A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges.

Annelies Overbeek,Jacqueline J Loonen,Gertjan Jl Kaspers,Marry M Van Den Heuvel-Eibrink,Marleen H Van Den Berg,Birgitta Versluys,Eline Van Dulmen-Den Broeder,Cornelis B Lambalk,Wim Je Tissing,Dorine Bresters,Leontien Cm Kremer,Flora E Van Leeuwen

doi:10.1186/1471-2407-12-363

Abstract

BackgroundAdvances 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.MethodsThe 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.DiscussionThe 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 registrationNTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922

Highlights

Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors
The study population consists of those female cancer survivors (CCS) who were treated for a malignancy or central nervous system tumour before the age of 18, who survived for at least 5 years after diagnosis, and who were at least 18 years at study entry (n = 2331)
A total of 1897 female childhood cancer survivors are eligible for participation in the DCOG LATER-VEVO study

Summary

Introduction

Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. 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. We designed the DCOG LATER-VEVO study (Dutch Childhood Oncology Group - Long term Effects after Childhood Cancer/ Fertility, Ovarian reserve and Premature Menopause (Dutch acronym)) in the Netherlands.

Objectives

Methods

Findings

Conclusion