndometrioma (-)\n(n=740)\nEndometrioma (+)\n(n=112) p value\nAge (years) 32.4 ± 4.5 32.7 ± 4.3 0.51\nDuration of infertility (years) 3.8 ± 5.8 3.7 ± 5.3 0.85\nPregnancy history 272 (36.8%) 25 (22.3%) 0.003\nAssociated infertile factors\nTubal 167 (22.6%) 42 (37.5%) 0.001\nMale 75 (10.1%) 17 (15.2%) 0.11\nAdenomyosis 17 (2.3%) 8 (7.1%) 0.005\nSize of endometrioma (cm) ― 4.5 ± 2.3\nPregnancy history (p=0.003), tubal factor infertility (p=0.001), and adenomyosis (p=0.005) were significantly higher in the patient group with \nendometrioma compared to the patient group without endometrioma. There were no differences between the two groups for the other factors.\nFig.1     The classification of patients with endometrioma.\n            Patients with endometrioma were divided into four groups according to the presence or absence of surgery\n             and ART.\n\nI.Tsuji et al.\n4\nFig.2     The differences in infertility treatment outcomes based on clinical diagnosis of endometriosis.\n            The X-axis shows the observation period, the Y-axis shows the cumulative pregnancy rates, and the circle graph shows \n            the ratios of the treatment methods used during pregnancy.\n            a: <35 years old\n            There were significant differences in the cumulative pregnancy rates among three groups (p=0.015). Many of the\n            pregnancies following treatment among the three groups in each age stratification were conceived without ART. \n            b: 35- 39 years old\n            There were significant differences in the cumulative pregnancy rates among three groups (p=0.034). Many of the \n            pregnancies following treatment among the three groups in each age stratification were conceived without ART.\n            c: ≥40 years old\n            There were no differences in the cumulative pregnancy rates among three groups (p=0.65).\n\nSurgery and endometrioma\n5\nin the patient group with suspected endometriosis \nand without endometrioma before surgery. One \nhundred percent of the patients (81/81) diagnosed \nwith endometrioma after surgery had also been di-\nagnosed before surgery.\nCollectively, the diagnosis of clinical endome-\ntriosis by symptoms and examination findings \ndoes not have an influence on infertility treatment \noutcomes in patients without endometrioma and is \ninaccurate since it often differs from the diagnosis \nafter surgery. Therefore, the following analyses \nwere performed based on the presence or absence \nof endometrioma. Furthermore, since the number \nof patients over 40 years old was small (N=51) \nand their infertility treatment outcomes were re-\nmarkably worse, the analysis was performed on \npatients ≤39 years old.\nThe analysis of ovarian function at the start of \ninfertility treatment\nOvarian function was compared among three \ngroups: patients without endometrioma (N=694), \npatients with unilateral endometrioma (N=77), \nand patients with bilateral endometrioma (N=30) \n(Table 2). In patients <35 years old, the mean \nbaseline FSH concentrations in the three groups \nwere 6.6 ± 6.9, 6.8 ± 2.3, and 7.6 ± 2.6 mIU/\nml (p=0.82), respectively, and the median AMH \nconcentrations were 4.5 (0.25-28.8), 1.6 (1.3-\n5.4), and 1.4 ng/ml (p=0.11), respectively. The \nproportion of patients diagnosed with reduced \novarian reserve according to baseline FSH ≥10 \nmIU/ml and AMH <2 ng/ml were 5.0%, 8.0% and \n10.5%, respectively, (p=0.41) (Table 2a). In 35- \nto 39-year-old patients, the mean baseline FSH \nconcentrations in the three groups were 7.6 ± 4.1, \n7.7 ± 2.3, and 10.2 ± 6.8 mIU/ml (p=0.13), re-\nspectively, and the median AMH concentrations \nwere 2.3 (0.4-8.0), 1.7 (0.1-13.1), and 1.3 (0.5-\n2.3) ng/ml (p=0.45), respectively. The proportion \nb: 35-39 years old\nEndometrioma (-)\n(n=192)\nUnilateral endometrioma\n(n=27)\nBilateral endometrioma\n(n=11) p value\nOvarian reserve\nBaseline FSH (mIU/ml) 7.6 ± 4.1 7.7 ± 2.3 10.2 ± 6.8 0.13\nAMH\n(ng/ml)\n2.3 (0.4-8.0)                 \nn=20\n1.7 (0.1-13.1)                              \nn=8\n1.3 (0.5-2.3)                                                    \nn=3 0.45\nThe ratio of patients with diminished \novarian reserve  \nFSH≧10mIU/ml or AMH<2ng/ml 30 (15.6%) 8 (29.6%) 5 (45.5%) 0.014\nMean baseline FSH concentrations and median AMH concentrations were not different among the three groups. There was a significant differ-\nence in the proportion of patients diagnosed with reduced ovarian reserve according to baseline FSH ≥10 mIU/ml and AMH <2 ng/ml among \nthe three groups (p=0.014).