{"paper_id":"c46f4002-c1e1-4e16-b850-40c719bbe2b4","body_text":"RESEARCH Open Access\n© The Author(s) 2023. Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, \nsharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and \nthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this \narticle are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included \nin the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will \nneed to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The \nCreative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available \nin this article, unless otherwise stated in a credit line to the data.\nWu et al. Reproductive Biology and Endocrinology           (2023) 21:59 \nhttps://doi.org/10.1186/s12958-023-01109-2\nReproductive Biology \nand Endocrinology\n†Qing Wu and Qingmei Yang contributed equally to this work.\n*Correspondence:\nTan Lin\nfjsllintan@sina.com\nFull list of author information is available at the end of the article\nAbstract\nObjective This study aimed to explore the optimal time of laparoscopic cystectomy for unilateral ovarian \nendometrioma patients and evaluate the influence on ovarian reserve.\nMaterials and methods This prospective randomized controlled study included 88 women with unilateral \novarian endometrioma at a tertiary teaching hospital. All patients received their first identified diagnosis of ovarian \nendometrioma by ultrasound (> 4 cm and ≤ 10 cm) and were administered an oral contraceptive pill (OC) for one \ncycle before laparoscopy. They were randomly divided into two groups: laparoscopy at the late luteal phase (group \nLLP) (n = 44) (termination of OC for two days) and laparoscopy at the early follicular phase (group EFP) (n = 44) (day \n3 after menstruation). Basic clinical characteristics were recorded. Serum Anti-Müllerian hormone (AMH) levels were \nmeasured at various times to predict ovarian reserve. Serum levels of Anti-Müllerian hormone (AMH) were measured \nat several time sites to predict the ovarian reserve; AMH and leukocyte esterase (LE) levels of the endometrioma wall \nwere measured.\nResults Before surgery, serum AMH levels decreased in both groups from preoperative to one week and six months \npostoperatively. In contrast, the difference values of group EFP were larger than those of group LLP at postoperative \none week and postoperative six months (1.87 ± 0.97 vs. 1.31 ± 0.93, P = 0.07; 1.91 ± 1.06 vs. 1.54 ± 0.93, P = 0.001). The \nmean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP , significantly higher than \nthose in group LLP (25.83% vs. 31.43%, P < 0.001). Ovarian endometrioma wall AMH of group LLP was significantly \nlower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P < 0.001). Meanwhile, ovarian endometrioma LE \nconcentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], \nP<0.001). There was also a significant inverse correlation between leukocyte esterase and AMH concentration in an \novarian endometrioma cyst wall (r=-0.564, P<0.001).\nConclusion(s) The optimal time for laparoscopic cystectomy for patients with first identified unilateral ovarian \nendometrioma is the late luteal phase, which reduces ovarian tissue loss and preserves ovarian reserve effectively and \nsafely.\nThe optimal time for laparoscopic excision \nof ovarian endometrioma: a prospective \nrandomized controlled trial\nQing Wu1†, Qingmei Yang1†, Yanling Lin2, Lin Wu3 and Tan Lin2*\n\nPage 2 of 7\nWu et al. Reproductive Biology and Endocrinology            (2023) 21:59 \nIntroduction\nEndometriosis (EMT) is a common gynecological con -\ndition characterized by endometrial tissue outside the \nuterine cavity resulting in dysmenorrhea, chronic pelvic \npain, pelvic masses, and infertility, which can seriously \naffect a woman’s health and quality of life. Ovarian endo-\nmetriomas are the most common type of EMT, with a \nprevalence of 17–44% in patients with endometriosis [ 1]. \nLaparoscopic cystectomy has become the gold standard \nin the surgical management of persistent adnexal masses, \nincluding ovarian endometriosis, with the surgical aim \nof removing all visible endometriosis lesions and restor -\ning anatomy [2]. However, ovarian cystectomy may harm \novarian reserves [ 3– 5]. In addition, surgical procedures \non the ovaries lead to ovarian tissue damage, which can \nstrip normal ovarian tissue and exacerbate the harm to \nthe remaining follicles, raising concerns of gynecologists \nregarding the use of different surgical procedures in this \nfield [6, 7]. However, only a few studies have focused on \nthe optimal time of surgery for ovarian endometrioma.