Artificial Insemination

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Section 6 Infertility and Recurrent Pregnancy Loss 

Chapter 

36 

Artificial Insemination 

Ashok Agarwal and Shyam S. R. Allamaneni 

INTRODUCTION 

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. 1 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 

(Table 36-1). 2,3 An accepted advantage of artificial insemination 

is that it is generally less expensive and invasive than other 

assisted reproductive technology (ART) procedures. 4 

This chapter provides a comprehensive description of 

indications for artificial insemination, issues to consider before 

donor insemination, complications associated with intrauterine 

insemination (IUI), factors affecting the success of artificial 

insemination, and the current evidence available on effectiveness 

of artificial insemination for different indications. 

HISTORY 

Artificial insemination has been used in clinical medicine for 

more than 200 years for the treatment of infertile couples. In 

1785 John Hunter, a Scottish surgeon from London, advised a 

man with hypospadias to collect his semen and have his wife 

inject it into her vagina. This was the first documented case of 

successful artificial insemination in a human. 

In the second half of the nineteenth century, numerous reports 

were published of human artificial insemination in France, England, 

Germany, and the United States. In 1909, the first account of 

successful donor artificial insemination was published in the 

United States. By 1949, improved methods of freezing and 

thawing sperm were being reported. 

Today, artificial insemination is frequently used in the treatment 

of couples with various causes of infertility, including ovulatory 

dysfunction, cervical factor infertility, and unexplained infertility 

as well as those with infertility caused by endometriosis, male, 

and immunologic factors. Artificial insemination with donor semen 

has become a well-accepted method of conception. 

GENERAL CONSIDERATIONS 

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 

Table 36-1 

Infertility Disorders with Proven Benefit from 

Partner Insemination 

Idiopathic infertility 

Cervical factor infertility 

Mild male factor infertility 

From Cohlen BJ: Should we continue performing intrauterine inseminations in the year 2004 

Gynecol Obstet Invest 59:3–13, 2004. 

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Infertility and Recurrent Pregnancy Loss 

540 

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 (4 mL) 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. 

EVALUATION 

Male Evaluation 

Semen Analysis 

The male partner is initially evaluated by obtaining a complete 

semen analysis and screen for sperm antibodies. A minimum of 

two samples provided over 1 to 2 months is analyzed. A third 

sample may be required if there is a discrepancy between 

the initial samples. All samples should be provided after 48 to 

72 hours of sexual abstinence. Samples should be analyzed within 

2 hours of collection. 

Antisperm Antibodies 

Male antisperm antibodies are found in approximately 10% of 

semen samples from infertile couples. Men with antisperm antibodies 

attached to their sperm are classified as having immunologic 

infertility. These antibodies are believed to decrease fertility by 

inducing agglutination or immobilization of the sperm. Studies 

have identified multiple antisperm antibodies that correspond to 

a variety of sperm components. 

There are multiple known risk factors for the development of 

male antisperm antibodies. 8 Vasectomy results in the development 

of antisperm antibodies in the majority of men. After successful 

vasovasostomy, more than half of these men will have detectable 

sperm-bound antibodies. The pregnancy rates will depend on 

many factors, including the titer and quantity of gross agglutination. 

Obstructive azospermia from any cause (e.g., congenital absence 

of the vas deferens, cystic fibrosis, infant hernia repair) increases 

the risk of antisperm antibodies. Reproductive infections (e.g., 

epididymitis, prostatitis, or orchitis) are also associated with 

antisperm antibodies. 

Antisperm antibody tests are performed as a routine part of 

a complete semen analysis during the initial infertility evaluation. 

The most commonly used test in clinical practice is probably the 

immunobead assay. 8 This quantitative assay evaluates live sperm 

and indicates percent bound, antibody isotype, and binding 

location. For routine screening, some andrology laboratories 

use a commercially available mixed antiglobulin reaction assay 

(SpermMar). 

Male subfertility is significantly increased when the antisperm 

antibody level is greater than 50%. 9,10 Antisperm antibodies 

interfere with sperm–zona pellucida binding and prevent embryo 

cleavage and early development. 

Complete Evaluation 

In the presence of persistently abnormal results on semen 

analysis, a complete history, physical examination, and laboratory 

evaluation is performed to find and treat any potentially reversible 

abnormalities (see Chapter 35). 

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. 

INDICATIONS 

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. 

