Background
The National Cancer Institute estimates that 5% of new cancer diagnoses occur in young adults aged 15 to 39 years,1 and the latest Australian data finds that 10% of females diagnosed with cancer in 2017 were aged 15 to 44 years.2 Cancer therapies frequently result in menstrual irregularities, yet the impact of these on the individual’s well-being is not clearly established.3,4
Chemotherapy predisposes people who menstruate to heavy menstrual bleeding due to thrombocytopenia, coagulopathy, or disruption of the hypothalamic-pituitary-gonadal axis.5–7 Other disturbances, such as anovulatory bleeding and amenorrhea, are also prevalent. Menorrhagia, typically defined by >80 mL of blood loss per cycle or bleeding for >7 days, increases infection risk in immunosuppressed patients with associated neutropenia,6 and potentiates iron deficiency, anemia, and thrombocytopenia, necessitating transfusion.8 There is conflicting evidence regarding the link between biochemical markers of reduced ovarian reserve and patients’ menstrual patterns9; however, cancer survivors with irregular menses have been found to have decreased ovarian reserve and reproductive potential.10,11
Gonadotoxic injury from cytotoxic therapy can manifest as the cessation of regular menses and development of menopausal symptoms, such as hot flushes, vaginal dryness, and dyspareunia, and also increases osteoporosis risk, all of which can negatively impact on patients’ quality of life.4,12 More than one-half of survivors of Hodgkin lymphoma and breast cancer report chemotherapy-induced amenorrhea, although the definition of this varies substantially across cancer literature.13 Overall, amenorrhea risk increases with older age at cancer diagnosis and higher total chemotherapy cycles.14 Those who continue menstruating during therapy are prone to irregular cycles, with prolonged intervals.12 An improved understanding of menstrual experiences through proactive and universal menstrual history-taking by clinicians is a vital step toward utilization of potentially protective tools, such as gonadotropin-releasing hormone (GnRH) agonists, that may prevent menorrhagia and decrease the risk of premature ovarian insufficiency.15
To our knowledge, this is the first study examining menstruation changes and the sequalae in a population undergoing immunochemotherapy treatment; no guidelines currently exist on how clinicians should address menstruation changes in this context. Current guidelines on the management of people who menstruate requiring cancer therapies focus on fertility preservation rather than the assessment and management of menstrual disturbances.
This study investigates the documentation of menstruation history-taking, counseling regarding menstrual care during cancer therapy, and incidence of menstrual disturbance during cancer treatment at a major metropolitan cancer center in Australia.
Patients and Methods
Participants
This study included females (self-reported) aged 18 to 49 years at the time of cancer diagnosis, diagnosed at St. Vincent’s Hospital Kinghorn Cancer Centre in Sydney, Australia between 2017 and 2020. Inclusion criteria were as follows: female sex (self-reported), 18 to 49 years of age at cancer diagnosis, premenopausal at diagnosis, date of new diagnosis between 2017 and 2020, diagnosis confirmed by tissue biopsy, treated with anticancer therapy (chemotherapy, hormonal therapy, immunotherapy, and/or radiation), and treated by a medical oncologist or hematologist. The Human Research Ethics Committee (HREC) of St. Vincent’s Hospital Australia approved this study (2020/ETH03136).
Recruitment
Patients who met the inclusion criteria were identified through databases including hospital records, clinic lists, the electronic medical record (MOSAIQ), and pathology and pharmacy records at St. Vincent’s Hospital Kinghorn Cancer Centre. A total of 964 female patients between 18 and 49 years of age were identified on searching for new appointments at Kinghorn Cancer Centre between 2017 and 2020. Of the 964 patients identified, 827 were excluded for not having histologic confirmation of diagnosis, being managed at a different site, or receiving their initial diagnosis prior to 2017.
Measures
Data collected from chart review included age at diagnosis, primary diagnosis, stage of cancer, contraception at time of diagnosis, treatment(s) received, rates of remission or progression, involvement of a specialist gynecologist across different stages of care, documentation of reproductive history (including menstrual history, parity, and gravidity), menstruation advice received (what information, from whom), and any documentation of menstrual disturbance, thromboembolic complications, fertility outcomes posttreatment, and diagnosis of early ovarian failure, amenorrhea, or oligomenorrhea. Taking a menstrual history was defined as the monitoring of periods and asking about regularity and features of cycles. Descriptive statistics were used to summarize the results.
