{"paper_id":"721477ac-4186-4349-8051-f75f49f5932f","body_text":"Endometriosis is a common disease affecting about 10% of\nwomen of reproductive age. Ovarian endometriomas could be\nfound in 17-44% of these patients which shows no symptoms\nin up to 50% of the cases ( 1 - 3 ). There is no accurate statistics\nin Iran but it seems near to 60% of the infertile couples in Iran\nhad endometriosis ( 4 ). For many years, the first line therapeutic\napproach to these cysts was laparoscopic surgery ( 5 ,  6 ). Since\nendometriomas lack a true capsule separating the cyst from\nthe ovarian tissue, it is inevitable to excise the cyst without\ncutting some of the normal tissue of the ovary. The point of\nquestion and worrisome in this approach is the damage to the\novarian reserve as a result of unintentionally excised normal\novarian tissue ( 7 ,  8 ).\nOvarian reserve is a potential predictor of a female’s\nreproductive system and is based on the number and\neventual quality of the ovum. In the last three decades,\nthe level of anti mullerian hormone (AMH) ( 9 ), follicular\nstimulating hormone (FSH), estradiol (E2) and inhibin\nB as well as the ovarian volume and the antral follicular\ncount (AFC) on transvaginal sonography have been\naccepted as reliable markers of ovarian reserve ( 10 - 12 ),\namong which AMH is the most attractive due to its ease\nof measurement and independency to the menstrual cycle\n( 1 ,  13 ,  14 ).\nDifferent studies have proved ovarian reserve decline\nafter laparoscopic excision of endometriomas assessing all\nor some of the aforementioned markers. In some studies cyst diameter, cyst bilateralism, preoperative AMH and\npatient’s age were shown to be relative to the degree of\novarian reserve decline. Meanwhile, other studies proved\nwise versa ( 15 - 18 ).\nThis study designed to find any risk factors that make\nit possible to predict which patients may have higher\ndeclines in ovarian reserve postoperatively using ovarian\ndecline rate as a marker showing the degree of the damage\nto the ovarian reserve and to give a more precise guide in\ncautious choice of patients for laparoscopy.\n\nThis prospective study was conducted in Yas and Arash\nHospitals affiliated to the Tehran University of Medical\nSciences. All participants signed the written informed\nconsent and were eager to participate in the study.\nWomen with ovarian endometrioma between 18 to 44\nyears old who were planned for laparoscopic excision of\nthe endometrioma between July 2020 and January 2021\nwere included. The exclusion criteria were a history of\nprevious adnexal surgery, hormonal replacement therapy,\nand endocrine disorder, ovarian mass suspicious for\nmalignancy, polycystic ovaries and endometriomas of\nless than 3 centimeters diameter.\nThis study was approved by the institutional review\nboard Tehran University of Medical Sciences (IR.TUMS.\nMEDICINE.REC.1399.272). The protocol of the study\nwas designed according to the ethical principles of\nthe Declaration of Helsinki. All participants agreed to\nparticipate in the study and the written informed consent\nwas obtained from all participants.\nThe sample size that was required with a power of 95 was\n70 cases, of which 100 cases were considered for this study.\np1: Preoperative AMH\np2: Postoperative AMH\nThe demographic (age, weight, height, age of\nmenarche, marital state) and obstetrical data (gravid and\npara), as well as the clinical symptoms (dysmenorrhea,\ndyspareunia, persistent pelvic pain, dysphasia, fear\nof sex) and history of infertility for female cause were\ngathered via a questionnaire that was filled by a physician\nor a nursing staff. Also, ultrasound imaging was done for\neach patient to see the precise diameter of the cysts and\ntheir laterality status. Patients also underwent laboratory\ntesting for the level of FSH, LH, AMH, CA125 and CA\n19-9 pre and 3 months post operatively.\nAlso, a new variable was created as AMH decline\nrate calculated by the below formula. AMH decline rate\nis a new variable to assess any correlation between the\nseverity of the damage to the ovarian reserve and any of\nthe other independent variables hypothesized as possible\nrisk factors.\nAll the procedures were performed by two expert\nlaparoscopic surgeons with more than 15 years of\nexperience in laparoscopic surgery, whose procedures\nwere to excise the cyst by stripping, avoiding to damage\novarian normal tissue as much as possible.\nAll the data were analyzed by the software package for\nsocial sciences (SPSS, IBM, USA) for windows version\n15.0. Quantitative values were presented as mean ± SD\nand qualitative values were presented as absolute and\nrelative frequency. Chi-Square test was used to assessed\nstatistical relations of qualitative variables. Comparison\nbetween the groups was performed using MannWhitney U test. Friedman M test was used to compare\nthe differences of serum AMH concentrations between\neach sampling point and the changes of serum AMH\nlevels For quantitative variables we used ANOVA and\nt test. Also for decreas the potential bias, multivariate\nanalysis was performed to evaluate the AMH decline\nrate with other characteristics. P<0.05 was considered to\nbe statically significant.\n\nOne hundred patients were included in the study. The\nmean ± SD age of the patients and menarche were 29.08\n± 4.6 (with a range of 19-41) and 12.56 ± 1.35 years\nrespectively. The characteristics of the patients with\nendometriomas preoperateivley are listed in  Table 1 . Also\nthe frequency of the clinical symptoms and the mean of\nBMI and hormonal profiles in the participants are listed\nin  Table 2 . As seen, dysmenorrhea is the most prevalent\nsymptom in these women.