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

BMC Cancer

Annelies Overbeek⁸  Marleen H van den Berg²  Leontien CM Kremer¹  Marry M van den Heuvel-Eibrink⁷  Wim JE Tissing⁵  Jacqueline J Loonen³  Birgitta Versluys⁴  Dorine Bresters⁹  Gertjan JL Kaspers²  Cornelis B Lambalk⁸  Flora E van Leeuwen⁶  Eline van Dulmen-den Broeder² 

[1] Department of Paediatric Oncology, Emma Children’s Hospital/Academic Medical Center, Amsterdam, The Netherlands

[2] Department of Paediatrics, Division of Paediatric Oncology/Haematology, VU University Medical Center, PO Box 7057, Amsterdam, 1007MB, The Netherlands

[3] Department of Pediatric Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

[4] Department of Pediatric Oncology, Wilhelmina’s Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

[5] Department of Pediatric Oncology, Beatrix Children’s Hospital/University Medical Center Groningen, Groningen, The Netherlands

[6] Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands

[7] Department of Pediatric Oncology, Sophia Children’s Hospital/Erasmus MC University Medical Center, Rotterdam, The Netherlands

[8] Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, The Netherlands

[9] Department of Pediatric Stem Cell Transplantation, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands

关键词: Methodological challenges;    Study design;    Female fertility;    Adverse effects;    Childhood cancer survivors;   

