{"paper_id":"be127a1a-1dc4-44df-a87b-cfee36247cd7","body_text":"Frontiers in Medical Science Research \nISSN 2618-1584 V ol. 4, Issue 9: 41-46, DOI: 10.25236/FMSR.2022.040908 \nPublished by Francis Academic Press, UK \n-41- \nA Real-world Study of Changes in Preoperative and \nPostoperative CA125, A and M H in Patients with \nEndometriosis \nSuwei Lan1,*, Xingcha Wang1, Penghua Cui1, Chunhui Wang1, Mingjing Zhai1, \nYang Li2, Lifeng Chang1 \n1Department of Gynecology, Affiliated Hospital of Chengde Medical College, Chengde, Hebei, China \n2Department of Pediatrics, Chengde Maternal and Child Health Center, Chengde, Hebei, China \n3Department of Obstetrics and Gynecology, Pingquan Hospital, Chengde, Hebei, China \n*Corresponding author: 15203242516@163.com \nAbstract: To investigate the changes of ovarian reserve function in real -world of patients diagnosed \nendometriosis with different stages, preoperative and postoperative, respectively. Ananlysis the \nrelationship between anti -mullerian hormone (AMH) and CA125. A total of 50 patients operatived \nbecause of uterine myoma and 185 patients diagnosed endometriosis from 2014 to June 2020 were \ninrolled. Of the endometriosis patients, 70 patients with stage Ⅰ-Ⅱ and 115 patients with stage Ⅲ-Ⅳ. The \ngroups were redivided into group A(≤35years) and group B (>36) based on age. The serum CA125 and \nAMH was tested preoperative, retested the AMH1 and 6 months postoperaive. Then analyzed these data \nby statistical methods. ① There is no statistical significance in the same age groups versus preoperative \nblood AMH in patients with Ⅰ -Ⅱ stage endometriosis groups and in the myoma patients (P> 0.05), \ncompared to the Ⅲ-Ⅳ stage of endometriosis, the A MH were high in the myoma groups and Ⅰ -Ⅱ stage \nendometriosis groups (P <0.05);  ② There was no significantly change of serum AMH in the uterine \nmyoma groups between preoperative and postoperative, the differental has no statistical significance \n(P>0.05)in the Ⅰ-Ⅱ stage endometriosis a groups, the AMH decreased 1 month after operation, whereas \nthere was no significant decrease 6 months after operation compared to preoperative, and the difference \nhad not statistically significance (P> 0.05). In the Ⅲ-Ⅳ stage endometriosis groups, the AMH decreased \nafter operation in 1 and 6 months, and the difference had statistically significance (P <0.05). ③ The \nCA125 was significantly higher in advanced endometriosis stages compared to the Ⅰ-Ⅱ stage groups and \nuterine myoma groups, and was negatively correlated with preoperative AMH. \nKeywords: Anti-mullerian hormone; Ovarian endometriosis cyst; CA125; Ovarian reserve function \n1. Introduction \nEndometriosis is a common and frequently occurring disease in women of childbearing age. In recent \nyears, with the increase of the proportion of cesarean section, the incidence rate of endometriosis is \ngradually increasing.  Ovarian endometriosis is the most common endometriosis, with an incidence of \n17%-44% [1]. In addition to dysmenorrh ea, infertility is also one of its important hazards. The main \ncause of infertility caused by endometriosis is the infiltration, erosion and destruction of ovarian tissue, \nwhich has a certain impact on the reserve function of ovary. Therefore, it needs act ive treatment. \nLaparoscopic ovarian exfoliation is currently recognized as the ‘gold standard’ for the treatment of \novarian endometriosis. However, whether the operation itself will damage the ovarian tissue and destroy \nthe reserve function of the ovary is still controversial [2]. \nIn recent years, anti -Mü llerian hormone (AMH) has attracted much attention in the evaluation of \novarian reserve. It is composed of two dimer monomers with a relative molecular mass of 72,000, which \nare connected to homodimeric gly coproteins by disulfide bonds, belonging to the transforming growth \nfactor-β superfamily members, these members play a very important role in tissue growth and \ndifferentiation. The synthesis of AMH in women is derived from follicular granulosa cells in the  early \nstages of follicular development and is a crucial hormone in the regulation of follicular maturation [3]. \nThere is a good correlation between AMH and the number of antral follicles and the number of primordial \nfollicles