Endometriosis, one of the most common gynecologic disorders, is found in 1–30% of women during their reproductive years, based on the different diagnostic criteria, and sometimes occurs in postmenopausal women. It is found in 70–90% of women with pelvic pain symptoms.1–3 Endometriosis remains an enigmatic disease and cause of pain, and can subsequently result in pelvic inflammation, adhesion, chronic pain, and infertility, and occasionally in malignant transformation.4,5 Since endometriosis-associated morbidity shows a significant negative impact on women's quality of life, it contributes to a long-term major health issue. This study report addresses the associations between endometriosis and other diseases from the domestic source in Taiwan. The majority of the data are obtained from a large-scale population-based study—the National Health Insurance Research Database (NHIRD).6,7
Epidemiologic studies may be helpful in defining populations at a high risk of endometriosis1,3–5; however, it is not easy to estimate the real incidence or prevalence of endometriosis precisely even when the gold-standard method, laparoscopy, is used. Variations may be influenced by the wide range of visual appearance of endometriosis and pathological confirmation, resulting in an unknown true prevalence or the real incidence of endometriosis. Hopton and Redwine8 noted that the visual appearance of endometriosis is important because therapy begins with a surgeon identifying the disease, and any inaccurate identification of endometriosis can introduce selection bias and confound all conclusions, leading to incorrect concepts of epidemiology, natural history, disease origin, and treatment. In 1995, Chu and colleagues’9 pioneered study of the prevalence of endometriosis in Taiwan showed a wide variation (5–42%) on the basis of different indications for 752 consecutive laparoscopic procedures. The prevalence of endometriosis was 42%, 33%, 25%, and 12%, respectively, in women indicated for pelvic adhesion, infertility, myoma, and sterilization; the researchers concluded that the overall prevalence of endometriosis in asymptomatic patients was 24.7%. This study was one of the earliest to investigate the prevalence of endometriosis in Taiwan. However, this study might overestimate or underestimate the prevalence of endometriosis in Taiwan. Since surgery is always applied in a certain type of population, for example, women with needs and indications, surgery itself might be one of the most significant confounding factors, contributing to the high possibility of selection bias. In addition, the “illusory tale of occult microscopic endometriosis” might underestimate the prevalence of endometriosis.8 Endometriosis is sometimes truly invisible to the surgeon because it is too small to see.8 In previous studies from Taiwan,1,3–5 the prevalence of endometriosis also varied markedly. With different criteria applied for enrollment of patients with endometriosis, the prevalence might be different. A recent report by Lee et al3 might be one of the best representatives. Their results showed that the prevalence of endometriosis during reproductive years could be up to 30.8% and as low as 1.5%.3 The dramatic difference in the prevalence could be well explained by the different criteria applied in the study. Yang et al1 showed that the estimated prevalence of women with endometriosis was 8.9% based on the NHIRD of Taiwan. However, only two-fifths of these women with a clinical diagnosis of endometriosis had a surgicopathological confirmation of their endometriosis, contributing to 3.7% of the prevalence rate,3 which was significantly lower than the 5–10% rate found in literature reviews.10
3. Comorbidity of endometriosis
Previous research suggests that a comorbidity relationship exists between endometriosis and many functional and/or pathological diseases,1,11,12 although the results of some studies were not consistent. For example, endometriosis was not associated with diabetes mellitus in one cross-sectional study,13 and reports showed that women with endometriosis might have a lower body mass index and be less frequently obese14,15; however, domestic nationwide population-based studies showed that women with endometriosis seemed to have a tendency of being obese and a higher rate of diabetes mellitus.4,5,11,12 One report showed 7.5% of women with diabetes mellitus in the endometriosis group compared with 5.8% in the nonendometriosis (control) group.4 Another report found diabetes mellitus in 16% of women with endometriosis compared with that in 13% of women without endometriosis.12 Besides a higher rate of diabetes mellitus in women with endometriosis, domestic data showed that Taiwanese women with endometriosis seemed to have a higher tendency to be obese.11,12 This finding was different from those of previous reports from Western countries14,15—a discrepancy that needs further investigation. Of course, different criteria might have resulted in the different prevalence estimations, suggesting that sampling differences might have contributed to this finding.
