The optimal time for laparoscopic excision of ovarian endometrioma: a prospective randomized controlled trial

Objective This study aimed to explore the optimal time of laparoscopic cystectomy for unilateral ovarian endometrioma patients and evaluate the influence on ovarian reserve.

This prospective randomized controlled study included 88 women with unilateral ovarian endometrioma at a tertiary teaching hospital. All patients received their first identified diagnosis of ovarian endometrioma by ultrasound (> 4 cm and ≤ 10 cm) and were administered an oral contraceptive pill (OC) for one cycle before laparoscopy. They were randomly divided into two groups: laparoscopy at the late luteal phase (group LLP) (n = 44) (termination of OC for two days) and laparoscopy at the early follicular phase (group EFP) (n = 44) (day 3 after menstruation). Basic clinical characteristics were recorded. Serum Anti-Müllerian hormone (AMH) levels were measured at various times to predict ovarian reserve. Serum levels of Anti-Müllerian hormone (AMH) were measured at several time sites to predict the ovarian reserve; AMH and leukocyte esterase (LE) levels of the endometrioma wall were measured.

Before surgery, serum AMH levels decreased in both groups from preoperative to one week and six months postoperatively. In contrast, the difference values of group EFP were larger than those of group LLP at postoperative one 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 mean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP , significantly higher than those in group LLP (25.83% vs. 31.43%, P < 0.001). Ovarian endometrioma wall AMH of group LLP was significantly lower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P < 0.001). Meanwhile, ovarian endometrioma LE concentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001). There was also a significant inverse correlation between leukocyte esterase and AMH concentration in an ovarian endometrioma cyst wall (r=-0.564, P<0.001). Conclusion(s) The optimal time for laparoscopic cystectomy for patients with first identified unilateral ovarian endometrioma is the late luteal phase, which reduces ovarian tissue loss and preserves ovarian reserve effectively and safely. The optimal time for laparoscopic excision of ovarian endometrioma: a prospective randomized controlled trial Qing Wu1†, Qingmei Yang1†, Yanling Lin2, Lin Wu3 and Tan Lin2* Page 2 of 7 Wu et al. Reproductive Biology and Endocrinology (2023) 21:59

Endometriosis (EMT) is a common gynecological con - dition characterized by endometrial tissue outside the uterine cavity resulting in dysmenorrhea, chronic pelvic pain, pelvic masses, and infertility, which can seriously affect a woman’s health and quality of life. Ovarian endo- metriomas are the most common type of EMT, with a prevalence of 17–44% in patients with endometriosis [ 1]. Laparoscopic cystectomy has become the gold standard in the surgical management of persistent adnexal masses, including ovarian endometriosis, with the surgical aim of removing all visible endometriosis lesions and restor - ing anatomy [2]. However, ovarian cystectomy may harm ovarian reserves [ 3– 5]. In addition, surgical procedures on the ovaries lead to ovarian tissue damage, which can strip normal ovarian tissue and exacerbate the harm to the remaining follicles, raising concerns of gynecologists regarding the use of different surgical procedures in this field [6, 7]. However, only a few studies have focused on the optimal time of surgery for ovarian endometrioma. Anti-Müllerian hormone (AMH) is produced by the granulosa cells of primary, preantral, and small antral follicles, not primordial ones. Therefore, AMH level indirectly represents the quantity of the ovarian follicle pool, estimated by the number of early growing-stage follicles. Moreover, serum AMH levels appear indepen - dent of the menstrual cycle and are unaffected by gonad - otropin-releasing hormone (GnRH) agonists or oral contraceptives [8– 11]. Therefore, serum AMH levels, as a promising and reliable parameter, have been used to assess the ovarian reserve around treatments that poten - tially cause ovarian damage [12– 15]. Currently, no precise data exist on whether laparo - scopic endometrial cystectomy with different menstrua - tion phases reduces the damage to ovarian function, shortens the operation time, reduces intraoperative blood loss, and accelerates patient recovery. Therefore, this study aimed to explore the optimal timing of the first laparoscopic cystectomy in ovarian endometrioma patients with unilateral and evaluate the influence on the patient’s ovarian reserve.