Results
Participant Characteristics
A total of 137 patients met the study inclusion criteria. Median age at diagnosis was 41 years (range, 19–49 years). The most common diagnosis was breast cancer (54.0%), followed by hematologic malignancy (20.4%) and gastrointestinal cancers (13.1%). Other diagnoses included head and neck cancers (4.4%), lung cancers (2.9%), melanomas (2.2%), cancers of the central nervous system (2.2%), and gynecologic malignancies (0.7%). Approximately one-quarter of patients were documented as nulliparous, and approximately one-quarter (25.9%) had no documented parity (Table 1).
Demographic and Pathologic Characteristics of the Study Population
At the time of diagnosis, the following was documented: 8.0% of patients were taking the combined oral contraceptive pill (COCP), 5.1% had an intrauterine device (IUD), 0.7% were taking the progesterone-only pill, and 0.7% had a contraceptive implant. After diagnosis, 24.8% were documented to have received contraception advice from a physician or a pharmacist, including avoiding pregnancy during treatment (20.6%) and recommending barrier contraception (17.6%), ceasing the COCP (5.9%), IUD removal (5.9%), and IUD insertion (11.8%).
Most patients underwent chemotherapy (86.7%) and/or surgery (70.6%). Other forms of cancer therapy included radiotherapy (40.6%), endocrine therapy (42.0%), and allogeneic stem cell transplantations (3.5%), and 5.6% of patients were treated with immunotherapy or an outpatient anticancer drug prescription.
Menstruation History
Of the 137 patients, only 22 (16.1%) had their menstrual history documented during the first consultation with their managing medical oncologist or hematologist; 68 (49.6%) had their history documented at a later stage by their hematologist/oncologists, whereas 12 (8.8%) had their history documented by another health professional. These health professionals ranged from gynecologists to endocrinologists and nursing staff. Consequently, 35 patients (25.5%) had no recorded information on their menstruation.
Menstruation advice given prior to treatment included informing patients of potential irregularity, amenorrhea, menopause, and hormone-based therapeutic options, and discussions of prophylactic oophorectomy. Of the patients who had their menstrual histories taken, 8 (7.8%) were counseled at their first consult and 17 (16.7%) were counseled at some point about malignancy and/or treatment-induced menstrual changes by their treating oncologist/hematologist (n=23), gynecologist (n=1), or nurse (n=1).
Breast cancer was associated with a menstrual history being taken (Χ2 [1, n=137] = 29.9; P<.001) (Table 2). Factors including cancer reoccurring or progressing, age, and prior children were not statistically significant (Table 2).
Factors Associated With Menstrual History-Taking
Menstrual Disturbances
Of the 102 patients who had their menstrual histories documented, 84 (82.4%) reported a menstrual disturbance (Table 3). The most common complaint was treatment-induced amenorrhea (48.0%), followed by menopause or menopause symptoms (20.6%), irregular menstrual bleeding (16.7%), menorrhagia (13.7%), dysmenorrhea (3.9%), and iron deficiency as a result of bleeding (2.9%). In terms of co-occurring symptoms reported, 2.9% had both menorrhagia and iron deficiency, 2.0% had both irregular menses and menorrhagia, and 0.7% reported menorrhagia, iron deficiency, and amenorrhea. A total of 35 (25.5%) patients did not have any documented experience of menstrual disturbance.
Documented Menstrual Disturbances
Table 3 describes the 6 different menstrual issues addressed by an intervention. Menopause or menopausal symptoms and iron deficiency were more likely to be treated than other disturbances. Only 3 patients with early menopause were treated with hormone replacement therapy (HRT). The first patient was 23 years of age with a diagnosis of acute lymphoblastic leukemia, the second patient was 41 years of age and diagnosed with ductal carcinoma in situ breast cancer, and the third was 35 years of age with metastatic breast cancer. Another patient with breast cancer who experienced early menopause received endocrine therapy, which may have been HRT.
Treatment-induced amenorrhea was the most common menstrual disturbance (n=49); however, only 4 (8.2%) patients received intervention (1 received topical vaginal estrogen, 1 received a GnRH agonist, 1 received HRT, and 1 was referred to a gynecologist). Interventions included ordering investigations to look for fibroids or polyps (1 patient, who underwent hysteroscopy, dilation of cervix and curettage, and polypectomy given a history of menorrhagia), gynecologist referral (1 patient, for dysmenorrhea), and iron infusions (2 patients: 1 for iron deficiency and 1 likely due to iron deficiency but menorrhagia only documented in notes). One patient was recommended to present to the emergency department for analgesia to relieve her dysmenorrhea.