A domestic study also found that a higher proportion of women with endometriosis had pelvic inflammatory disease (76.0% vs. 38.4%, endometriosis vs. controls, p < 0.0001), infertility (10.2% vs. 2.0%, p < 0.0001), cardiovascular diseases (4.9% vs. 3.5%, p < 0.0001), chronic liver disease (2.2% vs. 1.5%, p = 0.0002), and rheumatic disease (4.0% vs. 2.4%, p < 0.0001).4 Similar findings were also reported from another domestic population-based study.12 Wu et al12 showed that women with endometriosis frequently had hypertension (24.0% vs. 20.6%, p < 0.001) and hyperlipidemia (28.7% vs. 23.0%, p < 0.001). Both hypertension and hyperlipidemia might be considered among the important components of cardiovascular diseases, suggesting that women with endometriosis are frequently associated with metabolic and cardiovascular problems. By contrast, a recent domestic study showed that women with endometriosis had a lower rate of hypertension than women without endometriosis. Although this study did not support a higher incidence of hypertension in women with endometriosis, the finding could be discarded, mainly because Yu et al's11 study showed an unusually higher proportion of hypertension in their study population. More than one-half of their studied patients had hypertension status; this occurred in both cohort groups (50.7% of women with endometriosis and 55.7% of women without endometriosis, p < 0.001), suggesting that the study population might not really be representative of the general population. In addition, Yu et al11 also showed an unusually higher proportion of study population with hyperlipidemia (53.9% and 44.9% in women with and without endometriosis, respectively; p < 0.001) and diabetes mellitus (31.6% and 26.8% in women with and without endometriosis, respectively; p < 0.001) than that of the general population.
In addition to the higher comorbidity, women with endometriosis might also have a higher risk of other medical illnesses. For example, Wu et al12 showed that women with endometriosis had a higher rate of depression (1.0% vs. 0.5%, p < 0.001) than those without it. Taken together, women with endometriosis should be given much attention for medical care, since they not only have endometriosis-related health problems, such as dysmenorrhea, menorrhagia, and chronic pelvic pain,16–18 but also have many other medical illnesses.10
4. Risks for functional illnesses
As shown above, women with endometriosis often have other functional and/or pathological illnesses, which might worsen the established endometriosis-related diseases. A recent study showed that women with endometriosis had a higher risk of an attack of irritable bowel syndrome, with a hazard ratio (HR) of 1.79 and 95% confidence interval (CI) of 1.55–2.07 (p < 0.001).12 It is interesting that the new onset of irritable bowel syndrome was especially higher within the 1st year of follow-up (HR 1.90, 95% CI 1.42–2.55, p < 0.001) in women with endometriosis.12 In addition, the increased risk of irritable bowel syndrome could persist over 5 years.12 Wu and colleagues12 tried to explain the association between endometriosis and irritable bowel syndrome, and raised the hypothesis that both diseases might share similar risk and pathogenic factors, such as visceral hypersensitivity, similar inflammatory processes in the peritoneal cavity and gastrointestinal mucosa, and mast cell activation.
