Differences in gonadal tissue cryopreservation practices for differences of sex development across regions in the United States

ObjectiveSome individuals with differences of sex development (DSD) conditions undergo medically indicated prophylactic gonadectomy. Gonads of individuals with DSD can contain germ cells and precursors and patients interested in future fertility preservation and hormonal restoration can participate in DSD-specific research protocols to cryopreserve this tissue. However, it is unclear how many providers or institutions offer gonadal tissue cryopreservation (GTC) and how widespread GTC for DSD is across the United States (US). The Pediatric Initiative Network (PIN) and Non-Oncologic Conditions committees of the Oncofertility Consortium sought to assess the current state of GTC for patients with DSD.MethodsAn electronic survey was sent to providers caring for patients with DSD via special interest groups of professional societies and research networks.ResultsThe survey was administered between November 15, 2021 and March 14, 2022. A total of 155 providers responded to the survey, of which 132 respondents care for patients with DSD, and 78 work at facilities that offer medically indicated gonadectomy to patients with DSD diagnoses. They represented 55 US institutions including 47 pediatric hospitals, and 5 international sites (Canada, Denmark, Germany, Qatar). Of individual providers, 41% offer cryopreservation after prophylactic gonadectomy for patients with DSD (32/78). At an institutional level, GTC after medically indicated gonadectomy is available at 54.4% (24/46) of institutions. GTC is offered for a variety of DSD diagnoses, most commonly 45,X/46,XY DSD (i.e., Turner Syndrome with Y-chromosome material and mixed gonadal dysgenesis), ovotesticular DSD, complete androgen insensitivity syndrome (CAIS), and complete gonadal dysgenesis. Responses demonstrate regional trends in GTC practices with 83.3% of institutions in the Midwest, 66.7% in the Northeast, 54.6% in the West, and 35.3% in the South providing GTC. All represented institutions (100%) send gonadal tissue for pathological evaluation, and 22.7% preserve tissue for research purposes.ConclusionsGTC after gonadectomy is offered at half of the US institutions represented in our survey, though a minority are currently preserving tissue for research purposes. GTC is offered for several DSD conditions. Future research will focus on examining presence and quality of germ cells to support clinical decision making related to fertility preservation for patients with DSD

Induced pluripotent stem cell line generated from a patient with differences in sex development (DSD) and multiple genetic variants including a large deletion in NR5A1

The nuclear receptor subfamily 5, Group A, Member 1 (NR5A1) gene encodes steroidogenic factor 1 (SF1), which is necessary for development of steroid hormone-producing tissues including the gonad and adrenal gland. An induced pluripotent stem cell line (iPSC) LCHi002-B was generated from a participant with differences (disorders) of sex development (DSD) and multiple genetic variants including a large deletion in NR5A1, and three single nucleotide changes in DYNC2H1, PDE4D, and ZFPM2. The line presented typical morphology, expressed stem cell markers, differentiated into three germ layers, had normal karyotype, was mycoplasma-free, and carried mutations in NR5A1, DYNC2H1, PDE4D, and ZFPM2