{"paper_id":"27e49d8d-e38b-402b-8c43-d81665074abc","body_text":"1 Department of Obstetrics & Gynecology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku, Tokyo, Japan\n2 Department of Obstetrics & Gynecology, Social Welfare Foundation St. John Society Sakuramachi Hospital, 1-2-20 Sakuramachi, Koganei, Tokyo, Japan\nAbstract\nPurpose of investigation: To examine changes in anti-Müllerian\nhormone (AMH) levels following laparoscopic ovarian endometriotic cystectomy with\nabdominal wall lifting. Materials and methods: This prospective cohort\nstudy analyzed 32 patients with endometriomas who underwent laparoscopic surgery\nbetween October 2014 and December 2016 in private and university hospitals. We\nmeasured blood AMH levels at baseline and at 1, 3, 6, and 9 months following a\ncystectomy. We also examined the correlations of AMH levels with age at time of\nsurgery, bilateral cysts, cyst diameter, and Douglas fossa occlusion. Main\noutcome measures include the ovarian reserve based on AMH levels.\nResults: Compared to baseline (2.14\nKeywords\n- Cyst\n- Endometriosis\n- Fertility\n- Patients\n- Pouch\nEndometriosis, which occurs in 10% of women of childbearing age, is a disease\nthat causes dysmenorrhea and coital pain and markedly reduces women’s quality of\nlife. In addition, endometriosis is present in roughly 50% of women with\nunexplained infertility. It is commonly observed that inflammation plays a\ncentral role in the development and progression of endometriosis. The underlying\ncondition is an inflammatory process that leads to overproduction of inflammatory\nmediators such as prostaglandins, metalloproteinases, cytokines, and chemokines.\nIn addition, reactive oxygen species (ROS) and oxidative stress (OS) promote the\ngrowth and adhesion of endometrial cells in the abdominal cavity, leading to the\ndevelopment of endometriosis and difficulty in menstruation and infertility.\nRecent studies have revealed possible roles for OS and ROS, with ROS in\nparticular, increasing endothelial cell permeability and expression of adhesion\nmolecules, causing inflammatory processes. It is suggested that the OS substance\nis involved in the pathogenesis of endometriosis by activating macrophages [1, 2]. Taking into consideration cyst diameter, symptoms such as dysmenorrhea, and\nthe risk of malignant transformation, surgical treatment is often performed based\non the definitive diagnosis reached [3, 4]. Severe cases of endometriosis also\noften involve complete occlusion of the pouch of Douglas and deeply infiltrating\nendometriosis (DIE), which is defined as endometriosis which penetrates\nAccording to many recent studies, cystectomy for endometriomas may reduce the ovarian reserve and negatively affect fertility [5]. Endometriomas are generally considered to cause more injury to the normal ovarian parenchyma than other benign ovarian cysts. However, one study has reported that endometriomas and other benign ovarian cysts do not differ significantly in terms of reduced postoperative ovarian reserve [6]. Furthermore, while several studies have examined the differences in the ovarian reserve based on age, cyst diameter, and bilateral cysts, no consensus has been reached [7, 8, 9, 10]. The ovarian reserve refers to the maturation of fertilizable sperm by latent ovarian function and reserve capacity in female hormone production. Quantitative and qualitative ovarian decline has been indicated as the primary cause of age-related fertility decline. Although the serum levels of follicle-stimulating hormone (FSH) have long been used as an indicator of age-related fertility decline, measurement is hindered by menstrual cycle-related fluctuations and by a lack of sensitivity. Indicators of the ovarian reserve include antral follicle count (AFC) which are measured with ultrasonography and inhibit B which are measured with blood. However, anti-Müllerian hormone (AMH) is now the most widely used marker of the ovarian reserve because it is easier to measure and is more universal. The AMH is not expressed by primordial follicles but is expressed by granulosa cells in the preantral follicles, which are further along in the growth process; beyond this point in the growth process, expression of AMH declines. Thus, AMH is considered to reflect the ovarian reserve. The AMH inhibits FSH-induced follicular development, granulosa cell development, and aromatase. Specifically, AMH is considered to regulate follicular development via its relationship with inhibin and activin. Levels of AMH do not fluctuate based on menstrual cycles and are unaffected by hormone preparations; these characteristics make AMH an excellent marker of the ovarian reserve that can be measured at any time [11, 12].\nSurgery for endometriomas is often performed laparoscopically. Laparoscopic\nsurgery requires the creation of space to secure an intraperitoneal visual field,\nwhich can be done with two different methods: insufflation and abdominal wall\nlifting. Insufflation involves obtaining a visual field by inflating the\nperitoneal cavity with CO\nThe subjects included patients with endometriomas who underwent laparoscopic surgery between October 2014 and December 2016 at the Tokyo Medical University Hospital or its affiliated hospitals. All subjects provided informed consent. The subjects were women aged 18-45 years with a history of pregnancy. The desire to bear children (or lack thereof) was irrelevant to the present study. Exclusion criteria consisted of the following: history of adnexal surgery, hormonal therapy within the previous six months, endocrine disorders, and history of malignancies.