Knowledge of Iatrogenic Premature Ovarian Insufficiency Among Chinese Obstetricians and Gynecologists: A National Questionnaire Survey

Knowledge of Iatrogenic Premature Ovarian Insufficiency Among Chinese Obstetricians and Gynecologists: A National Questionnaire Survey | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Knowledge of Iatrogenic Premature Ovarian Insufficiency Among Chinese Obstetricians and Gynecologists: A National Questionnaire Survey Yanfang Wang, Ying Zou, Wei Wang, Qingmei Zheng, Ying Feng, Han Dong, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-80938/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Nov, 2020 Read the published version in Journal of Ovarian Research → Version 1 posted 8 You are reading this latest preprint version Abstract Background: With increasing cases of iatrogenic premature ovarian insufficiency (POI), more clinicians are required to counsel patients regarding the gonadotoxic effects of iatrogenic treatments. This survey aims to explore obstetricians and gynecologists’ knowledge regarding iatrogenic POI. A national online questionnaire survey was conducted across China. Respondents were asked to select the iatrogenic condition(s) that can cause POI based on their experience and knowledge. Results: Of the 5,523 returned questionnaires, 4,995 were analyzed. Among tumor therapies causing POI, most respondents agreed that radiotherapy (73.5% of respondents) and chemotherapy (64.1%) are risk factors for POI. While only 6.5% and 7.8% of the gynecological oncologists believed tumor immunotherapy and tumor-targeting therapy, respectively, may cause ovarian impairment, 31.8% and 22.2% of the non-gynecologic oncologists believed that these therapies could affect ovarian health. Most respondents believed that ovarian cystectomy (54.4%) was a risk factor for POI, while only a few respondents believed that hysterectomy with bilateral salpingectomy (39.6%) and uterine artery embolization (33.5%) could cause ovarian impairment. Only 30.5% respondents believed that immunosuppressants increased the risk of POI. Views differed with experience and hospital setting. Conclusions: The knowledge of gonadal toxicity due to traditional tumor treatments is generally high among Chinese obstetricians and gynecologists. A misunderstanding may exist in primary care hospitals and general gynecologists regarding a link between novel tumor treatments and POI, owing to the lack of convincing evidence. Knowledge of POI caused by hysterectomy and immunosuppressants should be improved. Sexual & Reproductive Medicine Cancer Biology Premature ovarian insufficiency iatrogenic menopause ovarian impairment knowledge national survey Figures Figure 1 Background Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years [ 1 ].The incidence of spontaneous POI, typically assumed to occur in approximately 1% of adult women [ 2 ], has increased to 2.4–2.8% in recent years [ 3 , 4 ]. As a consequence of being exposed to lower estrogen for a longer period, women with POI have an increased risk of premature morbidity and mortality [ 5 ], cardiovascular and cerebrovascular diseases [ 6 , 7 ], osteoporosis [ 8 , 9 ], impaired cognition [ 10 ], and diminished sexual health [ 11 ]. However, the etiologies of POI are largely unknown. Of the few identified causes, iatrogenic conditions account for a large proportion (~ 65%) of cases [ 12 ], including radiotherapy (RT), chemotherapy (CT), and drugs for various autoimmune diseases [ 13 , 14 ]. The incidence of iatrogenic POI has been reported to be growing owing to increasing survival rates following diverse cancer treatments [ 15 – 17 ]. In addition, accumulating evidence has revealed that women with endometriosis or a history of pelvic surgery are more likely to have severely compromised ovarian function, including POI [ 18 , 19 ]. Taken together, the increasing prevalence of iatrogenic POI has posed great challenges to clinicians, especially obstetricians and gynecologists. Fortunately, iatrogenic POI can be partially avoided or reduced using many preventative measures, including optimization of CT regimens or radiation field, application of gonadotropin-releasing hormone agonist (GnRH-a), and fertility-sparing surgical strategies, all of which are implemented by physicians. It has been continually emphasized that proper and comprehensive fertility counseling should be provided to patients who are within their reproductive ages prior to starting iatrogenic treatment so that they are informed on both the risk of treatment-related gonadotoxicity and the potential future needs of accessing an assisted reproductive clinic. To this end, the knowledge of iatrogenic POI among clinicians is particularly important. Therefore, we surveyed obstetricians and gynecologists across China about their general knowledge of iatrogenic POI to fully investigate the current understanding of this condition and any underlying challenges in this population. Results General background information of respondents Of the 5,524 questionnaires that were returned, 249 were answered by respondents who were neither obstetricians nor gynecologists and were excluded, leaving a qualified sample of 4,995 (95.5%). General background information about the respondents is presented in Table 1 . Most respondents were women (96.2%), aged 36–55 years (69.2%), with over 10 years of working experience. In terms of respondents’ work setting, 34.9% of respondents worked in tertiary hospitals and 49.0% in secondary hospitals. Meanwhile, 51.5% of respondents practice at general hospitals and 42.9% practice at maternity and children hospitals, or reproductive hospitals. Most participants (79.5%) specialized in gynecology, including reproductive endocrinologists, obstetricians-gynecologists (who work as a gynecologist and an obstetrician simultaneously), and gynecologists. Table 1 General background information about the respondents. Category N (%) Gender Female 4805 (96.2) Male 190 (3.8) Age in years 18–25 112 (2.2) 26–35 1079 (21.6) 36–45 2065 (41.3) 46–55 1529 (30.6) >55 210 (4.2) Length of service (years) ≤5 677 (13.6) 6 ~ 10 861 (17.2) 11 ~ 20 1517 (30.4) >20 1940 (38.8) Hospital level Tertiary hospital 1745 (34.9) Secondary hospital 2445 (49.0) Community hospital or others 448 (16.1) Hospital type General hospital 2572 (51.5) Maternity and child care hospital 2144 (42.9) Others 279 (5.6) Specialty type General gynecologist 3400 (68.1) Gynecologic or reproductive endocrinologist 345 (6.9) Obstetrician-gynecologist 147 (2.9) Gynecologic oncologist 77 (1.54) Obstetrician 1026 (20.5) Total 4995 (100) Iatrogenic condition(s) to induce POI A summary of Chinese obstetricians and gynecologists’ views on iatrogenic condition(s) that can induce POI is presented in Table 2 . Among the tumor therapies respondents thought would induce POI, RT ranked first (73.5%), followed by CT (64.1%), tumor immunotherapy (TIT) (31.8%), and tumor-targeting therapy (TTT; 22.2%) (p < 0.05). Table 2 Chinese obstetricians and gynecologists' views on iatrogenic condition(s) to induce POI. Variable N (%) χ² p Tumor therapies Radiotherapy 3669 (73.5) 1459.1 < 0.01 Chemotherapy 3202 (64.1) Tumor immunotherapy 1590 (31.8) Tumor-targeting therapy 1109 (22.2) Surgeries or procedures Ovarian cystectomy 2716 (54.4) 1288.4 < 0.01 Hysterectomy with bilateral salpingectomy 1980 (39.6) Uterine artery embolization 1675 (33.5) Bilateral salpingectomy 1246 (24.9) Bilateral tubal ligation 779 (15.6) Others Immunosuppressant 1523 (30.5) / / Most respondents believed that ovarian cystectomy (OC) could have an adverse impact on ovarian reserve (54.4% of respondents), whereas a minority believed that hysterectomy with bilateral salpingectomy (H&BS; 39.6%), uterine artery embolization (UAE; 33.5%), bilateral