Women with Endometriosis, Especially Those Who Conceived with Assisted Reproductive Technology, Have Increased Risk of Placenta Previa: Meta-analyses

전혜지,민지원,김덕경,서희경,김선경,김윤숙 대한의학회 2018 Journal of Korean medical science Vol.33 No.34

Background: Many women with endometriosis have become pregnant through assisted reproductive technology (ART), and have often experienced placenta previa (PP) during pregnancy. The objective of this study was to assess the association between women with endometriosis, especially those who conceived with ART, and the risk of PP. Methods: Two reviewers independently determined studies that were considered suitable for meta-analyses published in various medicine-related databases from March 1, 2004 through July 31, 2017 without language restrictions. Eight studies met the inclusion criteria, with a combined sample size of 21,930 women. Of these 21,930 pregnancies, 6,256 had endometriosis (endometriosis) and 15,674 had no endometriosis. Four of these studies included 8,161 women who conceived with ART, 1,640 of whom had endometriosis (endometriosis + ART), and 6,521 of whom did not have endometriosis. Meta-analyses were estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using random effect analysis according to heterogeneity of studies. Results: These meta-analyses showed women with endometriosis (endometriosis) have an increased risk of PP (OR, 4.038; 95% CI, 2.291–7.116; P = 0.000). These results showed women who conceived with ART (endometriosis + ART), have a substantially increased risk of PP (OR, 5.543; 95% CI, 1.659–18.523; P = 0.005). Conclusion: These meta-analyses demonstrate women with endometriosis have an increased risk of PP.

자궁내막증 환자에서 복강내의 IL-6와 IL-10의 변화양상에 관한 연구

이경석(Kyung Suk Lee),강정배(Jeong Bae Kang),김홍배(Hong Bae Kim),이근영(Keun Young Lee),강성원(Sung Won Kang) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.11

Objective: Endometriosis is a disease affecting a large population of women all over the world. A local sterile inflammation occurs in the peritonel cavity of patients with endometriosis. It suggests that immunological events play a major role in the pathogenesis of endometriosis. We have studied the levels of serveral T cell and monocyte derived cytokines, especially IL-6 (promoter of immune response) and IL-10 (inhibitor of immune response), in the peritoneal fluid of patients with endometriosis to characterize the change of immune response that occurs at the site of endometriosis. Method: This study was performed in Hallym university hospital from October, 1997 to October 1998 and enrolled 29 women with gross or microscopic findings of minimal to severe endometriosis in case group, and 28 women without visual evidence of pelvic endometriosis and with benign gynecologic disease in control group. IL-6 and IL-10 levels in the peritoneal fluid were determined using commercial ELISA and compared between endometriosis and controls and between fertile and infertile women with endometriosis and according to the revised American Fertility Society classification. Result: IL-6 was higher and IL-10 was lower in the peritoneal fluid of endometriosis group than of control group. Cyclic variations in the IL-6 concentrations were seen in endometriosis group : the concentrations in the secretory phase were significantly higher than those in the proliferative phase. In endometriosis group, IL-6 concentrations of infertile women were higher than fertile women. Both IL-6 and IL-10 in the peritoneal fluid of endomtriosis group did not show significant correlation according to r-AFS stages. Conclusion: Increased IL-6 and decreased IL-10 levels in the peritoneal fluid may be related to infertility and pathogenesis in the endometriosis, suggesting that partially contribute to the disturbed immune regulation observed in endometriosis.

자궁내막증 발생에 있어서의 환경적 인자에 관한 연구

김동호(DH Kim),지정석(JS Chi),김정구(JK Kim),김대원(DW Kim) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.3