This prospective clinical study was approved by the board of Fujian provincial hospital ethics committee (2018ky0024) and registered under the clinical trial regis- try number (ChiCTR1800019766). All patients provided preoperative informed consent after being informed of potential risks and complications. All patients provided preoperative informed consent after being informed of potential risks and complications. In total, 88 patients with unilateral ovarian endometrioma were recruited into this prospective study at the Department of Obstet - rics and Gynecology in Fujian provincial hospital from March 2019 to March 2021. After inclusion in the study, all patients were administered an oral contraceptive pill (OC, drospirenone, and ethinylestradiol) for one cycle to determine the timing of surgery. Inclusion criteria were as follows: (1) age 20–36 years; (2) regular menses; (3) clinical and ultrasonographic finding of unilateral ovar - ian endometrioma ≥ 4 cm and ≤ 10 cm the first time; (4) without pregnancy or plan to get pregnant in six months. Exclusion criteria were as follows: (1) any suspicious find- ing of malignant ovarian diseases; (2) ovarian, uterine, or tubal surgery history; (3) endocrine disease and treat - ment history; (4) long-term use of hormonal drugs for more than three months (e.g., gonadotropin-releasing hormone analogs); (5) smokers. Patients with infiltrated endometriosis were excluded from this study based on transvaginal ultrasound and gynecological examination. Patients who fulfilled the inclusion criteria and consented to participate in the study were enrolled. The study objec- tives and steps were explained to all patients before enrollment. All experimental procedures were performed following the guidelines for the Declaration of Helsinki. Our study was conducted according to the CONSORT guidelines [16]. Sample size calculation Using a two-sided equal-variance t-test, group sample sizes of 30 and 30 achieved 81.328% power to reject the null hypothesis of equal means when the mean popula - tion difference was 1.13. The standard deviation for both groups was 1.51, and the significance level (alpha) was 0.05 [ 3, 17]. Furthermore, considering the probability of dropouts during follow-up, the number of cases was further increased to more than 40 patients. The sample size was estimated using G*Power© software (Institutfür Experimentelle Psychologie, Heinrich Heine Universität, Düsseldorf, Germany) version 3.1.9.2. Randomization All patients were diagnosed with ovarian endometrioma by ultrasound and were administered OC for one cycle before laparoscopy to inhibit ovulation and identify the menstruation phase. After written consent, the random - ized number was concealed in an opaque, sealed envelope for each patient, and the envelopes were opened sequen - tially by a study nurse before surgery. Randomization was performed in a 1:1 ratio, according to a computer- generated number list, into two groups. The single num - ber drawn was included in the group LLP , and the double

Laparoscopy, Endometriosis, Ovarian reserve, AMH, Menstrual cycle Page 3 of 7 Wu et al. Reproductive Biology and Endocrinology (2023) 21:59 number was included in the group EFP . All patients were randomly divided into two groups: laparoscopy at late luteal phase (group LLP) (n = 44): termination of OC for two days; and laparoscopy at Early follicular phase (group EFP) (n = 44): day 3 after menstruation. Surgical technique All surgeries were performed by the same surgeons with extensive experience in endometriosis surgery, who were particularly aware of the necessity to avoid damag - ing or removing healthy ovarian tissue. Surgeons were blinded to the result of group Randomization. Laparo - scopic pneumoperitoneum was induced by CO 2 insuf - flation using a laparoscopic Veress needle. Umbilical 10-mm trocar and laparoscope entries were performed. Another three trocars were inserted through lower abdominal incisions under direct laparoscopic vision. If peri-ovarian adhesion and adhesion of Douglas fossa were present, Blunt dissection and sharp separation were combined to detach the adhesion. After mobilization of the cystic adnexa, ovarian cystectomy was performed by incising the cyst with cold scissors and carefully identi - fying, separating, and completely removing the entire cystic wall from the ovarian cortex by traction/counter traction using non-traumatic grasping forceps. Hemo - stasis was achieved using 3 − 0 absorbable sutures that were carefully selected (Vicryl; Ethicon Inc., New Jersey, USA) without electrocoagulation devices. Blood loss was estimated by combining the volume of blood collected within the suction canister with the gauze weight used during surgery. The endometriosis stage was determined based