\nEndometrioid cysts were preoperatively diagnosed by an\nobstetrician-gynecologist based on a bimanual examination and vaginal\nultrasonography (Sonovista 6.5 MHz probe, Konica Minolta, Inc., Tokyo, Japan).\nAll surgeries were performed laparoscopically using abdominal wall lifting\nmethod. The patient was placed in a 20\nWe examined changes in AMH levels before and after surgery. We also examined the\ncorrelations of AMH levels with age at surgery, bilateral cysts, cyst diameter,\nand pouch of Douglas occlusion. Statistical analysis consisted of the Student’s\nt-test and the Kruskal-Wallis test, with P\nThe subjects consisted of 32 patients; all of whom were diagnosed with\nendometriosis by postoperative pathologic examination. Patients’ characteristics\nare shown in Table 1. The subjects had a median age of 32 years and a median body\nmass index of 19.1 kg/m\n| N | 32 |\n| Bilateral/Unilateral (cases) | 18/14 |\n| Age |\n10/22 |\n| 17/15 | |\n| Closed/Open | 13/19 |\n| Age (yrs) (mean |\n31.7 ( |\n| BMI (kg/m |\n19.6 ( |\n| Cyst diameter (mm) (mean |\n6.5 ( |\n| rASRM score (mean |\n68.4 ( |\n| Operative time (min) (mean |\n128.2 ( |\n| Blood loss (mL) (mean |\n206.5 ( |\n| Preoperative AMH (ng/mL) (mean |\n2.14 ( |\n| Preoperative FSH (mIU/mL) (mean |\n4.41 ( |\nrASRM: revised American Society for Reproductive Medicine guidelines; AMH: anti-Müllerian hormone; FSH: follicle-stimulating hormone. |\nIntraoperative findings are shown on the Table 2.\n| CASE | ASRM | Frozen Pelvic |\nPeritoneal lesion | Adhesion |\n| NO.1 | 40 | mild | ||\n| NO.2 | 148 | strong | ||\n| NO.3 | 20 | − | mild | |\n| NO.4 | 74 | − | mild | |\n| NO.5 | 40 | − | mild | |\n| NO.6 | 116 | strong | ||\n| NO.7 | 38 | − | mild | |\n| NO.8 | 118 | strong | ||\n| NO.9 | 82 | − | strong | |\n| NO.10 | 108 | strong | ||\n| NO.11 | 33 | − | none | |\n| NO.12 | 37 | mild | ||\n| NO.13 | 36 | − | mild | |\n| NO.14 | 52 | − | mild | |\n| NO.15 | 27 | − | − | none |\n| NO.16 | 52 | − | mild | |\n| NO.17 | 104 | strong | ||\n| NO.18 | 55 | − | − | mild |\n| NO.19 | 100 | strong | ||\n| NO.20 | 29 | mild | ||\n| NO.21 | 46 | − | strong | |\n| NO.22 | 136 | strong | ||\n| NO.23 | 158 | strong | ||\n| NO.24 | 36 | − | − | strong |\n| NO.25 | 58 | − | strong | |\n| NO.26 | 148 | strong | ||\n| NO.27 | 52 | − | mild | |\n| NO.28 | 44 | − | mild | |\n| NO.29 | 24 | − | − | mild |\n| NO.30 | 48 | − | − | mild |\n| NO.31 | 78 | strong | ||\n| NO.32 | 58 | − | strong | |\n* * tubes or ovaries were defined as severe, and other adhesions were defined as mild. |\nAll of the 32 cases had cyst formation on either side or both sides of the ovaries and 18 cases were bilateral. Peritoneal lesions such as red, white, and black were present in 23 cases, and DIE was present in 13 cases. In all cases of deep endometriosis and obstruction of the Douglas fossa, the deep endometriosis was excised, and the Douglas fossa was freed except in one case. In one case, the patient’s family did not consent for the surgical invasion, so we limited to excision of the ovarian cyst.\nFig. 1 shows changes in AMH levels. The Kruskal-Wallis test revealed significant\ndifferences (P\nCompared to baseline, AMH levels were significantly reduced at 1 month and 3 months post-surgery. From 3 months onward, AMH levels recovered in some patients and did not differ significantly from baseline at 6 months or 9 months.\nWe examined the correlations of AMH levels with age at surgery, bilateral cysts,\ncyst diameter, and pouch of Douglas occlusion. For comparisons based on cyst\ndiameter, subjects with a cyst diameter\nThe figure shows the comparisons of AMH levels at baseline. No\nsignificant difference was observed in AMH levels at baseline based on cyst\ndiameter (P\nComparisons based on the presence of bilateral cysts revealed that baseline AMH levels were significantly lower among patients with bilateral cysts (P = 0.006).\nThis figure shows an age-based comparison. Patients who were\naged\nAssessment of Douglas obstruction was determined by laparoscopic findings during surgery. Patients with pouch of Douglas occlusion had significantly lower AMH levels than patients without pouch of Douglas occlusion (P = 0.002).\nSeveral studies have reported on the ovarian function after cystectomy in\npatients with ovarian endometriomas. However, previous studies involved\ninsufflation; and none of them included analyses of abdominal wall lifting\n[16, 17, 18, 19, 20, 21]. One previous study that used insufflation yielded results similar to the\npresent study in terms of patient characteristics such as age and body mass index\n[22]. However, we did not limit our subjects to infertile women; as a result, our\nstudy included many severe cases of endometriosis, and approximately 40% of the\npatients presented with a frozen pelvis. In the present study, subjects were\nobserved for a median period of 27.3 months following surgery. We collected blood\nand conducted ultrasonography until 9 months post-surgery and continued to\nconduct ultrasonography afterwards to monitor for recurrence. Among our 32\nsubjects, three dropped out of the study because they transferred to other\nhospitals. Defining postoperative recurrence of endometrioma as the formation of\na cyst\nAfter surgery, levels of AMH decreased transiently or consistently; these