present in ovarian tissue [4], whereas in ovarian endometriosis undergoing cyst enucleation, part \nof the primordial follicles in the ovarian cortex may be destroyed, thus affecting the function of the ovary, \n\nFrontiers in Medical Science Research \nISSN 2618-1584 V ol. 4, Issue 9: 41-46, DOI: 10.25236/FMSR.2022.040908 \nPublished by Francis Academic Press, UK \n-42- \nand because it is not affected by the regulation of the hypothalamic pituitary ovarian axis, thus making it \nbetter stable and non -cycle dependent, convenient to detect clinically. There have been a large number \nof studies confirmed that serum AMH level is a good indicator for evaluating ovarian reserve function \n[5-7], and it is abl e to predict the slight damage to the ovary at an early stage to predict and evaluate \nvarious situations that make the ovarian function impaired. \nCA125 is a high molecular glycoprotein surface antigen derived from coelomic epithelial cells, which \nmainly exists in human endometrial, cervical epithelium, fallopian tube, decidua, peritoneum and other \nglandular organs. Its elevated expression in serum is commonly found in endometriosis, acute pelvic \ninflammatory disease, early pregnancy, and ovarian and fallopi an tube cancer. The main source is the \nendometrium, and its concentration is closely related to the biological activity of the endometrium [8]. A \nlarge number of clinical studies have shown that the preoperative serum CA125 concentration in patients \nwith endometriosis is related to the stage. In patients with early or no obvious clinical symptoms, serum \nCA125 is generally within the normal range. With the progress of endometriosis, its expression is on the \nrise, and it can be significantly increased in patients with mid-late stage or typical symptoms. Therefore, \nfor patients with endometriosis, the level of blood CA125 indicates the disease degree of endometriosis, \nbut it is unknown whether its concentration is related to the change of postoperative ovarian reserve. \nIn this study, in the real world, 50 patients with uterine fibroids and 185 patients with ovarian \nendometriosis underwent preoperative and postoperative blood AMH and CA125 monitoring to evaluate \nthe ovarian endometriosis itself. Whether it has an y effect on ovarian reserve function and whether \nlaparoscopic ovarian endometriosis cystectomy has any effect on ovarian reserve function. The research \nresults are now reported as follows. \n2. Materials and methods \n2.1. Subjects and groups  \nA total of 50 patients who underwent laparoscopic myomectomy due to uterine fibroids at the \nAffiliated Hospital of Chengde Medical College from 2014 to June 2020 and 50 patients who underwent \nlaparoscopic ovarian myomectomy due to ovarian endometriosis were selected as study subjects, among \nwhich 70 patients with endometriosis were divided into stages I -II according to ASRM revised \nendometriosis staging method and 115 patients were divided into stages III-IV . The groups were further \ndivided into group A (≤ 35 years) and group B (> 36 years) based on age. Inclusion criteria of uterine \nfibroid group: ①uterine fibroids were suggested by color ultrasound before operation, and they were \npathologically confirmed after operation as uterine fibroids without degenera tion; ②Menstruation was \nregular preoperatively, and timing of surgery was chosen 3-7 days after clean menstruation; ③No history \nof taking hormone drugs in recent half a year; ④There were no other serious medical and surgical \ncomorbidities affecting surgery  or hormone determination. Inclusion criteria for the ovarian \nendometriosis group: ①preoperative color ultrasound suggested an ovarian cyst, the diameter of the cyst \nwas ≥ 4 cm, predominantly cystic, and dense punctate weak echogenicity was seen in it, whi ch was \npathologically confirmed as ovarian endometriosis after surgery; ②  Menstruation was regular \npreoperatively, and timing of surgery was chosen 3 -7 days after clean menstruation; ③ No history of \ntaking hormone drugs in recent half a year; ④ There were no other serious medical and surgical \ncomorbidities affecting surgery or hormone determination. All surgical approaches for patients were \nperformed laparoscopically and were performed by associate chief physicians