on the revised classification of the American Soci - ety of Reproductive Medicine (r-ASRM) [18]. Hormonal assays All patients provided serum specimens prior to anesthe - sia, as well as at one week and six months following the procedure. Venous blood samples were obtained, and serum was extracted by centrifugation. According to manufacturer’s instructions, serum E2 and P levels were measured by enzyme-linked fluorescent assay (ELISA; Beckman Coulter Inc., Ireland). Serum AMH level was measured by a commercially available enzyme-linked immunosorbent assay kit (ELISA; Beckman Coulter Inc., Ireland) and reported as nanograms per milliliter with a detection limit of 0.16 ng/mL. Postoperative serum AMH level and AMH decline were the primary outcome measures. Tissue sample collection After a naked-eye examination of the entire cyst wall, five pieces of the specimen of 5 mm2 were obtained from cyst walls at different portions. One was from the intermedi - ate part of the specimen, and the others were from the four quadrants. Other cyst walls were sent to the pathol - ogy laboratory, and a pathologic examination confirmed the ovarian endometriosis diagnosis. Leukocyte esterase concentration and tissue AMH levels in the cyst wall were measured using (LE/AMH) ELISA kit (Jiangsu Mei - main Co., Ltd., Jiangsu, China) as secondary endpoints. All hormonal measurements were performed at the same laboratory. Unilateral ovarian involvement We compared the potential role of unilateral ovarian involvement on preoperative levels and postoperative changes in AMH values after laparoscopic endometri - oma excision. AMH decline (% decline AMH) was used to compare the changes in AMH levels in endometrioma resected at different menstrual cycles. The rate of AMH decline was calculated using the following formula: (% decline AMH) = (preoperative AMH level – AMH at one week or six months postoperatively)/preoperative AMH level. Statistical analysis Categorical variables are described using proportions. Baseline patient characteristics were calculated via t-test for comparisons of normally distributed data and the rank-sum test for comparisons of non-normally dis - tributed data. Count data were summarized as percent - ages and compared using chi-square and Fisher’s exact tests. Analysis of variance (ANOVA) was used in intra- group comparison at different time points. A two-sided P-value of less than 0.05 was considered to be significant. The relationship between ovarian endometrioma wall AMH and leukocyte esterase concentration were gener - ated based on significant Pearson correlations between data. Statistical significance was set at p-value < 0.05. All data were analyzed using SPSS version 26 (IBM Corp., Armonk, NY, USA) and PRISM version 9.0 (GraphPad Software, La Jolla, CA, USA).

Baseline characteristics No significant differences existed in age, cyst size, gra - vidity, parity, infertility, dysmenorrhea, r-AFS Staging, blood loss volume, and operation time between the two groups. Serum progesterone was significantly higher in the late luteal phase than in the early follicular phase on the day of surgery ([2.46 ± 1.43] vs. [0.43 ± 0.34]; P < 0.001, Table 1). After laparoscopy, no severe deep-infiltrating endometriosis was observed in this study. Postopera - tive pathological diagnosis proved that all patients had ovarian endometrioma, consistent with the preoperative diagnosis. Page 4 of 7 Wu et al. Reproductive Biology and Endocrinology (2023) 21:59 AMH as the biomarker to evaluate an ovarian reserve and follicle loss There was no significant difference in preoperative AMH between the two groups. The serum AMH values one week after surgery were higher in group LLP than that in group EFP ([3.58 ± 1.65] vs. [3.02 ± 1.22], P = 0.075). However, AMH decrease value was significantly lower than that of group EFP ([1.31 ± 0.93] vs. [1.87 ± 0.97], P = 0.007). Serum AMH at postoperative six months in group LLP was significantly higher than that in group EFP ([3.35 ± 1.67] vs. [2.61 ± 1.15], P = 0.018). In contrast, AMH decrease values at postoperative six months were significantly higher in group EFP than that in group LLP ([1.54 ± 0.93] vs. [1.91 ± 1.06]; P < 0.001, Table  2). The mean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP , respectively, sig - nificantly higher than those of group LLP (25.83% vs. 31.43%) (P<0.001, Table 3). Ovarian endometrioma wall AMH of group LLP was significantly lower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P<0.001). Meanwhile, ovarian endo - metrioma leucocyte esterase concentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001, Table  4; Fig.  1). Moreover, significant negative correlation exists between LE and AMH concentration in the cyst wall of ovarian endometrioma (P<0.001, Fig. 2).