levels\nwere significantly lower at 1 and 3 months post-surgery compared to baseline but\nthey subsequently recovered, which was comparable to previous findings that used\ninsufflation. Previous studies have also reported that bilateral cysts and\nadvanced age (\nConcerning pelvic occlusion, while a previous study reported a significant decline in the ovarian reserve based on the American Society for Reproductive Medicine classification of endometriosis, the present study found that the ovarian reserve was significantly lower from baseline to 3 months in patients with pelvic occlusion [5]. In severe cases of endometriosis in which the pelvis is completely occluded, ovarian cysts generally adhere strongly to the posterior uterine wall or the pelvic floor [3, 4, 22]. The management of DIE by medication is not curative but used chiefly to alleviate symptoms and often causes serious side effects. It is not clear whether the medicine prevents disease progression, especially in severe endometriosis such as symptomatic DIE with colorectal dilation. Since the discontinuation of this treatment generally causes a recurrence, it can be argued that surgical management is the main treatment for severe endometriosis. Regardless of the location of endometriotic lesions such as endometrioma, peritoneal endometriosis, DIE, the most important therapeutic strategy is complete excision of the implant and preservation of normal tissue [30, 31]. Improving dysmenorrhea requires resection of cysts, resection of DIE, and opening of the pouch of Douglas. In these procedures, adhesion and detachment of the cyst wall may trigger injury in healthy ovarian tissue and interrupt blood flow around the hilum of the ovary. In light of previous studies reporting that excision of DIE improves outcomes in ART for patients with severe endometriosis who desire to bear children, the results of the present study indicate that if the decline in the ovarian reserve is only transient, the physician should consider the option of surgery with consideration of postoperative ART despite the decline in AMH levels [3, 4, 22].\nWith regard to coagulation in healthy ovarian tissue following cystectomy, several studies have stated that postoperative ovarian reserve was better preserved in patients who only had suturing than in patients who underwent bipolar coagulation or other forms of thermocoagulation [16, 17, 18, 19, 20, 21]. Abdominal wall lifting is performed in a manner similar to laparotomy and is thus performed with the same instruments used in laparotomy. Post-cystectomy coagulation is achieved with sutures alone without the use of a power source (such as bipolar coagulation) or specific bio-based products because suturing can be performed easily. In all cases in the present study, we performed subcutaneous abdominal wall lifting and achieved coagulation with simple ligation alone to protect the postoperative ovarian reserve.\nThis study has several limitations. First, the present study did not directly compare abdominal wall lifting with insufflation, thus preventing us from commenting on the superiority of abdominal wall lifting. Second, we did not limit subjects to infertile women, thus preventing us from discussing postoperative pregnancy rates or numbers of eggs collected. In the future, we intend to include a larger number of cases and conduct investigations limited to specific groups of participants, such as infertile women, patients with certain symptoms, and obese patients. By doing so, we hope to further examine the utility and efficacy of abdominal wall lifting compared to insufflation.\nThere is some evidence in the literature that suggests suture ligation alone results in better ovarian reserve. However, because surgery in our hospital was performed using only the wall lifting method, we could not directly compare this method with insufflation methods.\nUnfortunately, we could not recruit the planned number of cases within the study period, thus limiting the sample size. A larger prospective study is required to confirm the present findings.\nIn conclusion, in the present study, AMH levels transiently decreased postoperatively but improved from 6 months onwards to the point that they were no longer significantly different from baseline. Abdominal wall lifting in ovarian cystectomy results in the same changes in AMH levels as insufflation and is thus considered to be comparable with insufflation in terms of recurrence and protection of postoperative ovarian reserve. Although laparoscopic surgery is generally minimally invasive, it is more expensive than laparotomy owing to the use of disposable products and power sources. Most instruments used in abdominal wall lifting are cheap and reusable, and abdominal wall lifting does not require expensive insufflators, thus making it evidently superior to insufflation in terms of health care costs. Based on economics and minimal invasiveness in anesthesia management, abdominal wall lifting should be proactively considered when performing laparoscopic surgery for patients with endometriosis.\nMO, JK and EH designed the research study. MO, EH, YT performed the research. YT, TS provided help and advice on the ELISA experiments. MO, JK analyzed the data. MO, JK and HN wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.\nFunding for the present study was provided by Tokyo Medical University.\nThe authors declare no competing interests.","source_license":"CC0","license_restricted":false}