\nAMH levels decreased significantly 3 months after\nsurgery (P<0.000). The mean ± SD of AMH decline rate\nwas calculated to be 30.07 ± 2.30% among all patients.\nLH levels also declined significantly (P=0.013) but\nthere were no significant changes between the levels\nof FSH pre and postoperatively (P=0.527). There\nwas no correlation between patients’ charachteristics,\npreoperative AMH and CA125 with AMH decline rate\n( Table 3 ).\nCharacteristics of the patients with endometriomas undergoing\nlaparoscopy (n=100)\n*; Calculated in married cases. SD; standard deviation\nFrequency of clinical symptoms and the mean of BMI and\nhormonal profiles in the participants\n*\n; Percentage among 100 patients (married and unmarried), **; Percentage among\n69 married patients, BMI; Body mass index, FSH; Follicle stimulating hormone, LH;\nLuteinizing hormone, CA 125; Cancer antigen 125, and CA 19-9; Cancer antigen 19-9.\nCorrelation of the rate of AMH decline rate with patient’s\ncharacteristics and lab data\nBMI; Body mass index, AMH; Anti mullerian hormone, and CA 125; Cancer antigen 125.\nIn linear regression please the R and the relations of\nother factors with the outcome and their R quantity is\nlisted in Table 4.\nThe R square and adjusted R square for the laterality of the\novarian cyst and hormones\nAnd at last, the multivariate analysis between the\npotential predictors and AMH decline rate is shown in\nTable 5. As seen just CA 125 (P=0.160) and the grade of\nendometriosis (P=0.05) had significant correlation with\nAMH decline rate.\nMultivariate analysis between the potential predictors and AMH\ndecline rate\nβ*\n; Unstandardized beta, BMI; Body mass index, AMH; Anti mullerian hormone, and FSH;\nFollicular stimulating hormone.\n\nEndometriosis is an obscure disease defined by\nextrauterine growth of endometrial tissue. Ovaries are\none of the most prevalent sites for endometriosis to be\nfound. Laparoscopic excision of endometriomas for\nlong was accepted as the first line therapeutic approach\nin these cysts ( 6 ,  7 ), but the decreased number of the\novum's obtained through IVF cycles after endometrioma\ncyst excision, gave rise to some worrisome about this\napproach ( 19 ).\nIn the present study, a significant decline in AMH level\nas a marker of ovarian reserve was observed three months\npostoperatively. This indirectly addresses the inevitable\ndamage to the ovarian reserve with the surgery of these\ncysts. Different characteristics of endometriomas can\nlead to ovarian reserve decrease. Indeed, the AMH level\ndeclined postoperatively especially large and bilateral\nendometriomas ( 20 ). In another study AMH decreased\nsignificantely at 1, 3 and 6 months after surgery, although,\nno difference was detected from preoperative and AMH\nvalues at 12 months ( 21 ). Otherwise, Sugita et al. detected\nno significant difference 12 months after surgery ( 22 ).\nAlso the result of Goodman et al. study was interesting that showed AMH levels have recovered in 12 months\nafter a transient decrease ( 23 ).\nFSH levels did not increase significantly according to\nthe diminished AMH levels, this has also been explained\nin previous studies as FSH seems to be a less sensitive\nmarker in determining the changes of the ovarian\nreserve and its level does not increase significantly until\npremenopausal years.\nIn another study, the only risk factor proved to be\nrelated to the severity of AMH decline rate was the\npatients’ preoperative level of AMH, which was not\nproved in our study ( 24 ). Indeed, cyst diameter of greater\nthan 4 centimeters was proved to be a predictor of higher\nAMH decline rates postoperatively ( 25 ) and finally cyst\ndiameter≥7 centimeters, cyst bilateralism, preoperative\nAMH level and patients age were introduced to be\neffective and relative risk factors for greater decline in\novarian reserve ( 19 ). Otherwise, none of the mentioned\nitems were proved in our study.\nRegarding the importance of cyst size, in our study, we\nfound no correlation with AMH decline. However, the\nliterature is controversial. In one study the decline in AMH\nat 6 months after surgery was more evident in the patients\nwith larger endometriomas (>5 cm) ( 26 ). Otherwise A\nmeta-analysis showed the greater endometrioma may lead\nto the greater damage to ovarian reserves which leads to a\ndecrease in serum AMH levels ( 27 ).\nRegarding the importance of laterality we found no\nsignificant difference in post operative AMH levels in\npatients with bilateral compared to unilateral. This is in\nline with Suardi et al. study that serum AMH levels were\nnot influenced by their laterality ( 28 ).\nThe limitation of our study is the short follow up\nduration. Therefore further studies with longer follow up\nand investigation of the effect of surgery on the fertility\nrate with a focus on AMH are recommended. Also the\nnon-significant findings in the current study could also be\ncaused by the small number of the participants.\n\nSince the present study like other studies has shown\na significant decline in AMH levels postoperatively,\nwhile none of the independent variables were found as\na risk factor or predictor of the rate of this decline, we\ncan conclude that probably surgical intervention even in\npatients with the lowest risks can result in diminished\novarian reserve. This conclusion makes it necessary to\nselect patients for surgical intervention more cautiously\nat any age or with any clinical and paraclinical\npresentation.","source_license":"CC0","license_restricted":false}