Laparoscopic endometrioma cystectomy is a recom - mended and widely used method because it meets the diagnostic and treatment goals of endometriosis, which can reduce pain, increase the chance of spontaneous pregnancy, and reduce disease progression and recur - rence [19– 21]. However, in addition to the possible nega- tive effect of endometriosis on ovarian reserve, serum AMH levels significantly decrease after laparoscopic cystectomy for endometrioma [5, 22– 26]. Since the ovar- ian reserve responds to the woman’s reproductive func - tion, it must be preserved ultimately during laparoscopic cystectomy. Table 1 Clinical characteristics of the study subjects Variable LLP (n = 44) EFP (n = 44) P-value Age, (years) 30.71 ± 3.46 29.36 ± 3.15 0.058 Age of menarche, (years) 13.32 ± 1.16 13.02 ± 1.19 0.245 Endometrioma volume, (mm3) 117.71 ± 13.97 117.93 ± 15.79 0.954 Pre-operation serum E2, (pg/mL) 89 ± 68.26 90 ± 47.78 0.834 Pre-operation serum P , (ng/mL) 2.46 ± 1.43 0.43 ± 0.34 < 0.001*** Gravidity, n (%) 0 24(54.54%) 24 (54.54%) 1 ≥ 1 20(45.45%) 20 (45.45%) Parity, n (%) 0 24(54.54%) 26 (59.09%) 0.674 ≥ 1 20(45.45%) 18 (40.90%) Infertility, n (%) 15 16 0.823 Dysmenorrhea, n (%) 13(29.54%) 16 (36.36%) 0.501 r-AFS Staging, n (%) I-II 0 0 / III 18(40.90%) 21 (47.73%) 0.524 IV 26(59.09%) 23 (52.27%) Blood loss, (mL) 43.86 ± 9.72 43.86 ± 21.83 1 Operation time, (min) 65.82 ± 9.21 67.73 ± 10.26 0.355 ***: P < 0.01. LLP: Late luteal phase; EFP: Early follicular phase; E2: Estradiol; P: Progesterone Data are presented as mean ± SD or n (%). a: Groups compared by t-test; b: Groups compared by Pearson’s chi-squared test or Fisher’s exact test; Table 2 Serum AMH levels of pre-operation and post-operation in two groups Variable Pre-op- eration AMH (ng/ mL) 1 Week- Po AMH (ng/mL) DV1 6 months- Po AMH (ng/mL) DV6 LLP (n = 44) 4.89 ± 2.37 3.58 ± 1.65 1.31 ± 0.93 3.35 ± 1.67 1.54 ± 0.93 EFP (n = 44) 4.89 ± 1.56 3.02 ± 1.22 1.87 ± 0.97 2.61 ± 1.15 1.91 ± 1.06 P-value 1 0.075 0.007** 0.018** 0.001** LLP: Late luteal phase; EFP: Early follicular phase; Po: post-operation; AMH: anti-Müllerian hormone; DV: Difference Value, DV1: Difference between preoperative AMH and one-week postoperative AMH; DV6: Difference between preoperative AMH and six months postoperative AMH. **: P < 0.05 Table 3 Decrease rate of serum AMH levels of post-operation Variable Decrease rate of AMH 1 Week- Po (%) Decrease rate of AMH 6 months- Po (%) LLP (n = 44) 25.83 ± 10.12 31.43 ± 11.13 EFP (n = 44) 37.92 ± 14.13 46.34 ± 14.23 P-value < 0.001*** < 0.001*** LLP: Late luteal phase; EFP: Early follicular phase; AMH: anti-Müllerian hormone Decrease rate of AMH 1 Week-Po: Decrease rate of AMH at one-week post- operation compared to preoperative AMH; Decrease rate of AMH six months-Po: Decrease rate of AMH at six months post-operation compared to preoperative AMH; ***: P < 0.01 Table 4 Ovarian endometrioma wall AMH and leucocyte esterase concentration Variable Ovarian endo- metrioma wall AMH (ng/mL) Ovarian endome- trioma leucocyte esterase concen- tration (ng/mL) LLP (n = 44) 22.86 ± 3.74 482.83 ± 115.88 EFP (n = 44) 31.02 ± 5.23 371.68 ± 84.49 P-value < 0.001*** < 0.001*** LLP: Late luteal phase; EFP: Early follicular phase; AMH: anti-Müllerian hormone; ***: P < 0.01 Page 5 of 7 Wu et al. Reproductive Biology and Endocrinology (2023) 21:59 Anti-Müllerian Hormone (AMH) is a transforming growth factor-β family member secreted by primary, preantral, and antral follicles [ 27]. AMH levels correlate with the number of growing follicles and do not change significantly during the menstrual cycle [ 14, 28]. There- fore, AMH has been used to predict the decline of ovar - ian function and is the preferred biomarker of ovarian reserve [ 29, 30]. Several hypotheses have been formu - lated to explain the relationship between cyst excision and reduction of ovarian reserve. Some authors dem - onstrated that the removal of ovarian endometrioma, commonly characterized by the absence of a clear plane of cleavage between the endometrioma cyst and ovarian tissue, could result in unintentional