Semen Sources

The source of semen for artificial insemination can be either from the woman’s male partner or from a donor, who usually remains anonymous. When donor insemination first became widely available, the terms homologous artificial insemination and heterologous artificial insemination were used to differentiate these two alternative sources. However, the use of these biomedical terms in this manner is at variance with their scientific meaning, where they denote different species or organisms (as in, e.g., homologous and heterologous tissue grafts).

In the latter half of the 20th century, the terms artificial insemination, donor (AID) and artificial insemination, husband (AIH) found common use. However, the widespread use of the acronym AIDS for acquired immunodeficiency syndrome resulted in the replacement of AID with therapeutic donor insemination (TDI). An analogous alternative term for AIH has not evolved, probably in part because of the increasingly common situation where the woman’s partner is not her legal husband. In this chapter, artificial insemination using these two standard sperm sources will be designated simply as partner and donor insemination.

Techniques

Several different techniques have been used for artificial insemination. The original technique used for over 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.⁵

Intrauterine Versus Intracervical Insemination

A major breakthrough came in the 1960s when methods were developed for extracting enriched samples of motile sperm from semen. These purified samples were free of proteins and prostaglandins, and thus could be placed within the uterus using a technique designated intrauterine insemination (IUI). This technique was found to result in pregnancy rates 2 to 3 times those of intracervical insemination. However, intracervical insemination is still utilized in some practices.⁵

In an effort to further improve pregnancy rates, techniques were developed to place washed sperm samples directly into the tubes via transcerival cannulation (intratubal insemination) or into the peritoneal cavity via a needle placed through the posterior cul-de-sac (intraperitoneal insemination). Another technique developed in Europe, termed fallopian tube sperm perfusion, involves pressure injection of a large volume (4mL) of washed sperm sample while the cervix is sealed to prevent reflux of the sample.⁶ This technique appears to have a higher pregnancy rate than IUI in couples with unexplained infertility. The remainder of these technically difficult approaches have never been shown to result in better pregnancy rates than IUI. One prospective, randomized study found that simultaneous intratubal insemination actually decreased the pregnancy rates associated with IUI.⁷ In modern clinical practice in the United States, IUI is the predominant technique used for artificial insemination.

Male Evaluation

Female Evaluation

The female partner should undergo a basic infertility evaluation so that any correctable factors can be identified and treated before artificial insemination (see Chapter 34). In addition to a detailed history and physical examination, each woman considering partner or donor insemination should be evaluated with an imaging technique, usually a hysterosalpingogram, to document patent tubes. Unless oral or injectable medications are used to induce superovulation, ovulatory function should be evaluated with a urinary luteinizing hormone (LH) detection kit and midluteal serum progesterone level. Further evaluation is required in the event of detection of any clinical or laboratory abnormalities.

In the past, a great deal of time was spent investigating the possibility of cervical factor infertility by evaluating the character and sperm survivability in periovulatory cervical mucus, using what is termed a postcoital test. This test had many false-positive results, because it depended more on timing in the cycle and hormonal status than on static cervical characteristics. Except for exclusion of cervicitis during pelvic examination, timed evaluation of cervical mucus and sperm interaction is infrequently included in a fertility examination. This is because partner IUI is used as a basic fertility enhancement method for the majority of couples who have otherwise been unable to conceive regardless of diagnosis.

Partner Insemination

Partner insemination was originally developed as a treatment for male factor infertility. With the advent of IUI, partner insemination has been found to be an excellent treatment for a range of diagnoses, including cervical factor infertility, unexplained infertility, and subfertility, on the basis of other diagnoses or therapeutic measures (Table 36-2). This ability of partner insemination to increase pregnancy rates regardless of diagnosis has made this technique one of the fundamental approaches to infertility treatment today.

Table 36-2 Indications and Contraindications for Partner Insemination

Male Factor Infertility

Partner insemination appears to be of clear benefit when the couple’s infertility is the result of any condition that makes it difficult to place semen high in the vagina during coitus. Male conditions resulting in this situation are termed ejaculatory failure. The most common causes of ejaculatory failure are impotence, severe hypospadias, and retrograde ejaculation. A unique condition that has been found to be treatable with artificial insemination is impotence secondary to spinal cord injury.¹¹

Partner insemination is also commonly used as a treatment for male factor infertility documented by repeated abnormal results on semen analysis. In couples where there is mild male factor infertility, defined as a progressive sperm motility of at least 20% to 30%, the prognosis appears to be good with partner insemination. Theoretically, increasing the number of motile sperm reaching the egg should improve fertility whenever decreased numbers and motility of normally functioning sperm is the primary problem.