\nTable 2.    The analysis of ovarian function at the start of infertility treatment.\na: < 35 years old\nEndometrioma (-)\n(n=502)\nUnilateral endometrioma\n(n=50) \nBilateral endometrioma\n(n=19) p value\nOvarian reserve\nBaseline FSH (mIU/ml) 6.6 ± 6.9 6.8 ± 2.3 7.6 ± 2.6 0.82\nAMH\n(ng/ml)\n4.5 (0.25-28.8)                 \nn=15\n1.6 (1.3-5.4)                              \nn=5\n1.4                                                    \nn=1 0.11\nThe ratio of patients with diminished \novarian reserve  \nFSH≧10mIU/ml or AMH<2ng/ml 25 (5.0%) 4 (8.0%) 2 (10.5%) 0.41\nMean baseline FSH concentrations, median AMH concentrations, and the proportion of patients diagnosed with reduced ovarian reserve ac-\ncording to baseline FSH ≥10 mIU/ml and AMH <2 ng/ml were not different among the three groups.\n\nI.Tsuji et al.\n6\nof patients who had reduced ovarian reserve was \n15.6%, 29.6%, and 45.5%, and these proportions \nincreased significantly with the incidence of en-\ndometrioma (p=0.014) (Table 2b).\nDifferences in infertility treatment outcomes \nbased on the state of endometrioma\n1) Infertility treatment outcomes of patients \nwithout surgery\nThe cumulative pregnancy rates for patients \nwho did not undergo surgery and for patients \nprior to surgery were analyzed and compared \namong three groups: patients without endo-\nmetrioma (N=694), patients with unilateral \nendometrioma (N=77), and patients with bi-\nlateral endometrioma (N=30). The pregnancy \nrates were low in <35-year-old patients with \nendometrioma (59.9% vs 27.3% vs 18.0%, \np=0.008) (Fig 3a) and were not different \namong the three groups in patients between 35 \nand 39 years old (45.3% vs 38.0% vs 10.0%, \np=0.93) (Fig 3b). Many of the pregnancies \nFig.3     Infertility treatment outcomes of patients prior to surgery and patients who did not undergo surgery.\n            The X-axis shows the observation period, the Y-axis shows the cumulative pregnancy rates, and the circle graph shows \n            the ratios of the treatment methods used during pregnancy.\n            a: <35 years old\n            There were significant differences in the cumulative pregnancy rates among three groups (p=0.008). Many of the \n            pregnancies following treatment among the three groups in each age stratification were conceived without ART.\n            b: 35- 39 years old\n            There were no differences in the cumulative pregnancy rates among three groups (p=0.93). Many of the \n            pregnancies following treatment among the three groups in each age stratification were conceived without ART.\n\nSurgery and endometrioma\n7\nfollowing treatment among the three groups \nin each age stratification were spontaneously \nconceived (Fig 3a, b).\n2) Infertility treatment outcomes after surgery \nIn patients <35 years old, the cumulative \npregnancy rates after surgery were not differ -\nent among the three groups, suggesting that \nsurgery improved infertility treatment out-\ncomes (51.2% vs 45.2% vs 50.0%, p=0.71) \n(Fig 4a). In patients between 35 and 39 years \nold, the cumulative pregnancy rates after sur -\ngery were significantly different, especially \namong patients with bilateral endometrioma, \nnone of whom became pregnant, suggesting \nthat surgery reduced ovarian reserve (40.7% \nvs 31.3% vs 0%, p=0.025) (Fig 4b). The pro-\nportions of ART-mediated conceptions fol-\nlowing surgeries among the three groups were \nlarge (Fig 4a, b).\nFig.4     Infertility treatment outcomes after surgery\n            The X-axis shows the observation period, the Y-axis shows the cumulative pregnancy rates, and the circle graph shows \n            the ratios of the treatment methods used during pregnancy.