salpingectomy (BS; 24.9%), or bilateral tubal ligation (BTL; 15.6%, P < 0.05) could have an adverse impact on ovarian reserve. Only 30.5% respondents believed that immunosuppressants (IS) could lead to an increased risk of POI. Influencing factors Analysis demonstrated that the level of understanding about the risk of POI with different treatments varied with length of service and hospital setting. A visualization of the correspondence analysis is shown in Fig. 1 . For example, respondents with over 20 years of service were more likely to consider RT, BS, and H&BS as risk factors for POI than those in other age groups. Meanwhile, those with less than 5 years of service typically only indicated the risk of POI caused by OC. Physicians from tertiary hospitals might pay more attention to ovarian impairment caused by UAE, while those from secondary hospitals were more aware of the link between the ovarian impairment and CT and BTL. Interestingly, TTT, TIT, and IS were considered more often to be risk factors for POI by physicians from community hospital or others, where advanced treatments are less likely to be available. Finally, while 6.5% and 7.8% of the gynecological oncologists believed that TIT and TTT may adversely affect the ovarian reserve, respectfully, 31.8% and 22.2% of non-gynecologic oncologists believed that the same treatment may be a risk factor for POI. Discussion Tumor therapy In women, primordial germ cells (PGCs) enter meiosis at week 10, progressing to prophase I and remaining at this stage for a long period until ovulation [ 20 ]. This process makes PGCs extremely sensitive to the effects of CT and RT. Evidence suggests that the incidence of POI in female survivors of childhood and adolescent cancer is 2.1– 82.2% [ 21 ]. RT can be more damaging to ovarian tissue than CT because apart from being particularly irreversibly toxic to oocytes [ 22 , 23 ], its off-target effects can also affect the surrounding tissue [ 24 ]. A rapidly growing group of cancer survivors requires availability of more physicians to better counsel patients regarding the gonadotoxic effects of cancer treatment and provide them with appropriate options. However, a recent study in 2014 demonstrated that while 71% of oncologists were aware of the risk of POI following exposure to alkylating agents, only 15% of primary care physicians were aware of this risk [ 25 ]. This nationally representative study found that there is some general knowledge about tumor-treatment-related POI among Chinese obstetricians and gynecologists. Among respondents, 73.5% and 64.1% were aware that RT and CT, respectively, are the two main factors leading to the decline of ovarian reserve. Furthermore, respondents with more than 10 years of experience working in secondary or tertiary hospitals had better knowledge regarding risk factors for iatrogenic POI than others. Therefore, relevant fertility-related education should be provided in a more targeted manner in the future. Recently, novel therapies including TTT and TIT have been increasingly used in clinical settings. Despite their high selectivity, they may also affect healthy cells and tissues, including gonadal tissues, as highlighted by animal studies [ 26 ]. Unlike the direct toxicity of RT or CT, TTT tends to influence folliculogenesis, PGC establishment, or ovarian follicular growth and differentiation by acting on the corresponding signaling pathways [ 26 ]. However, available human data on the association between TTT and ovarian health are limited and heterogeneous [ 27 ]. Most existing data are from retrospective evaluations [ 28 ] or case reports [ 29 ]. For instance, Allegra et al [ 28 ] reported that new-onset POI occurred in 39% of patients treated with the combination of modified FOLFOX-6 and bevacizumab (a type of TTT) compared with 2.6% in the control group treated with modified FOLFOX-6. In this cohort, ovarian function recovered in 86% of patients after cessation of treatment. Regarding TIT, existing data are more limited, but experts in this field are optimistic about its efficacy [ 30 ]. The results of our survey demonstrated that most physicians from community hospitals or others tended to believe TIT and TTT may cause adverse effects to ovarian reserve, which, however, was not the case for most gynecological oncologists. These phenomena imply that the popularization and speed at which relevant information is updated among physicians practicing at different level hospitals and specialties vary considerably. With a lack of convincing public data, the chances are slim that primary care physicians will be aware of the risks of novel therapies to ovarian health without continually reviewing the literature. Therefore, to improve the reproductive health and long-term quality of life of cancer patients, both well-designed clinical observations and more accessible information and education for clinicians are required. Surgeries or procedures POI induced by non-oophorectomized surgeries is less common than traditional cancer treatment, but since these surgeries are regular treatment for many benign gynecological conditions or early tumors at any age, their impact on fertility should not be ignored. Evidence has confirmed that OC has been associated with a reduction in ovarian reserve, especially in patients with severe endometriosis [ 31 – 33 ]. Our survey demonstrated that OC-inducing ovarian impairment was commonly known among respondents, even in those with less than 5 years of service. This indicates that POI caused by OC may not be uncommon in clinical practice. Anatomically, H&BS, UAE, BS, and BTL may reduce blood supply to the ovaries to varying degrees, thus having a potential impact on ovarian reserve. Previous studies have demonstrated a certain reduction in ovarian function after H&BS [ 34 , 35 ]. In 2011, Moorman et al. published their prospective research including 2,410 patients aged between 30 and 47 years, revealing a nearly two-fold increased risk for ovarian failure among women undergoing hysterectomy without bilateral oophorectomy compared with women of similar age with intact uteri (level of evidence: II) [ 36 ]. With accelerating menopause and hormone deprivation caused by hysterectomy, an increased overall risk of morbidity and mortality is also revealed. A cohort study of 666,588 women demonstrated that hysterectomy without oophorectomy performed before age 35 and H&BS performed before age 45 were associated with an increase in all-cause mortality (hazard ratio, 1.29 and 1.15, respectively) [ 37 ] and the incidence of depression [ 38 ]. However, in our study, only 39.6% of the obstetricians and gynecologist respondents were aware of H&BS causing diminished ovarian reserve. From a public health perspective, these are vital issues that require further training and education for health professionals to avoid unnecessary hysterectomy. Women under age 40 appear not to be affected by UAE [ 39 ]. Out of 7.3% of cases of amenorrhea after UAE, 86% occurred in patients 45 years or older [ 40 ]. While a meta-analysis of 353 patients demonstrated that UAE may not result in impaired ovarian reserve, regardless of age [ 41 ], other studies with small sample sizes demonstrated the opposite result [ 42 , 43 ]. Our survey demonstrated that 33.5% of respondents still worried about UAE leading to POI, especially in tertiary hospitals where UAE procedures are completed more frequently. BS and BTL are less likely to induce POI, as they may have no short-term significant effects on ovarian function indicators [ 44 – 46 ]. However, their long-term effect on fertility outcomes remains uncertain [ 44 , 47 ]. Most respondents remained optimistic about the effects of BS and BTL on ovarian health. Immunosuppressants ISs are often used for long-term