To investigate the prevalence of endometriosis and its associated risk factors which influence the development of endometriosis in korean women in special, we have performed prospective case-control study for endometriosis in multicenter since May, 1, 1996. For 14 months from May 1, 1996 to June 30, 1997, 110 women with endometriosis were detected by laparoscopic operation. To conduct a case-control study, 226 patients with no evidence of endometriosis were randomly selected from a group of women who underwent laparoscopic surgery. Information obtained through physical examination and a questionnaire was studied by multivariate logistic regression analysis. The results are as follows: 1. Endometriosis was significantly higher among 30s age group[age 30∼39] 2. Educational and socioeconomic factors did not appear to be associated with the development of endometriosis. 3. Endometriosis was significantly greater in unmarried women than in married women[p=0.0001]. 4. The risk of development of endometriosis was higher in the group of patients with family history of endometriosis[OR=2.5, p<0.05]. 5. There were no ssignificant association between the constitutional factors, weight and height, and smoking and endometriosis. 6. The probability of endometriosis was lower among women with regular exercise[OR=0.6]. 7. Menarche age was not related with the development of endometriosis. 8. The risk for emdometriosis was significantly greater among women with menstrual cycle length 27 or less, moderate degree or more of dysmenorrhea, and longer duration of menstruation[8 day or more]. 9. The number of abortion, age of first pregnancy did no appear to be associated with the presence of endometriosis. 10. There seemed to be a trend for increasing risk among women with no experience of pregnancy and child birth[OR=1.4]. 11. The other factors such as vaginal douch after menstruation, use of oral contraceptives and intrauterine devices did not appear to be related with development of endometriosis.

자궁내막증과 동반된 불임환자의 보조생식술을 이용한 치료

문신용,이경순,노재숙,서창석,김석현,최영민,신창재,김정구,이진용,장윤석,Moon, Shin-Yong,Lee, Kyung-Soon,Roh, Jae-Sook,Suh, Chang-Suk,Kim, Seok-Hyun,Choi, Young-Min,Shin, Chang-Jae,Kim, Jung-Gu,Lee, Jin-Young,Chang, Yoon-Seok 대한생식의학회 1995 Clinical and Experimental Reproductive Medicine Vol.22 No.2

Though the endometriosis is not always related with infertility, endometriosis causes infertility in some patients. There are many treatment modalities of infertile patients who have endometriosis. In recent years, Assisted Reproductive Technology(ART) have been widely accepted as being a useful tool for the treatment of infertile endometriotic patients. The objective of this study was to evaluate the outcome of ART in infertile endometriotic patients who have been carried out IVF-ET from Jan, 1992 to Dec, 1994 and to compare the results between COH/IUI and IVF-ET in the patients with endometriosis stage I. Tubal disease only patients were grouped(308 patient, 956 cycles) as a control. Endometriosis group was subdivided into 4 groups according to American Fertility Society classification; endometriosis stage I (45 patients, 61 cycles), stage II (26 patients, 39 cycles), stage III (26 pateitns, 37 cycles), stage IV (33 patients, 50 cycles). The outcomes of IVF-ET in endometriosis patients were as follows; The oocyte recovery rates were significantly lower in stage III, IV endometriosis. In case of stage III endometriosis, the fertilization rate was significantly lower than other stages of endometriosis. Clinical pregnancy rates per cycle were not different between the tubal group(22%) and the endometriosis group(25%). According to endometriosis stage, the implantation rate and clinical pregnancy rate were significantly lower in stage IV (5.6%, 16%) compared with other stages (I; 10.0%, 26%, II;9.8%, 31%, III;12.6%, 32%). It suggests that some factor like autoantibodies may inhibit implantation of embryos in stage IV endometriosis. To evaluate the possibility that simply increasing the number of gametes at the site of fertilization might account for pregnancies attributed to IVF-ET, the authors retrospectively analyzed the outcome of couples undergoing IUI during hMG cycles and CC cycles between 1992 and 1994 in the women with endometriosis stage 1. In case of stage I endometriosis, though the COH/IUI group showed lower FSH level and lesser age profile than IVF-ET group, IUI group has resulted in lower pregnancy rates(19.2%) compared with the IVF-ET group(26.2%). In conclusion, endometriotic infertile patients can get comparable pregnancy rates with the tubal factor infertility patients during IVF-ET program. Moreover even in stage I endometriosis, IVF-ET may be an more effective treatment modality than COH/IUI.

