**2.3. Other genital abnormalities**

Genital abnormalities may develop early in CF, but in children these are less common than described in adults. In 2002, Blau et al. [10] described genital abnormalities in male children with CF, performing pelvic and scrotal ultrasonography in 12 CF boys aged 2–12 years. They found seminal vesicles hypoplasia, testicular microlithiasis, and abnormalities of the epididy‐ mal head, such as cysts, hypo-, or hyper-echogenicity. These findings are more frequent in pancreatic-insufficient than in pancreatic-sufficient CF patients. The reported experience represents a very small population of CF children, and larger longitudinal studies will be necessary to better define the onset and progression of urogenital abnormalities in CF males.

In CF adults, testes are usually symmetric and have a normal echogenicity, but mild inhomo‐ geneity or striated appearance can be documented with ultrasounds. Focal inhomogeneities seem to be rare, as testicular nodules. Didymus cysts, epididymal cysts (also multiple) with sediments and/or calcifications are common. Usually, vas deferens is absent, but a structure attributable to spermatic cord could be revealed bilaterally or unilaterally in some cases, usually with a significant stenosis.

Several features can influence the anatomical genital phenotype in these patients (as genotype, clinical features, age), and further studies will be crucial to find risk factors and significant correlation for these abnormalities in CF.

### **2.4. Fertility management in men with CF**

Over the last 20 years, the relevant improvement in survival of CF patients and the concomitant development of new assisted conception methods have significantly increased the opportu‐ nities for these patients to become parents. It is therefore very important to start an early and effective management of fertility issues in males with CF.

The clinical management of reproductive issues in males affected by CF has to begin during puberty with periodic evaluation of testicular volume/consistency and all the other virilization signs, indicating a congruous testosterone production. Hormonal levels (as LH, FSH, and testosterone serum concentration) are usually normal in male CF, indicating a regular spermatogenesis in most cases. It could be also useful as a deeper examination to detect the presence of vas deferens (usually palpable in the upper portion of scrotum), but the definitive diagnosis of CBAVD can be made with radiological exams.

There is not a considerable literature about the morphological study of the scrotum in adult CF patients, but trans-rectal ultrasounds could be considered a good instrument to evaluate abnormalities in shape, volume, and structure of testes, epididymis, and spermatic cord.

Also scrotal ultrasound with high-definition instruments is non-invasive and executable without any discomfort for the patient and could be useful in order to analyze the extra pelvic portion of the vas deferens (from the groin to the testicle) and all the scrotal structures.

The diagnosis of azoospermia could be simply supported and confirmed by semen analysis. In case of seminal vesicles abnormalities, semen analysis will also show an acid pH, due to lack of fructose concentrations in sperm, and often the volume of ejaculate is low: in these cases, the sperm is produced by the prostate, with no contribute from vesicles. Typically, men with the absence of the vas deferens have low-volume (often less than 0.5 ml) and acidic semen [11].