treatment of autoimmune diseases, such as systemic lupus erythematosus (SLE), which predominantly affect young women. Some of these agents have distinctive gonadal toxicity. For example, cyclophosphamide has been considered as an independent risk factor of POI in SLE patients [ 13 ]. During the administration of cyclophosphamide, the incidence of POI was < 50% of women under age 30 and 60% of women between ages 30 and 40 [ 48 ]. Reversible amenorrhea (64.3% of patients) [ 49 ] and irregular menstruation (70% of patients) [ 50 ] were also observed in premenopausal women following exposure to Tripterygium wilfordii Hook.f., a well-known Chinese herbal medicine with an immunosuppressive effect. However, 69.5% of respondents to our survey were not aware of the gonadal impairment of IS, which appeared more prevalent among respondents from tertiary hospitals. As IS agents are typically prescribed by an immunologist or an internal medicine physician, we speculate that these differences may be due to a high degree of departmental specialization in tertiary hospitals. Thus, it is necessary to conduct relevant training and education and strengthen the exchange of experience between different departments on IS use. Conclusions This national survey is the first to explore obstetricians and gynecologists’ knowledge and awareness regarding iatrogenic POI. Taking respondents’ background information into consideration, the results of this survey not only generate a clearer picture of the understanding of iatrogenic POI in this field, but also help us determine the underlying problems in knowledge translation. However, there were some limitations: the proportion of respondents with different backgrounds (gender, specialty, or hospital type) was unevenly distributed; the iatrogenic measures listed in the questionnaire were limited and we did not give a detailed explanation for the immunosuppressants included in the survey. Therefore, further investigations and improved survey design are needed to confirm and update our conclusions. Our survey demonstrated that the knowledge of gonadal toxicity of traditional tumor treatments is generally high among obstetricians and gynecologists, but there is still a relative lack of understanding among physicians with less experience and/or from community hospitals. A misunderstanding may exist in community hospitals and among non-gynecologic oncologists relating novel tumor treatments and ovarian health due to the lack of convincing evidence. Additionally, the knowledge of POI caused by hysterectomy and IS agents needs to be improved. Based on these results, we hope to carry out more purposeful and targeted doctor re-training in the future. Methods Study setting and implementation An online survey was administered to obstetricians and gynecologists across China between June 7 and July 3, 2020. The questionnaire was distributed with the assistance of the China Maternal and Child Health Association, Society of Gynecological Endocrinology and answered anonymously. The study was reviewed and approved by the Ethics Committee of Peking Union Medical College Hospital (Ethical code number: S-k1189-1; date of approval: May 08, 2020) and is in accordance with the Declaration of Helsinki. Questionnaire design The questionnaire included the following sections: (1) general background information of the respondent; (2) Tumor therapies and POI; (3) Surgeries or procedures and POI; and (4) Immunosuppressants and POI. There were 16 questions in total, and full questionnaire details are provided in Supplementary material. Statistical analysis Data analysis was performed using SPSS (ver. 25.0 IBM, Armonk, NY, USA). Categorical variables are presented as a number (frequency) and percentage. The association between two categorical variables was tested using the chi-square test. Due to the large variation in the sample size among subgroups, subgroup analyses were not performed based on physicians’ gender, specialty, or hospital type. An overlap existed among respondents regarding age and length of service, with the latter being more representative of work experience. Thus, subgroup analyses were conducted based on physicians’ length of service and hospital type (community, secondary, and tertiary). Statistically significant associations were defined as having P < 0.05. To better understand the discriminative variables, a correspondence analysis was conducted to visualize the correlation among variables. List of abbreviations BS Bilateral salpingectomy BTL Bilateral tubal ligation CH Community hospital CT Chemotherapy GnRH-a Gonadotropin-releasing hormone agonist H&BS Hysterectomy with bilateral salpingectomy IS Immunosuppressants OC Ovarian cystectomy PGC Primordial germ cells POI Premature ovarian insufficiency RT Radiotherapy SLE Systemic lupus erythematosus TIT Tumor immunotherapy TTT Tumor-targeting therapy UAE Uterine artery embolization Declarations Ethics approval and consent to participate The study was reviewed and approved by the Ethics Committee of Peking Union Medical College Hospital (Ethical code number: S-k1189-1; date of approval: May 08, 2020). Consent for publication Not applicable. Availability of data and materials Data and materials are summarized in the manuscript, figures, and tables. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors’ Contributions YFW and AJS implemented the research plan and were responsible for the questionnaire design. YFW, YZ, and AJS oversaw the formal analysis, conceptualization and writing of the manuscript. WW, QZ, YF, YZ, HD, ZYT, XQZ, YQZ, DHP, and XMY provided valuable comments and suggestions on the questionnaire revision and played a critical role in the distribution, completion, and collection of questionnaires. AJS and YZ provided a critical contribution to the organization and cooperation of this arduous task Acknowledgements The authors would like to thank all the Chinese obstetricians and gynecologists who participated in the survey for sharing their valuable views. We also thank China Maternal and Child Health Association, Society of Gynecological Endocrinology for supporting our survey. References [1] L. Webber, M. Davies, R. Anderson, J. 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Stepniak, P. Milart, T. Paszkowski, S. Wozniak, Comparison of the influence of three fibroid treatment options: supracervical hysterectomy, ulipristal acetate and uterine artery embolization on ovarian reserve - an observational study, J Ovarian Res 11(1) (2018) 45. [43] A. Mohr-Sasson, M. Spira, R. Rahav, D. Manela, E. Schiff, S. Mazaki-Tovi, R. Orvieto, E. Sivan, Ovarian reserve after uterine artery embolization in women with morbidly adherent placenta: A cohort study, PLoS One 13(11) (2018) e0208139. [44] A.A. Mohamed, A.H. Yosef, C. James, T.K. Al-Hussaini, M.A. Bedaiwy, S. Amer, Ovarian reserve after salpingectomy: a systematic review and meta-analysis, Acta Obstet Gynecol Scand 96(7) (2017) 795-803. [45] A.L. Silva, C. Ré, C. Dietrich, I.P. Fuhrmeister, A. Pimentel, H.V. Corleta, Impact of tubal ligation on ovarian reserve as measured by anti-Müllerian hormone levels: a prospective cohort study, Contraception 88(6) (2013) 700-5. [46] S. Kelekci, Z. Yorgancioglu, B. Yilmaz, L. Yasar, K. Savan, S. Sonmez, C. Kart, Effect of tubal ligation on ovarian reserve and the ovarian stromal blood supply, Aust N Z J Obstet Gynaecol 44(5) (2004) 449-51. [47] C.P. Vignarajan, N. Malhotra, N. Singh, Ovarian Reserve and Assisted Reproductive Technique Outcomes After Laparoscopic Proximal Tubal Occlusion or Salpingectomy in Women with Hydrosalpinx Undergoing in Vitro Fertilization: A Randomized Controlled Trial, J Minim Invasive Gynecol 26(6) (2019) 1070-1075. [48] K. Manger, L. Wildt, J. Kalden, B. Manger, Prevention of gonadal