\nAnti-Müllerian hormone (AMH) is produced by the \ngranulosa cells of primary, preantral, and small antral \nfollicles, not primordial ones. Therefore, AMH level \nindirectly represents the quantity of the ovarian follicle \npool, estimated by the number of early growing-stage \nfollicles. Moreover, serum AMH levels appear indepen -\ndent of the menstrual cycle and are unaffected by gonad -\notropin-releasing hormone (GnRH) agonists or oral \ncontraceptives [8– 11]. Therefore, serum AMH levels, as \na promising and reliable parameter, have been used to \nassess the ovarian reserve around treatments that poten -\ntially cause ovarian damage [12– 15].\nCurrently, no precise data exist on whether laparo -\nscopic endometrial cystectomy with different menstrua -\ntion phases reduces the damage to ovarian function, \nshortens the operation time, reduces intraoperative \nblood loss, and accelerates patient recovery. Therefore, \nthis study aimed to explore the optimal timing of the \nfirst laparoscopic cystectomy in ovarian endometrioma \npatients with unilateral and evaluate the influence on the \npatient’s ovarian reserve.\nMaterials and methods\nThis prospective clinical study was approved by the \nboard of Fujian provincial hospital ethics committee \n(2018ky0024) and registered under the clinical trial regis-\ntry number (ChiCTR1800019766). All patients provided \npreoperative informed consent after being informed of \npotential risks and complications. All patients provided \npreoperative informed consent after being informed of \npotential risks and complications. In total, 88 patients \nwith unilateral ovarian endometrioma were recruited \ninto this prospective study at the Department of Obstet -\nrics and Gynecology in Fujian provincial hospital from \nMarch 2019 to March 2021. After inclusion in the study, \nall patients were administered an oral contraceptive pill \n(OC, drospirenone, and ethinylestradiol) for one cycle to \ndetermine the timing of surgery. Inclusion criteria were \nas follows: (1) age 20–36 years; (2) regular menses; (3) \nclinical and ultrasonographic finding of unilateral ovar -\nian endometrioma ≥ 4 cm and ≤ 10 cm the first time; (4) \nwithout pregnancy or plan to get pregnant in six months. \nExclusion criteria were as follows: (1) any suspicious find-\ning of malignant ovarian diseases; (2) ovarian, uterine, \nor tubal surgery history; (3) endocrine disease and treat -\nment history; (4) long-term use of hormonal drugs for \nmore than three months (e.g., gonadotropin-releasing \nhormone analogs); (5) smokers. Patients with infiltrated \nendometriosis were excluded from this study based on \ntransvaginal ultrasound and gynecological examination. \nPatients who fulfilled the inclusion criteria and consented \nto participate in the study were enrolled. The study objec-\ntives and steps were explained to all patients before \nenrollment. All experimental procedures were performed \nfollowing the guidelines for the Declaration of Helsinki. \nOur study was conducted according to the CONSORT \nguidelines [16].\nSample size calculation\nUsing a two-sided equal-variance t-test, group sample \nsizes of 30 and 30 achieved 81.328% power to reject the \nnull hypothesis of equal means when the mean popula -\ntion difference was 1.13. The standard deviation for both \ngroups was 1.51, and the significance level (alpha) was \n0.05 [ 3, 17]. Furthermore, considering the probability \nof dropouts during follow-up, the number of cases was \nfurther increased to more than 40 patients. The sample \nsize was estimated using G*Power© software (Institutfür \nExperimentelle Psychologie, Heinrich Heine Universität, \nDüsseldorf, Germany) version 3.1.9.2.