TY - JOUR
T1 - Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma
AU - Kaspers, G.J.L.
AU - Drechsel, K. C. E.
AU - Broer, S. L.
AU - Stoutjesdijk, F. S.
AU - Twisk, J. W. R.
AU - van den Berg, M. H.
AU - Lambalk, C. B.
AU - van Leeuwen, F. E.
AU - Overbeek, A.
AU - van den Heuvel-Eibrink, M. M.
AU - van Dorp, W.
AU - de Vries, A. C. H.
AU - Loonen, J. J.
AU - van der Pal, H. J.
AU - Kremer, L. C.
AU - Tissing, W. J.
AU - the LATER-VEVO study group
AU - Versluys, B.
AU - van Dulmen-den Broeder, E.
AU - Veening, M. A.
N1 - Funding Information: The authors gratefully thank Maya Schulpen, epidemiologist from the Princess Maxima Center, for sharing her thoughts on the statistical analyses plan of this manuscript. Funding Information: The VEVO-Later DCOG study was supported by the Dutch Cancer Society (Grant number: VU 2006–3622), and the Children Cancer Free Foundation (Grant Number: 20). The funders were not involved in study design, data collection and/or analysis of the data. Publisher Copyright: © 2023, The Author(s).
PY - 2023/11
Y1 - 2023/11
N2 - Purpose: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. Methods: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. Results: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. Conclusion: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.
AB - Purpose: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. Methods: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. Results: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. Conclusion: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.
KW - Anti-Mullerian hormone
KW - Childhood Hodgkin lymphoma
KW - Ovarian reserve
KW - Pregnancy
KW - Reproductive ability
UR - http://www.scopus.com/inward/record.url?scp=85166344722&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00432-023-05035-z
DO - https://doi.org/10.1007/s00432-023-05035-z
M3 - Article
C2 - 37522923
SN - 0171-5216
VL - 149
SP - 13677
EP - 13695
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
IS - 15
ER -