toxicity and preservation of gonadal function and fertility in young women with systemic lupus erythematosus treated by cyclophosphamide: the PREGO-Study, Autoimmunity reviews 5(4) (2006) 269-72. [49] C. Gu, [Cause of amenorrhea after treatment with tripterygium wilfordii F], Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 11(2) (1989) 151-3. [50] Y. Zhou, L. Zhao, H. Chen, Y. Zhang, D. Wang, L. Huang, Q. Lv, B. Liu, Z. Li, W. Wei, H. Li, X. Liao, H. Liu, X. Liu, H. Jin, J. Wang, Y. Fei, Q. Wu, W. Zhang, Q. Shi, W. Zheng, F. Zhang, F. Tang, P. Lipsky, X. Zhang, Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study, Arthritis research & therapy 20(1) (2018) 70. Supplementary Files supplement1.pdf Supplementary Table 2. Comparison of views on iatrogenic condition(s) to induce POI among respondents from different level hospitals. supplement2.pdf Supplementary Table 1. Comparison of views on iatrogenic condition(s) to induce POI among respondents with different length of service (years). supplement3.pdf Questionnaire Cite Share Download PDF Status: Published Journal Publication published 18 Nov, 2020 Read the published version in Journal of Ovarian Research → Version 1 posted Editorial decision: Minor revision 20 Oct, 2020 Review # 1 received at journal 14 Oct, 2020 Reviewer # 1 agreed at journal 29 Sep, 2020 Reviewers invited by journal 23 Sep, 2020 Editor assigned by journal 22 Sep, 2020 First submitted to journal 21 Sep, 2020 Submission checks completed at journal 21 Sep, 2020 Editor invited by journal 21 Sep, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-80938","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":2643345,"identity":"24f49467-ab6c-401f-bdc1-5ea972586945","order_by":0,"name":"Yanfang Wang","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanfang","middleName":"","lastName":"Wang","suffix":""},{"id":2643346,"identity":"c1e33e13-0b5c-4b34-979c-c55ba6b478e7","order_by":1,"name":"Ying Zou","email":"","orcid":"","institution":"Hunan Province Maternal and Child Health Care Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Zou","suffix":""},{"id":2643347,"identity":"e54e6848-641a-44a7-9245-5b94d1cb0e1e","order_by":2,"name":"Wei Wang","email":"","orcid":"","institution":"The Second Hospital of Hebei Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Wang","suffix":""},{"id":2643348,"identity":"5815860f-630c-4f4f-af04-6ba4bbc11bae","order_by":3,"name":"Qingmei Zheng","email":"","orcid":"","institution":"The Second Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Qingmei","middleName":"","lastName":"Zheng","suffix":""},{"id":2643349,"identity":"542273e4-274e-418d-8768-88a9c0313d59","order_by":4,"name":"Ying Feng","email":"","orcid":"","institution":"The Second Affiliated Hospital of Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Feng","suffix":""},{"id":2643350,"identity":"43b5991d-cf2a-4eb9-b88f-24516d469b88","order_by":5,"name":"Han Dong","email":"","orcid":"","institution":"Women and Children's Hospital of Jinzhou","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"","lastName":"Dong","suffix":""},{"id":2643351,"identity":"dbceb476-c309-4238-b5c6-604dbeff4533","order_by":6,"name":"Zhangyun Tan","email":"","orcid":"","institution":"Xinhui Maternity and Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhangyun","middleName":"","lastName":"Tan","suffix":""},{"id":2643352,"identity":"d678cdc4-6c0c-44b7-9765-0d0ea5eb5856","order_by":7,"name":"Xiaoqin Zeng","email":"","orcid":"","institution":"Guangzhou Women and Children's Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Xiaoqin","middleName":"","lastName":"Zeng","suffix":""},{"id":2643353,"identity":"67d074c1-b6cc-4778-bac7-4fa905a82ae9","order_by":8,"name":"Yinqing Zhao","email":"","orcid":"","institution":"Xinhui Maternity and Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yinqing","middleName":"","lastName":"Zhao","suffix":""},{"id":2643354,"identity":"5ba0af41-7cd7-4c52-aa59-1afa831d06e8","order_by":9,"name":"Danhong Peng","email":"","orcid":"","institution":"Zhongda Hospital Southeast University","correspondingAuthor":false,"prefix":"","firstName":"Danhong","middleName":"","lastName":"Peng","suffix":""},{"id":2643355,"identity":"610bb19f-fd04-4f41-a927-2682a4adf81a","order_by":10,"name":"Xiaomin Yang","email":"","orcid":"","institution":"Liuzhou Maternity and Child Healthcare Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaomin","middleName":"","lastName":"Yang","suffix":""},{"id":2643356,"identity":"c41640db-e02f-4193-ad56-19b858ca231c","order_by":11,"name":"Ai-jun Sun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYHCCBDBpwN7AcIBELTwHiNcCAQYSCUSqlG8/8IC5sG2bvLnk84eHC2oY5PnFCFhmcCYhgXlm223DnbNzDA7POMZgOHM2AesMGIBaeNtuJxjczmE4zMPGAGQQ0CLf/wCq5ebxB4d5/hGhheEGzJYbDAaHeduI0GJwA2jLjHO3DTecAfqFt0+CsF/k+3MSmAvKbssbHD/++DPPNxt5fmlCDmPgSf+NxJMgpBwE2A8wE6NsFIyCUTAKRjAAABw5RRXKmWI1AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0049-0906","institution":"Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China","correspondingAuthor":true,"prefix":"","firstName":"Ai-jun","middleName":"","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2020-09-20 10:26:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-80938/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-80938/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13048-020-00739-z","type":"published","date":"2020-11-18T15:01:18+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2627404,"identity":"56e009ed-4a20-44d8-9983-b47d649bacd2","added_by":"3c660abf-5171-4564-85c7-424add6c715f","created_at":"2020-09-25 21:03:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":44369,"visible":true,"origin":"","legend":"Visualization of the correspondence analysis by physician’s length of service (A), and level of hospital (B). The interpretation rate in each dimension is: 87.7% (Dimension 1) and 7.50% (Dimension 2) in A; and 98.9% (Dimension 1), 1.1% (Dimension 2) in B. More details are available in Supplementary Table 1 and Supplementary Table 2. Abbreviations: RT: radiotherapy; CT: chemotherapy; TIT: tumor immunotherapy; TTT: tumor-targeting therapy; OC: ovarian cystectomy; H\u0026BS: hysterectomy with bilateral salpingectomy; UAE: uterine artery embolization; BS: bilateral salpingectomy; BTL: bilateral tubal ligation; IS: immunosuppressant.","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-80938/v1/figure_1.jpg"},{"id":13597707,"identity":"dd71e2f1-b4e5-485e-bc46-068864094457","added_by":"auto","created_at":"2021-09-17 05:33:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":408754,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-80938/v1/4afd25c8-5d79-4902-9717-66ec2b137b20.pdf"},{"id":2626995,"identity":"a8a6d20b-924e-4b25-8069-469bed8f5725","added_by":"acdc","created_at":"2020-09-25 21:03:21","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":40767,"visible":true,"origin":"acdc-supplements-supplement","legend":"Supplementary Table 2. Comparison of views on iatrogenic condition(s) to induce POI among respondents from different level hospitals.","description":"{\"primaryId\":\"undefined\",\"secondaryId\":\"JOVR-D-20-00348\",\"acdcId\":\"undefined\",\"revision\":\"undefined\",\"timestamp\":\"2020-09-22T22:56:49\",\"document\":\"supplements\",\"linkRel\":\"supplement\"}","filename":"supplement1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-80938/v1/supplement_1.pdf"},{"id":2626997,"identity":"262bf354-8de3-49cc-b022-211c4211607c","added_by":"acdc","created_at":"2020-09-25 21:03:21","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":41910,"visible":true,"origin":"acdc-supplements-supplement","legend":"Supplementary Table 1. Comparison of views on iatrogenic condition(s) to induce POI among respondents with different length of service (years).","description":"{\"primaryId\":\"undefined\",\"secondaryId\":\"JOVR-D-20-00348\",\"acdcId\":\"undefined\",\"revision\":\"undefined\",\"timestamp\":\"2020-09-22T22:56:49\",\"document\":\"supplements\",\"linkRel\":\"supplement\"}","filename":"supplement2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-80938/v1/supplement_2.pdf"},{"id":2626996,"identity":"ed810812-baa7-4062-bb94-430ce26d9d0d","added_by":"acdc","created_at":"2020-09-25 21:03:21","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":66701,"visible":true,"origin":"acdc-supplements-supplement","legend":"Questionnaire","description":"{\"primaryId\":\"undefined\",\"secondaryId\":\"JOVR-D-20-00348\",\"acdcId\":\"undefined\",\"revision\":\"undefined\",\"timestamp\":\"2020-09-22T22:56:49\",\"document\":\"supplements\",\"linkRel\":\"supplement\"}","filename":"supplement3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-80938/v1/supplement_3.