ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Clin Endocrinol (Oxf). 2019, Aug; 91: 237–44. doi: https://www.ncbi.nlm.nih.gov/pubmed/31004515

Fertility issues in individuals with a DSD has attracted increasing attention over the past decade and are summarized in this and other reviews. The various genetic defects that cause DSD and their underlying mechanism may impair fertility in a variety of ways. In addition, in many cases gonadectomy is performed due to high malignancy risks. With increasing knowledge on gonadal differentiation and development, the possibilities for fertility treatment may increase in the future.

Cryopreservation of sperm is standard care in most places. Today many centers also perform cryopreservation of testicular tissue or spermatogonial stem cells, mainly before cancer treatment. For prepubertal boys, this is a possibility to try to preserve future fertility.

Studies in humans and animals indicate that in vitro maturation of spermatogonial stem cells may be possible in the future. However, whether spermatogonial stem cells of testicular tissue from individuals with 46,XY DSD can be used for fertility treatment is unknown. Moreover, cryopreservation of prepubertal testicular tissue and spermatogonial stem cells is still experimental.

The efficacy of the techniques used in assisted reproduction, testicular sperm extraction (TESE), intracytoplasmic sperm injection (ICSI) in vitro fertilization (IVF) has improved (1), increasing the potential of fertility for individuals with 5-alfa-reductase deficiency and ovotesticular DSD. In addition, there is evidence that sperm may be present in the gonads of some individuals with other forms of DSD. In up to 40% of persons with a Klinefelter syndrome, TESE may lead to success because of focal sperm production. Similarly, among men with mixed gonadal dysgenesis (MGD) focal areas of spermatogenesis have been identified (2).

More studies are certainly required, but if the results continue to be encouraging, clinicians should inform families with DSD about their fertility preservation opportunities and provide access to these treatment options.

References:

1. Male fertility preservation in DSD, XXY, pre-gonadotoxic treatments - Update, methods, ethical issues, current outcomes, future directions. Giudice MG, Del Vento F, Wyns C. Best Pract Res Clin Endocrinol Metab. 2019, Jun; 33: 101261; DOI 10.1016/j.beem.2019.01.002, PMID 30718080. https://www.ncbi.nlm.nih.gov/pubmed/30718080.

2. Disorders of Sex Development-Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation. Gomes NL, Chetty T, Jorgensen A, Mitchell RT. Int J Mol Sci. 2020 Mar 26;21(7):2282. doi: 10.3390/ijms21072282. PMID: 32224856; PMCID: PMC7178030.