Endometriosis might be also associated with other painful diseases. For example, Dr Yang and colleagues1 found that women with endometriosis were more likely to be diagnosed with migraine headache during the follow-up (HR 1.70, 95% CI 1.59–1.82, p < 0.001) than controls, and the diagnosis of migraine headache was often made after the diagnosis of endometriosis. Although the cause of comorbidity of endometriosis and migraine headache is unknown, a number of aspects of the pathophysiological pathways may explain the apparent relationship, including the activation of sensory nerve fibers within the endometriosis leading to central nervous system hypersensitivity, and activation and degranulation of mast cells within the endometriosis inducing the release of proinflammatory and allergic mediators, which sensitize primary afferent meningeal nociceptive neurons and cause hypersensitivity and hyperalgesia.1
5. Increased risk of malignant tumors in women with endometriosis
Women with endometriosis not only have the abovementioned benign diseases or health problems, but also might be associated with much more severe health problems, for example, development of malignancy. As early as 1925, Sampson found a possible correlation between endometriosis and epithelial ovarian cancer (EOC), and soon after, many epidemiologic studies, systematic reviews, and meta-analyses indicated that women with endometriosis were at a risk of the development of EOC.3 At least five domestic studies focusing on the correlation between endometriosis and EOC have been reported.3–5,19,20
The first study investigated the microenvironmental biomarkers of different types of ovarian cancers arising from endometriosis and found that these EOC displayed the following characteristics and appeared frequently: 56% for cyclooxygenase-2, 47% for AT-rich interactive domain 1A mutation (expressed by the loss of the corresponding protein BAF250a), 43% for estrogen receptor, 38% for hepatocyte nuclear factor-1 beta, 37% for loss of phosphatase and tensin homolog, and 13% for p53 mutation.19 Furthermore, studying endometriosis-associated EOCs, such as clear cell carcinoma and endometrioid cell carcinoma, Lai et al19 showed significantly high positive rates of estrogen receptor in endometrioid cell carcinoma (91%) and hepatocyte nuclear factor-1 beta in clear cell carcinoma (65%). In addition, they found that the staining results were similar between atypical endometriosis glandular epithelium and contiguous malignant portions, suggesting that endometriosis-associated EOCs may share common molecular and genetic features between precursors and cancers.19
The remaining four reports were epidemiologic studies.3–5,20 The first attempt to evaluate a possible correlation between endometriosis and an increased risk of EOC in Taiwan appeared in 2014.5 This study was performed using data from the NHIRD of Taiwan and showed that the EOC incidence rates of women with and without endometriosis were 3.31 per 10,000 person-years and 0.99 per 10,000 person-years, respectively, contributing to an adjusted HR of 3.28 (95% CI 1.37–7.85, p < 0.01).5 This estimated three-fold increase of the risk of EOC in women with endometriosis was neither influenced by exposure time nor biased by surveillance.5 Another study investigated the correlation between endometriosis and EOC.4 Results showed that women with a new surgically confirmed endometriosis had a higher risk of EOC than those without.4 The EOC incidence rate of women with endometriosis consistently increased with increasing age, with 4.99 per 10,000 person-years in women aged <30 years and 35.81 per 10,000 person-years in those aged more than 50 years, contributing to a risk of EOC constantly increasing with age.4 The final study used data from the NHIRD to explain why the risk of EOC in women with endometriosis varied greatly; results showed that the risk of EOC in women with endometriosis might be more apparent than that previously estimated by either systematic reviews or meta-analyses, because data enrolled for analysis are often based on recalled endometriosis, which resulted in only a two-fold increase.3
Besides the well-known correlation between endometriosis and EOC, a correlation between endometriosis and other malignancies, especially gynecologic cancers,11,20 has also been evaluated in Taiwan. One study showed that women with endometriosis had a significantly higher risk of endometrial cancer than those without during a 10-year follow-up, with an adjusted HR of 2.83 (95% CI 1.49–5.35, p < 0.01).11 The results of Yu et al's11 study also showed that age at diagnosis of endometriosis might play an important role, since women with endometriosis who were younger than 40 years did not have an apparent increased risk of endometrial cancer compared with those without endometriosis, but the risk for the development of endometrial cancer was significantly increased in women with endometriosis when they were older than 40 years, with an adjusted HR of 7.08 (95% CI 2.33–21.55, p = 0.007).
