{"paper_id":"b0a2a4bf-c408-4985-adb7-c394344d0341","body_text":"Kaiyrlykyzy et al. BMC Women’s Health          (2021) 21:393  \nhttps://doi.org/10.1186/s12905-021-01526-8\nRESEARCH\nPipelle endometrial biopsy for abnormal \nuterine bleeding: do patient’s pain and anxiety \nreally impact on sampling success rate?\nAiym Kaiyrlykyzy1 , Faina Linkov2,3 , Faye Foster4* , Gauri Bapayeva5 , Talshyn Ukybassova5 , \nGulzhanat Aimagambetova6 , Kamila Kenbayeva5 , Bakytkali Ibrayimov7 ,  \nAlla Lyasova8  and Milan Terzic3,4,5  \nAbstract \nBackground: Pipelle endometrial biopsy is vital for the early diagnostics of endometrial pathology and is performed \nin outpatient setting in minimally invasive manner. One of the reported disadvantages of sampling with Pipelle \ncurette is failure to collect enough tissue for histological analysis. The role of psychological factors such as anxiety and \npain sensitivity in obtaining adequate samples is not well known. The study’s objective was to explore whether there \nis relationship between severe pain, anxiety, and the rate of Pipelle failure.\nMethods: Study included 158 women with median age of 42 who underwent Pipelle endometrial biopsy at Clinical \nAcademic Department of Women’s Health of the University Medical Center (UMC), Nur-Sultan City, Kazakhstan with \nan abnormal uterine bleeding from June 2019 to April 2021. Women were asked to fill survey on pain, anxiety before, \nduring and after the procedure.\nResults: 3.8%, 15.19% and 4.43% of women reported severe pain and 39.24%, 34.18% and 14.56% of women \nreported severe anxiety prior, during and after procedure, respectively. Women who experienced severe pain during \nprocedure tend to be more anxious during procedure (p = 0.0001) and have higher number of sampling attempts \n(p = 0.0040). Pain level was higher among patients sampled by the junior OB/GYN specialist (p < 0.0001). We found \nno differences in Pipelle biopsy success rates in relationship to baseline, during and postprocedural pain and anxiety \nscores.\nConclusion: Anxiety during procedure performance was significantly associated with severe pain during the proce-\ndure but did not represent a key element for the success of Pipelle biopsy.\nKeywords: Pipelle endometrial biopsy, Pipelle sampling, Endometrial sampling, Pipelle failure, Pain, Anxiety\n© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco \nmmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nIntroduction\nEndometrial cancer (EC) is the most common gyneco -\nlogic malignancy in the developed world. Due to \nincreasing obesity rates and little access to preventive \nservices, EC mortality in Kazakhstan is higher than in \ncomparison to the US and other developed countries. \nOffice vacuum aspiration (Pipelle) for endometrial \nbiopsy (EMB) sampling plays an important role in early \ncancer diagnosis, preoperative assessment, and treat -\nment planning for endometrial pathologies [1 ]. Use of \na Pipelle suction curette (flexible plastic curette used \nfor minimally invasive tissue collection) has emerged \nas the most common method for endometrial tissue \nOpen Access\n*Correspondence:  faye.foster@nuedu.kz\n4 Department of Medicine, Nazarbayev University School of Medicine, \nZhanybek-Kerey Khans Street, 5/1, 010000 Nur-Sultan, Kazakhstan\nFull list of author information is available at the end of the article\n\nPage 2 of 6Kaiyrlykyzy et al. BMC Women’s Health          (2021) 21:393 \nsampling [2 ], often indicated for evaluation of abnor -\nmal uterine bleeding [3 , 4], which is responsible for \n~ 70% of all peri- and post-menopausal gynecological \nvisits [5 ]. EMB has been reported to be an equivalent \nand sometimes even superior tool for detecting EC \ncompared to other endometrial sampling techniques \n[2] with diagnostic accuracy comparable to dilatation \nand curettage (D&C) sampling for some types of endo -\nmetrial pathology, including endometrial hyperplasia, \nhyperplasia with atypia, and EC [3 , 6, 7]. Compared to \nD&C sampling conducted in the operation room, EMB \nis relatively inexpensive, associated with less morbidity, \nsafe, accurate, and can be performed in an office setting \n[2].\nDespite the documented benefits there are risks for \nfailure associated with Pipelle procedure, one of the main \nbeing the failure to obtain satisfactory samples for histo -\nlogical examination [2]. Thus, it is important to establish \nfactors that may have an impact the ability to collect an \nadequate endometrial sample.