removal of the ovar - ian cortex and loss of follicles, with a potential reduction in follicular reserve [ 31, 32]. Furthermore, the amount of ovarian parenchyma loss seems to increase proportion - ally to the increase in cyst diameter [ 33]. According to this hypothesis, damage to the ovarian reserve can result from permanent loss of ovarian tissue and should per - sist over time after surgery [ 23]. This study investigated the optimal surgical timing to perform a cystectomy. It can reduce ovarian function damage by evaluating serial changes in serum AMH levels after laparoscopic endo - metriosis cystectomy for endometriosis and evaluating ovarian endometrioma wall AMH and ovarian endome - trioma leucocyte esterase concentration. Our results displayed that serum AMH levels decreased significantly at one week and six months after surgery. However, the decreasing trend of serum AMH levels in group LLP was significantly lower than in group EFP . A systematic review and meta-analysis showed that the median preoperative AMH level was 3.1 ng/mL, which significantly decreased to 1.51 ng/mL within 1–9 months after surgery, with a decline rate of 51.29% [ 3]. A prospective longitudinal study showed that the rate of decrease in AMH was 52.2%, 53.7%, and 54.8% at 1, 3, and 6 months after surgery compared to baseline lev - els, respectively [ 34]. In this study, compared with base - line levels, patients who underwent surgical treatment in the late luteal phase had AMH decline rates of 25.8% and 31.4% at one week and six months postoperatively, respectively. However, patients treated surgically at the early follicular phase had AMH decline rates of 37.9% and 46.3% at one week and six months postoperatively, respectively. Hoang Tong et al. found that unilateral ovar- ian cystectomy with a 43.4–48% decrease in serum AMH from 1 to 6 months after surgery was the same as the cys- tectomy results performed in the early follicular phase in this study [ 34]. Zhou Liu et al. estimated the distance to restore ovarian reserve after laparoscopic unilateral ovar- ian cystectomy to be six months [ 35]. Urman et al. found a significant decrease in AMH concentration and antral follicle count (AFC) one month after surgery, a reduction that persisted six months postoperatively [ 36]. Therefore, Fig. 2 Correlation analysis between ovarian endometrioma wall AMH and leucocyte esterase concentration. AMH: anti-M?llerian hormone; P < 0.05 means the difference was statistically significant Fig. 1 Ovarian endometrioma wall AMH and leucocyte esterase concentration. LLP: Late luteal phase; EFP: Early follicular phase; AMH: anti-Müllerian hormone; ***: P < 0.01 Page 6 of 7 Wu et al. Reproductive Biology and Endocrinology (2023) 21:59 we conclude that laparoscopic cystectomy for unilateral ovarian endometrioma at the late luteal phase may reach a content result about follicle loss and ovarian reserve. AMH is produced by granulosa cells of primary, pre - antral, and small antral follicles. Although there have been few studies on detecting ovarian endometrioma wall AMH, we believe it is closely related to the number of granulosa cells in the endometrioma wall, reflecting the quantity of ovarian tissue and follicles in the endo - metrioma wall. Leukocyte esterase activity is commonly used for sensitive detection of leukocytes. Leukocytes infiltrate the ovarian endometrioma wall, resulting in endometrioma wall edema and loose tissue. Our study also found that ovarian endometrioma wall AMH of group LLP in patients with first ovarian cystectomy was significantly lower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P<0.001). In contrast, the ovarian endo- metrioma leucocyte esterase concentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001). A sig - nificant inverse relationship was observed between leu - kocyte esterase and AMH concentration in the ovarian endometrioma cyst wall ( P < 0.001). Our results revealed that ovarian cystectomy with different menstrual cycles may affect the rate of decrease in AMH levels after lapa - roscopic ovarian cystectomy in patients