Provision of Anticipatory Guidance or Referral/Interventions to Address Menstrual Health Issues
According to the International Federation of Gynaecology and Obstetrics (FIGO), any patient with heavy menstrual bleeding should have a gynecologic history taken, including menstrual frequency, volume as quantified by number of pads/tampons changed per day, presence of flooding or clots, and symptoms of anemia.16 Dysmenorrhea should be assessed in terms of disturbances to activities of daily living, need for analgesics, and associated symptoms, which may include dyschezia, dyspareunia, and mood disturbance.16 Medication history, such as use of anticoagulants and iron supplementation, is important.16 Basic investigations for menorrhagia and dysmenorrhea should include a full blood count, iron studies, and pelvic ultrasound.16 General practitioners can initiate medical management of heavy menstrual bleeding without anemia, and gynecology referral is recommended if anemia is present.17 If pelvic pathology is suspected to be causing menstrual pain, gynecology referral is recommended.
Discussion
To the best of our knowledge, this is the first study investigating the incidence of menstruation history-taking, counseling regarding menstrual care during cancer therapy, and the incidence of menstrual disturbances during cancer treatment. A recent study on documenting fertility discussions and preservation referrals in this population showed unacceptably low rates, and the authors assert that if it was not documented, it did not happen.18 In our study, we found that 16.1% of patients had their menstrual history taken in their first consultation or baseline assessment. Furthermore, most (82.4%) of those who had a menstrual history documented reported menstrual disturbance. However, only 18.2% of all patients were counseled on menstrual disturbance at some point in time, and only 7.8% were counseled at the first consultation. A diagnosis of breast cancer was significantly associated with menstruation history documentation.
Menstruation is a normal physiologic process that is significantly affected by chemotherapy.3,12 Although menstruation and menstrual changes are key elements of patient care in people who menstruate, they have historically been negatively regarded.19 To address the taboo of menstruation, society change is necessary in the realms of education, paid employment, and access to birth control; indeed, some regard society’s attitude toward menstruation as a barometer for equity and progress.20,21 Yet this societal progress is not reflected in oncology/hematology practice, highlighted by the fact that this is the first study to explore the issue. People who menstruate deserve gender-specific care,22 and therefore appropriate recognition of perturbations in menstrual pattern may facilitate timely and specific medical management.
Menstrual health is a fundamental aspect of health, and has been promoted as a vital sign.23,24 It is important for clinicians to understand the menstrual patterns of their patients at baseline, differentiate between normal and abnormal menstruation, and evaluate and treat the oncology/hematology patient’s menstrual changes. Discussing and documenting a patient’s menstruation history early in cancer assessment is essential, given cancer treatment’s implications on a patient’s fertility,13,25–29 bleeding risk,30 and psychosocial well-being.31 If treating physicians do not establish and document their patients baseline menstruation patterns, including menopause, it becomes difficult to appropriately educate patients regarding when to seek help, and identify need for intervention. Oncologists treating breast cancer performed better, perhaps because patients diagnosed with breast cancer tend to be younger than those with other cancers, and health issues have been well documented in this patient population.32
Prior research has found that people with cancer wish they had been better prepared for potential reproductive issues by their cancer providers.5 Treatment-induced amenorrhea can be a sign of adversely affected fertility33 and premature menopause, which warrants consideration of HRT, calcium, vitamin D, bisphosphonates, and exercise to manage menopausal symptoms and negative cardiovascular sequelae.4,34,35 In some patients, HRT may be contraindicated due to the underlying malignancy (eg, hormone-sensitive breast cancer); however, evidence supports an individual risk–benefit assessment.35–37 Just under half of patients who had their histories taken in this study reported treatment-induced amenorrhea, similar to figures published from studies on Hodgkin lymphoma38 and breast cancer.13
