Establishing reproductive potential and advances in fertility preservation techniques for XY individuals with differences in sex development

Abstract

Background Discordance between gonadal type and gender identity has often led to an assumption of infertility in patients with differences in sex development (DSD). However, there is now greater recognition of fertility being an important issue for this group of patients. Currently, gonadal tissue that may have fertility potential is not being stored for individuals with DSD and, where gonadectomy forms part of management, is often discarded. The area of fertility preservation has been predominantly driven by oncofertility which is a field dedicated to preserving the fertility of patients undergoing gonadotoxic cancer treatment. The use of fertility preservation techniques could be expanded to include individuals with DSD where functioning gonads are present. Methods This is a systematic literature review evaluating original research articles and relevant reviews between 1974 and 2018 addressing DSD and fertility, in vitro maturation of sperm, and histological/ultrastructural assessment of gonadal tissue in complete and partial androgen insensitivity syndrome, 17β‐hydroxysteroid dehydrogenase type 3 and 5α‐reductase deficiency. Conclusion Successful clinical outcomes of ovarian tissue cryopreservation are paving the way for similar research being conducted using testicular tissue and sperm. There have been promising results from both animal and human studies leading to cryopreservation of testicular tissue now being offered to boys prior to cancer treatment. Although data are limited, there is evidence to suggest the presence of reproductive potential in the gonads of some individuals with DSD. Larger, more detailed studies are required, but if these continue to be encouraging, individuals with DSD should be given the same information, opportunities and access to fertility preservation as other patient groups.

Disorders of Sex Development—Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation

“…This has largely been applied to children due to receive gonadotoxic treatment for cancer [168]. For these patients, the only option available is to cryopreserve and store gonadal tissue with the aim of preserving germ cells that can be used to generate gametes for ART or for re-transplantation to restore fertility [169]. Whilst ovarian cryopreservation and re-transplantation has successfully restored fertility in females, there are no proven clinical methods to restore fertility using prepubertal testis tissues [136].…”

Standardised data collection for clinical follow-up and assessment of outcomes in differences of sex development (DSD): recommendations from the COST action DSDnet

“…in vitro generation of induced primordial germ cell-like cells) (56) may further increase fertility rates in the future. Assessment and documentation of reproductive capacity of the gonads independent of the patients' social gender has the aim of understanding condition-specific fertility chances (57). It can also facilitate access to international research protocols in this field through recruitment of registered patients.…”

Gonadectomy in conditions affecting sex development: a registry-based cohort study

“…In some of these conditions that are associated with a disorder of androgen synthesis, the indication for early gonadectomy was the avoidance of pubertal virilisation in an XY girl. Given that more children with XY DSD are being raised as boys ( 12), there is a greater prospect of preserving gonadal function and fertility (16,17) and there is a greater emphasis on the patient's own views on gonadectomy (4,18,19), there has been an increased emphasis on retaining gonads until the age when patients with DSD can decide for themselves (20). Mitigation of tumour risk was the commonest reported indication for performing gonadectomy and therefore as expected, in the current study, the number of cases that actually had any evidence of tumour development was very small.…”

“…Data are presented as n (%) or as median (range). 17 (10,19) 15 (14,16) 17 (7,28) 14 (7,18) 13 (8,17) 16 (1,28) 16 (1,28) Prior to presentation at specialist centre † 1 (6%)…”