Longitudinal follow-up in female Childhood Cancer Survivors: no signs of accelerated ovarian function loss.
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?



The median decline of AMH levels in long-term female CCS is not accelerated and similar to that observed in healthy controls.



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.



Longitudinal single-centre cohort study in 192 CCS in Rotterdam, The Netherlands, between 2001 and 2014.



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 P50of AMH in healthy controls.



Median AMH levels were below the P50at 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.



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.



While prospective longitudinal research is required to strengthen our findings, they may help physicians to counsel female CCS about their expected reproductive lifespan.



A.L.F.v.d.K., M.M.v.d.H.-E. and S.M.F.P. are supported by FP7-PanCare LIFE. J.S.E.L. has received grants from the following companies (in alphabetical order): Ferring, Merck Serono, Merck Sharp and Dome, Organon, Serono, Shering Plough and Shering. The other authors have no conflicts of interest to declare.
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC-University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands a.vanderkooi@erasmusmc.nl.|Princess Maxima Center for Pediatric Oncology, Lundlaan 6, 3584 EA Utrecht, the Netherlands.|Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital, Wytemaweg 40, 3015 GJ Rotterdam, the Netherlands.
A L F
AL
van der Kooi
Princess Maxima Center for Pediatric Oncology, Lundlaan 6, 3584 EA Utrecht, the Netherlands.|Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital, Wytemaweg 40, 3015 GJ Rotterdam, the Netherlands.
M M
MM
van den Heuvel-Eibrink
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC-University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
A
A
van Noortwijk
Department of Endocrinology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands.
S J C M M
SJ
Neggers
Princess Maxima Center for Pediatric Oncology, Lundlaan 6, 3584 EA Utrecht, the Netherlands.|Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital, Wytemaweg 40, 3015 GJ Rotterdam, the Netherlands.
S M F
SM
Pluijm
Department of Paediatrics, Division of Paediatric Oncology/Haematology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands.
E
E
van Dulmen-den Broeder
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC-University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
W
W
van Dorp
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC-University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
J S E
JS
Laven
D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood*; D000073116:Cancer Survivors; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008875:Middle Aged; D065851:Ovarian Reserve / Q000502:physiology*; D010053:Ovary / Q000473:pathology*; D055815:Young Adult
D054304:Anti-Mullerian Hormone
anti-Müllerian hormone / ovarian function/ childhood cancer / females / follow-up studies / longitudinal studies / reproductive health / survivors / neoplasms