TY - JOUR
T1 - A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer
T2 - Design and methodological challenges
AU - Overbeek, Annelies
AU - van den Berg, Marleen H.
AU - Kremer, Leontien C.M.
AU - van den Heuvel-Eibrink, Marry M.
AU - Tissing, Wim J.E.
AU - Loonen, Jacqueline J.
AU - Versluys, Birgitta
AU - Bresters, Dorine
AU - Kaspers, Gertjan J.L.
AU - Lambalk, Cornelis B.
AU - van Leeuwen, Flora E.
AU - van Dulmen-den Broeder, Eline
AU - Beerendonk, C. C.M.
AU - Bökkerink, J. P.
AU - van den Bos, C.
AU - van Dorp, W.
AU - van Engelen, M. P.
AU - Huizinga, G. A.
AU - Jaspers, M. W.M.
AU - Laven, J. S.
AU - Louwerens, M.
AU - van der Pal, H. J.H.
AU - Ronckers, C. M.
AU - Simons, A. H.M.
AU - Tonch, N.
AU - Verkerk, E. C.M.
N1 - Funding Information:
Both AO and MHB wrote the manuscript and contributed equally. All authors contributed to the design of the study and its coordination. AO and MHB are responsible for study logistics, patient recruitment, and data collection. EDB, CBL, FEL, and GJK are principal investigators. EVD was responsible for writing the grant proposals for funding of the study. LCK, MMHE, WJT, JJL, BV, and DB supported local patient recruitment and are clinically responsible for, respectively, the Emma Children’s Hospital/Academic Medical Center, the Sophia Children’s Hospital/Erasmus MC University Medical Center, the Beatrix Children’s Hospital/University Medical Center Groningen, the Radboud University Nijmegen Medical Center, the Wilhelmina’s Children’s Hospital/ University Medical Center Utrecht, the Willem-Alexander Children’s Hospital/ Leiden University Medical Center. All authors contributed to and approved the final manuscript.
PY - 2012/8/23
Y1 - 2012/8/23
N2 - Background: Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.Methods: The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.Discussion: The DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatric cancer patients as well as long-term survivors of childhood cancer. Other investigators planning to conduct large cohort studies on late effects may encounter similar challenges as those encountered during this study. The solutions to these challenges described in this paper may be useful to these investigators.Trial registration: NTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922.
AB - Background: Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.Methods: The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.Discussion: The DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatric cancer patients as well as long-term survivors of childhood cancer. Other investigators planning to conduct large cohort studies on late effects may encounter similar challenges as those encountered during this study. The solutions to these challenges described in this paper may be useful to these investigators.Trial registration: NTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922.
KW - Adverse effects
KW - Childhood cancer survivors
KW - Female fertility
KW - Methodological challenges
KW - Study design
UR - http://www.scopus.com/inward/record.url?scp=84865222253&partnerID=8YFLogxK
U2 - 10.1186/1471-2407-12-363
DO - 10.1186/1471-2407-12-363
M3 - Article
C2 - 22917040
AN - SCOPUS:84865222253
SN - 1471-2407
VL - 12
JO - BMC Cancer
JF - BMC Cancer
M1 - 363
ER -