\nRandomization\nAll patients were diagnosed with ovarian endometrioma \nby ultrasound and were administered OC for one cycle \nbefore laparoscopy to inhibit ovulation and identify the \nmenstruation phase. After written consent, the random -\nized number was concealed in an opaque, sealed envelope \nfor each patient, and the envelopes were opened sequen -\ntially by a study nurse before surgery. Randomization \nwas performed in a 1:1 ratio, according to a computer-\ngenerated number list, into two groups. The single num -\nber drawn was included in the group LLP , and the double \nKeywords Laparoscopy, Endometriosis, Ovarian reserve, AMH, Menstrual cycle\n\nPage 3 of 7\nWu et al. Reproductive Biology and Endocrinology            (2023) 21:59 \nnumber was included in the group EFP . All patients were \nrandomly divided into two groups: laparoscopy at late \nluteal phase (group LLP) (n = 44): termination of OC for \ntwo days; and laparoscopy at Early follicular phase (group \nEFP) (n = 44): day 3 after menstruation.\nSurgical technique\nAll surgeries were performed by the same surgeons with \nextensive experience in endometriosis surgery, who \nwere particularly aware of the necessity to avoid damag -\ning or removing healthy ovarian tissue. Surgeons were \nblinded to the result of group Randomization. Laparo -\nscopic pneumoperitoneum was induced by CO 2 insuf -\nflation using a laparoscopic Veress needle. Umbilical \n10-mm trocar and laparoscope entries were performed. \nAnother three trocars were inserted through lower \nabdominal incisions under direct laparoscopic vision. \nIf peri-ovarian adhesion and adhesion of Douglas fossa \nwere present, Blunt dissection and sharp separation were \ncombined to detach the adhesion. After mobilization of \nthe cystic adnexa, ovarian cystectomy was performed by \nincising the cyst with cold scissors and carefully identi -\nfying, separating, and completely removing the entire \ncystic wall from the ovarian cortex by traction/counter \ntraction using non-traumatic grasping forceps. Hemo -\nstasis was achieved using 3 − 0 absorbable sutures that \nwere carefully selected (Vicryl; Ethicon Inc., New Jersey, \nUSA) without electrocoagulation devices. Blood loss was \nestimated by combining the volume of blood collected \nwithin the suction canister with the gauze weight used \nduring surgery. The endometriosis stage was determined \nbased on the revised classification of the American Soci -\nety of Reproductive Medicine (r-ASRM) [18].\nHormonal assays\nAll patients provided serum specimens prior to anesthe -\nsia, as well as at one week and six months following the \nprocedure. Venous blood samples were obtained, and \nserum was extracted by centrifugation. According to \nmanufacturer’s instructions, serum E2 and P levels were \nmeasured by enzyme-linked fluorescent assay (ELISA; \nBeckman Coulter Inc., Ireland). Serum AMH level was \nmeasured by a commercially available enzyme-linked \nimmunosorbent assay kit (ELISA; Beckman Coulter Inc., \nIreland) and reported as nanograms per milliliter with \na detection limit of 0.16 ng/mL. Postoperative serum \nAMH level and AMH decline were the primary outcome \nmeasures.\nTissue sample collection\nAfter a naked-eye examination of the entire cyst wall, five \npieces of the specimen of 5 mm2 were obtained from cyst \nwalls at different portions. One was from the intermedi -\nate part of the specimen, and the others were from the \nfour quadrants. Other cyst walls were sent to the pathol -\nogy laboratory, and a pathologic examination confirmed \nthe ovarian endometriosis diagnosis. Leukocyte esterase \nconcentration and tissue AMH levels in the cyst wall \nwere measured using (LE/AMH) ELISA kit (Jiangsu Mei -\nmain Co., Ltd., Jiangsu, China) as secondary endpoints. \nAll hormonal measurements were performed at the same \nlaboratory.\nUnilateral ovarian involvement\nWe compared the potential role of unilateral ovarian \ninvolvement on preoperative levels and postoperative \nchanges in AMH values after laparoscopic endometri -\noma excision. AMH decline (% decline AMH) was used \nto compare the changes in AMH levels in endometrioma \nresected at different menstrual cycles. The rate of AMH \ndecline was calculated using the following formula: (% \ndecline AMH) = (preoperative AMH level – AMH at one \nweek or six months postoperatively)/preoperative AMH \nlevel.