\nMany invasive diagnostic procedures have been \nreported in the literature to induce discomfort in patients \nby causing anxiety [8, 9]. This is supported by a substan -\ntial body of evidence that links elevated state anxiety to \nan increase in pain intensity and decrease in pain toler -\nance [10, 11]. For example, level of anxiety affects the \ntolerability of the office hysteroscopy [9, 12]. The role of \npsychological factors such as anxiety and pain sensitivity \nin obtaining adequate samples, have rarely been investi -\ngated as an increased risk of biopsy failure.\nThe Pipelle procedure has shown better or equal toler -\nability by patients compared to other office-based devices \n[13, 14], however, although most women tolerate it well, \nsome do experience significant discomfort, which may \naffect the efficacy of the procedure. Adambekov et  al. \nsuggest the strong links between anxiety before a Pipelle \nbiopsy and patients’ experiences of extreme pain during \nthe procedure [1, 15].\nThis study has been designed to improve our under -\nstanding of acceptability and factors influencing success -\nful use of EMB by investigating the relationship between \nsevere pain, anxiety, and the rate of Pipelle failure.\nTaking into account that Kazakhstan has a higher rate \nof mortality due to EC than in western countries, and \ndespite EMB reported to be a preferred modality for \ndiagnosing gynecological pathologies in the Western \nworld, EMB is not widely utilized in the clinical practice \nas a diagnostic tool in Kazakhstan. The main method \nof endometrial sampling in Kazakhstan remains D&C, \nwhich requires hospitalization, anesthesia, antibiotic use, \nand is more invasive. By improving our understanding \nof acceptability and factors influencing successful use of \nEMB, the results of this study will take us one step closer \nto enabling the timely diagnosis of current endometrial \npathology, will have an important impact on healthcare \nsafety and efficiency, and improve overall treatment out -\ncomes and the quality of life of Kazakhstani women.\nMethods\nWe performed an observational study on data of women \nwho met the criteria for endometrial biopsy. These crite -\nria/indications included abnormal uterine bleeding, pre- \nand postmenopausal bleeding. Recruitment took place \nfrom June 2019 to April 2021 at the Clinical Academic \nDepartment of Women’s Health of the University Medi -\ncal Center (UMC), Nur-Sultan City, Kazakhstan.\nInclusion criteria included: female; age 18+; with an \nintact uterus and cervix; endometrial biopsy recom -\nmendation due to (but not limited to) abnormal uter -\nine bleeding and irregular cycles (for pre-menopausal \nwomen) or post-menopausal problem bleeding.\nExclusion criteria included: cervical cancer, pregnancy, \nacute pelvic inflammatory disease, clotting disorders, \nacute cervical or vaginal infection, uterine anomalies/\nmalformations, hysterectomy, previous endometrial abla-\ntion, or any intervention/procedure done for Asherman.\nEndometrial sample collection: The Pipelle endometrial \nsampling was carried out in the gynecological outpatient \nclinic of the UMC. If the tissue obtained was considered \ninadequate under visual assessment, the procedure was \nrepeated to optimize sampling. The endometrial tissues \nobtained were fixed in 10% buffered formalin and trans -\nported to the pathology laboratory for histopathological \nstudies. The patient was then transferred to the operat -\ning room for D&C under general anesthesia. The D&C \nwas performed according to hospital protocols and the \nendometrial tissues were fixed in 10% buffered formalin \nas described above. Procedures were performed by one \nsenior (> 35 years of experience) and one junior (< 5 years \nof experience) specialists in obstetrics and gynecology \n(OBGYN). Required training for OBGYN specialists in \nKazakhstan is minimum of three-year residency pro -\ngram. The coupled endometrial biopsy samples were \nsubjected to histopathological studies. Histopathologi -\ncal evaluation and diagnosis included all morphologic \nabnormalities that were observed in the coupled samples.\nBiopsy failure was defined as the inability to access \nthe uterine cavity or the inability to obtain a sufficient \namount of tissue for histological examination. Two inde -\npendent experts in gynecologic histopathology evaluated \nthe obtained specimens and followed the guidelines for \nclassification of entities related to endometrial pathologi-\ncal findings.