Assisted Reproduction

Assisted reproductive techniques have become increasingly popular for the management of idiopathic male infertility, unexplained infertility, or in cases in which no therapy is available or has effectively resulted in conception. These techniques involve the manipulation of sperm, ova, or both in an attempt to improve the chances of conception. Controlled ovarian hyperstimulation is used to induce simultaneous development of multiple ova in females by giving oral clomiphene citrate or parenteral gonadotrophins.

Artificial Insemination

Artificial insemination is an assisted conception method that can be used to alleviate infertility in selected couples. The rationale behind the use of artificial insemination is to increase the gamete density near the site of fertilization. Several different techniques have been used for artificial insemination. The original technique used for more than a century was intravaginal insemination, where an unprocessed semen sample is placed high in the vagina. In the latter half of the 20th century, the cervical cap was developed to maintain the highest concentration of semen at the external os of the cervix. It was soon discovered that placing the semen sample into the endocervix (intracervical insemination) resulted in pregnancy rates similar to that obtainable using a cervical cap and superior to those seen with high vaginal insemination.

The effectiveness of artificial insemination has been clearly established in specific subsets of infertile patients such as those with idiopathic infertility, infertility related to a cervical factor, or a mild male factor infertility (Keck et al, 1997; Cohlen, 2004). An accepted advantage of artificial insemination is that it is generally less expensive and less invasive than other assisted reproductive technology (ART) procedures (Goverde et al, 2000). The source of semen for artificial insemination can be either from the woman’s male partner or a donor, who usually remains anonymous. In the past, the only available options for couples with severe male factor infertility including severe oligospermia or failure to conceive using partner insemination were either donor insemination or adoption. Since the widespread availability of IVF using ICSI, many couples with severe male factor infertility have chosen to procreate their own genetic children using these techniques. However, donor insemination remains an option when IVF/ICSI has been unsuccessful. Alternatively, many candidates for IVF/ICSI initially choose donor insemination because it is less invasive and ultimately more likely to achieve pregnancy for couples with limited resources. Some women choose donor insemination because they are not candidates for IVF/ICSI. Perhaps the most obvious situation is women without male partners who seek pregnancy. The use of donor insemination is also indicated when the male partner has no viable sperm or when IVF/ICSI fails to achieve fertilization. Finally, men with a known genetic disorder often choose donor insemination to avoid transmission to their children.

Thorough evaluation of all potential sperm donors other than sexually intimate partners is necessary to avoid inadvertent transmission of sexually transmitted diseases or known genetic syndromes (ASRM, 1990). All donors should undergo a review of relevant medical records, personal and family history, and a physical examination. Determination of normal semen characteristics is extremely important. In addition, blood grouping and karyotyping are performed. Each donor must be screened for risk factors and clinical evidence of communicable diseases including human immunodeficiency virus types 1 and 2; human T-lymphotropic virus types I and II; hepatitis B and C; cytomegalovirus; human transmissible spongiform encephalopathy (including Creutzfeldt-Jakob disease); Treponema pallidum; Chlamydia trachomatis; and Neisseria gonorrheae. If the donor is deemed acceptable and is aware of the ethical and legal implications, semen can be collected. All donor semen samples are cryopreserved and quarantined for 6 months. Before a donor sample is used for insemination, the donor is retested and his eligibility is determined.

Presently, there is no general consensus as to the best sperm preparation technique for IUI. In general, swim-up, simple sperm washing, density gradient centrifugation, and glass wool filtration methods all effectively produce adequate sperm samples. However, some preparation techniques appear better suited for particular types of samples; thus the technique chosen should be tailored to individual samples. The preparation techniques most commonly used today are the double-density gradient centrifugation and the glass wool filtration sperm washing techniques. These techniques have been shown to improve the number of morphologically normal spermatozoa with grade A motility and normal chromatin condensation in the prepared sample (Erel et al, 2000; Sakkas and Tomlinson, 2000; Hammadeh et al, 2001). In addition, these techniques best reduce the amount of reactive oxygen species and leukocytes in the prepared sample and provide spermatozoa with minimal chromatin and nuclear DNA anomalies and high nuclear maturity rates. For semen samples with normal or near-normal sperm parameters, it has been shown that swim-up and density gradient techniques result in higher pregnancy rates compared with the washing, swim-down, and refrigeration/heparin techniques (Carrell et al, 1998). For poor samples, the density gradient centrifugation and glass wool filtration techniques appear to be superior. In cases of very low sperm counts, simple sperm washing will recover the highest number of sperm, both motile and nonmotile.

In-Vitro Fertilization/ICSI

IVF involves using controlled ovarian hyperstimulation to recruit multiple oocytes during each cycle from the female partner. Follicular development is monitored ultrasonically, and ova are harvested before ovulation with the use of ultrasound-guided needle aspiration. The recovered oocytes are mixed with processed semen to perform in-vitro fertilization. The developing embryos are incubated for 2 to 3 days in culture and then placed transcervically into the uterus. Generally, only 20% to 30% of transferred embryos result in clinical pregnancies.

Notwithstanding the broad success of in-vitro fertilization (IVF), failure to achieve fertilization still plagues a substantial group of patients, with sperm abnormalities being the main culprit. In the 1980s, several micromanipulation procedures were adopted from animal husbandry to assist gamete interaction, and this resulted in the development of intracytoplasmic sperm injection (ICSI), a procedure through which an oocyte can be fertilized independently of the morphology and/or motility of the single spermatozoon injected. The procedure was first used in cases of fertilization failure after standard IVF or when an inadequate number of sperm cells were available. The consistency of fertilization independent of the functional quality of the spermatozoon has extended the application of ICSI to immature spermatozoa retrieved surgically from the epididymis and testis. Moreover, the need to denude the oocyte has allowed assessment of the nuclear maturity of the oocyte. ICSI is also preferred in conjunction with preimplantation genetic diagnosis and has recently been used to treat HIV-discordant couples, where there is a pressing need to minimize the exposure of the oocyte to a large number of spermatozoa. For all ages and with all the different sperm types used, fertilization after ICSI is at approximately 70% to 80% and it ensures a clinical pregnancy rate of up to 45%. These results have made ICSI a procedure comparable in popularity with IVF and have minimized the need for couples suffering from all forms of male infertility to resort to adoption or the use of donor sperm (Palermo et al, 2009).