Another study by Kok and colleagues20 examined the correlation between endometriosis and other malignancies, including endometrial, breast, colorectal, and other cancers. Overall, this study found that women with endometriosis and adenomyosis had a higher risk of malignancy, with adjusted HRs of 1.8 (95% CI 1.4–2.4, p < 0.05) and 1.8 (95% CI 1.3–2.7, p < 0.05), respectively.20 In terms of the localization of endometriosis, women with ovarian endometriosis associated with/without endometriosis variants (endometriosis at another site) had a higher risk of EOC and endometrial cancer, with adjusted HRs of 4.56 (95% CI 1.72–12.11, p < 0.05) and 4.05 (95% CI 1.20–13.66, p < 0.05), respectively.20 By contrast, women with main endometriosis within the uterus accompanied with/without other areas of endometriosis also had a higher risk of EOC and endometrial cancer, with adjusted HRs of 5.50 (95% CI 1.95–15.50, p < 0.05) and 4.38 (95% CI 1.22–15.72, p < 0.05), respectively. With regard to the risk of endometrial cancer, women with pure adenomyosis without endometriosis in other sites had an unusually higher risk of endometrial cancer (adjusted HR 5.13, 95% CI 1.36–19.40, p < 0.05).20 However, it is interesting to find that women with uterine endometriosis (adenomyosis) mixing with other sites of endometriosis had much higher risks of ovarian and colorectal cancers, with adjusted HRs of 10.35 (95% CI 3.07–34.91, p < 0.05) and 13.04 (95% CI 2.21–77.04, p < 0.05), respectively.20 Although colon and rectum are reported as the second most common extragonadal sites for malignant transformation of endometriosis,21 it is not clear why women with adenomyosis mixing with other sites of endometriosis are at a risk of colorectal cancer. It is relatively confusing that estrogen promotes endometriosis growth,22 but estrogen might be beneficial for protection from the development of colorectal cancer, based on the findings from a previous scientific review23 and a recent prospective study.24 In addition, if the theory of estrogen is acceptable for the pathogenesis of endometriosis, EOC, and endometrial cancer, it can be further supposed that there is a possible correlation between endometriosis and breast cancer. However, domestic data did not show any correlation between endometriosis and breast cancer,20 and from literature reviews, the available published evidence is inconclusive.25
6. Study limitation
This review was mainly based on the results from domestic data published between 2012 and 2015, and the data used for these published articles were all obtained from the NHIRD. The major issue with respect to the NHIRD is the accuracy of the diagnosis; therefore, without further validation, the results should be read more carefully and the conclusion should avoid a hasty generalization. Lee et al3 also confirmed this, since they found that the incidence of endometriosis varied greatly. In fact, to report the incidence of endometriosis, so far, nobody could demonstrate the reality of the incidence.2 However, as reported by Lee et al,3 women with endometriosis really had a higher risk of ovarian cancer than those without, regardless of which criteria were used, suggesting that the association between endometriosis and comorbidity is somewhat present. In addition, numerous excellent articles are available in the literature, including many in the top journals, such as Lancet Oncology, Annals of Internal Medicine, JAMA Internal Medicine, Medicine, etc.,26–30 which report on studies based on the data from the NHIRD, suggesting that information from the NHIRD in Taiwan is valuable for clinical reference. Although evidence from molecular or genetic studies might partly explain the possibly similar pathogenesis or genetic background between endometriosis and some of these comorbidities, for example, ovarian cancers,31–33 we note that the evidence is still not strong enough to establish a bridge between the two.
In conclusion, evidence from nationwide large-scale population-based studies using domestic data suggests that women with endometriosis might be at a higher risk of several chronic diseases, including diabetes mellitus, cardiovascular disease, chronic liver disease, and rheumatoid arthritis, as well as fertility and pelvic inflammatory diseases, but possibly at a lower risk of chronic renal disease,34 although we considered the evidence for some comorbidities to be of low quality. In addition to the abovementioned benign medical illnesses, these women might have higher risks of many kinds of malignancies, such as ovarian cancer and uterine cancers. The risk of comorbidity might be higher in women with endometriosis than was previously supposed, and these comorbidities might be harmful to long-term health in such women. More research is needed to determine whether women with endometriosis are really at a risk of these comorbidities.