\nPain intensity before, during and after Pipelle sampling \nwas evaluated using Numerical Rating Scale (NRS) [16], \nwhere “0” represents no pain at all, “10”—the worst pain \n\nPage 3 of 6\nKaiyrlykyzy et al. BMC Women’s Health          (2021) 21:393 \n \never possible. Pain rating was categorized as 1–6—mild \nto moderate, 7 and above as severe pain. Anxiety was \nassessed using 0–10 numeric rating, where “0” represents \nno anxiety, “10”—As anxious as I could be. Demographic \nand clinical data were obtained from each participant \nduring a medical interview.\nDescriptive statistics were reported as median (IQR) \nfor continuous variables and n (%) for categorical vari -\nables. Comparison of patients’ characteristics by pain \nintensity groups (no pain, mild to moderate pain and \nsevere pain) was performed using Kruskal–Wallis test. \nA binomial logistic regression was run to assess the rela -\ntionship between anxiety and pain. Comparison of anxi -\nety and pain scores between biopsy outcome groups was \nperformed using non-parametric Mann–Whitney U test. \nP-values < 0.05 were considered significant. All statistical \nanalyses were performed with Stata 16 (StatCorp).\nResults\nThe study included 158 patients, with a median age of \n42 (34–48.3) years old, with 30 (18.99%) women who \nwere postmenopausal. Inadequate biopsy samples were \nobtained in 25 out of 158 patients (18.8%). Severe pain \nprior, during and after procedure experienced 3.8%, \n15.19% and 4.43% of women, respectively. 39.24%, 34.18% \nand 14.56% of women reported severe anxiety before, \nduring and after Pipelle sampling, respectively (Fig. 1).\nThe median pain score during procedure was 2 (0–4) \nwith the senior OB/GYN specialist, while women who \nunderwent Pipelle sampling with a junior special -\nist reported median biopsy pain as 5 (4–7) (p < 0.0001). \nNo significant relationships  were observed between \npain  experienced and menopausal status, provider and \nbiopsy outcome.\nIn Table 1 we outlined patients’ age, BMI, anxiety prior \nand during procedure, number of attempts to obtain \nsample by reported pain intensity. Women who expe -\nrienced severe pain during procedure tend to be more \nanxious during procedure (p = 0.0001) and have higher \nnumber of sampling attempts (p = 0.0040) compared to \nthose who had no or mild to moderate pain.\nA binomial logistic regression was used to predict pain \nbased on anxiety. Results show that anxiety during pro -\ncedure performance was significantly associated with \nsevere pain during the procedure (OR = 1.66 (95% CI \n1.32, 2.07), p < 0.001). After adjusting for anxiety before \nprocedure, number of biopsy attempts, type of provider \nand women menopausal the relationship remained sig -\nnificant (OR = 1.85 (95% CI 1.24, 2.55, p < 0.001).\nIn our study results we did not observe any significant \nassociation between pain and the Pipelle biopsy outcome.\nDiscussion\nIn our study, anxiety during procedure performance was \nsignificantly associated with severe pain during the pro -\ncedure but did not represent a key element for the suc -\ncess of Pipelle biopsy.\nOne of the reported issues with Pipelle sampling is \nthe inability to obtain sufficient samples for histologi -\ncal analysis. However, the role of patient’s psychological \nfactors such as anxiety and pain perception in obtaining \nadequate samples is not clearly understood. Thus, the \nFig. 1 Pain and anxiety before, during and after procedure\n\nPage 4 of 6Kaiyrlykyzy et al. BMC Women’s Health          (2021) 21:393 \nobjective of this study was to evaluate the relationship \nbetween severe pain, anxiety, and Pipelle failure rate.\nEven though Pipelle biopsy is regarded as a painless \nor mildly painful procedure when compared to other \napproaches, we found that nearly half of the patients \nexperienced pain of varying degrees during the proce -\ndure, and that pain was increased with providers of less \nexperience. Moreover, we observed anxiety during proce-\ndure was associated with severity of pain during proce -\ndure, which is in line with Adambekov et al. ’s [15] finding \nthat extremely anxious patients before the procedure \nhave 2.3 times higher chances of severe pain during the \nprocedure.