Others  :  1080245
DOI  :  10.1186/1471-2407-12-363

 received in 2012-07-18, accepted in 2012-08-16,  发布年份 2012

【 摘 要 】

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 webcite

【 授权许可】

   
2012 Overbeek et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Chemaitilly W, Mertens AC, Mitby P, Whitton J, Stovall M, Yasui Y, Robison LL, Sklar CA: Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab 2006, 91:1723-1728.
• [2]Green DM, Sklar CA, Boice JD Jr, Mulvihill JJ, Whitton JA, Stovall M, Yasui Y: Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol 2009, 27:2374-2381.
• [3]Madanat-Harjuoja LM, Malila N, Lahteenmaki PM, Boice JD Jr, Gissler M, Dyba T: Preterm delivery among female survivors of childhood, adolescent and young adulthood cancer. Int J Cancer 2010, 127:1669-1679.
• [4]Reulen RC, Zeegers MP, Wallace WH, Frobisher C, Taylor AJ, Lancashire ER, Winter DL, Hawkins MM: Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009, 18:2239-2247.
• [5]Signorello LB, Mulvihill JJ, Green DM, Munro HM, Stovall M, Weathers RE, Mertens AC, Whitton JA, Robison LL, Boice JD Jr: Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study. Lancet 2010, 376:624-630.
• [6]Sklar CA, Mertens AC, Mitby P, Whitton J, Stovall M, Kasper C, Mulder J, Green D, Nicholson HS, Yasui Y, Robison LL: Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 2006, 98:890-896.
• [7]van Beek RD, van den Heuvel-Eibrink MM, Laven JS, de Jong FH, Themmen AP, Hakvoort-Cammel FG, van den Bos C, van den Berg H, Pieters R, de Muinck Keizer-Schrama SM: Anti-Mullerian hormone is a sensitive serum marker for gonadal function in women treated for Hodgkin's lymphoma during childhood. J Clin Endocrinol Metab 2007, 92:3869-3874.
• [8]Lie FS, van den Heuvel-Eibrink MM, Eijkemans MJ, Schipper I, Hukkelhoven CW, Laven JS: Pregnancy outcome in female childhood cancer survivors. Hum Reprod 2010, 25:1206-1212.
• [9]van Dorp W, van Beek RD, Laven JS, Pieters R, de Muinck Keizer-Schrama SM, van den Heuvel-Eibrink MM: Long-term endocrine side effects of childhood Hodgkin's lymphoma treatment: a review. Hum Reprod Update 2012, 18:12-28.
• [10]Armstrong GT, Whitton JA, Gajjar A, Kun LE, Chow EJ, Stovall M, Leisenring W, Robison LL, Sklar CA: Abnormal timing of menarche in survivors of central nervous system tumors: A report from the Childhood Cancer Survivor Study. Cancer 2009, 115:2562-2570.
• [11]Byrne J, Fears TR, Gail MH, Pee D, Connelly RR, Austin DF, Holmes GF, Holmes FF, Latourette HB, Meigs JW: Early menopause in long-term survivors of cancer during adolescence. Am J Obstet Gynecol 1992, 166:788-793.
• [12]Chiarelli AM, Marrett LD, Darlington G: Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964–1988 in Ontario, Canada. Am J Epidemiol 1999, 150:245-254.
• [13]Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, Pendergrass TW, Robison LL: Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Am J Obstet Gynecol 2002, 187:1070-1080.
• [14]Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, Donaldson SS, Byrne J, Robison LL: Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 2009, 27:2677-2685.
• [15]Magelssen H, Melve KK, Skjaerven R, Fossa SD: Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood. Hum Reprod 2008, 23:178-186.
• [16]Mueller BA, Chow EJ, Kamineni A, Daling JR, Fraser A, Wiggins CL, Mineau GP, Hamre MR, Severson RK, Drews-Botsch C: Pregnancy outcomes in female childhood and adolescent cancer survivors: a linked cancer-birth registry analysis. Arch Pediatr Adolesc Med 2009, 163:879-886.
• [17]Reinmuth S, Liebeskind AK, Wickmann L, Bockelbrink A, Keil T, Henze G, Borgmann A: Having children after surviving cancer in childhood or adolescence - results of a Berlin survey. Klin Padiatr 2008, 220:159-165.
• [18]Sudour H, Chastagner P, Claude L, Desandes E, Klein M, Carrie C, Bernier V: Fertility and pregnancy outcome after abdominal irradiation that included or excluded the pelvis in childhood tumor survivors. Int J Radiat Oncol Biol Phys 2010, 76:867-873.
• [19]Winther JF, Boice JD Jr, Svendsen AL, Frederiksen K, Stovall M, Olsen JH: Spontaneous abortion in a Danish population-based cohort of childhood cancer survivors. J.Clin.Oncol 2008, 26:4340-4346.
• [20]Bath LE, Critchley HO, Chambers SE, Anderson RA, Kelnar CJ, Wallace WH: Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement. Br J Obstet Gynaecol 1999, 106:1265-1272.
• [21]Bath LE, Wallace WHB, Shaw MP, Fitzpatrick C, Anderson RA: Depletion of ovarian reserve in young women after treatment for cancer in childhood: Detection by anti-Mullerian hormone, inhibin B and ovarian ultrasound. Hum Reprod 2003, 18:2368-2374.
• [22]Lantinga GM, Simons AH, Kamps WA, Postma A: Imminent ovarian failure in childhood cancer survivors. Eur J Cancer 2006, 42:1415-1420.
• [23]Larsen EC, Muller J, Rechnitzer C, Schmiegelow K, Andersen AN: Diminished ovarian reserve in female childhood cancer survivors with regular menstrual cycles and basal FSH <10 IU/l. Hum Reprod 2003, 18:417-422.