Intestinal Endometriosis: Clinicopathologic Analysis of 15 Cases Including a Case of Endometrioid Adenocarcinoma

이희진,김규래 대한병리학회 2009 Journal of Pathology and Translational Medicine Vol.43 No.2

Background : Since many patients with intestinal endometriosis present with gastrointestinal symptoms without a history of endometriosis, endoscopic examination of the intestinal tract is initially performed, often leading to a misdiagnosis. Methods : We reviewed the clinicopathologic findings of 18 samples from 15 patients with intestinal endometriosis who underwent endoscopic biopsy and/or surgical resection to identify diagnostically helpful findings. Results : All 7 biopsy specimens displayed relatively well-defined submucosal lesions, with non-mucinous glands lined by ciliated epithelium and surrounding cellular stroma containing spiral arteriolelike blood vessels. The stroma was immunopositive for CD10 in all cases. All but one specimen exhibited immunopositivity for ER and PR in both glandular and stromal components. In contrast to the overlying normal colonic mucosa, glandular epithelium with endometriosis was immunopositive for cytokeratin (CK) 7, but immunonegative for CK20 in all cases. Three cases were associated with adenocarcinoma in the same or different segments; specifically, two primary rectal adenocarcinomas and one endometrioid adenocarcinoma arising from endometriosis. Conclusions : The characteristic features of endometrial glands and stroma, including nonmucinous glands without goblet cells, ciliated columnar epithelium, and cellular stroma with spiral arterioles, facilitate the accurate diagnosis of intestinal endometriosis, which can be confirmed by immunohistochemical staining. Background : Since many patients with intestinal endometriosis present with gastrointestinal symptoms without a history of endometriosis, endoscopic examination of the intestinal tract is initially performed, often leading to a misdiagnosis. Methods : We reviewed the clinicopathologic findings of 18 samples from 15 patients with intestinal endometriosis who underwent endoscopic biopsy and/or surgical resection to identify diagnostically helpful findings. Results : All 7 biopsy specimens displayed relatively well-defined submucosal lesions, with non-mucinous glands lined by ciliated epithelium and surrounding cellular stroma containing spiral arteriolelike blood vessels. The stroma was immunopositive for CD10 in all cases. All but one specimen exhibited immunopositivity for ER and PR in both glandular and stromal components. In contrast to the overlying normal colonic mucosa, glandular epithelium with endometriosis was immunopositive for cytokeratin (CK) 7, but immunonegative for CK20 in all cases. Three cases were associated with adenocarcinoma in the same or different segments; specifically, two primary rectal adenocarcinomas and one endometrioid adenocarcinoma arising from endometriosis. Conclusions : The characteristic features of endometrial glands and stroma, including nonmucinous glands without goblet cells, ciliated columnar epithelium, and cellular stroma with spiral arterioles, facilitate the accurate diagnosis of intestinal endometriosis, which can be confirmed by immunohistochemical staining.

자궁내막증 병변에서의 Cytokine mRNA의 발현 양상

이택후(Taek Hoo Lee),김광수(Gwang Soo Kim),김일규(Il Gyu Kim),전상식(Sang Sik Chun),조영래(Young Lae Cho) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.9

Objective: The pathogenesis of endometriosis is generally accepted that retrograde menstruation and alterations in the local pelvic immune environment. This study was performed to help elucidate what kind of role various cytokines might play in the pathogenesis of endometriosis. Method: Concentrations of peritoneal fluid cytokines were compared in 7 women with normal pelvic finding and 23 women with endometriosis by enzyme-linked immunosorbent assay(ELISA). The patterns of cytokine mRNA expression in 8 ovarian endometrioma and 12 superficial pelvic endometriosis lesions were investigated by reverse transcription-polymerase chain reaction(RT-PCR) amplification method. Result: Both IL-6 and IL-10 levels in peritoneal fluid specimens with endometriosis tended to be higher than normal. However, there were no significant differences between peritoneal fluid concentrations of IFN-γ, TNF-α, IL-1β, and IL-5 of women with and without endometriosis. The levels of IL-6 and IL-10 were significantly higher in peritoneal fluid of women with severe endometriosis compared to women with mild endometriosis. IL-1β mRNA was expressed in all of 8 deep and 12 superficial endometriosis lesions. IL-5 and IL-6 mRNA were expressed in only two black lesions respectively, however, both were not expressed in the all deep lesions. Expressions of IL-10 mRNA occurred in one red and one black lesion while this was expressed in only one of the deep lesions. TNF-α mRNA was expressed in one red and one black lesion of 12 superficial lesions compared with four of the deep lesions. There was the difference between kinds of increased cytokines in the peritoneal fluid and those of expressed cytokines in the endometriotic lesions of patients with endometriosis. Conclusion: This study supports the concept that local immunologic factors may be important in the pathogenesis and pathophysiology of endometriosis. The pattern of cytokine mRNA expression of endometriotic lesions would seem to indicate that proinflammatory cytokines such as IL-1β and TNF-α are responsible for the development or progression of endometriosis.