Unfortunately, the pregnancy rates after partner IUI for the treatment of severe male factor infertility have been disappointing.¹² This is probably because markedly abnormal parameters on routine semen analysis often reflect a sperm defect that decreases the ability to fertilize eggs. This type of defect is unlikely to be overcome by increasing the number of sperm to which the egg is exposed at the site of fertilization. In patients with severely abnormal parameters on semen analysis and those with male factor infertility not amenable to partner insemination, more effective treatment will be either donor insemination or in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI).

Female Factor Infertility

Female reproductive conditions can also make it difficult to place semen high in the vagina during coitus. Such conditions that can benefit from partner insemination include severe vaginismus and other psychological problems, and less common anatomic conditions. Little data exists documenting the success of partner insemination for these conditions.

Women with cervical factor infertility will benefit from IUI, because this approach bypasses the cervical abnormalities that decrease fertility. This includes women with abnormal cervical mucus secondary to noninfectious chronic cervicitis and women with scant mucus or cervical stenosis, usually the result of cervical surgery. However, even women with a normal cervix and mucus appear to benefit from IUI, because the cervix appears to be the limiting factor in sperm reaching the site of fertilization in the tube.

An Adjunct to Other Infertility Treatments

Partner IUI appears to be of value for increasing per cycle fecundity when inducing ovulation in women with ovulatory dysfunction.¹³ After ovulation induction with clomiphene citrate, partner IUI might work by overcoming the decreased cervical mucus associated with the use of clomiphene.¹⁴ With gonadotropins, partner IUI might compensate for subtle changes in sperm transport within the uterus or tubes related to marked alterations in circulating estrogen and progesterone levels associated with their use.

Partner IUI also appears to be of some benefit when women with mild and minimal endometriosis are trying to achieve pregnancy. After appropriate surgical treatment, the monthly improvement in fecundity with partner IUI appears to be similar to that seen in patients with idiopathic infertility.¹⁵

Women with severe endometriosis or tubal disease have a far lower fecundity rate and often an increased rate of ectopic pregnancies. For this reason, these patients appear to benefit more from IVF than from partner IUI combined with superovulation.

Unexplained Infertility

Unexplained (i.e., idiopathic) infertility is diagnosed after all known etiologies of infertility have been excluded. In these cases, semen analyses are normal and there is no evidence of any female causes of infertility, such as ovulation defects, tubal factor, endometriosis, and cervical factor. The average incidence of unexplained infertility is approximately 15% among infertile couples.

In couples with unexplained infertility, partner IUI has been demonstrated to improve pregnancy rates when used in conjunction with superovulation.¹³ In a meta-analysis of almost 1000 superovulation cycles for unexplained infertility, partner IUI was found to almost double pregnancy rates (20%) compared to timed intercourse alone (11%).

Partner IUI appears to overcome one or more unknown fertility deficiencies that we cannot currently detect. Theoretically, this might be decreased sperm transport from the vagina to the tube secondary to either a sperm defect or an abnormality in sperm transport mechanisms in the female reproductive tract. In other cases, a subtle sperm fertilization defect might exist that is surmounted by increasing the absolute number of sperm reaching the egg.

Donor Selection

Couples choose a donor from profiles of nonidentifiable information. This information usually includes racial or ethnic background, blood type, physical characteristics, and certain social characteristics. Many women who become pregnant as a result of donor insemination desire to use the same donor for further pregnancies.

Donor Evaluation

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.¹⁶ All donors 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 is performed.

Each donor must be screened for risk factors and clinical evidence of communicable diseases, including:

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 determined if eligible.

Success Rate

The actual per cycle fecundity rate with donor IUI is dependent on multiple factors. A meta-analysis of seven studies demonstrated that IUI yielded a higher pregnancy rate per cycle than intracervical insemination with donor frozen sperm.¹⁷ Overall, the average live birth rate per cycle of donor IUI is approximately 10%.¹⁸

Timing