testosterone therapy (which is administered systemically) cannot achieve these required high local concentrations (at least not without extremely supraphysiological dosages). Moreover, exogenous androgen therapy can actually impair or abolish male fertility by suppressing gonadotropin secretion from the pituitary gland, as seen in users of androgens/anabolic steroids (who often have partially or completely suppressed sperm production). This is because suppression of gonadotropin levels results in decreased testicular androgen production (causing diminished local concentrations in the testes) and because FSH is independently critical for spermatogenesis. In contrast to FSH, LH has little role in male fertility outside of inducing gonadal testosterone production. Estrogen, at some concentration, has been found to be essential for male fertility/spermatogenesis. However, estrogen levels that are too high can impair male fertility by suppressing gonadotropin secretion and thereby diminishing intratesticular androgen levels. As such, clomiphene citrate (an antiestrogen) and aromatase inhibitors such as testolactone or anastrozole have shown effectiveness in benefiting spermatogenesis. Low-dose estrogen and testosterone combination therapy may improve sperm count and motility in some men, including in men with severe oligospermia. Research Researchers at Münster University developed in vitro culture conditions using a three-dimensional agar culture system which induces mouse testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation. If reproduced in humans, this could potentially enable infertile men to father children with their own sperm. Researchers from Montana State University developed precursors of sperm from skin cells of infertile men. Sharpe et al. comment on the success of intracytoplasmic sperm injection (ICSI) in women saying, "[t]hus, the woman carries the treatment burden for male infertility, a fairly unique scenario in medical practice. Ironically, ICSI's success has effectively diverted attention from identifying what causes male infertility and focused research onto the female, to optimize the provision of eggs and a receptive endometrium, on which ICSI's success depends." Prevalence Currently, there are no solid numbers on how many couples worldwide experience infertility, but the World Health Organization estimates between 60 and 80 million couples are affected. The population in different regions have varying amounts of infertility. Starting in the late 20th century, scientists have expressed concerns about the declining semen quality in men. A study was done in 1992 with men who had never experienced infertility showed that the amount of sperm in semen had declined by 1% per year since 1938. Further research a few years later also confirmed the decline in