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eKnowledge of Iatrogenic Premature Ovarian Insufficiency Among Chinese Obstetricians and Gynecologists: A National Questionnaire Survey\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003ePremature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40\u0026nbsp;years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].The incidence of spontaneous POI, typically assumed to occur in approximately 1% of adult women [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], has increased to 2.4\u0026ndash;2.8% in recent years [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As a consequence of being exposed to lower estrogen for a longer period, women with POI have an increased risk of premature morbidity and mortality [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], cardiovascular and cerebrovascular diseases [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], osteoporosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], impaired cognition [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and diminished sexual health [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, the etiologies of POI are largely unknown. Of the few identified causes, iatrogenic conditions account for a large proportion (~\u0026thinsp;65%) of cases [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], including radiotherapy (RT), chemotherapy (CT), and drugs for various autoimmune diseases [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The incidence of iatrogenic POI has been reported to be growing owing to increasing survival rates following diverse cancer treatments [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In addition, accumulating evidence has revealed that women with endometriosis or a history of pelvic surgery are more likely to have severely compromised ovarian function, including POI [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Taken together, the increasing prevalence of iatrogenic POI has posed great challenges to clinicians, especially obstetricians and gynecologists.\u003c/p\u003e \u003cp\u003eFortunately, iatrogenic POI can be partially avoided or reduced using many preventative measures, including optimization of CT regimens or radiation field, application of gonadotropin-releasing hormone agonist (GnRH-a), and fertility-sparing surgical strategies, all of which are implemented by physicians. It has been continually emphasized that proper and comprehensive fertility counseling should be provided to patients who are within their reproductive ages prior to starting iatrogenic treatment so that they are informed on both the risk of treatment-related gonadotoxicity and the potential future needs of accessing an assisted reproductive clinic. To this end, the knowledge of iatrogenic POI among clinicians is particularly important. Therefore, we surveyed obstetricians and gynecologists across China about their general knowledge of iatrogenic POI to fully investigate the current understanding of this condition and any underlying challenges in this population.\u003c/p\u003e "},{"header":"Results","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eGeneral background information of respondents\u003c/h2\u003e \u003cp\u003eOf the 5,524 questionnaires that were returned, 249 were answered by respondents who were neither obstetricians nor gynecologists and were excluded, leaving a qualified sample of 4,995 (95.5%). General background information about the respondents is presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Most respondents were women (96.2%), aged 36\u0026ndash;55\u0026nbsp;years (69.2%), with over 10\u0026nbsp;years of working experience. In terms of respondents\u0026rsquo; work setting, 34.9% of respondents worked in tertiary hospitals and 49.0% in secondary hospitals. Meanwhile, 51.5% of respondents practice at general hospitals and 42.9% practice at maternity and children hospitals, or reproductive hospitals. Most participants (79.5%) specialized in gynecology, including reproductive endocrinologists, obstetricians-gynecologists (who work as a gynecologist and an obstetrician simultaneously), and gynecologists.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral background information about the respondents.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4805 (96.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge in years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112 (2.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26\u0026ndash;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1079 (21.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36\u0026ndash;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2065 (41.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e46\u0026ndash;55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1529 (30.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e210 (4.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of service (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e677 (13.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026thinsp;~\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e861 (17.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u0026thinsp;~\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1517 (30.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1940 (38.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTertiary hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1745 (34.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2445 (49.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCommunity hospital or others\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e448 (16.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2572 (51.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternity and child care hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2144 (42.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e279 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecialty type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral gynecologist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3400 (68.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGynecologic or reproductive endocrinologist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e345 (6.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstetrician-gynecologist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e147 (2.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGynecologic oncologist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (1.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstetrician\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1026 (20.