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

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Table 36-2 

Indications and Contraindications for Partner Insemination 

Indications 

Male Factor Infertility 

Disorders of semen density, motility, 

and morphology (mild oligospermia, 

asthenozoospermia, 

teratozoospermia) 

Immunologic factors 

Ejaculatory failure 

Mechanical factors (malformed 

urethra, hypospadias) 

Female Factor Infertility 

Cervical factor 

Vaginismus 

Mild endometriosis 

Ovulatory dysfunction 

Unexplained Fertility 

Contraindications 

Absolute Contraindications 

Rh blood factor incompatibility 

Medical conditions that could endanger 

the patient’s life 

A partner with hereditable disease 

Cervical neoplasia 

Blocked tubes 

Active genital tract infection in either 

partner 

Relative Contraindications 

Severely abnormal semen parameters 

Multiple failures at previous partner 

insemination attempts 

Recent chemotherapy or radiotherapy 

Coexisting multiple infertility etiologies 

Pelvic surgery 

Older age woman 

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. 

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. 

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 Insemination 

In the past, the only available options for couples with severe male 

factor infertility (e.g., severe oligospermia, or failure to conceive 

using partner insemination) desiring children 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 

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542 

has no viable sperm (i.e., azoospermia) 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. 

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: 

● 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 

● 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 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 

IUI TIMING, COST, AND FREQUENCY 

Timing 

Timing of insemination in relationship to ovulation is one of the 

crucial factors in the success of IUI. Although viable sperm 

remain in the female reproductive tract for up to 120 hours 

after coitus, the best pregnancy rates are obtained when IUI is 

performed as close as possible to ovulation. 19,20 

In the past, IUI was performed on the estimated day of 

ovulation based on basal body temperature rises during previous 

cycles. However, to optimize fecundity, modern prospective 

timing strategies are based on either detection of a urinary LH 

surge or administration of an ultrasound-timed dose of human 

chorionic gonadotropin (hCG ) to trigger ovulation. 

LH Surge 

A commonly used method for timing of IUI is based on urinary 

LH measurement. Ovulation occurs 40 to 45 hours after the 

onset of the LH surge. 21 Insemination is thus planned for the 

day after detection of a rise in urinary LH. This approach offers 

the simplest and most cost-effective of the indirect methods 

for predicting ovulation and is just as effective in achieving 

pregnancy as more complex ones. 22,23 

Ultrasound and Human Chorionic Gonadotropin 

Transvaginal ultrasonography is widely used to monitor the size 

of the follicles and to assess the timing of ovulation. Follicles 

become recognizable once they grow to 2 to 3 mm in diameter. 

After 8 mm, linear follicular growth occurs at a rate of approximately 

2 to 3 mm per day. Ovulation occurs during a natural 

cycle when the lead follicle reaches 15 to 24 mm in size. 

Injection of hCG can be given to induce predictable ovulation 

when at least one follicle diameter is between 17 and 21 mm. 

For optimal pregnancy rates, IUI is scheduled 24 to 36 hours 

after the injection. 

IUI Cost 

The cost-effectiveness of the treatment is an important consideration 

when deciding on the most appropriate infertility 

treatment option. 24 The cost of insemination varies from clinic 

to clinic, but is presently less than $500 per IUI, including sperm 

preparation and injection of the prepared sample. This compares 

favorably with the cost of other appropriate ART approaches. 

Even when the cost of ovulation induction medication and 

monitoring are included, the cost per live birth for IUI after 

superovulation has been calculated to be less than half the cost 

of IVF treatment. 25 

IUI Frequency 

It is recommended that IUI be performed either one or two 

times during each cycle. Performing two inseminations per cycle 

is likely to be especially advantageous when timing in relationship 

to ovulation is less precise. Although it seems intuitive that 

fecundity should be increased by two inseminations per cycle, it 

remains inconclusive whether the increased fecundity is worth 

doubling the patients’ cost and inconvenience compared to one 

insemination per cycle. 26–30 A recent meta-analysis of more than 

1000 IUI cycles revealed a slightly higher but statistically 

insignificant difference between the per cycle fecundity rate for 

two inseminations (14.9%) compared to one insemination per 

cycle (11.4%). 31 Accordingly, one well-timed insemination appears 

to offer the best balance between efficacy and cost. 

SPERM PREPARATION FOR IUI 

Sperm preparation methods are used to process semen samples 

such that viable sperm are separated from seminal plasma. This 

is necessary before IUI to avoid the consequences of intrauterine 

injecting of semen plasma proteins and prostaglandins. 32 

Although seminal plasma protects the spermatozoa from stressful

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Chapter 36 


Table 36-3 

Common Techniques Used for Sperm Preparation Prior to 

Intrauterine Insemination 

Washing 

Swim-up techniques 

Swim-up from pellet 

Swim-up from ejaculate 

Swim-up from ejaculate into hyaluronic acid 

Density gradient centrifugation 

Glass wool filtration 

Mechanical aids 

conditions such as oxidative stress, 33 it also contains factors that 

inhibit the fertilizing ability of the spermatozoa and reduce the 

induction of capacitation. 34,35 Sperm preparation involves removing 

the seminal plasma efficiently and quickly and eliminating dead 

sperm, leukocytes, immature germ cells, epithelial cells, and 

microbial contamination. Several methods for sperm preparation 

are currently used (Table 36-3). 