• [24]Larsen EC, Muller J, Schmiegelow K, Rechnitzer C, Andersen AN: Reduced ovarian function in long-term survivors of radiation- and chemotherapy-treated childhood cancer. J Clin Endocrinol Metab 2003, 88:5307-5314.
• [25]Lie Fong S, Lugtenburg PJ, Schipper I, Themmen AP, de Jong FH, Sonneveld P, Laven JS: Anti-mullerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies. Hum Reprod 2008, 23:674-678.
• [26]Lie Fong S, Van Den Heuvel-Eibrink M: Pregnancy outcome in female childhood cancer survivors. In Molecular Human Reproduction Conference: 25th Annual Meeting of the European Society of Human Reproduction and Embryology, ESHRE. Amsterdam Netherlands: Conference Publication; 2009:i101. Conference Start: 20090628 Conference End: 20090701
• [27]Wallace WH, Thomson AB, Saran F, Kelsey TW: Predicting age of ovarian failure after radiation to a field that includes the ovaries. Int J Radiat Oncol Biol Phys 2005, 62:738-744.
• [28]de Boer EJ, Den Tonkelaar I, Burger CW, van Leeuwen FE: Validity of self-reported causes of subfertility. Am J Epidemiol 2005, 161:978-986.
• [29]van Leeuwen FE, Klip H, Mooij TM, van de Swaluw AM, Lambalk CB, Kortman M, Laven JS, Jansen CA, Helmerhorst FM, Cohlen BJ, Willemsen WN, Smeenk JM, Simons AH, van der Veen F, Evers JL, van Dop PA, Macklon NS, Burger CW: Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort. Hum Reprod 2011, 26:3456-3465.
• [30]Hoonakker P, Carayo P: Questionnaire Survey Nonresponse: A Comparison of Postal Mail and Internet Surveys. Int J Hum Comput Interact 2009, 25:348-373.
• [31]Pealer LN, Weiler RM, Pigg RM Jr, Miller D, Dorman SM: The feasibility of a web-based surveillance system to collect health risk behavior data from college students. Health Educ Behav 2001, 28:547-559.
• [32]Vereecken CA, Maes L: Comparison of a computer-administered and paper-and-pencil-administered questionnaire on health and lifestyle behaviors. J Adolesc Health 2006, 38:426-432.
• [33]van den Berg MH, Overbeek A, van der Pal HJ, Versluys AB, Bresters D, van Leeuwen FE, Lambalk CB, Kaspers GJ, van Dulmen-den Broeder E: Using web-based and paper-based questionnaires for collecting data on fertility issues among female childhood cancer survivors: differences in response characteristics. J Med Internet Res 2011, 13:e76.
• [34]Coolman M, de Groot CJ, Jaddoe VW, Hofman A, Raat H, Steegers EA: Medical record validation of maternally reported history of preeclampsia. J Clin Epidemiol 2010, 63:932-937.
• [35]Olson JE, Shu XO, Ross JA, Pendergrass T, Robison LL: Medical record validation of maternally reported birth characteristics and pregnancy-related events: a report from the Children's Cancer Group. Am J Epidemiol 1997, 145:58-67.
• [36]Rice F, Lewis A, Harold G, van den BM, Boivin J, Hay DF, Owen MJ, Thapar A: Agreement between maternal report and antenatal records for a range of pre and peri-natal factors: the influence of maternal and child characteristics. Early Hum Dev 2007, 83:497-504.
• [37]Overbeek A, van den Berg MH, Hukkelhoven CWPM, Malhoe P, Kaspers GJ, Lambalk CB, van Dulmen-den Broeder E, van Leeuwen FE: Validity of self-reported data on pregnancies: a comparison of self-report with data from a nationwide population-based registry. Accepted(11-10-2012)/ in press Human Reproduction
• [38]de Boer EJ, Den Tonkelaar I, te Velde ER, Burger CW, van Leeuwen FE: Increased risk of early menopausal transition and natural menopause after poor response at first IVF treatment. Hum Reprod 2003, 18:1544-1552.
• [39]Jayaprakasan K, Walker KF, Clewes JS, Johnson IR, Raine-Fenning NJ: The interobserver reliability of off-line antral follicle counts made from stored three-dimensional ultrasound data: a comparative study of different measurement techniques. Ultrasound Obstet Gynecol 2007, 29:335-341.
• [40]Jayaprakasan K, Campbell BK, Clewes JS, Johnson IR, Raine-Fenning NJ: Three-dimensional ultrasound improves the interobserver reliability of antral follicle counts and facilitates increased clinical work flow. Ultrasound Obstet Gynecol 2008, 31:439-444.
• [41]Merce LT, Gomez B, Engels V, Bau S, Bajo JM: Intraobserver and interobserver reproducibility of ovarian volume, antral follicle count, and vascularity indices obtained with transvaginal 3-dimensional ultrasonography, power Doppler angiography, and the virtual organ computer-aided analysis imaging program. J Ultrasound Med 2005, 24:1279-1287.
• [42]Scheffer GJ, Broekmans FJ, Bancsi LF, Habbema JD, Looman CW, te Velde ER: Quantitative transvaginal two- and three-dimensional sonography of the ovaries: reproducibility of antral follicle counts. Ultrasound Obstet Gynecol 2002, 20:270-275.
• [43]Ness KK, Leisenring W, Goodman P, Kawashima T, Mertens AC, Oeffinger KC, Armstrong GT, Robison LL: Assessment of selection bias in clinic-based populations of childhood cancer survivors: a report from the childhood cancer survivor study. Pediatr Blood Cancer 2009, 52:379-386.