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4995 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eIatrogenic condition(s) to induce POI\u003c/h2\u003e \u003cp\u003eA summary of Chinese obstetricians and gynecologists\u0026rsquo; views on iatrogenic condition(s) that can induce POI is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among the tumor therapies respondents thought would induce POI, RT ranked first (73.5%), followed by CT (64.1%), tumor immunotherapy (TIT) (31.8%), and tumor-targeting therapy (TTT; 22.2%) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChinese obstetricians and gynecologists' views on iatrogenic condition(s) to induce POI.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eχ\u0026sup2;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor therapies\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3669 (73.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e1459.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3202 (64.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor immunotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1590 (31.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor-targeting therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1109 (22.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgeries or procedures\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOvarian cystectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2716 (54.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e1288.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHysterectomy with bilateral salpingectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1980 (39.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine artery embolization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1675 (33.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral salpingectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1246 (24.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral tubal ligation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e779 (15.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOthers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1523 (30.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMost respondents believed that ovarian cystectomy (OC) could have an adverse impact on ovarian reserve (54.4% of respondents), whereas a minority believed that hysterectomy with bilateral salpingectomy (H\u0026amp;BS; 39.6%), uterine artery embolization (UAE; 33.5%), bilateral salpingectomy (BS; 24.9%), or bilateral tubal ligation (BTL; 15.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) could have an adverse impact on ovarian reserve. Only 30.5% respondents believed that immunosuppressants (IS) could lead to an increased risk of POI.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eInfluencing factors\u003c/h2\u003e \u003cp\u003eAnalysis demonstrated that the level of understanding about the risk of POI with different treatments varied with length of service and hospital setting. A visualization of the correspondence analysis is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. For example, respondents with over 20\u0026nbsp;years of service were more likely to consider RT, BS, and H\u0026amp;BS as risk factors for POI than those in other age groups. Meanwhile, those with less than 5\u0026nbsp;years of service typically only indicated the risk of POI caused by OC. Physicians from tertiary hospitals might pay more attention to ovarian impairment caused by UAE, while those from secondary hospitals were more aware of the link between the ovarian impairment and CT and BTL. Interestingly, TTT, TIT, and IS were considered more often to be risk factors for POI by physicians from community hospital or others, where advanced treatments are less likely to be available. Finally, while 6.5% and 7.8% of the gynecological oncologists believed that TIT and TTT may adversely affect the ovarian reserve, respectfully, 31.8% and 22.2% of non-gynecologic oncologists believed that the same treatment may be a risk factor for POI.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e "},{"header":"Discussion","content":" \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eTumor therapy\u003c/h2\u003e \u003cp\u003eIn women, primordial germ cells (PGCs) enter meiosis at week 10, progressing to prophase I and remaining at this stage for a long period until ovulation [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This process makes PGCs extremely sensitive to the effects of CT and RT. Evidence suggests that the incidence of POI in female survivors of childhood and adolescent cancer is 2.1\u0026ndash; 82.2% [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. RT can be more damaging to ovarian tissue than CT because apart from being particularly irreversibly toxic to oocytes [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], its off-target effects can also affect the surrounding tissue [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A rapidly growing group of cancer survivors requires availability of more physicians to better counsel patients regarding the gonadotoxic effects of cancer treatment and provide them with appropriate options. However, a recent study in 2014 demonstrated that while 71% of oncologists were aware of the risk of POI following exposure to alkylating agents, only 15% of primary care physicians were aware of this risk [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This nationally representative study found that there is some general knowledge about tumor-treatment-related POI among Chinese obstetricians and gynecologists. Among respondents, 73.5% and 64.1% were aware that RT and CT, respectively, are the two main factors leading to the decline of ovarian reserve. Furthermore, respondents with more than 10\u0026nbsp;years of experience working in secondary or tertiary hospitals had better knowledge regarding risk factors for iatrogenic POI than others. Therefore, relevant fertility-related education should be provided in a more targeted manner in the future.\u003c/p\u003e \u003cp\u003eRecently, novel therapies including TTT and TIT have been increasingly used in clinical settings. Despite their high selectivity, they may also affect healthy cells and tissues, including gonadal tissues, as highlighted by animal studies [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Unlike the direct toxicity of RT or CT, TTT tends to influence folliculogenesis, PGC establishment, or ovarian follicular growth and differentiation by acting on the corresponding signaling pathways [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, available human data on the association between TTT and ovarian health are limited and heterogeneous [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Most existing data are from retrospective evaluations [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] or case reports [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. For instance, Allegra et al [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] reported that new-onset POI occurred in 39% of patients treated with the combination of modified FOLFOX-6 and bevacizumab (a type of TTT) compared with 2.6% in the control group treated with modified FOLFOX-6. In this cohort, ovarian function recovered in 86% of patients after cessation of treatment. Regarding TIT, existing data are more limited, but experts in this field are optimistic about its efficacy [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The results of our survey demonstrated that most physicians from community hospitals or others tended to believe TIT and TTT may cause adverse effects to ovarian reserve, which, however, was not the case for most gynecological oncologists. These phenomena imply that the popularization and speed at which relevant information is updated among physicians practicing at different level hospitals and specialties vary considerably. With a lack of convincing public data, the chances are slim that primary care physicians will be aware of the risks of novel therapies to ovarian health without continually reviewing the literature. Therefore, to improve the reproductive health and long-term quality of life of cancer patients, both well-designed clinical observations and more accessible information and education for clinicians are required.