Prognostic importance of atypical endometriosis with architectural hyperplasia versus cytologic atypia in endometriosis-associated ovarian cancer

Isabel Ñiguez Sevilla,Francisco Machado Linde,Maria del Pilar Marín Sánchez,Julián Jesús Arense,Amparo Torroba,Anibal Nieto Díaz,Maria Luisa Sánchez Ferrer 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.4

Objective: Patients with endometriosis are at increased risk of ovarian cancer. It has been suggested that atypical endometriosis is a precursor lesion of endometriosis-associated ovarian cancer (EAOC). The aim of this study is to evaluate if cytologic (cellular) atypia and architectural atypia (hyperplasia), histologic findings described as atypical endometriosis, play a different role in patients with EAOC. Methods: A prospective study was conducted between January 2014 and April 2017 at our institution with patients undergoing surgery with a histologic diagnosis of endometriosis, ovarian cancer, or EAOC. The prevalence and immunohistologic study (Ki-67, BAF250a, COX-2) of cases of cellular and architectural atypia in endometriosis were analyzed. Results: Two hundred and sixty-six patients were included: the diagnosis was endometriosis alone in 159 cases, ovarian cancer in 81, and EAOC in 26. Atypical endometriosis was reported in 23 cases (12.43%), 39.13% of them found in patients with EAOC. Endometriosis with cellular atypia was found mainly in patients without neoplasm (71.4%), and endometriosis with architectural atypia was seen in patients with ovarian cancer (88.9%) (p=0.009). Ki-67 was significantly higher in endometriosis patients with architectural atypia than those with cellular atypia. Conclusion: The diagnosis of endometriosis with architectural atypia is important because it may be a precursor lesion of ovarian cancer; therefore, pathologists finding endometriosis should carefully examine the surgical specimen to identify any patients with hyperplasia-type endometriosis, as they may be at higher risk of developing EAOC.

자궁내막증 환자의 복강액내 IGF가 자궁내막 기질세포 증식에 미치는 영향

김정구,서창석,김석현,최영민,문신용,이진용,Kim, Jung-Gu,Suh, Chang-Seok,Kim, Seok-Hyun,Choi, Young-Min,Moon, Shin-Yong,Lee, Jin-Yong 대한생식의학회 1999 Clinical and Experimental Reproductive Medicine Vol.26 No.3

The purposes of this study were to evaluate the effects of insulin-like growth factor (IGF)s in peritoneal fluid (PF) from patients with and without endometriosis on the proliferation of endometrial stromal cells and to investigate the effects of type I IGF receptor antibody on the response of endometrial stromal cells to PF from patients with endometriosis. IGFs in PF from patients with endometriosis (n=14) and without endometriosis (n=10) were measured by immunoradiometric assay and PF samples were divided into low IGF-I PF group (less than 85 ng/ml) and high IGF-I PF group (more than 85 ng/ml). Endometrial stromal cells from patients without endometriosis were cultured in serum free media in the presence or absence of 1 % PF and thymidine incorporation test were used to evaluate the proliferation of endometrial stromal cells. Also cultures were incubated with type I IGF receptor monoclonal antibody (${\alpha}IR_3$) before adding PF. PF from patients with endometriosis and without endometriosis increased thymidine incorporation in endometrial stromal cells. In patients with endometriosis, high IGF-I PF group had high IGF-II levels and resulted in higher thymidine incorporation than low IGF-I PF group but no significant difference in increase in thymidine incorporation between high IGF-I and low IGF-I PF group was noted in patients without endometriosis. There was not a significant correlation between increase in thymidine incorporation and IGF-I levels in PF from patients without endometriosis but in PF from patients with endometriosis. Preincubation with ${\alpha}IR_3$ significantly inhibited the mitogenic response of endometrial stromal cells to PF. Our data indicate that IGF-I in PF may be involved in the growth of ectopic endometrium in patients with endometriosis.