with endome - triosis. The border density between endometrioma and normal ovarian tissue may fluctuate during the menstrual cycle. Loosening of the border and inflammatory edema of the tissue allows the cyst wall to be more easily peeled off in the late luteal phase, reducing the loss of normal ovarian tissue. This study had some limitations. First, this study ana - lyzed data from one single center. Second, this study was conducted only in patients with the first identified single ovarian endometrioma. The results were unavailable for patients with previous endometrioma and pelvic surgery. Third, patients with bilateral ovarian endometrioma cysts were not investigated. Finally, this study had a short fol - low-up period (six months). We used oral contraceptive to control the menstrual cycle to ensure that surgery was performed in the late luteal phase. The specific mecha - nism needs to be further studied. Whether surgery can achieve the same effect after the withdrawal of other exogenous progesterone is worth studying. In conclusion, our findings suggest that laparoscopic cystectomy in the late luteal phase is an advantageous option for patients with endometrioma, as it has been shown for the first time to effectively and safely reduce ovarian tissue loss and preserve ovarian reserve. We also recommend that once the endometriosis cyst is diag - nosed and laparoscopic surgery is proposed, OC should be performed to control the menstrual cycle immediately and inhibit disease progression. In addition, drug therapy should be continued after surgery to achieve efficient disease management and protect ovarian function as far as possible. However, more prospective studies, longer follow-ups, and multiple-center data are required to sup - port clinical practice and underlying mechanisms.

We are grateful to everyone involved in conducting the study, analyzing the data, and producing the manuscript. Author Contributions Qing Wu and Tan Lin not only conceived and designed the study but also participated in the drafting and writing of the manuscript. They also supervised the study and critically revised the manuscript. Qing Wu, Qingmei Yang, Lin Wu and Yanling Lin collected the clinical data. Qing Wu, Qingmei Yang and Tan Lin were responsible for drafting and writing the manuscript and conducting statistical analyses. All the authors substantially contributed to the revision of the manuscript. Funding This study was supported by the Zhejiang Chinese Traditional Medicine Scientific Research Fund Project (2021ZB025) and Health Science and Technology Program of Zhejiang Province (2023KY054). The funders had no role in the study design, data collection and analysis, publication decision, or manuscript preparation. Data Availability Data from this study are publicly unavailable owing to ethical and legal restrictions. However, data may be made available upon reasonable request to the corresponding author. Declarations Competing interests The authors declare no competing interests. Ethical approval and consent to participate Ethical approval (2018ky0024) to conduct the study was provided by the Institutional Ethics Committee of Fujian provincial hospital ethics committee and registered under the clinical trial registry number (ChiCTR1800019766). Consent for publication Not applicable. Provenance and peer review Not commissioned, externally peer-reviewed. Author details 1Reproductive Medicine Center, Department of Gynecology, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P .R. China 2Department of Obstetrics and Gynecology, Fujian Provincial Hospital, Clinical Medical School of Fujian Medical University, Fuzhou 350001, Fujian, P .R. China 3Department of Clinical Laboratory, School of Medicine, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen 361101, China Received: 9 May 2023 / Accepted: 12 June 2023