\nParticipant’s pain and anxiety were more intense in the \nprocess of sampling, which is an expected result since \nPipelle endometrial sampling usually performed without \nuse of anesthesia [17]. Consistent with previous studies, \npain intensity during endometrial sampling depended on \nthe experience of health care provider, number of Pipelle \npasses made and patient’s anxiety during procedure [1, \n15, 18].\nOne of the most important factors associated with \noffice hysteroscopy failure has been reported to be pain \n[12, 19], our study however found that neither pain nor \nanxiety scores affected Pipelle biopsy success. Further -\nmore, although it has been reported that Pipelle is more \npainful, thus less acceptable for postmenopausal aged \nwomen [20–22], we did not find significant difference in \npain scores between pre and postmenopausal women.\nAlthough anxiety did not represent a key element for \nthe success of Pipelle biopsy, our findings suggest the \npatient experience of endometrial biopsy procedure \ncould be considerably improved by measures aimed at \nreducing anxiety. A clear description provided before \nthe procedure, as well as psychological support during \nthe procedure, may improve the patient’s acceptance \nof the predictable pain associated with an endometrial \nbiopsy. This is an important finding considering that in \nthe outpatient environment, the ideal endometrial biopsy \napproach is simple to operate and obtains a sufficient \nendometrial sample without causing discomfort to the \npatient. It is important that health care providers ensure \nthat patients are relaxed and that procedures are con -\nducted safely as minor gynecologic procedures transfer \nfrom the operating room to the office [23].\nKazakhstan is one of the post-soviet republics of Cen -\ntral Asia. Collapse of the Soviet Union led Kazakhstan \nto economic recession and the healthcare systems of the \ncountry has gone through decades of profound revolu -\ntions. Recently Kazakhstan moved from lower middle-\nincome to upper middle-income country according to \nthe World Bank classification. However, despite recent \nimprovements in health care in response to the reforms, \nKazakhstan still lags behind other post-soviet independ -\nent states with only 3.4% of GDP allocated for healthcare \nsystem.\nFor the past years, EMB in Kazakhstani gynecological \npractice was done mostly using classic D&C procedure \ndue to lack of access to the Pipelle tool as a new tech -\nnique requiring additional budget. Moreover, Pipelle \nbiopsy utilization guideline was approved by the Ministry \nof Healthcare of the Republic of Kazakhstan only in 2018. \nNow, Pipelle is among the suggested/approved methods \nfor endometrial biopsy and is increasingly used for moni -\ntoring of endometrial histology during hormone therapy. \nAlthough it is in use now, but only in the large cities’ ter-\ntiary care hospitals, which can afford to buy the Pipelle \nsampling tool.\nIntroduction of EMB in Kazakhstan ambulatory care \nsettings is needed to improve the rate of early diagnosis \nof endometrial pathologies and improve overall patient \noutcomes. For patients who have indications for D&C, \nintroducing Pipelle biopsy in the office settings would be \na safe, reliable, and cost-effective outpatient procedure \nfor diagnosing endometrial pathologies, including endo -\nmetrial cancer.\nNonetheless, the study has some limitations. Since \ngroup stratification by biopsy result is based on small \nTable 1 Comparison of patients by pain intensity groups\n*Kruskal–Wallis test was performed to compare differences in patients’ characteristics between pain intensity groups\nPain intensity during procedure (0–10) P value*\nNo pain (0)\nN = 33 (20.89%)\nMild to moderate (1 to 6)\nN = 101 (63.92%)\nSevere pain (7 and above)\nN = 24 (15.19%)\nAge 35 (31–45) 43 (35–49) 42.5 (35–46.5) 0.0713\nBody Mass Index 26.57 (21.48–30.38) 25.6 (22.39–29.74) 26.49 (23.7–30.63) 0.6803\nAnxiety before procedure 5 (1–7) 6 (3–8) 5.5 (4–7) 0.1419\nAnxiety during procedure 1 (0–4) 5 (2–7) 8 (7–8) 0.0001\nAnxiety after procedure 2 (0–4) 3 (1–5) 5.5 (4–7) 0.0001\nNumber of biopsy attempts 1 (1–3) 2 (1–3) 3 (2–3) 0.0040\n\nPage 5 of 6\nKaiyrlykyzy et al. BMC Women’s Health          (2021) 21:393 \n \nsample of women, it should be considered exploratory. \nSecondly, we did not utilize the Spielberger State-Trait \nAnxiety Index (STAI) and thus did not differentiate a \npresent anxiety state from a long-term trait anxiety. This \nstudy will however, serve as the groundwork for future \nresearch aimed at the development and testing of new \nintervention strategies for increasing the use of EMB \nrather than D&C sampling for endometrial cancer diag -\nnoses in Kazakhstan.