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSurgeries or procedures\u003c/h2\u003e \u003cp\u003ePOI induced by non-oophorectomized surgeries is less common than traditional cancer treatment, but since these surgeries are regular treatment for many benign gynecological conditions or early tumors at any age, their impact on fertility should not be ignored. Evidence has confirmed that OC has been associated with a reduction in ovarian reserve, especially in patients with severe endometriosis [\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Our survey demonstrated that OC-inducing ovarian impairment was commonly known among respondents, even in those with less than 5\u0026nbsp;years of service. This indicates that POI caused by OC may not be uncommon in clinical practice.\u003c/p\u003e \u003cp\u003eAnatomically, H\u0026amp;BS, UAE, BS, and BTL may reduce blood supply to the ovaries to varying degrees, thus having a potential impact on ovarian reserve. Previous studies have demonstrated a certain reduction in ovarian function after H\u0026amp;BS [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In 2011, Moorman et al. published their prospective research including 2,410 patients aged between 30 and 47 years, revealing a nearly two-fold increased risk for ovarian failure among women undergoing hysterectomy without bilateral oophorectomy compared with women of similar age with intact uteri (level of evidence: II) [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. With accelerating menopause and hormone deprivation caused by hysterectomy, an increased overall risk of morbidity and mortality is also revealed. A cohort study of 666,588 women demonstrated that hysterectomy without oophorectomy performed before age 35 and H\u0026amp;BS performed before age 45 were associated with an increase in all-cause mortality (hazard ratio, 1.29 and 1.15, respectively) [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] and the incidence of depression [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. However, in our study, only 39.6% of the obstetricians and gynecologist respondents were aware of H\u0026amp;BS causing diminished ovarian reserve. From a public health perspective, these are vital issues that require further training and education for health professionals to avoid unnecessary hysterectomy.\u003c/p\u003e \u003cp\u003eWomen under age 40 appear not to be affected by UAE [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Out of 7.3% of cases of amenorrhea after UAE, 86% occurred in patients 45\u0026nbsp;years or older [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. While a meta-analysis of 353 patients demonstrated that UAE may not result in impaired ovarian reserve, regardless of age [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], other studies with small sample sizes demonstrated the opposite result [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Our survey demonstrated that 33.5% of respondents still worried about UAE leading to POI, especially in tertiary hospitals where UAE procedures are completed more frequently. BS and BTL are less likely to induce POI, as they may have no short-term significant effects on ovarian function indicators [\u003cspan additionalcitationids=\"CR45\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. However, their long-term effect on fertility outcomes remains uncertain [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Most respondents remained optimistic about the effects of BS and BTL on ovarian health.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eImmunosuppressants\u003c/h2\u003e \u003cp\u003eISs are often used for long-term treatment of autoimmune diseases, such as systemic lupus erythematosus (SLE), which predominantly affect young women. Some of these agents have distinctive gonadal toxicity. For example, cyclophosphamide has been considered as an independent risk factor of POI in SLE patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. During the administration of cyclophosphamide, the incidence of POI was \u0026lt;\u0026thinsp;50% of women under age 30 and 60% of women between ages 30 and 40 [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Reversible amenorrhea (64.3% of patients) [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e] and irregular menstruation (70% of patients) [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e] were also observed in premenopausal women following exposure to \u003cem\u003eTripterygium wilfordii\u003c/em\u003e Hook.f., a well-known Chinese herbal medicine with an immunosuppressive effect. However, 69.5% of respondents to our survey were not aware of the gonadal impairment of IS, which appeared more prevalent among respondents from tertiary hospitals. As IS agents are typically prescribed by an immunologist or an internal medicine physician, we speculate that these differences may be due to a high degree of departmental specialization in tertiary hospitals. Thus, it is necessary to conduct relevant training and education and strengthen the exchange of experience between different departments on IS use.\u003c/p\u003e \u003c/div\u003e "},{"header":"Conclusions","content":" \u003cp\u003eThis national survey is the first to explore obstetricians and gynecologists\u0026rsquo; knowledge and awareness regarding iatrogenic POI. Taking respondents\u0026rsquo; background information into consideration, the results of this survey not only generate a clearer picture of the understanding of iatrogenic POI in this field, but also help us determine the underlying problems in knowledge translation. However, there were some limitations: the proportion of respondents with different backgrounds (gender, specialty, or hospital type) was unevenly distributed; the iatrogenic measures listed in the questionnaire were limited and we did not give a detailed explanation for the immunosuppressants included in the survey. Therefore, further investigations and improved survey design are needed to confirm and update our conclusions. Our survey demonstrated that the knowledge of gonadal toxicity of traditional tumor treatments is generally high among obstetricians and gynecologists, but there is still a relative lack of understanding among physicians with less experience and/or from community hospitals. A misunderstanding may exist in community hospitals and among non-gynecologic oncologists relating novel tumor treatments and ovarian health due to the lack of convincing evidence. Additionally, the knowledge of POI caused by hysterectomy and IS agents needs to be improved. Based on these results, we hope to carry out more purposeful and targeted doctor re-training in the future.\u003c/p\u003e "},{"header":"Methods","content":" \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting and implementation\u003c/h2\u003e \u003cp\u003eAn online survey was administered to obstetricians and gynecologists across China between June 7 and July 3, 2020. The questionnaire was distributed with the assistance of the China Maternal and Child Health Association, Society of Gynecological Endocrinology and answered anonymously. The study was reviewed and approved by the Ethics Committee of Peking Union Medical College Hospital (Ethical code number: S-k1189-1; date of approval: May 08, 2020) and is in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eQuestionnaire design\u003c/h2\u003e \u003cp\u003eThe questionnaire included the following sections: (1) general background information of the respondent; (2) Tumor therapies and POI; (3) Surgeries or procedures and POI; and (4) Immunosuppressants and POI. There were 16 questions in total, and full questionnaire details are provided in Supplementary material.