Many cancer physicians39 and patients with cancer3 avoid discussions about menstruation due to feelings of discomfort or awkwardness, or because patients’ prognosis may be poor. However, patients confirm that early inclusion of menstrual history in patient–doctor consultation establishes clear avenues of communication for subsequent discussions.3 Without appropriate counseling, patients rely on their peers for potentially less evidence-based information.3 Higher engagement could be achieved by better educating medical students and doctors on the relevant questions patients should be asked,40,41 and the importance of timely menstrual history-taking.42 In the hospital, higher engagement could be attained through automating this history-taking process via templates in the electronic medical record,43,44 which has been successful in improving oncology/hematology referral rates for fertility preservation.45–47 Regular audits of the electronic documentation process and use of the menstrual tool could also be performed to monitor compliance.48 Alliances between cancer and fertility specialists have also been shown to improve referral rates,49 and departments could do more to foster these relationships through multidisciplinary meetings and hospital events. Furthermore, accessible patient information on menstruation and cancer should be readily available to encourage patient awareness and promote discussion, which has been shown to be beneficial in the setting of fertility preservation.50,51
The limitations of this study include its retrospective nature. However, this study was collected from a major metropolitan tertiary center and the data are an important first step in examining a gap in current practice. Due to the nature of retrospective data, inherent challenges lie in different clinicians’ and/or patients’ definitions of oligomenorrhea, amenorrhea, dysmenorrhea, and menorrhagia; however, this was a useful first step to assess data quality in the available electronic health record documentation.52 This study was from a single institution, and these results should be explored across multiple centers, electronic health records, and geographic locations. Menstruation histories may have occurred but were not documented.18 However, the lack of documentation itself is a clinical quality metric that has clinical implications for people who menstruate. Collection of baseline medical information at the time of a cancer diagnosis is a basic element of clinical practice in oncology and hematology. Menstrual and reproductive histories should be a core requirement in this process for all people who menstruate.
Conclusions
To the best of our knowledge, this is the only study examining menstrual disturbances in patients receiving anticancer treatment. Most people who menstruate receiving treatment experience menstrual disturbance. Physicians need to prioritize and normalize menstrual history-taking at initial and subsequent consults, because menstrual disturbances can be life- and fertility-threatening. Future research should explore ways to improve this, as well as the uptake of interventions such as menstrual suppression and the efficacy of different agents, because few data exist on these topics. Guidelines are needed and physicians should use menstrual history-taking tools to ask their patients relevant questions, discuss options available for menstruation suppression, counsel on criteria for patients to seek medical care, and offer treatment options.
References
- 1.↑
National Cancer Institute. SEER: cancer stat facts: cancer among adolescents and young adults (AYAs) (ages 15–39). Accessed February 1, 2022. Available at: https://seer.cancer.gov/statfacts/html/aya.html
- 2.↑
Australian Institute of Health and Welfare. Book 1a - cancer incidence (age-standardised rates and 5-year age groups). Accessed February 1, 2022. Available at: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/data
- 3.↑
Close AG, Ghuman A, Friehling E, et al. Experiences with menses and menstrual suppression of young women with a history of cancer. J Adolesc Young Adult Oncol 2020;9:23–29.
- 4.↑
Gotti M, Fiaccadori V, Bono E, et al. Therapy-related late adverse events in Hodgkin’s lymphoma. Lymphoma 2013;2013:952698.
- 5.↑
Close AG, Jones KA, Landowski A, et al. Current practices in menstrual management in adolescents with cancer: a national survey of pediatric oncology providers. Pediatr Blood Cancer 2019;66:e27961.
- 6.↑
Sofiyeva N, Siepmann T, Barlinn K, et al. Gonadotropin-releasing hormone analogs for gonadal protection during gonadotoxic chemotherapy: a systematic review and meta-analysis. Reprod Sci 2019;26:939–953.
- 7.↑
Practice Committee of American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril 2013;100:1214–1223.
- 8.↑
Walker MH, Coffey W, Borger J. Menorrhagia. Accessed February 1, 2022. Available at: https://www.statpearls.com/point-of-care/24986
- 9.↑
Poorvu PD, Frazier AL, Feraco AM, et al. Cancer treatment-related infertility: a critical review of the evidence. JNCI Cancer Spectr 2019;3:pkz008.
- 10.↑
Jacobson MH, Mertens AC, Spencer JB, et al. Menses resumption after cancer treatment–induced amenorrhea occurs early or not at all. Fertil Steril 2016;105:765–772.E4.