This work was supported by grants from the Ministry of Science and Technology, Executive Yuan (MOST 103-2314-B-010-043-MY3), and Taipei Veterans General Hospital (V102C-141, V103C-112, V104C-095, V105C-096, V102E4-003, and V103E4-003). We also appreciate the Clinical Research Core Laboratory and the Medical Science & Technology Building of Taipei Veterans General Hospital for providing experimental space and facilities.
1. Yang MH, Wang PH, Wang SJ, Sun WZ, Oyang YJ, Fuh JL. Women with endometriosis are more likely to suffer from migraines: a population-based study. PLoS One
2. The Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril
3. Lee WL, Chang WH, Wang KC, Guo CY, Chou YJ, Huang N, et al. The risk of epithelial ovarian cancer of women with endometriosis may be varied greatly if diagnostic criteria are different. Medicine
4. Wang KC, Chang WH, Lee WL, Huang N, Huang HY, Yen MS, et al. An increased risk of epithelial ovarian cancer in Taiwanese women with a new surgico-pathological diagnosis of endometriosis. BMC Cancer
5. Chang WH, Wang KC, Lee WL, Huang N, Chou YJ, Feng RC, et al. Endometriosis and the subsequent risk of epithelial ovarian cancer. Taiwan J Obstet Gynecol
6. Kuan AS, Chen YT, Teng CJ, Wang SJ, Chen MT. Risk of meningioma in patients with head injury: a nationwide population-based study. J Chin Med Assoc
7. Chou HP, Chang HT, Chen CK, Shih CC, Sung SH, Chen TJ, et al. Outcome comparison between thoracic endovascular and open repair for type B aortic dissection: a population-based longitudinal study. J Chin Med Assoc
8. Hopton EN, Redwine DB. Eyes wide shut: the illusory tale of ‘occult’ microscopic endometriosis. Human Reprod
9. Chu KK, Chen FP, Chang SD. Prevalence of endometriosis among women undergoing laparoscopic procedures. Diagn Ther Endosc
10. Kvaskoff M, Mu F, Terry KL, Harris HR, Poole EM, Farland L, et al. Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update
11. Yu HC, Lin CY, Chang WC, Shen BJ, Chang WP, Chuang CM, et al. Increased association between endometriosis and endometrial cancer: a nationwide population-based retrospective cohort study. Int J Gynecol Cancer
12. Wu CY, Chang WP, Chang YH, Li CP, Chuang CM. The risk of irritable bowel syndrome in patients with endometriosis during a 5-year follow-up: a nationwide population-based cohort study. Int J Colorectal Dis
13. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod
14. Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. Am J Epidemiol
15. Ferrero S, Anserini P, Remorgida V, Ragni N. Body mass index in endometriosis. Eur J Obstet Gynecol Reprod Biol
16. Tsui KH, Lee FK, Seow KM, Chang WC, Wang JW, Chen SU, et al. Conservative surgical treatment of adenomyosis to improve fertility: controversial values, indications, complications, and pregnancy outcomes. Taiwan J Obstet Gynecol
17. Tsui KH, Lee WL, Chen CY, Chen YJ, Sheu BC, Yen MS, et al. Medical treatment for adenomyosis and/or adenomyoma. Taiwan J Obstet Gynecol
18. Horng HC, Chen CH, Chen CY, Tsui KH, Liu WM, Wang PH, et al. Uterine-sparing surgery for adenomyosis and/or adenomyoma. Taiwan J Obstet Gynecol
19. Lai CR, Hsu CY, Chen YJ, Yen MS, Chao KC, Li AF. Ovarian cancers arising from endometriosis: a microenvironmental biomarkers study including ER, HNF1beta, p53, PTEN, BAF520a, and COX-2. J Chin Med Assoc
20. Kok VC, Tsai HJ, Su CF, Lee CK. The risks for ovarian, endometrial, breast, colorectal and other cancers in women with newly diagnosed endometriosis or adenomyosis: a population-based study. Int J Gynecol Cancer
21. Wong DD, Havlat MF, Thin LW. Colonic endometriosis with malignant transformation mimicking a diverticular abscess. Int J Colorectal Dis
22. Chen YJ, Li HY, Huang CH, Twu NF, Yen MS, Wang PH, et al. Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis. J Pathol
23. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA
24. Murphy N, Strickler HD, Stanczyk FZ, Xue X, Wassertheil-Smoller S, Rohan TE, et al. A prospective evaluation of endogenous sex hormone levels and colorectal cancer risk in postmenopausal women. J Natl Cancer Inst. 2015;107:pii: djv210.