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analysis was performed using SPSS (ver. 25.0 IBM, Armonk, NY, USA). Categorical variables are presented as a number (frequency) and percentage. The association between two categorical variables was tested using the chi-square test. Due to the large variation in the sample size among subgroups, subgroup analyses were not performed based on physicians\u0026rsquo; gender, specialty, or hospital type. An overlap existed among respondents regarding age and length of service, with the latter being more representative of work experience. Thus, subgroup analyses were conducted based on physicians\u0026rsquo; length of service and hospital type (community, secondary, and tertiary). Statistically significant associations were defined as having P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. To better understand the discriminative variables, a correspondence analysis was conducted to visualize the correlation among variables.\u003c/p\u003e \u003c/div\u003e "},{"header":"List of abbreviations","content":"\u003cp\u003eBS Bilateral salpingectomy\u003c/p\u003e\n\u003cp\u003eBTL Bilateral tubal ligation\u003c/p\u003e\n\u003cp\u003eCH Community hospital\u003c/p\u003e\n\u003cp\u003eCT Chemotherapy\u003c/p\u003e\n\u003cp\u003eGnRH-a Gonadotropin-releasing hormone agonist\u003c/p\u003e\n\u003cp\u003eH\u0026amp;BS Hysterectomy with bilateral salpingectomy\u003c/p\u003e\n\u003cp\u003eIS Immunosuppressants\u003c/p\u003e\n\u003cp\u003eOC Ovarian cystectomy\u003c/p\u003e\n\u003cp\u003ePGC Primordial germ cells\u003c/p\u003e\n\u003cp\u003ePOI Premature ovarian insufficiency\u003c/p\u003e\n\u003cp\u003eRT Radiotherapy\u003c/p\u003e\n\u003cp\u003eSLE Systemic lupus erythematosus\u003c/p\u003e\n\u003cp\u003eTIT Tumor immunotherapy\u003c/p\u003e\n\u003cp\u003eTTT Tumor-targeting therapy\u003c/p\u003e\n\u003cp\u003eUAE Uterine artery embolization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was reviewed and approved by the Ethics Committee of Peking Union Medical College Hospital (Ethical code number: S-k1189-1; date of approval: May 08, 2020).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData and materials are summarized in the manuscript, figures, and tables.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYFW and AJS implemented the research plan and were responsible for the questionnaire design. YFW, YZ, and AJS oversaw the formal analysis, conceptualization and writing of the manuscript. WW, QZ, YF, YZ, HD, ZYT, XQZ, YQZ, DHP, and XMY provided valuable comments and suggestions on the questionnaire revision and played a critical role in the distribution, completion, and collection of questionnaires. AJS and YZ provided a critical contribution to the organization and cooperation of this arduous task\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the Chinese obstetricians and gynecologists who participated in the survey for sharing their valuable views. We also thank China Maternal and Child Health Association, Society of Gynecological Endocrinology for supporting our survey.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e[1] L. Webber, M. Davies, R. Anderson, J. Bartlett, D. Braat, B. Cartwright, R. Cifkova, S. de Muinck Keizer-Schrama, E. Hogervorst, F. Janse, L. 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Zhang, Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow\u0026nbsp;up of a randomized, non-blinded, controlled study, Arthritis research \u0026amp; therapy 20(1) (2018) 70.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Premature ovarian insufficiency, iatrogenic menopause, ovarian impairment, knowledge, national survey","lastPublishedDoi":"10.21203/rs.3.rs-80938/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-80938/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e With increasing cases of iatrogenic premature ovarian insufficiency (POI), more clinicians are required to counsel patients regarding the gonadotoxic effects of iatrogenic treatments. This survey aims to explore obstetricians and gynecologists’ knowledge regarding iatrogenic POI. A national online questionnaire survey was conducted across China. Respondents were asked to select the iatrogenic condition(s) that can cause POI based on their experience and knowledge.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOf the 5,523 returned questionnaires, 4,995 were analyzed. Among tumor therapies causing POI, most respondents agreed that radiotherapy (73.5% of respondents) and chemotherapy (64.1%) are risk factors for POI. While only 6.5% and 7.8% of the gynecological oncologists believed tumor immunotherapy and tumor-targeting therapy, respectively, may cause ovarian impairment, 31.8% and 22.2% of the non-gynecologic oncologists believed that these therapies could affect ovarian health. Most respondents believed that ovarian cystectomy (54.4%) was a risk factor for POI, while only a few respondents believed that hysterectomy with bilateral salpingectomy (39.6%) and uterine artery embolization (33.5%) could cause ovarian impairment. Only 30.5% respondents believed that immunosuppressants increased the risk of POI. Views differed with experience and hospital setting.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The knowledge of gonadal toxicity due to traditional tumor treatments is generally high among Chinese obstetricians and gynecologists. A misunderstanding may exist in primary care hospitals and general gynecologists regarding a link between novel tumor treatments and POI, owing to the lack of convincing evidence. Knowledge of POI caused by hysterectomy and immunosuppressants should be improved.\u003c/p\u003e","manuscriptTitle":"Knowledge of Iatrogenic Premature Ovarian Insufficiency Among Chinese Obstetricians and Gynecologists: A National Questionnaire Survey","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-09-25 16:26:56","doi":"10.21203/rs.3.rs-80938/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-10-20T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-10-14T12:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"reviewerAgreed","content":"","date":"2020-09-29T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-09-23T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-09-22T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-09-21T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-09-21T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-09-21T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cb930364-ac90-4de0-9f60-060918ac10af","owner":[],"postedDate":"September 25th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":612697,"name":"Sexual \u0026 Reproductive Medicine"},{"id":612698,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2020-11-22T15:02:07+00:00","versionOfRecord":{"articleIdentity":"rs-80938","link":"https://doi.org/10.1186/s13048-020-00739-z","journal":{"identity":"journal-of-ovarian-research","isVorOnly":false,"title":"Journal of Ovarian Research"},"publishedOn":"2020-11-18 15:01:18","publishedOnDateReadable":"November 18th, 2020"},"versionCreatedAt":"2020-09-25 16:26:56","video":"","vorDoi":"10.1186/s13048-020-00739-z","vorDoiUrl":"https://doi.org/10.1186/s13048-020-00739-z","workflowStages":[]},"version":"v1","identity":"rs-80938","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-80938","identity":"rs-80938","version":["v1"]},"buildId":"k6vKHA0u1VdKjwwnw531e","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}