- 11.↑
Hu KL, Gan K, Ying Y, et al. Oligo/Amenorrhea is an independent risk factor associated with low ovarian response. Front Endocrinol (Lausanne) 2021;12:612042.
- 12.↑
Gharwan H, Lai C, Grant C, et al. Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B-cell lymphomas. Leuk Lymphoma 2016;57:1616–1624.
- 13.↑
Zavos A, Valachis A. Risk of chemotherapy-induced amenorrhea in patients with breast cancer: a systematic review and meta-analysis. Acta Oncol 2016;55:664–670.
- 14.↑
Akhtar S, Youssef I, Soudy H, et al. Prevalence of menstrual cycles and outcome of 50 pregnancies after high-dose chemotherapy and auto-SCT in non-Hodgkin and Hodgkin lymphoma patients younger than 40 years. Bone Marrow Transplant 2015;50:1551–1556.
- 15.↑
Lambertini M, Moore HC, Leonard R, et al. Gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in premenopausal patients with early breast cancer: a systematic review and meta-analysis of individual patient-level data. J Clin Oncol 2018;36:1981–1990.
- 16.↑
Munro MG, Critchley HO, Broder MS, et al. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011;113:3–13.
- 17.↑
Queensland Government, Metro South Health. Heavy menstrual bleeding (HMB). Accessed February 1, 2022. Available at: https://metrosouth.health.qld.gov.au/referrals/gynaecology/heavy-menstrual-bleeding
- 18.↑
Quinn GP, Block RG, Clayman ML, et al. If you did not document it, it did not happen: rates of documentation of discussion of infertility risk in adolescent and young adult oncology patients’ medical records. J Oncol Pract 2015;11:137–144.
- 19.↑
Young K, Fisher J, Kirkman M. “Do mad people get endo or does endo make you mad?”: clinicians’ discursive constructions of Medicine and women with endometriosis. Fem Psychol 2019;29:337–356.
- 20.↑
Maybin JA, Critchley HO. Menstrual physiology: implications for endometrial pathology and beyond. Hum Reprod Update 2015;21:748–761.
- 21.↑
Tingen CM, Halvorson LM, Bianchi DW. Revisiting menstruation: the misery, mystery, and marvel. Am J Obstet Gynecol 2020;223:617–618.
- 22.↑
Pender K. Ending period ‘taboo’ gave USA marginal gain at World Cup. The Telegraph. July 13, 2019. Accessed February 1, 2022. Available at: https://www.telegraph.co.uk/world-cup/2019/07/13/revealed-next-frontier-sports-science-usas-secret-weapon-womens/
- 23.↑
Diaz A, Laufer MR, Breech LL, et al. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics 2006;118:2245–2250.
- 24.↑
Committee on Adolescent Health Care. ACOG committee opinion no. 651: menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Obstet Gynecol 2015;126:e143–146.
- 25.↑
Anderson RA, Brewster DH, Wood R, et al. The impact of cancer on subsequent chance of pregnancy: a population-based analysis. Hum Reprod 2018;33:1281–1290.
- 26.↑
Melo AS, Paula CTV, Rufato MAF, et al. Fertility optimization in women with cancer: from preservation to contraception. JBRA Assist Reprod 2019;23:418–429.
- 27.↑
Gerstl B, Sullivan E, Koch J, et al. Reproductive outcomes following a stem cell transplant for a haematological malignancy in female cancer survivors: a systematic review and meta-analysis. Support Care Cancer 2019;27:4451–4460.
- 28.↑
Griffiths MJ, Winship AL, Hutt KJ. Do cancer therapies damage the uterus and compromise fertility? Hum Reprod Update 2020;26:161–173.
- 29.↑
Palinska-Rudzka KE, Ghobara T, Parsons N, et al. Five-year study assessing the clinical utility of anti-Müllerian hormone measurements in reproductive-age women with cancer. Reprod Biomed Online 2019;39:712–720.
- 30.↑
American College of Obstetricians and Gynecologists’ Committee on Adolescent Health Care. Options for prevention and management of menstrual bleeding in adolescent patients undergoing cancer treatment: ACOG committee opinion, number 817. Obstet Gynecol 2021;137:e7–15.
- 31.↑
Bártolo A, Santos IM, Valério E, et al. Depression and health-related quality of life among young adult breast cancer patients: the mediating role of reproductive concerns. J Adolesc Young Adult Oncol 2020;9:431–435.