25. Anifantaki F, Boutas I, Kalampokas T, Kalampokas E, Sofoudis C, Salakos N. Association of endometriosis and breast cancer: mini review of the literature. Arch Gynecol Obstet
26. Lin JN, Lin L, Lin MC, Lai CH, Lin HH, Yang CH, et al. Risk of leukemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study. Lancet Oncol
27. Ou SM, Shih CJ, Chao PW, Chu H, Kuo SC, Lee YJ, et al. Effects on clinical outcomes of adding dipeptidyl peptidase-4 inhibitors versus sulfonylureas to metformin therapy in patients with type 2 diabetes mellitus. Ann Intern Med
28. Yang CY, Chen CH, Deng ST, Huang CS, Lin YJ, Chen YJ, et al. Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan
. JAMA Intern Med
29. Chien SC, Ou SM, Shih CJ, Chao PW, Li SY, Lee YJ, et al. Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in terms of major cardiovascular disease outcomes in elderly patients: a nationwide population-based cohort study. Medicine (Baltimore)
30. Shih CJ, Wu YL, Lo YH, Kuo SC, Tarng DC, Lin CC, et al. Association of hypoglycemia with incident chronic kidney disease in patients with type 2 diabetes: a nationwide population-based study. Medicine (Baltimore)
31. King CM, Barbara C, Prentice A, Brenton JD, Charnock-Jones DS. Models of endometriosis and their utility in studying progression to ovarian clear cell carcinoma. J Pathol
32. Lee AW, Templeman C, Stram DA, Beesley J, Tyrer J, Berchuck A, et al. Evidence of a genetic link between endometriosis and ovarian cancer. Fertil Steril. 2016;105:35–43.e1–10.
33. Burghaus S, Häberle L, Schrauder MG, Heusinger K, Thiel FC, Hein A, et al. Endometriosis as a risk factor for ovarian or endometrial cancer—results of a hospital-based case–control study. BMC Cancer
34. Huang BS, Chang WH, Wang KC, Huang N, Guo CY, et al. Endometriosis might be inversely associated with developing chronic kidney disease: a population-based cohort study in Taiwan
. Int J Mol Sci. 17(7): 2016 Jul 7, http://dx.doi.org/10.3390/ijms17071079
The Taiwan Society of Gynecology Systematic Review Group includes the following members:
Yen-Hou Chang, Yi Chang, Kuan-Chong Chao, Yi-Jen Chen, Chi-Mu Chuang, Chen-Yu Huang, Ling-Yu Jiang, Hsin-Yang Li, Chia-Hao Liu, Pi-Lin Sun, Kuo-Chang Wen, Hua-Hsi Wu, and Hann-Chin Yu, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, R.O.C.
Fong-Yuan Ju, Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
Chih-Ping Tsai, Emergency Department, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
Wen-Hsun Chang, Yen-Mei Hsu, Shu-Yun Huang, and Na-Rong Lee, Department of Obstetrics and Gynecology, and Department of Nursing, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, R.O.C.