\nStatistical analysis\nCategorical variables are described using proportions. \nBaseline patient characteristics were calculated via t-test \nfor comparisons of normally distributed data and the \nrank-sum test for comparisons of non-normally dis -\ntributed data. Count data were summarized as percent -\nages and compared using chi-square and Fisher’s exact \ntests. Analysis of variance (ANOVA) was used in intra-\ngroup comparison at different time points. A two-sided \nP-value of less than 0.05 was considered to be significant. \nThe relationship between ovarian endometrioma wall \nAMH and leukocyte esterase concentration were gener -\nated based on significant Pearson correlations between \ndata. Statistical significance was set at p-value < 0.05. All \ndata were analyzed using SPSS version 26 (IBM Corp., \nArmonk, NY, USA) and PRISM version 9.0 (GraphPad \nSoftware, La Jolla, CA, USA).\nResults\nBaseline characteristics\nNo significant differences existed in age, cyst size, gra -\nvidity, parity, infertility, dysmenorrhea, r-AFS Staging, \nblood loss volume, and operation time between the two \ngroups. Serum progesterone was significantly higher in \nthe late luteal phase than in the early follicular phase on \nthe day of surgery ([2.46 ± 1.43] vs. [0.43 ± 0.34]; P < 0.001, \nTable 1). After laparoscopy, no severe deep-infiltrating \nendometriosis was observed in this study. Postopera -\ntive pathological diagnosis proved that all patients had \novarian endometrioma, consistent with the preoperative \ndiagnosis.\n\nPage 4 of 7\nWu et al. Reproductive Biology and Endocrinology            (2023) 21:59 \nAMH as the biomarker to evaluate an ovarian reserve and \nfollicle loss\nThere was no significant difference in preoperative AMH \nbetween the two groups. The serum AMH values one \nweek after surgery were higher in group LLP than that \nin group EFP ([3.58 ± 1.65] vs. [3.02 ± 1.22], P = 0.075). \nHowever, AMH decrease value was significantly lower \nthan that of group EFP ([1.31 ± 0.93] vs. [1.87 ± 0.97], \nP = 0.007). Serum AMH at postoperative six months in \ngroup LLP was significantly higher than that in group \nEFP ([3.35 ± 1.67] vs. [2.61 ± 1.15], P = 0.018). In contrast, \nAMH decrease values at postoperative six months were \nsignificantly higher in group EFP than that in group \nLLP ([1.54 ± 0.93] vs. [1.91 ± 1.06]; P < 0.001, Table  2). \nThe mean rates of postoperative serum AMH decline \nwere 37.92% and 46.34% in group EFP , respectively, sig -\nnificantly higher than those of group LLP (25.83% vs. \n31.43%) (P<0.001, Table 3).\nOvarian endometrioma wall AMH of group LLP was \nsignificantly lower than that of group EFP ([22.86 ± 3.74] \nvs. [31.02 ± 5.23], P<0.001). Meanwhile, ovarian endo -\nmetrioma leucocyte esterase concentration of group \nLLP was significantly higher than that of group EFP \n([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001, Table  4; \nFig.  1). Moreover, significant negative correlation exists \nbetween LE and AMH concentration in the cyst wall of \novarian endometrioma (P<0.001, Fig. 2).\nDiscussion\nLaparoscopic endometrioma cystectomy is a recom -\nmended and widely used method because it meets the \ndiagnostic and treatment goals of endometriosis, which \ncan reduce pain, increase the chance of spontaneous \npregnancy, and reduce disease progression and recur -\nrence [19– 21]. However, in addition to the possible nega-\ntive effect of endometriosis on ovarian reserve, serum \nAMH levels significantly decrease after laparoscopic \ncystectomy for endometrioma [5, 22– 26]. Since the ovar-\nian reserve responds to the woman’s reproductive func -\ntion, it must be preserved ultimately during laparoscopic \ncystectomy.