- 32.↑
Lovelace DL, McDaniel LR, Golden D. Long‐term effects of breast cancer surgery, treatment, and survivor care. J Midwifery Womens Health 2019;64:713–724.
- 33.↑
Barbieri R. Female infertility. In: Strauss J, Barbieri R, eds. Yen and Jaffe’s Reproductive Endocrinology. 8th ed. Elsevier; 2017:556–581.
- 34.↑
Naessén S, Bergström I, Ljungman P, et al. Long-term follow-up of bone density, general and reproductive health in female survivors after treatment for haematological malignancies. Eur J Haematol 2014;93:137–142.
- 35.↑
Deli T, Orosz M, Jakab A. Hormone replacement therapy in cancer survivors: review of the literature. Pathol Oncol Res 2020;26:63–78.
- 36.↑
D’Alonzo M, Bounous VE, Villa M, et al. Current evidence of the oncological benefit-risk profile of hormone replacement therapy. Medicina (Kaunas) 2019;55:573.
- 37.↑
Langer RD, Hodis HN, Lobo RA, et al. Hormone replacement therapy - where are we now? Climacteric 2021;24:3–10.
- 38.↑
Boltežar L, Pintarić K, Jezeršek Novaković B. Fertility in young patients following treatment for Hodgkin’s lymphoma: a single center survey. J Assist Reprod Genet 2016;33:325–333.
- 39.↑
Frederick NN, Campbell K, Kenney LB, et al. Barriers and facilitators to sexual and reproductive health communication between pediatric oncology clinicians and adolescent and young adult patients: the clinician perspective. Pediatr Blood Cancer 2018;65:e27087.
- 40.↑
The Society of Obstetricians and Gynaecologists of Canada. Abnormal pain and menstrual bleeding—heavy menstrual bleeding (HMB) overview. Accessed January 11, 2021. Available at: https://www.yourperiod.ca/abnormal-pain-and-menstrual-bleeding/heavy-menstrual-bleeding/
- 41.↑
Singh S, Best C, Dunn S, et al. No. 292—abnormal uterine bleeding in pre-menopausal women. J Obstet Gynaecol Can 2018;40:e391–415.
- 42.↑
Chang DH, Dumanski SM, Ahmed SB. Female reproductive and gynecologic considerations in Chronic kidney disease: adolescence and young adulthood. Kidney Int Rep 2022;7:152–164.
- 43.↑
Esquivel A, Sittig DF, Murphy DR, et al. Improving the effectiveness of electronic health record-based referral processes. BMC Med Inform Decis Mak 2012;12:107.
- 44.↑
Hyman D, Neiman J, Rannie M, et al. Innovative use of the electronic health record to support harm reduction efforts. Pediatrics 2017;139:e20153410.
- 45.↑
Johnson RH, Kroon L. Optimizing fertility preservation practices for adolescent and young adult cancer patients. J Natl Compr Canc Netw 2013;11:71–77.
- 46.↑
Reinecke JD, Kelvin JF, Arvey SR, et al. Implementing a systematic approach to meeting patients’ cancer and fertility needs: a review of the Fertile Hope Centers Of Excellence program. J Oncol Pract 2012;8:303–308.
- 47.↑
Sheth KR, Sharma V, Helfand BT, et al. Improved fertility preservation care for male patients with cancer after establishment of formalized oncofertility program. J Urol 2012;187:979–986.
- 48.↑
Hut-Mossel L, Ahaus K, Welker G, et al. Understanding how and why audits work in improving the quality of hospital care: a systematic realist review. PLoS One 2021;16:e0248677.
- 49.↑
Dyer KE, Quinn GP. Cancer and fertility preservation in Puerto Rico: a qualitative study of healthcare provider perceptions. Support Care Cancer 2016;24:3353–3360.
- 50.↑
Kim J, Mersereau JE, Su HI, et al. Young female cancer survivors’ use of fertility care after completing cancer treatment. Support Care Cancer 2016;24:3191–3199.
- 51.↑
Wang Y, Anazodo A, Logan S. Systematic review of fertility preservation patient decision aids for cancer patients. Psychooncology 2019;28:459–467.
- 52.↑
Weiskopf NG, Weng C. Methods and dimensions of electronic health record data quality assessment: enabling reuse for clinical research. J Am Med Inform Assoc 2013;20:144–151.
