Before the era of ICSI, attempts were made to modify and refine conventional IVF to achieve increased rates of conception in cases of male-factor infertility. Today, ICSI has clearly overshadowed the use of modified IVF procedures (including high insemination concentration) for the treatment of severe male-factor infertility. ICSI requires only one spermatozoon with a functional genome and centrosome for the fertilization of each oocyte. Indications for ICSI are not restricted to impaired morphology of the spermatozoa, but also include low sperm counts and impaired kinetic quality of the sperm cells. ICSI can also be used with spermatozoa from the epididymis or testis when there is an obstruction in the excretory ducts. Azoospermia caused by testicular failure can be treated by ICSI if enough spermatozoa can be retrieved in testicular tissue samples. Table 1 gives an overview of the current indications for ICSI.
Table 1 Current Indications for Intracytoplasmic Sperm Injection
Asthenozoospermia (caveat for 100% immotile spermatozoa) Teratozoospermia (<4% normal morphology using strict criteria-caveat for globozoospermia) High titers of antisperm antibodies Repeated fertilization failure after conventional IVF Autoconserved frozen sperm from cancer patients in remission Ejaculatory disorders (e.g., electroejaculation, retrograde ejaculation) Epididymal spermatozoa
Congenital bilateral absence of the vas deferens
Obstruction of both ejaculatory ducts
All indications for epididymal sperm
Failure of epididymal sperm recovery because of fibrosis
Azoospermia caused by testicular failure (maturation arrest, germ-cell aplasia)
Abbreviation: IVF, in vitro fertilization.
ICSI with ejaculated spermatozoa can be used successfully in patients with fertilization failures after conventional IVF and also in patients with too few morphologically normal and progressive motile spermatozoa present in the ejaculate (<500,000). High fertilization and pregnancy rates can be obtained when a motile spermatozoon is injected. Injection of only immotile or probably non-vital spermatozoa results in lower fertilization rates (25). In cases where only non-vital sperm cells are present in the ejaculate, the use of testicular sperm is indicated (26). Other semen parameters, such as concentration, morphology (except for globozoospermia) (27), and high titers of antisperm antibodies (28) do not influence the success rates of ICSI (25). Successful ICSI has also been described for patients with acro-someless spermatozoa (29,30).
Any form of infertility due to obstruction of the excretory ducts can be treated by ICSI with spermatozoa microsurgically recovered from either the epididymis (31-33) or the testis (34-36). Obstructive azoospermia can result from congenital bilateral absence of the vas deferens, failed vasectomy reversal, or vaso-epididymostomy. When no motile spermatozoa can be retrieved from the epididymis due to epididymal fibrosis, testicular spermatozoa can be isolated from a testicular biopsy specimen.
Testicular biopsy has also proven to be useful in some cases of non-obstructive azoospermia (37-40). In patients with severely impaired testicular function due to (incomplete) germ-cell aplasia (Sertoli-cell-only syndrome), hypo-spermatogenesis, or incomplete maturation arrest, spermatozoa may be recovered, sometimes only, after taking multiple biopsies. Testicular sperm recovery may not always be successful in all azoospermic patients. Cryopreservation of supernumerary spermatozoa recovered from the epididymis (41) or the testis (42) is an important issue because microinjection of cryo-thawed sperm cells can avoid repeated surgery in future ICSI cycles.
The ICSI procedure cannot be carried out in approximately 3% of the scheduled cycles. The most common causes for cancellation are either no cumulus-oocyte complexes or metaphase II oocytes are available, or no spermatozoa are found in testicular biopsies of patients with non-obstructive azoospermia.
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