\nTable 1 Clinical characteristics of the study subjects\nVariable LLP (n = 44) EFP (n = 44) P-value\nAge, (years) 30.71 ± 3.46 29.36 ± 3.15 0.058\nAge of menarche, (years) 13.32 ± 1.16 13.02 ± 1.19 0.245\nEndometrioma volume, \n(mm3)\n117.71 ± 13.97 117.93 ± 15.79 0.954\nPre-operation serum E2, \n(pg/mL)\n89 ± 68.26 90 ± 47.78 0.834\nPre-operation serum P , \n(ng/mL)\n2.46 ± 1.43 0.43 ± 0.34 < 0.001***\nGravidity, n (%)\n0 24(54.54%) 24 (54.54%) 1\n≥ 1 20(45.45%) 20 (45.45%)\nParity, n (%)\n0 24(54.54%) 26 (59.09%) 0.674\n≥ 1 20(45.45%) 18 (40.90%)\nInfertility, n (%) 15 16 0.823\nDysmenorrhea, n (%) 13(29.54%) 16 (36.36%) 0.501\nr-AFS Staging, n (%)\nI-II 0 0 /\nIII 18(40.90%) 21 (47.73%) 0.524\nIV 26(59.09%) 23 (52.27%)\nBlood loss, (mL) 43.86 ± 9.72 43.86 ± 21.83 1\nOperation time, (min) 65.82 ± 9.21 67.73 ± 10.26 0.355\n***: P < 0.01. LLP: Late luteal phase; EFP: Early follicular phase; E2: Estradiol; P: \nProgesterone\nData are presented as mean ± SD or n (%). a: Groups compared by t-test; b: \nGroups compared by Pearson’s chi-squared test or Fisher’s exact test;\nTable 2 Serum AMH levels of pre-operation and post-operation \nin two groups\nVariable Pre-op-\neration \nAMH (ng/\nmL)\n1 Week-\nPo AMH \n(ng/mL)\nDV1 6 \nmonths-\nPo AMH \n(ng/mL)\nDV6\nLLP \n(n = 44)\n4.89 ± 2.37 3.58 ± 1.65 1.31 ± 0.93 3.35 ± 1.67 1.54 ± 0.93\nEFP \n(n = 44)\n4.89 ± 1.56 3.02 ± 1.22 1.87 ± 0.97 2.61 ± 1.15 1.91 ± 1.06\nP-value 1 0.075 0.007** 0.018** 0.001**\nLLP: Late luteal phase; EFP: Early follicular phase; Po: post-operation; AMH: \nanti-Müllerian hormone; DV: Difference Value, DV1: Difference between \npreoperative AMH and one-week postoperative AMH; DV6: Difference between \npreoperative AMH and six months postoperative AMH.\n**: P < 0.05\nTable 3 Decrease rate of serum AMH levels of post-operation\nVariable Decrease rate \nof AMH 1 Week-\nPo (%)\nDecrease \nrate of AMH \n6 months-\nPo (%)\nLLP (n = 44) 25.83 ± 10.12 31.43 ± 11.13\nEFP (n = 44) 37.92 ± 14.13 46.34 ± 14.23\nP-value < 0.001*** < 0.001***\nLLP: Late luteal phase; EFP: Early follicular phase; AMH: anti-Müllerian hormone\nDecrease rate of AMH 1 Week-Po: Decrease rate of AMH at one-week post-\noperation compared to preoperative AMH; Decrease rate of AMH six months-Po: \nDecrease rate of AMH at six months post-operation compared to preoperative \nAMH; ***: P < 0.01\nTable 4 Ovarian endometrioma wall AMH and leucocyte \nesterase concentration\nVariable Ovarian endo-\nmetrioma wall \nAMH (ng/mL)\nOvarian endome-\ntrioma leucocyte \nesterase concen-\ntration (ng/mL)\nLLP (n = 44) 22.86 ± 3.74 482.83 ± 115.88\nEFP (n = 44) 31.02 ± 5.23 371.68 ± 84.49\nP-value < 0.001*** < 0.001***\nLLP: Late luteal phase; EFP: Early follicular phase; AMH: anti-Müllerian hormone; \n***: P < 0.01\n\nPage 5 of 7\nWu et al. Reproductive Biology and Endocrinology            (2023) 21:59 \nAnti-Müllerian Hormone (AMH) is a transforming \ngrowth factor-β family member secreted by primary, \npreantral, and antral follicles [ 27]. AMH levels correlate \nwith the number of growing follicles and do not change \nsignificantly during the menstrual cycle [ 14, 28]. There-\nfore, AMH has been used to predict the decline of ovar -\nian function and is the preferred biomarker of ovarian \nreserve [ 29, 30]. Several hypotheses have been formu -\nlated to explain the relationship between cyst excision \nand reduction of ovarian reserve. Some authors dem -\nonstrated that the removal of ovarian endometrioma, \ncommonly characterized by the absence of a clear plane \nof cleavage between the endometrioma cyst and ovarian \ntissue, could result in unintentional removal of the ovar -\nian cortex and loss of follicles, with a potential reduction \nin follicular reserve [ 31, 32]. Furthermore, the amount of \novarian parenchyma loss seems to increase proportion -\nally to the increase in cyst diameter [ 33]. According to \nthis hypothesis, damage to the ovarian reserve can result \nfrom permanent loss of ovarian tissue and should per -\nsist over time after surgery [ 23]. This study investigated \nthe optimal surgical timing to perform a cystectomy. It \ncan reduce ovarian function damage by evaluating serial \nchanges in serum AMH levels after laparoscopic endo -\nmetriosis cystectomy for endometriosis and evaluating \novarian endometrioma wall AMH and ovarian endome -\ntrioma leucocyte esterase concentration.