Long Term Reproductive Health Outcomes in Women Treated for Osteosarcoma During Childhood: A Systematic Review

To review the evidence on reproductive health outcomes in women treated for osteosarcoma during childhood (<15 years old).

We searched the following electronic databases from inception to May 2025: MEDLINE (Ovid), EMBASE (Ovid), Scopus, Web of Science and The Cochrane Library. The search strategy involved variations on key search terms relating to: "osteosarcoma," "childhood" and "fertility." Eligible papers where those that included patients treated for osteosarcoma during childhood and reported on reproductive health outcomes. We assessed the risk of bias of included papers using the Newcastle Ottawa Scale. Results were synthesized narratively.

After deduplication, 2,683 titles were screened and a total of 8 studies were eligible for inclusion in the review, with a total of 231 participants. Seven studies were retrospective. The length of follow-up ranged from 3 months to the longest median follow up of 23.9 years. Menstrual function was the most commonly used marker of reproductive health. There were ten cases who had irregular menstrual cycles following treatment and 6 cases of primary amenorrhea, there was 1 case of delayed puberty requiring hormone replacement therapy. Three papers reported on biochemical markers of ovarian reserve, including anti-Müllerian hormone (AMH), inhibin B and follicle-stimulating hormone (FSH). Only 2 studies reported pregnancy outcomes.

Most participants in the included studies did not experience any immediate impact to their reproductive health following treatment for osteosarcoma in childhood. However, our findings should be interpreted with caution and are limited by small sample sizes, relatively short follow up periods and variation in treatment protocols. Additionally, pregnancy outcomes were not reported in most studies. As a result, the long-term impact of childhood osteosarcoma treatment on future fertility remains unclear. This uncertainty highlights the importance of fertility counselling and proactive discussions about fertility preservation options before gonadotoxic treatment for osteosarcoma.