with extensive experience \nin our hospital and those with job titles above. Two methods of hemostasis after ovarian cystectomy \ninclude bipolar coagulation and suture hemostasis. The uterus was shaped by suture after myomectomy. \nPostoperative pathology was diagnosed by the experienced chief physicia n of our hospital. The \nprocedures followed in this study conformed to the ethical standards established by the Affiliated \nHospital of Chengde Medical College, and were approved by the committee, and the patients themselves \nsigned an informed consent form for clinical research. \n2.2. Methods  \n2.2.1. Ovariohysterectomy and myomectomy \nOvarian endometriosis cystectomy: All endometriosis patients underwent laparoscopic EMS \nconservative surgery, including ovarian cystectomy, pelvic adhesion release, ectopic lesion resection and \nelectrocautery technique. The operation is carried out 3-7 days after menstruation is clean. Specific steps: \n\nFrontiers in Medical Science Research \nISSN 2618-1584 V ol. 4, Issue 9: 41-46, DOI: 10.25236/FMSR.2022.040908 \nPublished by Francis Academic Press, UK \n-43- \n① Insert laparoscope for comprehensive exploration and progressive clinical staging. ② Perform \nadhesion release and cystectomy to expose the operative field, and then suture the ovary with absorbable \nsutures to stop the bleeding and perform ovarian shaping. If there is still bleeding, use bipolar coagulation \nat last. ③ After the operation, the basin and abdominal cavity should be washed repeatedly with a large \namount of normal saline. The resected tissue was sent for histopathological examination. \nMyomectomy: all enrolled patients with uterine fibroids underwent myomectomy laparoscopically. \nSurgery was performed within 3 -7 days after clean menstrua tion. Specific steps: ① Laparoscopy was \nplaced for full exploration. ② Monopolar incision of the serosal layer of the uterine fibroid to expose \nthe fibroid nodule, such as bleeding from coarse blood vessels during stripping to give timely \nelectrocoagulation and hemostasis, combined with bending forceps to completely denude the fibroid. ③ \nThe fibroid is pulverized by a fibroid rotator, and removed. The uterus was sutured by barbed thread to \nstop bleeding and shaped. As there was still oozing blood at the needle eye, and finally hemostasis with \nbipolar electrocoagulation. ④ The application of a large amount of normal saline repeatedly rinses the \nbasin and abdominal cavity. The resected tissues were sent for histopathological examination. \n2.2.2. Serum anti-mullerian hormone test \nAll patients were given an empty stomach before surgery and in the early morning of 1 and 6 months \nafter surgery, 5 ml of venous blood was drawn, and the serum was separated by centrifugation after \nstanding for 2 hours at 3500 rpm and AMH was detected by Roche E411 automatic chemiluminescence \nanalyzer. \n2.2.3. Serum CA125 Detection \n5ml of venous blood was drawn from all patients on an empty stomach in the early morning before \nsurgery, and after standing for 2 hours, the serum was separated by centrifugation at a speed of 3500 rpm, \nand CA125 was detected. \n2.3. Follow up  \nSerum AMH levels we re measured in all patients preoperatively at 1 day, 1 month, and 6 months \npostoperatively, and long-term follow-up of pregnancy outcomes was performed at 2 years by using 2 \nmethods: regular review with telephone follow -up, in which the follow -up of pregna nt patients was \ncompleted just before, and in some patients, the follow-up was lost. \n2.4. Statistical analysis observation indicators  \nSPSS 19.0 software was used for data processing, and the measurement data were expressed as mean \n±  standard deviation one-way analysis of variance was used, the relationship between two variables was \nanalyzed by correlation, and the comparison between groups was performed by T-test. Inspection of the \nlevel of α=0.05 and P < 0.05 were considered statistically significant. \n3. Results \n3.1. General information on the study population  \nA total of 235 patients were included in this study, including 50 patients with uterine fibroids, 24 \npatients in group A, 26 patients in group B, and 70 patients with stage I -II endometriosis, including 25 \npatients in group A, there were 45 patients in