TY - JOUR
T1 - Longitudinal follow-up in female Childhood Cancer Survivors
T2 - no signs of accelerated ovarian function loss
AU - Van Der Kooi, A. L.F.
AU - Van Den Heuvel-Eibrink, M. M.
AU - Van Noortwijk, A.
AU - Neggers, S. J.C.M.M.
AU - Pluijm, S. M.F.
AU - Van Dulmen-Den Broeder, E.
AU - Van Dorp, W.
AU - Laven, J. S.E.
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - STUDY QUESTION Is the long-term decline of ovarian function, as reflected by a decrease in serum anti-Müllerian hormone (AMH) concentration, accelerated over time in female childhood cancer survivors (CCS) as compared to healthy women of the same age? SUMMARY ANSWER The median decline of AMH levels in long-term female CCS is not accelerated and similar to that observed in healthy controls. WHAT IS KNOWN ALREADY Gonadal function is compromised in female CCS treated with chemotherapy and/or radiation therapy. Ovarian function is most compromised in survivors treated with total body irradiation, abdominal or pelvic irradiation, stem cell transplantation or high doses of alkylating agents. STUDY DESIGN SIZE, DURATION Longitudinal single-centre cohort study in 192 CCS in Rotterdam, The Netherlands, between 2001 and 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Serum AMH levels of 192 adult female CCS were assessed, at least five years after cessation of treatment and at a follow-up visit with a median of 3.2 years (range: 2.1-6.0) later and were compared to the age-based P50 of AMH in healthy controls. MAIN RESULTS AND THE ROLE OF CHANCE Median AMH levels were below the P50 at both visit 1 (-0.59 μg/L) and at visit 2 (-0.22 μg/L). In women with a sustained ovarian function (AMH > 1.0 μg/L), the decline in AMH is similar to that in the normal population (difference in decline per year: -0.07 μg/L (range: -2.86 to 4.92), P = 0.75). None of the treatment modalities was correlated with a significant acceleration of decline of AMH per year. LIMITATIONS REASONS FOR CAUTION We selected CCS that visited our late effect outpatient clinic and who had two AMH levels available. It is conceivable that women without any apparent late effects of treatment as well as women with extreme late effects, which might be the ones with the largest impact on ovarian function, could be more likely to be lost to follow-up. However, general characteristics did not differ between the included and excluded patients. WIDER IMPLICATIONS OF THE FINDINGS While prospective longitudinal research is required to strengthen our findings, they may help physicians to counsel female CCS about their expected reproductive lifespan.
AB - STUDY QUESTION Is the long-term decline of ovarian function, as reflected by a decrease in serum anti-Müllerian hormone (AMH) concentration, accelerated over time in female childhood cancer survivors (CCS) as compared to healthy women of the same age? SUMMARY ANSWER The median decline of AMH levels in long-term female CCS is not accelerated and similar to that observed in healthy controls. WHAT IS KNOWN ALREADY Gonadal function is compromised in female CCS treated with chemotherapy and/or radiation therapy. Ovarian function is most compromised in survivors treated with total body irradiation, abdominal or pelvic irradiation, stem cell transplantation or high doses of alkylating agents. STUDY DESIGN SIZE, DURATION Longitudinal single-centre cohort study in 192 CCS in Rotterdam, The Netherlands, between 2001 and 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Serum AMH levels of 192 adult female CCS were assessed, at least five years after cessation of treatment and at a follow-up visit with a median of 3.2 years (range: 2.1-6.0) later and were compared to the age-based P50 of AMH in healthy controls. MAIN RESULTS AND THE ROLE OF CHANCE Median AMH levels were below the P50 at both visit 1 (-0.59 μg/L) and at visit 2 (-0.22 μg/L). In women with a sustained ovarian function (AMH > 1.0 μg/L), the decline in AMH is similar to that in the normal population (difference in decline per year: -0.07 μg/L (range: -2.86 to 4.92), P = 0.75). None of the treatment modalities was correlated with a significant acceleration of decline of AMH per year. LIMITATIONS REASONS FOR CAUTION We selected CCS that visited our late effect outpatient clinic and who had two AMH levels available. It is conceivable that women without any apparent late effects of treatment as well as women with extreme late effects, which might be the ones with the largest impact on ovarian function, could be more likely to be lost to follow-up. However, general characteristics did not differ between the included and excluded patients. WIDER IMPLICATIONS OF THE FINDINGS While prospective longitudinal research is required to strengthen our findings, they may help physicians to counsel female CCS about their expected reproductive lifespan.
KW - anti-Müllerian hormone
KW - childhood cancer
KW - females
KW - follow-up studies
KW - longitudinal studies
KW - neoplasms
KW - ovarian function
KW - reproductive health
KW - survivors
UR - http://www.scopus.com/inward/record.url?scp=85021178962&partnerID=8YFLogxK
U2 - 10.1093/humrep/dew278
DO - 10.1093/humrep/dew278
M3 - Article
C2 - 27821706
AN - SCOPUS:85021178962
SN - 0268-1161
VL - 32
SP - 193
EP - 200
JO - Human Reproduction
JF - Human Reproduction
IS - 1
ER -