\n            a: <35 years old\n            There were no differences in the cumulative pregnancy rates among three groups (p=0.71). The proportions of \n            ART-mediated conceptions following treatments resulting in pregnancy among the three groups were large compared with \n            infertility treatment outcomes in patients who did not undergo surgery.\n            b: 35- 39 years old\n            There were significant differences in the cumulative pregnancy rates among three groups (p=0.025). \n            The cumulative pregnancy rates in the patient group with bilateral endometrioma were very low.\n\nI.Tsuji et al.\n8\nThe analysis of ART treatment outcomes in pa-\ntients who underwent ART\nART treatment outcomes were compared among \nthree groups: patients without endometrioma \n(N=694), patients with unilateral endometrioma \n(N=77), and patients with bilateral endometrioma \n(N=30). The mean number of retrieved oocytes per \ncycle among the three groups were 8.6±6.3, 4.1± \n1.6, and 4.6± 2.4 (p=0.008), respectively, in pa-\ntients <35 years old and 5.4 ± 4.5, 5.3 ± 4.8, and 1.9 \n± 0.6 (p=0.035), respectively, in patients between \n35 and 39 years old; these results were significantly \ndifferent. However, the pregnancy rates were not \ndifferent among the three groups (Table 3).\nDiscussion\nWhether the presence of endometrioma reduc-\nes ovarian reserve is unclear. However, the fol-\nlowing mechanisms have been proposed. An en-\ndometrioma contains reactive oxygen species. \nReactive oxygen species potentially permeating \nthe surrounding ovarian tissues are likely to cause \nthe substitution of normal ovarian cortical tis-\nsue with fibrous tissue and intraovarian vascular \ninjury, followed by follicular loss.\n39 In a recent \nmeta-analysis, the baseline FSH was higher in pa-\ntients with endometrioma than in patients without \nendometrioma.\n14 Some reports have shown that \nAMH in patients with endometrioma is lower than \nthat in control groups without endometrioma,\n40 \nwhile other studies have reported no difference. 41 \nIn this study, the mean baseline FSH and median \nAMH were not different among three groups: pa-\ntients without endometrioma, patients with unilat-\neral endometrioma, and patients with bilateral en-\ndometrioma. The number of patients with reduced \novarian reserve at the start of infertility treatment \nincreased with the presence of endometrioma, es-\npecially among patients 35 to 39 years old (Table \n2). Reduced ovarian reserve due to the presence \nof endometrioma may be remarkable in patients \nwith reduced ovarian reserve due to old age.\nCystectomy has been performed in infertile pa-\ntients with endometrioma.\n9-11 However, there is \nno consensus as to whether cystectomy should \nbe performed since cystectomy reduces ovarian \nreserve.\n14,16,17  To date, only one prospective ran-\ndomized study on this subject has been reported. 42 \nDemirol et al. examined intracytoplasmic sperm \ninjection (ICSI) treatment outcomes by compar -\ning the surgery group (49 patients) to the non-\nsurgery group (50 patients), and reported that the \npregnancy rates did not differ between the two \ngroups (surgery group: 34.4%, nonsurgery group: \n38.2%). Because this study was conducted in a \nsmall group limited to patients who underwent \nICSI, whether cystectomies should be performed \nfor endometrioma or not in infertility patients re-\nmains inconclusive.\nTo our knowledge, there are 10 retrospective \nstudies that examined pregnancy rates by com-\nb: 35-39 years old\nEndometrioma (-)\n(n=192)\nUnilateral endometrioma\n(n=27)\nBilateral endometrioma\n(n=11) p value\nThe mean number of \nretrieved oocytes per cycle 5.4 ± 4.5 5.3 ± 4.8 1.9 ± 0.6 0.035\nClinical pregnancy rate per patient 20.0% (10/50) 20.0% (1/5) 0% (0/6) 0.48\nThere was a significant difference in the mean number of retrieved oocytes per cycle among the three groups (p=0.035). Clinical pregnancy rate \nper patient was not different among the three groups.