자궁절제술 환자의 자궁내막증 유병률

김미연 ( Mi Yeon Kim ),최민혜 ( Min Hye Choi ),배진영 ( Jin Young Bae ),김미주 ( Mi Ju Kim ),조영래 ( Young Lae Cho ),박일수 ( Il Soo Park ),이윤순 ( Yoon Soon Lee ) 대한산부인과학회 2008 Obstetrics & Gynecology Science Vol.51 No.10

Objective: We investigated whether surgical methods, age, parity and obesity were correlated to endometriosis in patients who had hysterectomy. Methods: This research was surveyed and reviewed of patients who underwent total abdominal hysterectomy, laparoscopic hysterectomy and vaginal hysterectomy in Kyungpook National University Hospital from 1999 to 2006, based on clinical recordings and pathologic reports. Based on these data, we investigated whether age, parity, obesity and pathologic diagnosis were correlated to prevalence rate of endometriosis. Also we investigated the correlations with anatomic lesion of endometriosis and surgical methods. SPSS version 12.0 chi-square test was conducted as the statistical data. Results: The total 4,830 cases of hysterectomy were undergone. Out of these, endometriosis was found at 125 cases (2.5%). Among them, 76 cases of endometriosis were found at 2,260 cases of abdominal hysterectomy (3.3%). 31 cases of endometriosis were found at 1,589 cases of vaginal hysterectomy (1.95%), and 18 cases of endometriosis were found at 981 cases of laparoscopic hysterectomy (1.83%). The correlation with laparoscopic hysterectomy and endometriosis had the statistically significant high rate (P<0.005). For anatomic site of endometriosis, 109 cases were found at ovary (87.2%), 7 cases were found at uterosacral ligament (5.6%), 4 cases were found at peritoneum (3.2%), 3 cases were found at cul-de-sac (2.4%), 3 cases were found at ovarian fossa (2.4%), 1 case was found at abdominal wall, rectal wall, vaginal wall and small intestine (0.8%), respectively. Age, parity, patologic diagnosis and obesity did not show the significant correlation with the prevalence rate of endometriosis (P>0.05). Conclusion: Even the prevalence of endometriosis was low (2.5%) in total cases of hysterectomy, laparoscopic hysterectomy had more prevalence rate of endometriosis than other types of hysterectomy. because suspicious lesions were inspected carefully, Magnified laparoscopic view make us to identify suspicious endometriotic lesion more clearly than other type of hysterectomy.

CYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women

Ledan Wang,Xiaosheng Lu,Danhan Wang,,Wenju Li,Xiaowen Xu,Qiusui Huang,Xueying Han,Jieqiang Lv,Wanglei Qu 생화학분자생물학회 2014 Experimental and molecular medicine Vol.46 No.-

An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case–control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes atrs2236722:T4C, rs700518:A4G, rs10046:T4C and [TTTA]n polymorphisms were identified. Allelic and genotypic frequencies were compared between the control group and case groups by chi-square analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by logistic regression analysis to predict the association of CYP19 gene polymorphisms with the risk of endometriosis, the related chocolate cysts and infertility. The genotype distributions of the tested CYP19 gene polymorphisms were not significantly different between the healthy control group and the endometriosis/endometriosis with the chocolate cyst group. However, the CYP19 rs700518AA genotype was significantly associated with an increased risk of endometriosis-related infertility (55.4% in the infertility group vs 25.3% in the control group, Po0.001;OR (95% CI): 3.66 (2.06–6.50)) under the recessive form of the A allele. Therefore, we concluded that in Chinese Han females CYP19 gene polymorphisms are not associated with susceptibility to endometriosis or chocolate cysts, whereas CYP19 rs700518AA genotype confers genetic susceptibility to endometriosis-related infertility.