Microscopic testicular sperm extraction in 46,XY differences in sex development caused by 5-alpha reductase type 2 deficiency

The 46,XY differences in sex development (DSD) caused by 5-alpha reductase type 2 (5ARD2) often presents with bilateral undescended testicles, otherwise normal internal reproductive structures, prostate hypoplasia and undervirilized male genitalia. Notably, as one of the few DSDs where fertility is possible, the clinical presentation of this disease is diverse, and reported cases of assisted reproduction are scarce. The fertility potential, reproductive counseling and treatment depend on the clinical presentation of this DSD, especially the testicular position and urethral anatomy. The influence of the timing and modality of surgery for hypospadias and cryptorchidism should be considered. We aimed to describe the use of microscopic testicular sperm extraction (micro-TESE) in this population. We provide a descriptive analysis of how micro-TESE is a possible potential tool for assisted reproduction in 5ARD2-deficient patients. A 33-year-old male who underwent bilateral orchidopexy, phalloplasty, and urethroplasty at the age of 9 years presented successful sperm retrieval but failed embryo development after intracytoplasmic sperm injection. Testicular histology revealed late spermatogenic arrest. A 28-year-old male with bilateral orchidopexy, phalloplasty, and urethroplasty at age 25 with unsuccessful sperm retrieval. Testicular histology revealed a Sertoli cell-only pattern. 5ARD2-deficient patients are singular patients. The potential impact of the time between atypical genitalia procedures and orchidopexy on fertility should be highly considered. Micro-TESE is a technique that may be used to assist azoospermic patients in this population. Early orchidopexy and penile and urethral corrections should be considered key strategies to preserve the fertility potential of 5ARD2 patients.