Marloes Nies1, Astrid E P Cantineau2, Eus G J M Arts2, Marleen H van den Berg3, Flora E van Leeuwen4, Anneke C Muller Kobold5, Mariëlle S Klein Hesselink1, Johannes G M Burgerhof6, Adrienne H Brouwers7, Eveline W C M van Dam8, Bas Havekes9, Marry M van den Heuvel-Eibrink10,11, Eleonora P M Corssmit12, Leontien C M Kremer3,10, Romana T Netea-Maier13, Helena J H van der Pal3,14, Robin P Peeters15,16, John T M Plukker17, Cécile M Ronckers3,10,18, Hanneke M van Santen10,19, Anouk N A van der Horst-Schrivers1, Wim J E Tissing10,20, Gianni Bocca21, Eline van Dulmen-den Broeder3, Thera P Links1. 1. Department of Endocrinology, Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 2. Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3. Paediatric Oncology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 4. Department of Epidemiology and Biostatistics, Netherlands Cancer Institute, Amsterdam, The Netherlands. 5. Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 6. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 7. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 8. Department of Internal Medicine, VU University Medical Center Amsterdam UMC, Amsterdam, The Netherlands. 9. Division of Endocrinology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands. 10. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. 11. Department of Pediatric Oncology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands. 12. Division of Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands. 13. Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. 14. Department of Medical Oncology, Academic Medical Center, Amsterdam UMC, Amsterdam, The Netherlands. 15. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. 16. Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands. 17. Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 18. Medical University Brandenburg, Neuruppin, Germany. 19. Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands. 20. Department of Paediatric Oncology and Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 21. Department of Pediatric Endocrinology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Abstract
Background: Differentiated thyroid carcinoma (DTC) during childhood is a rare disease. Its excellent survival rate requires a focus on possible long-term adverse effects. This study aimed to evaluate fertility in female survivors of childhood DTC by assessing various reproductive characteristics combined with anti-Müllerian hormone (AMH) levels (a marker of ovarian reserve). Methods: Female survivors of childhood DTC, diagnosed at ≤18 years of age between 1970 and 2013, were included. Survivors were excluded when follow-up time was less than five years or if they developed other malignancies before or after diagnosis of DTC. Survivors filled out a questionnaire regarding reproductive characteristics (e.g., age at menarche and menopause, pregnancies, pregnancy outcomes, need for assisted reproductive therapy). Survivors aged <18 years during evaluation received an altered questionnaire without questions regarding pregnancy and pregnancy outcomes. These data were combined with information from medical records. AMH levels were measured in serum samples and were compared with AMH levels from 420 women not treated for cancer. Results: Fifty-six survivors with a median age of 31.0 (interquartile range, IQR, 25.1-39.6) years were evaluated after a median follow-up of 15.4 (IQR 8.3-24.7) years. The median cumulative dose of 131I administered was 7.4 (IQR 3.7-13.0) GBq/200.0 (IQR 100.0-350.0) mCi. Twenty-five of the 55 survivors aged 18 years or older during evaluation reported 64 pregnancies, 45 of which resulted in live birth. Of these 55, 10.9% visited a fertility clinic. None of the survivors reported premature menopause. Age at AMH evaluation did not differ between DTC survivors and the comparison group (p = 0.268). Median AMH levels did not differ between DTC survivors and the comparison group [2.0 (IQR 1.0-3.7) μg/L vs. 1.6 (IQR 0.6-3.1) μg/L, respectively, p = 0.244]. The cumulative dose of 131I was not associated with AMH levels in DTC survivors (rs = 0.210, p = 0.130). Conclusions: Female survivors of DTC who received 131I treatment during childhood do not appear to have major abnormalities in reproductive characteristics nor in predictors of ovarian failure.
Background: Differentiated thyroid carcinoma (DTC) during childhood is a rare disease. Its excellent survival rate requires a focus on possible long-term adverse effects. This study aimed to evaluate fertility in female survivors of childhood DTC by assessing various reproductive characteristics combined with anti-Müllerian hormone (AMH) levels (a marker of ovarian reserve). Methods: Female survivors of childhood DTC, diagnosed at ≤18 years of age between 1970 and 2013, were included. Survivors were excluded when follow-up time was less than five years or if they developed other malignancies before or after diagnosis of DTC. Survivors filled out a questionnaire regarding reproductive characteristics (e.g., age at menarche and menopause, pregnancies, pregnancy outcomes, need for assisted reproductive therapy). Survivors aged <18 years during evaluation received an altered questionnaire without questions regarding pregnancy and pregnancy outcomes. These data were combined with information from medical records. AMH levels were measured in serum samples and were compared with AMH levels from 420 women not treated for cancer. Results: Fifty-six survivors with a median age of 31.0 (interquartile range, IQR, 25.1-39.6) years were evaluated after a median follow-up of 15.4 (IQR 8.3-24.7) years. The median cumulative dose of 131I administered was 7.4 (IQR 3.7-13.0) GBq/200.0 (IQR 100.0-350.0) mCi. Twenty-five of the 55 survivors aged 18 years or older during evaluation reported 64 pregnancies, 45 of which resulted in live birth. Of these 55, 10.9% visited a fertility clinic. None of the survivors reported premature menopause. Age at AMH evaluation did not differ between DTC survivors and the comparison group (p = 0.268). Median AMH levels did not differ between DTC survivors and the comparison group [2.0 (IQR 1.0-3.7) μg/L vs. 1.6 (IQR 0.6-3.1) μg/L, respectively, p = 0.244]. The cumulative dose of 131I was not associated with AMH levels in DTC survivors (rs = 0.210, p = 0.130). Conclusions: Female survivors of DTC who received 131I treatment during childhood do not appear to have major abnormalities in reproductive characteristics nor in predictors of ovarian failure.