\nTable 3.    The analysis of ART treatment outcomes in patients who underwent ART.\na: < 35 years old\nEndometrioma (-)\n(n=502)\nUnilateral endometrioma\n(n=50)\nBilateral endometrioma\n(n=19) p value\nThe mean number of \nretrieved oocytes per cycle 8.6 ± 6.3 4.1 ± 1.6 4.6 ± 2.4 0.008\nClinical pregnancy rate per patient 47.8% (33/69) 53.8% (7/13) 75.0% (3/4) 0.55\nThere was a significant difference in the mean number of retrieved oocytes per cycle among the three groups (p=0.008). Clinical pregnancy rate \nper patient was not different among the three groups.\n\nSurgery and endometrioma\n9\nparing patients who had cystectomies performed \nfor endometrioma to those who did not have cys-\ntectomies.\n18,20-22,29,31-34,36  Several studies have sug-\ngested that there is no difference in the pregnan-\ncy rates between surgery groups and nonsurgery \ngroups,\n18,20,21,29,32-34,36  while other reports suggest \nthat the pregnancy rates in surgery groups were \nhigher than those in nonsurgery groups.\n22,31  Retro-\nspective studies seem to be affected by selection \nbias because the comparisons in these studies are \nbased on differences in treatment method. That is, \nmore aggressive treatments might be performed \nin patients with severe conditions, making it diffi-\ncult to evaluate treatment efficacy.\nThere were three retrospective studies analyz-\ning pregnancy rates based on the endometrioma \nstatus of the patient but not the difference in treat-\nment method. Some studies have reported that the \npregnancy rates did not differ between patients \nwith unilateral versus bilateral endometrioma,\n25 \nwhile other studies have reported that the preg-\nnancy rates among patients with bilateral endo-\nmetrioma were lower.\n28,30  These studies did not \nconduct analyses according to age stratification, \nwhich may be the reason for the inconsistent re-\nsults because ovarian reserve is remarkably re-\nduced as age increases.\nThe current study compared pregnancy rates \nbased on the endometrioma status according to \nage stratification. As a result, the cumulative \npregnancy rates in endometrioma patients <35 \nyears old who did not undergo surgery were lower \nthan the pregnancy rates in patients without endo-\nmetrioma (Fig 3a), and the pregnancy rates after \nsurgery did not differ between the two groups (Fig \n4a). Previous studies have suggested that surgery \nimproves fertility by correcting the pelvic envi-\nronment, such as endometrioma, tubal pathology \nand adenomyosis,\n44,45  in patients <35 years old. \nConsistent with this idea, endometrioma patients \nhad higher rates of tubal pathology and adenomy-\nosis (Table 1). The cumulative pregnancy rates in \nendometrioma patients 35 to 39 years old who did \nnot undergo surgery did not significantly differ \nfrom the rates in patients without endometrioma \n(Fig 3b), and the rates after surgery were lower \nthan those for patients without endometrioma (Fig \n4b). In agreement with our results, it has been re-\nported that reduced ovarian reserve by cystecto-\nmy increases with age,\n7,14,16,17  and ovarian reserve \nis remarkably reduced after surgery for bilateral \nendometrioma.\n7,40,43\nIn this study, the number of retrieved oocytes, \nreflecting ovarian reserve, decreased among en-\ndometrioma patients (Table 3). This finding \nis consistent with the results of a previous me-\nta-analysis.\n14\nThe limitations of this study are that it was a \nretrospective study that was conducted at one in-\nstitution and included a relatively small sample \nsize. However, we conducted careful analyses to \navoid selection bias and obtained results that sup-\nport the recent hypothesis of the association of \ninfertility with endometrioma. In the future, pro-\nspective, multicenter randomized trials are need-\ned to establish a standard therapy for this disease, \nand the results of this study could be a resource \nfor future protocol preparation.