1. Ajossa S, Mais V, Guerriero S, Paoletti AM, Caffiero A, Murgia C, et al. The prevalence of endometriosis in premenopausal women undergoing gyneco- logical surgery. Clin Exp Obstet Gynecol. 1994;21:195–7. Page 7 of 7 Wu et al. Reproductive Biology and Endocrinology (2023) 21:59 2. Atwi D, Kamal M, Quinton M, Hassell LA. Malignant transformation of mature cystic teratoma of the ovary. J Obstet Gynaecol Res. 2022;48:3068–76. https:// doi.org/10.1111/jog.15409. 3. Raffi F, Metwally M, Amer S. The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012;97:3146–54. https://doi.org/10.1210/jc.2012-1558. 4. Lee DY, Young Kim N, Jae Kim M, Yoon BK, Choi D. Effects of laparoscopic sur- gery on serum anti-mullerian hormone levels in reproductive-aged women with endometrioma. Gynecol Endocrinol. 2011;27:733–6. https://doi.org/10.3 109/09513590.2010.538098. 5. Sugita A, Iwase A, Goto M, Nakahara T, Nakamura T, Kondo M, et al. One-year follow-up of serum antimullerian hormone levels in patients with cystec- tomy: are different sequential changes due to different mechanisms causing damage to the ovarian reserve? Fertil Steril. 2013;100:516–522e513. https:// doi.org/10.1016/j.fertnstert.2013.03.032. 6. Dhanawat J, Pape J, Freytag D, Maass N, Alkatout I. Ovariopexy-before and after endometriosis surgery. Biomedicines. 2020;8. https://doi.org/10.3390/ biomedicines8120533. 7. Ruiz-Flores FJ, Garcia-Velasco JA. Is there a benefit for surgery in endome- trioma-associated infertility? Curr Opin Obstet Gynecol. 2012;24:136–40. https://doi.org/10.1097/GCO.0b013e32835175d9. 8. Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clini- cal consequences. Endocr Rev. 2009;30:465–93. https://doi.org/10.1210/ er.2009-0006. 9. La Marca A, Stabile G, Artenisio AC, Volpe A. Serum anti-mullerian hormone throughout the human menstrual cycle. Hum Reprod. 2006;21:3103–7. https://doi.org/10.1093/humrep/del291. 10. Deb S, Campbell BK, Pincott-Allen C, Clewes JS, Cumberpatch G, Raine-Fen- ning NJ. Quantifying effect of combined oral contraceptive pill on functional ovarian reserve as measured by serum anti-mullerian hormone and small antral follicle count using three-dimensional ultrasound. Ultrasound Obstet Gynecol. 2012;39:574–80. https://doi.org/10.1002/uog.10114. 11. Kristensen SL, Ramlau-Hansen CH, Andersen CY, Ernst E, Olsen SF, Bonde JP , et al. The association between circulating levels of antimullerian hormone and follicle number, androgens, and menstrual cycle characteristics in young women. Fertil Steril. 2012;97:779–85. https://doi.org/10.1016/j. fertnstert.2011.12.017. 12. van Disseldorp J, Lambalk CB, Kwee J, Looman CW, Eijkemans MJ, Fauser BC, et al. Comparison of inter- and intra-cycle variability of anti-mullerian hormone and antral follicle counts. Hum Reprod. 2010;25:221–7. https://doi. org/10.1093/humrep/dep366. 13. La Marca A, Giulini S, Tirelli A, Bertucci E, Marsella T, Xella S, et al. Anti-mul- lerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology. Hum Reprod. 2007;22:766–71. https://doi.org/10.1093/humrep/del421. 14. Hehenkamp WJ, Looman CW, Themmen AP , de Jong FH, Te Velde ER, Broek- mans FJ. Anti-mullerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab. 2006;91:4057– 63. https://doi.org/10.1210/jc.2006-0331. 15. Chang HJ, Han SH, Lee JR, Jee BC, Lee BI, Suh CS, et al. Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-mullerian hormone levels. Fertil Steril. 2010;94:343–9. https://doi.org/10.1016/j. fertnstert.2009.02.022. 16. Schulz KF, Altman DG, Moher D, Group C. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2011;9:672–7. https://doi.org/10.1016/j.ijsu.2011.09.004. 17. Shaltout MF, Elsheikhah A, Maged AM, Elsherbini MM, Zaki SS, Dahab S, et al. A randomized controlled trial of a new technique for laparoscopic management of ovarian endometriosis preventing recurrence and keep- ing ovarian reserve. J Ovarian Res. 2019;12:66. https://doi.org/10.1186/ s13048-019-0542-0. 18. Revised American Society for Reproductive Medicine classification of endometriosis. : 1996, Fertil Steril. 67(1997)817–821. https://doi.org/10.1016/ s0015-0282(97)81391-x. 19. Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29:400–12. https://doi.org/10.1093/humrep/det457. 20. M. Practice Committee of the American Society for Reproductive, Endo- metriosis and infertility: a committee opinion, Fertil Steril. 