\nOur results displayed that serum AMH levels \ndecreased significantly at one week and six months after \nsurgery. However, the decreasing trend of serum AMH \nlevels in group LLP was significantly lower than in group \nEFP . A systematic review and meta-analysis showed that \nthe median preoperative AMH level was 3.1 ng/mL, \nwhich significantly decreased to 1.51 ng/mL within 1–9 \nmonths after surgery, with a decline rate of 51.29% [ 3]. \nA prospective longitudinal study showed that the rate \nof decrease in AMH was 52.2%, 53.7%, and 54.8% at 1, \n3, and 6 months after surgery compared to baseline lev -\nels, respectively [ 34]. In this study, compared with base -\nline levels, patients who underwent surgical treatment \nin the late luteal phase had AMH decline rates of 25.8% \nand 31.4% at one week and six months postoperatively, \nrespectively. However, patients treated surgically at the \nearly follicular phase had AMH decline rates of 37.9% \nand 46.3% at one week and six months postoperatively, \nrespectively. Hoang Tong et al. found that unilateral ovar-\nian cystectomy with a 43.4–48% decrease in serum AMH \nfrom 1 to 6 months after surgery was the same as the cys-\ntectomy results performed in the early follicular phase in \nthis study [ 34]. Zhou Liu et al. estimated the distance to \nrestore ovarian reserve after laparoscopic unilateral ovar-\nian cystectomy to be six months [ 35]. Urman et al. found \na significant decrease in AMH concentration and antral \nfollicle count (AFC) one month after surgery, a reduction \nthat persisted six months postoperatively [ 36]. Therefore, \nFig. 2 Correlation analysis between ovarian endometrioma wall AMH and \nleucocyte esterase concentration. AMH: anti-M?llerian hormone; P < 0.05 \nmeans the difference was statistically significant\n \nFig. 1 Ovarian endometrioma wall AMH and leucocyte esterase concentration. LLP: Late luteal phase; EFP: Early follicular phase; AMH: anti-Müllerian \nhormone; ***: P < 0.01\n \n\nPage 6 of 7\nWu et al. Reproductive Biology and Endocrinology            (2023) 21:59 \nwe conclude that laparoscopic cystectomy for unilateral \novarian endometrioma at the late luteal phase may reach \na content result about follicle loss and ovarian reserve.\nAMH is produced by granulosa cells of primary, pre -\nantral, and small antral follicles. Although there have \nbeen few studies on detecting ovarian endometrioma \nwall AMH, we believe it is closely related to the number \nof granulosa cells in the endometrioma wall, reflecting \nthe quantity of ovarian tissue and follicles in the endo -\nmetrioma wall. Leukocyte esterase activity is commonly \nused for sensitive detection of leukocytes. Leukocytes \ninfiltrate the ovarian endometrioma wall, resulting in \nendometrioma wall edema and loose tissue. Our study \nalso found that ovarian endometrioma wall AMH of \ngroup LLP in patients with first ovarian cystectomy was \nsignificantly lower than that of group EFP ([22.86 ± 3.74] \nvs. [31.02 ± 5.23], P<0.001). In contrast, the ovarian endo-\nmetrioma leucocyte esterase concentration of group \nLLP was significantly higher than that of group EFP \n([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001). A sig -\nnificant inverse relationship was observed between leu -\nkocyte esterase and AMH concentration in the ovarian \nendometrioma cyst wall ( P < 0.001). Our results revealed \nthat ovarian cystectomy with different menstrual cycles \nmay affect the rate of decrease in AMH levels after lapa -\nroscopic ovarian cystectomy in patients with endome -\ntriosis. The border density between endometrioma and \nnormal ovarian tissue may fluctuate during the menstrual \ncycle. Loosening of the border and inflammatory edema \nof the tissue allows the cyst wall to be more easily peeled \noff in the late luteal phase, reducing the loss of normal \novarian tissue.\nThis study had some limitations. First, this study ana -\nlyzed data from one single center. Second, this study was \nconducted only in patients with the first identified single \novarian endometrioma. The results were unavailable for \npatients with previous endometrioma and pelvic surgery. \nThird, patients with bilateral ovarian endometrioma cysts \nwere not investigated. Finally, this study had a short fol -\nlow-up period (six months). We used oral contraceptive \nto control the menstrual cycle to ensure that surgery was \nperformed in the late luteal phase. The specific mecha -\nnism needs to be further studied. Whether surgery can \nachieve the same effect after the withdrawal of other \nexogenous progesterone is worth studying.