group B and 115 patients with stage III-IV endometriosis, \nincluding 55 patients in group A and 60 patients in group B. In group A and group B, there were no \nstatistically significant differenc es in age and BIM between the groups. However, there was no \nstatistically significant difference in AMH in preoperative blood AMH between the uterine fibroids group \nand the stage I-II group in the same age group (P>0.05,); compared with the stage III-IV group Compared \nwith the uterine fibroids group and the Ⅰ-Ⅱ stage endometriosis group, the preoperative blood AMH was \nhigher, and the difference was statistically significant (P<0.05). The preoperative general information \nand serum AMH values are shown in Table 1 and Table 2, respectively.\n\nFrontiers in Medical Science Research \nISSN 2618-1584 V ol. 4, Issue 9: 41-46, DOI: 10.25236/FMSR.2022.040908 \nPublished by Francis Academic Press, UK \n-44- \nTable 1: General data and serum AMH levels of the patients in group A. \nGroup Age (years) BIM (kg/m2) AMH (ng/ml) \nuterine myoma 27.38± 4.89 20.59± 0.54 4.33± 1.19 \nⅠ-Ⅱendometriosis 28.44± 4.67 21.23± 0.33 4.12± 0.92 \nⅢ-Ⅳendometriosis 28.02± 4.02 20.86± 0.31 3.05± 1.02 \nP >0.05 >0.05 <0.05 \nTable 1: General data and serum AMH levels of the patients in group B. \nGroup Age (years) BIM (kg/m2) AMH (ng/ml) \nuterine myoma 40.46± 3.17 21.32± 0.58 3.42± 0.85 \nⅠ-Ⅱendometriosis 40.22± 3.21 20.82± 0.61 2.69± 0.93 \nⅢ-Ⅳendometriosis 41.8± 3.82 21.93± 0.71 1.84± 0.84 \nP >0.05 >0.05 <0.05 \n3.2. Correlation  \nThere was no significant correlation between the preoperative blood CA125 level and AMH in the \npatients with stage Ⅰ-Ⅱ endometriosis, while there was a positive correlation between the preoperative \nblood AMH and CA125 level in the patients with stage Ⅲ-Ⅳ endometriosis (Figure 1). \n \nFigure 1: Preoperative blood AMH and CA125 in the stage I- V endometriosis group \n3.3. Statistics of changes in blood AMH \nThere was no significant decrease in blood AMH in the uterine fibroids group at 1 month and 6 \nmonths after operation, and the difference was not statistically significant (P>0.05). Monthly blood AMH \ndecreased compared with that before operation, and the difference was statistically significant (P<0.05), \nbut there was no significant decrease compared with preoperative 6 months after operation, and the \ndifference was not statistically significant (P>0.05). The blood AMH in stage III-IV group decreased at \n1 month and 6 months after operation, and the difference was statistically significant (P<0.05) (Figure2). \n \nFigure 2: Preoperative and postoperative changes of the patient's AMH \n\n\nFrontiers in Medical Science Research \nISSN 2618-1584 V ol. 4, Issue 9: 41-46, DOI: 10.25236/FMSR.2022.040908 \nPublished by Francis Academic Press, UK \n-45- \n4. Conclusions \n(1) Compared with other patients of the same age group, patients with advanced endometriosis have \nlower preoperative blood AMH and higher blood CA125. Considering that advanced endometriosis itself \nhas an impact on ovarian reserve function, it is negatively correlated with the level of CA125.  \n(2) In the early and young patients with endometriosis, the blood AMH decreased in a short period of \ntime compared with that before the operation, but the effect on ovarian function was reversible, and there \nwas no significant difference between the two afte r six months. Postoperative blood AMH in patients \nwith late endometriosis has a greater decline. Considering that surgery has a serious impact on the decline \nof ovarian reserve, and the effect is irreversible, the degree of AMH decline is negatively correlated with \nthe preoperative CA125 level. \n(3) For women with reproductive needs, patients with endometriosis should undergo surgery as soon \nas possible to avoid the progression of the disease, which will eventually affect ovarian function and lead \nto infertility. \n5. Discussion \nEndometriosis refers to the growth of endometrial tissue with growth function in other parts of the \nuterus. According to its anatomical location, it can be divided into three categories: pelvic adhesion type, \novarian cyst type and deep infiltration type. Among them, ectopic endometrial cysts located in the ovarian \nparenchyma can directly affect the female ovarian reserve [9]. The number of primordial follicles in the \novaries affected by endometriotic cysts decreases, while the number of atr etic follicles and primary \nfollicles increases. The results in this experiment are consistent with this theory. The explanation for this \nphenomenon is that the ovaries affected by ovarian endometriotic cyst lesions have an inflammatory \nresponse, which stimulates more primordial follicles that should have been dormant to be recruited into \nthe growth and development track, and the inflammatory response of local lesions makes Ovarian fibrosis \naffects its blood supply, so that the follicles entering the growth stage cannot receive sufficient nutritional \nsupport, thus leading to atresia. Hence the seemingly contradictory phenomenon that both primary \nfollicles entering the growth phase are increased in atretic follicles in the ipsilateral ovarian cortex [10]. \nThis forms a vicious circle and accelerates the depletion of the diseased follicle reserve. In recent years, \nmany experimental results have shown that the content of inflammatory mediators such as IL -6, IL-8, \nIL-18, TNF-a and monocyte chemotactic factor -1 in t he follicular fluid, peritoneal washing fluid and \nblood of patients with endometriotic cysts is significantly increased, which further confirmed the \nscientific hypothesis that ovarian endometrioma cysts increase the recruitment of follicles through the \ninflammatory response, thereby promoting the depletion of ovarian reserve. \nThe serum CA125 concentration is closely related to the biological activity of the endometrium. The \nserum CA125 concentration of women in menstrual period is higher than that in non -menstrual period, \nand the serum CA125 concentration in endometriosis is higher than that in non -endometriosis. Pan[11] \nselected 60 observers who were diagnosed with endometriosis by surgery and 60 control subjects with \nnormal physical examination, and detect ed serum CA125 in the two groups respectively. The results \nshowed that the average level of serum CA125 in the control group was (13.32± 6.24) IU/ ml, while the \nstage I-II endometriosis was (42.91± 20.13) IU/ml, and the stage III-IV was (55.91± 39.20) IU/ml, and the \ndifference was statistically significant. Consistent with the results of this experimental study, this \nexperiment further analyzed the correlation between the preoperative serum CA125 concentration and \nthe postoperative serum AMH decrease, and concluded that the two were negatively correlated. \nBoth AMH level and Antral Follicle Count (AFC) have good predictive value for ovarian reserve, \nand AMH is the gold standard for predicting ovarian reserve [12]. Through a prospective cohort study, \nsome researchers found that compared with the control group, the AMH levels and AFC in the patients \nwith ovarian endometriosis of reproductive age were decreased [13]. This experiment further confirmed \nthat the serum AMH decreased in patients with advanced endometriosis before surgery, but there was no \nobvious change in the early stage. After laparoscopic endometriosis cystectomy, the postoperative AMH \ndecrease was more obvious in patients with advanced endometriosis, while the decrease in postoperative \nAMH was not obvious in patients with early stage and loose adhesions. \nReal-world research is a study that collects real diagnosis and treatment data of patients in real clinical, \ncommunity or family environments to evaluate the real impact of treatment measures on patients’ health. \nA powerful supplement [14]. The subjects in this study are all from the real clinical environment. \nCompared with randomized controlled clinical studies, the criteria for inclusion and exclusion are \n\nFrontiers in Medical Science Research \nISSN 2618-1584 V ol. 4, Issue 9: 41-46, DOI: 10.25236/FMSR.2022.040908 \nPublished by Francis Academic Press, UK \n-46- \nrelatively loose. Endometriosis and the effects of surgery on ovarian function are useful supplements to \nprospective randomized clinical studies. \nEndometriosis cystectomy: The surgical indication for ovarian endometriosis is asymptomatic, and \nsurgery is feasible for patients with a diameter greater th an 4 cm. In fact, the statement that surgical \ntreatment of early ovarian endometrioma is a ‘double-edged