*2.5.1. Counseling*

**2.3. Other genital abnormalities**

114 Cystic Fibrosis in the Light of New Research

usually with a significant stenosis.

correlation for these abnormalities in CF.

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

effective management of fertility issues in males with CF.

diagnosis of CBAVD can be made with radiological exams.

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,

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

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

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

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 CF men and their partners, who want to start assisted reproduction treatments, need an adequate genetic, medical, and psychological counseling. Genetic tests have to be performed in the patient (if not already done) and in the partner, in order to define the risk of generating an affected child. In case of incomplete genetic assessment or high risk of CF recurrence, prenatal or pre-implantation genetic diagnosis could also be recommended; it is important to consider ethic and legislative issues, because in some countries pre-implantation genetic tests are not allowed. All these procedures have relevant psychological, ethical, and sanitary costs, so alternative measures (as adoption or use of sperm donor) could be considered.

Another important issue is the prognosis of the potential father affected by CF. This delicate aspect asks the intervention of CF-clinician and psychologist, together with an experienced fertility specialist.

### *2.5.2. Sperm collection*

Sperm retrieval is a procedure used to obtain sperm for fertility purposes. In general, it is necessary in case of azoospermia or if men are unable to ejaculate. In almost all cases, sperm retrieval must be utilized in combination with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for reasonable pregnancy rates to be obtained [12].

The sperm collection could be performed by aspiration from epididymis or directly from the testis. In CF the proximal part of the epididymis is usually present, so the procedure is usually quietly simple. The techniques of collection include:


**Figure 2.** Percutaneous testicular aspiration (TESA) performed with local anesthetization

**Figure 3.** Percutaneous testicular biopsy

Cryopreservation of sperm is possible and represents a good chance for future use, but usually repeated epididymal aspiration is required. These procedures are usually performed on the same day of the partner's oocytes collection (Figure 5) to assure high counts of motile sperm in the time of fecundation.

**Figure 4.** Microsurgical identification of tubules with spermatogenesis (TESE technique)

**Figure 5.** Oocytes culture

**Figure 2.** Percutaneous testicular aspiration (TESA) performed with local anesthetization

Cryopreservation of sperm is possible and represents a good chance for future use, but usually repeated epididymal aspiration is required. These procedures are usually performed on the same day of the partner's oocytes collection (Figure 5) to assure high counts of motile sperm

**Figure 3.** Percutaneous testicular biopsy

116 Cystic Fibrosis in the Light of New Research

in the time of fecundation.

### *2.5.3. Assisted reproduction treatments*

The first experience of in vitro fertilization with sperm obtained by epididymal aspiration was in 1985 [13]; in the next years, several experiences also in CBAVD patients have been reported [14]. In that period, the fertilization rates were low (less than 20%), with very poor birth rates.

A dramatic increase in assisted reproduction outcomes for men with obstructive azoospermia has been represented by ICSI, introduced first in the 1990s. The first large experience with ICSI in the United States was published by Sherins et al. in 1995 [15]. This technique is generally performed following an in vitro fertilization procedure to extract one to several oocytes from a woman. The procedure is done under a microscope, using multiple micromanipulation devices, in order to allow the direct injection of a single sperm in a human oocyte.

This technique is currently the most used fertilization treatment worldwide and it has deeply increased the chances of successful fertilizations and pregnancies; ICSI technique allows to have the same fertilization and pregnancy rates between CF males and men with no vas deferens obstructive disease (Figure 6).

**Figure 6.** ICSI technique