\nConclusion\nThe overall goal of this study was to fill important gaps in \nthe current understanding of factors relevant to attempt -\ning and conducting successful EMB Pipelle endometrial \nbiopsy and guide clinicians to choose an appropriate \napproach for obtaining an endometrial sample in a par -\nticular patient and current circumstances.\nWe found that anxiety and pain did not impact on \nPipelle success rate, but that OBGYN specialists expe -\nrience and anxiety maybe considered predictors of \nprocedural pain, highlighting the need for health care \nproviders, particularly less experienced providers, to \nensure that patients are relaxed to guarantee that pro -\ncedures are conducted safely as minor gynecologic \nprocedures.\nIn the future, this study could have a signifi -\ncant  impact  at both individual patient and healthcare \nlevel in Kazakhstan. Proper patient information/educa -\ntion, understanding of Pipelle tool sampling benefits, \nincluding lower pain and anxiety, would facilitate a wide \nimplementation of the technique across the gynecologi -\ncal settings in the country, especially in the private clin -\nics. We hope this study will have  a positive  impact  on \nstrategies for providing high-quality care for patients.\nAcknowledgements\nNot applicable\nAuthors’ contributions\nMT, FL, AK, GB, contributed to the conception, design of work. TU, KK, col-\nlected data. AK, FL, GA, BI, AL, analyzed and interpreted data. AK, FF, FL, MT \nwere major contributors in writing the manuscript. All authors read and \napproved the final manuscript.\nFunding\nThis study was supported by the Nazarbayev University Grant Number \n110119FD4540, 2019–2021.\nAvailability of data and materials\nThe datasets used and/or analysed during the current study are available from \nthe corresponding author on reasonable request.\nDeclarations\nEthics approval and consent to participate\nEthical approval: All protocols and data collections and storage performed in \nthis study involving human participants were approved by the Institutional \nResearch Ethics Committee of Nazarbayev University (NU IREC: 392/24032021) \nand UMC (February 25, 2019) and were in accordance with the 1964 Helsinki \ndeclaration and its later amendments. Informed consent: Full informed \nconsent procedure was followed and written Informed consent was obtained \nfrom all individual participants included in the study.\nConsent for publication\nAll authors read and approved the final manuscript.\nCompeting interests\nThe authors declare that they have no competing interests.\nAuthor details\n1 National Laboratory of Astana, Nazarbayev University, Kabanbay Batyr Street, \n53, 010000 Nur-Sultan, Kazakhstan. 2 Department of Health Administration \nand Public Health, John G. Rangos, Sr. School of Health Sciences Duquesne \nUniversity, 600 Grant St, Pittsburgh, PA 15282, USA. 3 Department of Obstet-\nrics, Gynecology and Reproductive Sciences, University of Pittsburgh School \nof Medicine, 300 Halket St, Pittsburgh, PA 15213, USA. 4 Department of Medi-\ncine, Nazarbayev University School of Medicine, Zhanybek-Kerey Khans \nStreet, 5/1, 010000 Nur-Sultan, Kazakhstan. 5 Clinical Academic Department \nof Women’s Health, National Research Center of Mother and Child Health, \nUniversity Medical Center, Turan Ave. 32, 010000 Nur-Sultan, Kazakhstan. \n6 Department of Biomedical Sciences, School of Medicine, Nazarbayev \nUniversity, Zhanybek-Kerey Khans Street, 5/1, 010000 Nur-Sultan, Kazakhstan. \n7 Clinical Academic Department of Laboratory Medicine, Pathology and Genet-\nics, University Medical Center, Republican Diagnostic Center, 2 Syganaq Street, \nNur-Sultan 010000, Kazakhstan. 8 Pathology Bureau of Nur-Sultan City Adminis-\ntration, Zhansugirov Street, 1, 010000 Nur-Sultan, Kazakhstan. \nReceived: 14 June 2021   Accepted: 26 October 2021\nReferences\n 1. 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Available from: https:// www. ncbi. \nnlm. nih. gov/ pmc/ artic les/ PMC36 51543/.\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in pub-\nlished maps and institutional affiliations.","source_license":"CC0","license_restricted":false}