\nIn conclusion, our findings suggest that laparoscopic \ncystectomy in the late luteal phase is an advantageous \noption for patients with endometrioma, as it has been \nshown for the first time to effectively and safely reduce \novarian tissue loss and preserve ovarian reserve. We also \nrecommend that once the endometriosis cyst is diag -\nnosed and laparoscopic surgery is proposed, OC should \nbe performed to control the menstrual cycle immediately \nand inhibit disease progression. In addition, drug therapy \nshould be continued after surgery to achieve efficient \ndisease management and protect ovarian function as far \nas possible. However, more prospective studies, longer \nfollow-ups, and multiple-center data are required to sup -\nport clinical practice and underlying mechanisms.\nAcknowledgements\nWe are grateful to everyone involved in conducting the study, analyzing the \ndata, and producing the manuscript.\nAuthor Contributions\nQing Wu and Tan Lin not only conceived and designed the study but \nalso participated in the drafting and writing of the manuscript. They also \nsupervised the study and critically revised the manuscript. Qing Wu, Qingmei \nYang, Lin Wu and Yanling Lin collected the clinical data. Qing Wu, Qingmei \nYang and Tan Lin were responsible for drafting and writing the manuscript \nand conducting statistical analyses. All the authors substantially contributed \nto the revision of the manuscript.\nFunding\nThis study was supported by the Zhejiang Chinese Traditional Medicine \nScientific Research Fund Project (2021ZB025) and Health Science and \nTechnology Program of Zhejiang Province (2023KY054). The funders had no \nrole in the study design, data collection and analysis, publication decision, or \nmanuscript preparation.\nData Availability\nData from this study are publicly unavailable owing to ethical and legal \nrestrictions. However, data may be made available upon reasonable request to \nthe corresponding author.\nDeclarations\nCompeting interests\nThe authors declare no competing interests.\nEthical approval and consent to participate\nEthical approval (2018ky0024) to conduct the study was provided by the \nInstitutional Ethics Committee of Fujian provincial hospital ethics committee \nand registered under the clinical trial registry number (ChiCTR1800019766).\nConsent for publication\nNot applicable.\nProvenance and peer review\nNot commissioned, externally peer-reviewed.\nAuthor details\n1Reproductive Medicine Center, Department of Gynecology, Affiliated \nPeople’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou \nMedical College, Hangzhou, Zhejiang 310014, P .R. China\n2Department of Obstetrics and Gynecology, Fujian Provincial Hospital, \nClinical Medical School of Fujian Medical University, Fuzhou 350001, \nFujian, P .R. China\n3Department of Clinical Laboratory, School of Medicine, Xiang’an Hospital \nof Xiamen University, Xiamen University, Xiamen 361101, China\nReceived: 9 May 2023 / Accepted: 12 June 2023\nReferences\n1. Ajossa S, Mais V, Guerriero S, Paoletti AM, Caffiero A, Murgia C, et al. The \nprevalence of endometriosis in premenopausal women undergoing gyneco-\nlogical surgery. Clin Exp Obstet Gynecol. 1994;21:195–7.\n\nPage 7 of 7\nWu et al. Reproductive Biology and Endocrinology            (2023) 21:59 \n2. Atwi D, Kamal M, Quinton M, Hassell LA. Malignant transformation of mature \ncystic teratoma of the ovary. J Obstet Gynaecol Res. 2022;48:3068–76. https://\ndoi.org/10.1111/jog.15409.\n3. Raffi F, Metwally M, Amer S. The impact of excision of ovarian endometrioma \non ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol \nMetab. 2012;97:3146–54. https://doi.org/10.1210/jc.2012-1558.\n4. Lee DY, Young Kim N, Jae Kim M, Yoon BK, Choi D. 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