Fertility loss reversal (AMAB)

OK, you probably know by now that starting cross-sex hormones will render you sterile temporarily, if not permanently. Science is a little unclear about when sterility becomes irreversible, but in any event you should bank sperm now if you're just starting hormones and think any future you might want bio-kids.

Cause of sterility
In the HPG axis, GnRH pulses from the hypothalamus stimulate the production of FSH and LH in the pituitary gland. In the testes, FSH binds to Sertoli "nurse" cells. Sertoli cells produce Androgen Binding Protein (ABP), which increases the concentration of testosterone in the testes. Also in the testes, LH binds to Leydig "structural" cells, causing them to produce testosterone, supporting the production of sperm, and inhibin. Inhibin suppresses the strength of GnRH pulses and reduces the FSH and LH produced, acting as a negative feedback loop to regulate the endocrine system. Estradiol acts as a neurosteroid, on a separate axis in the brain, suppressing GnRH pulses in a negative feedback loop.

The testes contain a constantly-dividing pool of spermatogonia, bound to the Leydig cells. Spermatogonia differentiate through a series of stages into sperm.

Taking exogenous estradiol takes the HPG axis off the hook. Estradiol will suppress GnRH production through its neuroendocrine axis, as well as suppressing FSH and LH production in the hypothalamus. My theory is without the FSH and LH inputs to the Sertoli cells, ABP is reduced decreasing the testosterone seen by the testes. Without testosterone, temporary sterility will occur. If testosterone is necessary for the spermatogonia progenitor cells to divide, then the population of these progenitor cells will dwindle into non-existence, causing permanent sterility.

Reversing sterility
Clomiphene has been used successfully to treat hypogonadism caused by dysregulation of the HPG axis. It probably increases fertility by acting as an estrogen antagonist in the neuroendocrine axis of GnRH production and in the hypothalamus where LH and FSH are produced, restoring this axis and driving the production of testosterone. It's not clear In one case study, 50mg 3x/day was used, but daily doses of 50mg are most common.

The entire process of spermatogenesis, from start to finish, takes roughly 74 days. Assuming it takes roughly 11 weeks to fully restart the HPG axis (as borne out by one study), you'd expect regaining fertility to take anywhere from 3-6 months. After this point, it's time to start considering more serious options.

More serious options

 * Cryopreservation of testicular tissue.
 * Undifferentiating skin cells into iPSC, and re-differentiating them into sperm cells (successful in mice, I've heard.)