title: Assisted reproductive technology use and outcomes among women with a history of cancer.
abstract: OBJECTIVE
  How do the assisted reproductive technology (ART) outcomes of women presenting for ART after cancer diagnosis compare to women without cancer?
  
  
  CONCLUSIONS
  The likelihood of a live birth after ART among women with prior cancer using autologous oocytes is reduced and varies by cancer diagnosis but is similar to women without cancer when donor oocytes are used.
  
  
  BACKGROUND
  Premenopausal patients faced with a cancer diagnosis frequently present for fertility preservation.
  
  
  METHODS
  Population-based cohort study of women treated with ART in NY, TX and IL, USA.
  
  
  METHODS
  Women with their first ART treatment between 2004 and 2009 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database and linked to their respective State Cancer Registries based on name, date of birth and social security number. Years were rounded, i.e. year 1 = 6-18 months before treatment. This study used reports of cancer from 5 years, 6 months prior to treatment until 6 months after first ART treatment. Women who only presented for embryo banking were omitted from the analysis. The likelihood of pregnancy and of live birth with ART using autologous oocytes was modeled using logistic regression, with women without prior cancer as the reference group, adjusted for woman's age, parity, cumulative FSH dosage, infertility diagnosis, number of diagnoses, number of ART cycles, State of residency and year of ART treatment. Results of the modeling are reported as adjusted odds ratios (AORs) and (95% confidence intervals).
  
  
  RESULTS
  The study population included 53 426 women; 441 women were diagnosed with cancer within 5 years prior to ART cycle start. Mean (±SD) age at cancer diagnosis was 33.4 ± 5.7 years; age at start of ART treatment was 34.9 ± 5.8 for women with cancer compared with 35.3 ± 5.3 years for women without cancer (P = 0.03). Live birth rates among women using autologous oocytes differed substantially by cancer status (47.7% without cancer versus 24.7% with cancer, P < 0.0001), and cancer diagnosis (ranging from 53.5% for melanoma to 14.3% for breast cancer, P < 0.0001. The live birth rates among women using donor oocytes did not vary significantly by cancer status (60.4% for women with any cancer versus 64.5% for women without cancer), or by cancer diagnosis (ranging from 57.9% for breast cancer to 63.6% for endocrine cancer). Women with breast cancer make up about one-third of all cancers in this cohort. Among women with breast cancer, 2.8% of the 106 women who underwent ART within 6 months of being diagnosed with cancer used donor oocytes compared with 34.8% of the 46 women who received ART treatment a longer time after being diagnosed with cancer (P < 0.0001). We conjecture that the former group were either unaware that they had cancer or decided to undergo ART therapy prior to cancer treatment. However, their live birth rate was only 11.7% compared with 28.8%, the overall live birth rate for all women with cancer using autologous oocytes (P < 0.0001). The live birth rate for women diagnosed with breast cancer more than 6 months before ART (23.3%) did not differ significantly from the overall live birth rate for cancer (P = 0.49). If this difference is substantiated by a larger study, it would indicate a negative effect of severe recent illness itself on ART success, rather than the poor outcome being only related to the destructive effects of chemotherapies on ovarian follicles. Alternatively, because of the short time difference between cancer diagnosis and ART treatment, these pre-existing cancers may have been detected due to the increased medical surveillance during ART therapy. In women who only used autologous oocytes, women with prior cancers were significantly less likely to become pregnant and to have a live birth than those without cancer (adjusted odds ratio (AOR): 0.34, [95% confidence interval (CI): 0.27, 0.42] and 0.36 [0.28, 0.46], respectively). This was also evident with specific cancer diagnoses: breast cancer (0.20 [0.13, 0.32] and 0.19 [0.11, 0.30], respectively), cervical cancer (0.36 [0.15, 0.87] and 0.33 [0.13, 0.84], respectively) and all female genital cancers (0.49 [0.27, 0.87] and 0.47 [0.25, 0.86], respectively). Of note, among women with cancer who became pregnant, their likelihood of having a live birth did not differ significantly from women without cancer (85.8 versus 86.7% for women using autologous oocytes, and 85.3 versus 86.9% for women using donor oocytes).
  
  
  CONCLUSIONS
  Women may not have been residents of the individual States for the entire 5-year pre-ART period, and therefore some cancers may not have been identified through this linkage. As a result, the actual observed number of cancers may be an underestimate. In addition, the overall prevalence is low due to the age distributions. Also, because we restricted the pre-ART period to 5 years prior, we would not have identified women who were survivors of early childhood cancers (younger than age 13 years at cancer diagnosis), or who had ART more than 5 years after being diagnosed with cancer. Additional analyses are currently underway evaluating live birth outcomes after embryo banking among women with cancer prior to ART, cycles which were excluded from the analyses in this paper. Future studies are planned which will include more States, as well as linkages to vital records to obtain information on spontaneous conceptions and births, to further clarify some of the issues raised in this analysis.
  
  
  CONCLUSIONS
  Since the live birth rates using donor oocytes were not reduced in women with a prior cancer, but were reduced with autologous cycles, this suggests that factors acting in the pre- or peri-conceptional periods may be responsible for the decline.
  
  
  BACKGROUND
  The study was funded by grant R01 CA151973 from the National Cancer Institute, National Institutes of Health, USA. B.L. is a research consultant for the Society for Assisted Reproductive Technology. All other authors report no conflict of interest.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI, USA lukeb@msu.edu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Luke
authors.affiliation: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Morton B
authors.initials: MB
authors.lastname: Brown
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Missmer
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Logan G
authors.initials: LG
authors.lastname: Spector
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Leach
authors.affiliation: Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, TX, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Williams
authors.affiliation: Illinois State Cancer Registry, Illinois Department of Public Health, Springfield, IL, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Koch
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Yolanda R
authors.initials: YR
authors.lastname: Smith
authors.affiliation: Department of Obstetrics and Gynecology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Stern
authors.affiliation: Seattle Reproductive Medicine, Seattle, WA, USA.
authors.forename: G David
authors.initials: GD
authors.lastname: Ball
authors.affiliation: Bureau of Cancer Epidemiology, New York State Cancer Registry, New York State Department of Health, Albany, NY, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Schymura
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D050498:Live Birth / Q000453:epidemiology; D009369:Neoplasms / Q000453:epidemiology; D018587:Oocyte Donation / Q000706:statistics & numerical data*; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D011247:Pregnancy; D012042:Registries; D027724:Reproductive Techniques, Assisted / Q000706:statistics & numerical data*; D017741:Survivors / Q000706:statistics & numerical data
keywords: assisted reproduction; breast cancer; cancer among women; cohort study; live births; oncofertility