98(2012)591–8. https://doi.org/10.1016/j.fertnstert.2012.05.031. 21. Chapron C, Marcellin L, Borghese B, Santulli P . Rethinking mechanisms, diag- nosis and management of endometriosis. Nat Rev Endocrinol. 2019;15:666– 82. https://doi.org/10.1038/s41574-019-0245-z. 22. Lind T, Hammarstrom M, Lampic C, Rodriguez-Wallberg K. Anti-mullerian hormone reduction after ovarian cyst surgery is dependent on the histologi- cal cyst type and preoperative anti-mullerian hormone levels. Acta Obstet Gynecol Scand. 2015;94:183–90. https://doi.org/10.1111/aogs.12526. 23. Alborzi S, Keramati P , Younesi M, Samsami A, Dadras N. The impact of laparo- scopic cystectomy on ovarian reserve in patients with unilateral and bilateral endometriomas. Fertil Steril. 2014;101:427–34. https://doi.org/10.1016/j. fertnstert.2013.10.019. 24. Vignali M, Mabrouk M, Ciocca E, Alabiso G, Barbasetti di Prun A, Gentilini D, et al. Surgical excision of ovarian endometriomas: does it truly impair ovarian reserve? Long term anti-mullerian hormone (AMH) changes after surgery. J Obstet Gynaecol Res. 2015;41:1773–8. https://doi.org/10.1111/jog.12830. 25. Wang Y, Ruan X, Lu D, Sheng J, Mueck AO. Effect of laparoscopic endo- metrioma cystectomy on anti-mullerian hormone (AMH) levels. Gynecol Endocrinol. 2019;35:494–7. https://doi.org/10.1080/09513590.2018.1549220. 26. Kovacevic VM, Andelic LM, Mitrovic A, Jovanovic. Changes in serum antimul- lerian hormone levels in patients 6 and 12 months after endometrioma stripping surgery. Fertil Steril. 2018;110:1173–80. https://doi.org/10.1016/j. fertnstert.2018.07.019. 27. Somigliana E, Berlanda N, Benaglia L, Vigano P , Vercellini P , Fedele L. Surgical excision of endometriomas and ovarian reserve: a systematic review on serum antimullerian hormone level modifications. Fertil Steril. 2012;98:1531– 8. https://doi.org/10.1016/j.fertnstert.2012.08.009. 28. Moolhuijsen LME, Visser JA. Hormone and Ovarian Reserve: update on assess- ing ovarian function. J Clin Endocrinol Metab. 2020;105:3361–73. https://doi. org/10.1210/clinem/dgaa513. 29. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP , Visser JA, et al. Anti-mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004;10:77–83. https://doi.org/10.1093/molehr/gah015. 30. Anderson RA, Nelson SM, Wallace WH. Measuring anti-mullerian hormone for the assessment of ovarian reserve: when and for whom is it indicated? Maturitas. 2012;71:28–33. https://doi.org/10.1016/j.maturitas.2011.11.008. 31. Muzii L, Bianchi A, Croce C, Manci N, Panici PB. Laparoscopic excision of ovar- ian cysts: is the stripping technique a tissue-sparing procedure? Fertil Steril. 2002;77:609–14. https://doi.org/10.1016/s0015-0282(01)03203-4. 32. Hachisuga T, Kawarabayashi T. Histopathological analysis of laparoscopically treated ovarian endometriotic cysts with special reference to loss of follicles. Hum Reprod. 2002;17:432–5. https://doi.org/10.1093/humrep/17.2.432. 33. Roman H, Tarta O, Pura I, Opris I, Bourdel N, Marpeau L, et al. Direct propor- tional relationship between endometrioma size and ovarian parenchyma inadvertently removed during cystectomy, and its implication on the management of enlarged endometriomas. Hum Reprod. 2010;25:1428–32. https://doi.org/10.1093/humrep/deq069. 34. Anh ND, Ha NTT, Tri NM, Huynh DK, Dat DT, Thuong PTH, et al. Long-term Follow-Up of anti-mullerian hormone levels after laparoscopic endome- trioma cystectomy. Int J Med Sci. 2022;19:651–8. https://doi.org/10.7150/ ijms.69830. 35. Li H, Yan B, Wang Y, Shu Z, Li P , Liu Y, et al. The optimal time of Ovarian Reserve Recovery after laparoscopic unilateral ovarian non-endometriotic cystec- tomy. Front Endocrinol (Lausanne). 2021;12:671225. https://doi.org/10.3389/ fendo.2021.671225. 36. Urman B, Alper E, Yakin K, Oktem O, Aksoy S, Alatas C, et al. Removal of unilateral endometriomas is associated with immediate and sustained reduc- tion in ovarian reserve. Reprod Biomed Online. 2013;27:212–6. https://doi. org/10.1016/j.rbmo.2013.04.016. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.