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      Variability in the Practice of Fertility Preservation for Patients with Cancer

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          Abstract

          Fertility is important to women and men with cancer. While options for fertility preservation (FP) are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs). A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases—particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS) in patients with estrogen receptor positive (ER+) breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines—knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14–2.90). These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP.

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          Physician referral for fertility preservation in oncology patients: a national study of practice behaviors.

          Cancer survival rates are improving, and the focus is moving toward quality survival. Fertility is a key aspect of quality of life for cancer patients of childbearing age. Although cancer treatment may impair fertility, some patients may benefit from referral to a specialist before treatment. However, the majority of studies examining patient recall of discussion and referral for fertility preservation (FP) show that less than half receive this information. This study examined the referral practices of oncologists in the United States. This study examined oncologists' referral practice patterns for FP among US physicians using the American Medical Association Physician Masterfile database. A 53-item survey was administered via mail and Internet to a stratified random sample of US physicians. Forty-seven percent of respondents routinely refer cancer patients of childbearing age to a reproductive endocrinologist. Referrals were more likely among female physicians (P = .004), those with favorable attitudes (P = .043), and those whose patients routinely ask about FP (odds ratio = 2.09; 95% CI, 1.31 to 3.33). Less than half of US physicians are following the guidelines from the American Society of Clinical Oncology, which suggest that all patients of childbearing age should be informed about FP.
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            Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation.

            To develop safe ovarian stimulation methods to perform in vitro fertilization (IVF) in breast cancer patients who wish to preserve their fertility via embryo cryopreservation before chemotherapy. Sixty women (age range, 24 to 43 years) with breast cancer were prospectively studied. Twenty-nine patients underwent 33 ovarian stimulation cycles with either tamoxifen 60 mg/d alone (Tam-IVF) or in combination with low-dose follicle-stimulating hormone (TamFSH-IVF) or letrozole 5 mg in combination with FSH (Letrozole-IVF). After IVF, all resultant embryos were cryopreserved to preserve fertility. Recurrence rates were compared with controls (n = 31) who elected not to undergo IVF. Compared with Tam-IVF, both TamFSH-IVF and Letrozole-IVF patients had greater numbers of follicles (2 +/- 0.3 v 6 +/- 1 and 7.8 +/- 0.9, respectively; P < .0001), mature oocytes (1.5 +/- 0.3 v 5.1 +/- 1.1 and 8.5 +/- 1.6, respectively; P < .001), and embryos (1.3 +/- 0.2 v 3.8 +/- 0.8 and 5.3 +/- 0.8, respectively; P < .001). Peak estradiol (E2) levels were lower with Letrozole-IVF and Tam-IVF compared with TamFSH-IVF. After 554 +/- 31 days (range, 153 to 1,441 days) of follow-up, cancer recurrence rate was similar between IVF and control patients (three of 29 v three of 31 patients, respectively; hazard ratio, 1.5; 95% CI, 0.29 to 7.4), and this estimate was not affected by cancer stage. The combination of low-dose FSH with tamoxifen (TamFSH-IVF) or letrozole (Letrozole-IVF) results in higher embryo yield compared with Tam-IVF. Recurrence rates do not seem to be increased, but the letrozole protocol may be preferred because it results in lower peak E2 levels.
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              Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: a prospective controlled study.

              Because of the accompanying increase in estrogen levels, safety of performing in vitro fertilization (IVF) in women with breast cancer is unknown. Our goal was to determine the effect of controlled ovarian stimulation (COS) using a combination of letrozole with standard fertility medications on disease-free survival in women undergoing embryo or oocyte cryopreservation before adjuvant chemotherapy. A total of 215 women with breast cancer were prospectively evaluated for fertility preservation before adjuvant chemotherapy. Of those, 79 elected to undergo COS with letrozole and gonadotropins for embryo or oocyte cryopreservation. The remaining 136 patients underwent no fertility-preserving procedure and served as controls. Study and control groups were similar at enrollment except for a trend for higher estrogen-receptor positivity in the COS group (P = .08). Time between surgery and chemotherapy was longer for IVF patients (45.08 v 33.46 days; P < .01). Peak estradiol levels ranged from 58.4 to 1,166 pg/mL (mean, 405.94 +/- 256.64 pg/mL or 1,486.76 +/- 942.13 pmol/L) in COS patients. The median follow-up after chemotherapy was 23.4 months (range, 7.5 to 63.6 months) in the COS group and 33.05 months (range, 4.5 to 63.6) in the control group. The hazard ratio for recurrence after IVF was 0.56 (95% CI, 0.17 to 1.9), and the survival was not compromised compared with controls (P = .36). Ovarian stimulation with gonadotropins and letrozole for the purpose of fertility preservation is unlikely to cause substantially increased recurrence risk. Further research, including longer-term follow-up is needed to confirm these findings.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 May 2015
                2015
                : 10
                : 5
                : e0127335
                Affiliations
                [1 ]Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, United States of America
                [2 ]Division of Public Health Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America
                [3 ]Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
                [4 ]Research Service, St. Louis Veterans Affairs Medical Center, St. Louis, Missouri, United States of America
                University Hospital of Münster, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KAR JSR ARC VSR KRC ESJ. Performed the experiments: KAR NMG JSR ESJ. Analyzed the data: KAR ESJ. Contributed reagents/materials/analysis tools: KAR NMG ESJ. Wrote the paper: KAR NMG JSR ARC VSR KRC ESJ.

                Article
                PONE-D-15-05334
                10.1371/journal.pone.0127335
                4444257
                26010087
                bc49be88-29d0-4a74-a8d1-40417ca09c91
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 12 February 2015
                : 14 April 2015
                Page count
                Figures: 1, Tables: 2, Pages: 9
                Funding
                This work was supported by National Institutes of Health Grants: T32 HD0040135 (KAR, JSR), and K12 HD063086 (ESJ, ARC).
                Categories
                Research Article
                Custom metadata
                The raw data was collected under our IRB which requires that the data be kept confidential and that they not be shared publicly. With approval from the Washington University IRB data could be made available for interested researchers. The contact information for the Washington University IRB is as follows: http://hrpo.wustl.edu/ 314-747-6800 The summarized data are presented in the manuscript.

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