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Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk

  • Francesca Parissone ORCID logo EMAIL logo , Rossana Di Paola , Rita Balter , Simone Garzon ORCID logo , Stefano Zaffagnini , Maria Neri , Virginia Vitale , Gloria Tridello and Simone Cesaro ORCID logo
Published/Copyright: October 19, 2020
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 34 Issue 1

Abstract

Objectives

Childhood and adolescent cancer survivors (CACSs) are at risk of adverse reproductive outcomes. Assessment of follicle-stimulating hormone (FSH) levels is the most common test used to diagnose premature ovarian insufficiency (POI) whereas anti-m|llerian hormone (AMH) and antral follicle count (AFC) have been proposed as ovarian reserve markers. We assessed the correlation between these markers and treatment gonadotoxicity risk (GR) in CACSs.

Methods

A total of 55 female CACSs were enrolled. GR was graded as low, medium, or high according to classifications based on disease and treatments and on cyclophosphamide equivalent dose score. FSH, AMH, and AFC were determined. POI was defined by amenorrhea and FSH>30 IU/L. For remaining patients, diminished ovarian reserve (DOR) was defined by AMH<5th centile. FSH and AFC cut-offs proposed in the literature as DOR markers were also considered (FSH>10 IU/L or >95th centile; AFC<8 or <5th centile).

Results

Ovarian reserve results to be compromised in 23 (41.8%) patients: 14 with DOR and 9 with an established POI. Results showed GR classifications to be a good predictor of ovarian reserve, with significantly lower AMH and AFC in the high-risk groups. AFC resulted to be directly correlated with AMH (r=0.75, p<0.001).

Conclusions

In CACSs, GR classifications correlate with post-treatment AMH and AFC. These are useful tools in the early identification of young patients with DOR, who may benefit from reproductive and fertility preservation counseling. Further studies are needed to determine the rate and time of progression from DOR to POI in this population.

Keywords: anti-m|llerian hormone; antral follicle count; gonadotoxicity risk; ovarian reserve; premature ovarian insufficiency; young childhood cancer survivors
Corresponding author: Francesca Parissone, Obstetrics and Gynecology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, P.le Stefani, 1,37126 Verona, Italy, Phone: +390458127147, E-mail:

  1. Research funding: None declared.

  2. Author contributions: FP, SC, RDP for study concepts; FP and SC for study designed; FP, RDP, MN, RB and VV for data collection; FP, GT and SG for quality control of data and algorithms; GT, FP, SZ and SC for data analysis and interpretation; GT for statistical analysis; FP and SG for manuscript preparation; SC, and GT for manuscript editing; RB, SZ and VV for manuscript review; all the authors decided to submit the paper for publication. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interests: None declared.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: All patients and their parents in the case of minors, provided informed consent for the research and for data collection for the purposes of the study, as approved by the institutional review board of Verona. All procedures followed the Italian laws for personal data protection and were in accordance with the tenets of the Helsinki Declaration.

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Supplementary material

The online version of this article offers supplementary material (DOI: https://doi.org/10.1515/j_jpem-2020-0272).

Received: 2020-05-14
Accepted: 2020-08-31
Published Online: 2020-10-19
Published in Print: 2021-01-27

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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  4. Adverse effects of metabolic disorders in childhood on adult reproductive function and fertility in the male
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https://doi.org/10.1515/jpem-2020-0272
Keywords for this article
anti-m|llerian hormone; antral follicle count; gonadotoxicity risk; ovarian reserve; premature ovarian insufficiency; young childhood cancer survivors

Articles in the same Issue

  1. Frontmatter
  2. Review Articles
  3. Association between muscle strength and risk factors for metabolic syndrome in children and adolescents: a systematic review
  4. Adverse effects of metabolic disorders in childhood on adult reproductive function and fertility in the male
  5. Original Articles
  6. Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk
  7. Anthropometric indices and cardiometabolic risk factors in a Ghanaian adolescent population
  8. Effectiveness of basal LH in monitoring central precocious puberty treatment in girls
  9. Combination of sleep duration, TV time and body mass index is associated with cardiometabolic risk moderated by age in youth
  10. Serum level of NPTX1 is independent of serum MKRN3 in central precocious puberty
  11. Training using a simulation-based workshop reduces inaccuracies in estimations of testicular volume
  12. Longitudinal 15-year follow-up of women with former early puberty: abnormal metabolic profiles not associated with earlier age at onset of puberty, but associated with obesity
  13. Prenatal smoke exposure is associated with increased anogenital distance in female infants: a prospective case–control study
  14. Evaluation of the efficiency of serum biotinidase activity as a newborn screening test in Turkey
  15. Characterization and outcome of 11 children with non-diabetic ketoacidosis
  16. Challenges of following patients with inherited metabolic diseases during the COVID-19 outbreak. A cross-sectional online survey study
  17. The utility of 68Ga-DOTATATE PET/CT in localizing primary/metastatic pheochromocytoma and paraganglioma in children and adolescents – a single-center experience
  18. Impact of sodium phenylbutyrate treatment in acute management of maple syrup urine disease attacks: a single-center experience
  19. Case Reports
  20. Delayed phenylketonuria diagnosis: a challenging case in child psychiatry
  21. Late diagnosis of 3β-Hydroxysteroid dehydrogenase deficiency: the pivotal role of gas chromatography-mass spectrometry urinary steroid metabolome analysis and a novel homozygous nonsense mutation in the HSD3B2 gene
  22. Differentiating syndrome of inappropriate ADH, reset osmostat, cerebral/renal salt wasting using fractional urate excretion
  23. Ectopic ACTH production by thymic and appendiceal neuroendocrine tumors – two case reports
  24. New onset diabetes with diabetic ketoacidosis in a child with multisystem inflammatory syndrome due to COVID-19
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