ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This narrative review summarized 75 published studies on reproductive function in survivors of childhood, adolescent, and young adult Hodgkin lymphoma (HL). 41 papers reported on 5057 female HL survivors. Most young female survivors had regular menstrual cycles. The incidence of premature ovarian failure (POI) varied between 6-34%. Biochemical evidence for impaired ovarian reserve or function was frequent (low AMH 55–59%. elevated FSH 17–100%). 51 studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was common (33–100%). A few studies reported recovery of semen up to 12 years post-treatment. Elevated FSH and low inhibin B levels were also common (elevated FSH 0–100%; low inhibin B 19–50%). LH and testosterone levels were less affected (elevated LH 0–57%; low testosterone 0–43%).

In both sexes, impaired reproductive ability was associated with pelvic radiotherapy and a higher cumulative chemotherapy doses. However, an impaired ovarian reserve did not exclude the chance of a live birth, and males with aberrant gonadal markers could still conceive. The presence of markers of impaired fertility before treatment (low AMH in females and azoospermia in males) indicates that the disease itself may disrupt reproductive function.

These findings indicate the need for longitudinal follow up with repeated measurements and a combination of reproductive markers (semen analysis, FSH and inhibin B in males; and AMH, antral follicle count and FSH in females) in all young adults affected by HL. Treatment related parameters such as abdominal radiotherapy, CED score (cyclophosphamide equivalent dose), using the cutoff >6000 mg/m2 in girls and >4000 mg/m2 in boys, and age at diagnosis (pre-/post pubertal) should be always assessed. The review also highlights that the adverse effects of newer/novel drugs that are believed to be non-gonadotoxic (e.g., Brentuximab, Nivolumab, and Pembrolizumab) are still largely unknown.

References: 1. Mulder RL, Font-Gonzalez A, Green DM, Loeffen EAH, Hudson MM, Loonen J et al. Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 2021;22: e57–e67.2. Mulder RL, Font-Gonzalez A, Hudson MM, van Santen HM, Loeffen EAH, Burns KC et al. Fertility preservation for female patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 2021;22: e45–e56.