\nPregnancy rates are lower in infertile patients \nwith endometrioma than in those without endo-\nmetrioma. In patients <35 years old, the pregnan-\ncy rates in patients who underwent surgery for \nendometrioma were the same as the pregnancy \nrates in patients without endometrioma. This re-\nsult may involve fertility improvements that occur \nby correcting the pelvic environment. For patients \n<35 years old, cystectomy should be recommend-\ned but carries the risk of reduced ovarian reserve. \nHowever, in patients 35 to 39 years old, pregnan-\ncy rates were lower in patients who underwent \nsurgery for endometrioma than in patients with-\nout endometrioma. The reduction in ovarian re-\nserve due to surgery may cause this result. In the \nfuture, prospective, multicenter randomized trials \nare needed to establish standard therapy.\nConflict of interest\nThe authors have no conflicts of interest.\nReferences\n 1. Eskenazi B, \nWarner ML (1997) Epidemiology of \nendometriosis. Obstet Gynecol Clin North Am 24: 235-\n258\n 2. Balasch \nJ, et al. (1996) Visible and non-visible \nendometriosis at laparoscopy in fertile and infertile \nwomen and in patients with chronic pelvic pains: a \nprospective study. Hum Reprod 11: 387-391\n 3. Meuleman C, et al. (2009) High prevalence of\n \nendometriosis in infertile women with normal ovulation \nand normospermic partners. Fertil Steril 92: 68-74\n 4\n.\n de \nZiegler D, Borghese B, Chapron C (2010) Endometriosis \nand infertility: pathophysiology and management. Lancet \n376: 730-738\n 5\n.\n Lessey \nBA, Kim JJ (2017) Endometrial receptivity in the \n\nI.Tsuji et al.\n10\neutopic endometrium of women with endometriosis: it is \naffected, and let me show you why. 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(2014) Sur\ngical treatment for endome-\ntrioma does not increase clinical pregnancy rate or live \nbirth/ongoing pregnancy rate after fresh IVF/ICSI treat-\nment. Am J Transl Res 5: 163-168\n35.\n W\nahd SA, Alalaf SK, Al-Shawaf T, Al-Tawil NG (2014) \nOvarian reserve markers and assisted reproductive technique \n(ART) outcomes in women with advanced endometriosis. \nReprod Biol Endocrinol doi:10.1186/1477-7827-12-120\n36.\n Guler I, et al. (2017) \nThe Impact of laparoscopic sur -\ngery of peritoneal endometriosis and endometrioma on \nthe outcome of ICSI cycles. Syst Biol Reprod Med 63: \n324-430\n37.\n van Montfrans JM, et al. (2000) Predictive value of bas\n-\nal follicle-stimulating hormone concentrations in a gener -\nal subfertility population. Fertil Steril 74: 97-103\n\nSurgery and endometrioma\n11\n38. Stochino-Loi E, et al. (2017) Does preoperative an -\ntimüllerian hormone level influence postoperative preg-\nnancy rate in women undergoing surgery for severe endo-\nmetriosis? Fertil Steril 107: 707-713.e3\n39.\n Sanchez \nAM, et al. (2014) The distinguishing cellular \nand molecular features of the endometriotic ovarian cyst: \nfrom pathophysiology to the potential endometrioma-me-\ndiated damage to the ovary. Hum Reprod Update 20: 217-\n230\n40.\n Goodman LR, et al. (2016) Ef\nfect of surgery on ovari-\nan reserve in women with endometriomas, endometriosis \nand controls. Am J Obstet Gynecol 215: 589.e1-6\n41.\n Ercan CM, et al. (2010) \nAntimullerian hormone levels \nafter laparoscopic endometrioma stripping surgery. Gyne-\ncol Endocrinol 26: 468-472\n42.\n Demirol \nA, Guven S, Baykal C, Gurgan T (2006) Effect \nof endometrioma cystectomy on IVF outcome: a prospec-\ntive randomized study. Reprod Biomed Online 12: 639-\n643\n43.\n Chen \nY , et al. (2014) The impact of endometrioma and \nlaparoscopic cystectomy on ovarian reserve and the ex-\nploration of related factors assessed by serum anti-Mulle-\nrian hormone: a prospective cohort study. J Ovarian Res \ndoi: 10.1186/s13048-014-0108-01\n44.\n Osada H, et \nal. (2011) Surgical procedure to conserve \nthe uterus for future pregnancy in patients suffering from \nmassive adenomyosis. Reprod Biomed Online. 2011 22: \n94-99\n45.\n Soriano D, et al. (2016) Fertility outcome of laparo\n-\nscopic treatment in patients with severe endometriosis \nand repeated in vitro fertilization failures. Fertil Steril. \n106: 1264-1269","source_license":"CC0","license_restricted":false}