Sperm retrieval and intracytoplasmic sperm injection outcomes in men with cystic fibrosis disease versus congenital bilateral absence of the vas deferens

Recent data suggest that cystic fibrosis transmembrane conductance regulator(CFTR)gene alterations negatively impact male fertility beyond obstruction.We sought to compare gene alterations,sperm retrieval rates,and intracytoplasmic sperm injection(ICSI)outcomes among men with cystic fibrosis(CF)disease and congenital bilateral absence of the vas deferens(CBAVD)only.We retrospectively evaluated all men who underwent surgical sperm retrieval at two academic,high-volume andrology centers from 2010 to 2018.Only men with documented CFTR alterations and obstructive azoospermia from either CBAVD or CF were included.Differences between groups for CFTR abnormality,sperm retrieval,and ICSI outcomes were statistically analyzed.Overall,39 patients were included with 10 in the CF and 29 in the CBAVD groups.Surgical sperm retrieval rates were significantly lower in the CF group for sperm concentration(14.8×10^(6)ml^(-1)vs 61.4×10^(6)ml^(−1),P=0.02)and total motile sperm count(2.9 million vs 11.4 million,P=0.01).This difference was only predicted by homozygous delta F508 CFTR mutations(P<0.05).The CF group also demonstrated a significantly higher rate of rescue testicular sperm extraction(70.0%vs 27.6%,P<0.03)and lower fertilization rate with ICSI(32.5%vs 68.9%,P<0.01).In conclusion,those with CF demonstrated lower sperm quality,greater difficulty with sperm retrieval,and worse ICSI outcomes compared with CBAVD-only patients.Homozygous delta F508 CFTR mutations appear to significantly impair spermatogenesis and sperm function.

Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use

The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids （AAS） within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal （HPG） axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.