sword’ has been controversial in recent years. \nIn recent years, with the opening of the country's ‘second child’ and ‘third child’, especially for patients \nwith ovarian endometriosis cysts who have reproductive needs, the risk of delaying surgery is that the \ndisease progresses after the diagnosis is delayed, resulting in aggravation of pelvic adhesions. The \ninvolved ovarian lesions are further destroyed and fibrotic, resulting in egg loss and decreased ovarian \nreserve. This experiment also confirmed that patients with advanced endometriotic cysts had lower blood \nAMH than in the early stage. However, at the same time as the operation, the ovarian cortex is inevitably \ndamaged, thereby destroying the ovarian reserve function. This experiment also confirmed this point of \nview. Therefore, the operation requires higher requirements for the operator, and more attention should \nbe paid to the protection of the ovar y. The results of this experiment show that the early excision of \novarian endometriomas has relatively little effect on the ovary because of its slightly loose adhesion, and \nit is reversible. Surgical treatment can better protect the ovarian reserve functi on, and at the same time, \nit can also be diagnosed early, inform the patient of the disease, plan the time of birth, and reduce the risk \nof malignant transformation. \nAcknowledgements \nThis work was supported by the Analysis of the correlation between the pr ognosis of patients with \nendometriosis and AMH (grant number 201904A 040). \nReferences \n[1] Ball BA, Almeida, Conley, AJ, Determination of serum anti -mtillerian hormone concentrations for \nthe diagnosis of granulose-cell tumors in mares [J]. Equine VJ, 2013, 45 [2]. 199-203. \n[2] Krawczuk-Rybak M, -Leszczynska E, etal, Anti-millerian hormone as a sensitive marker of Ovarian \nfunction in young cancer survivors [J]. Int J Endocrinol, 2013, 1250-1280. \n[3] Wilson JD, George FW, Griffin JE. The hormoal control of sex ual development [J]. Science, 1981, \n211(4488): 1278-1284. \n[4] Hansen KR, Hodnett GM, Knowlton N, et al. Correlation of ovarian reserve tests with histologically \ndetermined primordial follicle number[J]. Fertil Steril, 2011,95(1):170-175. \n[5] Iosca S, Lumia  D, Bracchi E, et al. Multislice computed tomography with colon water distension \n(MSCT-c) in the study of intestinal and ureteral endometriosis [J]. Clinical imaging, 2013, 37(6), 1061. \n[6] La Marca A, Stabile G, Artenisio AC, et al. Serum anti -mullerian hormone throughout the human \nmenstrual cycle [J]. Hum Reprod, 2006, 21: 3103-3107. \n[7] Bentzen J G, Forman J L, johannsen T H, etal. Ovarian antral foilocle subclasses and anti-mullerian \nhormone during normal reproductive aging [J]. J Clin Endocrinol Metab, 2013, 98: 1602-1611. \n[8] Sayegh L, Gel -H F, Nassar AH. Vitamin D in endometriosis:acausative or confounding factor [J]. \nMetabolism Clinical &Experimental, 2014, 63(1): 32-41 \n[9] Kitajima M, Dolmans MM, Donnez 0, et al. Enhanced follicular recruitment and  atresia in cortex \nderived from ovaries with endometriomas [J]. Fertil Steril, 2014, 101 (4): 1031 -1037. DOI: 10.1016/j. \nfertnstert.2013.12.049.  \n[10] Da Broi MG, De Albuquerque FO, De Andrade AZ, et al. Increased concentration of 8-hydroxy-2'-\ndeoxyguanosine in follicular fluid of infertile women with endometriosis [J]. Cell Tissue Res, 2016, \n366(1): 231-242. DOI: 10.1007/ S00441-016-2428-4. \n[11] Junmei Pan, Hongfang Wang. Accuracy and sensitivity of ultrasound and serum CA125 level \ndetection in the diagnos is of patients with endometriosis cyst [J]. Imaging Research and Medical \nApplication, 2018, 2(2): 93-95. \n[12] Fleming R, Seifer DB, Frattarelli JL, et al.Assessing ovarian response: antral follicle count versus \nanti-Mü llerian hormone [J]. Reprod Biomed Online, 2015, 31(4): 486-496. \n[13] Gurkan U, Isil K, Kemal O, et al. Prospective assessment of the impact of endometriomas and their \nremoval on ovarian reserve and determinants of the rate of decline in ovarian reserve [J]. Hum Reprod, \n2013, 28(8): 2140-2145. \n[14] Song Yang, Longteng Ma, Jingjing Zhang. Standard of Practice for real-world Research on Clinical \nMedicine in China [J]. The PLA Medical Journal, 2018, 43(1): 1-6.","source_license":"CC0","license_restricted":false}