Chih-Yao Chen, Dianthus MFM Center Minquan, Dianthus MFM Group, and National Yang-Ming University, Taipei, Taiwan, R.O.C.
Ting-Chen Chang, Wen-Chun Chang, Chii-Hou Chen, Ruey-Jian Chen, Song-Nan Chow, Yih-Ron Lien, Bor-Ching Sheu, Pao-Ling Torng, and Men-Luh Yen, Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan, R.O.C.
Wen-Ling Lee, Department of Medicine, Cheng-Hsin General Hospital, Taipei, and Department of Nursing, Oriental Institute of Technology, New Taipei City, Taiwan, R.O.C.
Kuan-Chin Wang, Department of Nursing, Oriental Institute of Technology, New Taipei City, Taiwan, R.O.C.
Chih-Long Chang, Chih-Ping Chen, Jen-Ruei Chen, Tze-Chien Chen, Jian-Pei Huang, Ming-Chao Huang, and Yeou-Lih Wang, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.
Cheng-Chang Chang, Jah-Yao Liu, Her-Young Su, Yu-Chi Wang, and Mu-Hsien Yu, Department of Obstetrics and Gynecology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, R.O.C.
Ching-Chuang Chu, Lee-Wen Huang, and Kok-Min Seow, Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C.
Tsung-Hsuan Lai and Fa-Kung Lee, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan, R.O.C.
Ching-Hui Chen and Wei-Min Liu, Department of Obstetrics and Gynecology, Taipei Medical University Hospital and Taipei Medical University, Taipei, Taiwan, R.O.C.
Jyh-Shin Chiou, Ben-Shian Huang, and Yen-Feng Lu, Department of Obstetrics and Gynecology, National Yang-Ming University Hospital, Ilan, Taiwan, R.O.C.
Sheng-Mou Hsiao, Hsu-Dong Sun, and Wen-Yih Wu, Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei City, Taiwan, R.O.C.
Kuo-Hu Chen and Jeng-Hsiu Hung, Department of Obstetrics and Gynecology, Taipei Buddhist Tzu Chi General Hospital, New Taipei City, Taiwan, R.O.C.
Hung-Cheng Lai and Chiou-Chung Yuan, Department of Obstetrics and Gynecology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan, R.O.C.
Ching-Hung Hsieh, Department of Obstetrics and Gynecology, Clinic of Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C.
Chin-Jung Wang, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, and Chang Gung University, Taoyuan, Taiwan, R.O.C.
Chia-Hao Chan, Shing-Jyh Chang, and Chuan-Chi Shih, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Hsinchu, Taiwan, R.O.C.
Man-Jung Hung, Department of Obstetrics and Gynecology, Asia University Hospital, Taichung, Taiwan, R.O.C.
Shih-Tien Hsu, Yu-Min Ke, Chien-Hsing Lu, and Lou Sun, Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
Wei-Chun Chang, Yao-Ching Hung, and Wu-Chou Lin, Department of Obstetrics and Gynecology, China Medical University Hospital and China Medical University, Taichung, Taiwan, R.O.C.
Po-Hui Wang, Department of Obstetrics and Gynecology, Chung-Shang General Hospital and Chung-Shang Medical University, Taichung, Taiwan, R.O.C.
Tze-Ho Chen, Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
Yiu-Tai Li, Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan, R.O.C.
Meng-Hsing Wu, Department of Obstetrics and Gynecology, National Cheng Kung University Hospital and National Cheng Kung University, Tainan, Taiwan, R.O.C.
Kuo-Feng Huang, Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C.
Fei-Chi Chuang, Hung-Chun Fu, Fu-Tsai Kung, and Kuan-Hui Huang, Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, and Chang Gung University, Taoyuan, Taiwan, R.O.C.
San-Nung Chen, An-Jen Chiang, Ju-Yueh Li, Li-Te Lin, Hsiao-Wen Tsai, and Kuan-Hao Tsui, Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.