The ideal sperm preparation method recovers highly functional 

spermatozoa and enhances sperm quality and function without 

inducing damage. It is also cost-effective and allows for the 

processing of a large volume of the ejaculate, which in turn 

maximizes the number of spermatozoa that are available. 36 The 

ideal sperm preparation method minimizes the risk of reactive 

oxygen species generation, which can adversely affect DNA 

integrity and sperm function in vitro. 33,37 Several preparation 

methods incorporate methylxanthines and pentoxifyllines to 

increase sperm motility and improve the fertilization outcome. 

The first step in sperm preparation is the performance of a 

semen analysis according to the World Health Organization 

(WHO) standards to determine the prewash quality of the 

sample. Throughout the semen analysis and preparation, it is 

important to use sterile technique and media both to minimize 

the risk of iatrogenic intrauterine infection and because sperm 

can be damaged by bacterial contamination. 

Swim-up Techniques 

Swim-up techniques are based on active self-migration of motile 

spermatozoa into the washing medium. Allowing sperm to swim 

up from ejaculate avoids the need for centrifugation, which can 

lead to oxidative damage of the sperm. However, this technique 

can be used only for ejaculate with a high degree of progressive 

motile spermatozoa, because the percentage of motile sperm 

recovered depends on sperm motility. 

For the swim-up technique, a layer of wash media is gently 

layered over the semen sample. The sample is incubated so that 

the motile sperm can swim out of the semen sample into the 

media. The media is then carefully removed from the semen 

fluid and used for IUI. If the initial semen sample has normal 

sperm parameters, recovery of reasonable number of sperm with at 

least 90% motility is common. The entire procedure takes 2 hours. 

Basic Sperm Washing 

Sperm washing, the oldest and perhaps the simplest technique, 

removes the seminal fluid with little enrichment of motile sperm. 

The semen sample is diluted in a sperm wash media containing 

antibiotics and protein supplements in a conical centrifuge tube. 

The specimen is centrifuged such that all cells congregate in a 

pellet, and the supernatant wash solution is carefully removed. 

The pellet is resuspended in wash media, and the centrifugation 

is repeated. The final pellet, from which all seminal fluid has 

been eliminated, is resuspended in a small volume of wash media 

for IUI. The entire procedure takes less than an hour. 

Density Gradient Centrifugation 

The density gradient method is a sperm washing method that 

both removes semen fluid and separates living sperm from other 

material, including dead sperm cells, white blood cells, and 

bacteria. For this method, a density gradient is prepared by 

layering suspensions of different concentrations of coated colloidal 

silica particles (e.g., Percoll) in a conical centrifuge tube, with 

the higher concentrations more superior. The liquefied semen 

sample is placed over the upper layer and the tube is centrifuged. 

The supernatant is removed from the pellet, and the process is 

repeated. The final pellet is resuspended in wash media and used 

for IUI. Density gradient sperm washes take approximately 1 hour. 

Glass Wool Filtration 

The glass wool filtration method is another method for removing 

seminal fluid and separating living sperm from other cellular 

material after sperm has been washed. For this technique, the 

semen samples are first diluted with wash media and centrifuged 

in a manner similar to sperm washing. The resulting pellet is 

resuspended in wash media and placed on glass wool columns, 

created by inserting glass wool into the barrel of a 3-mL syringe. 

The washed sperm solution is allowed to filter through the 

column by gravity, and the filtrate is collected for IUI. 

Which Preparation Method is the Best 

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 morphologic normal 

spermatozoa with grade A motility and with normal chromatin 

condensation in the prepared sample. 38–40 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, 

one study has shown that swim-up and density gradient 

techniques result in higher pregnancy rates compared to the 

washing, swim-down, and refrigeration/heparin techniques. 41 

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. 

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A 

curved tip is directed in a new course and re-advanced. This 

procedure is continued until the catheter can be advanced 

without resistance approximately 5 to 6 cm into the uterine 

cavity. Rarely, a cervical tenaculum is required to apply downward 

traction on the cervix to “straighten” an exceptionally 

tortuous canal. 

A second method for navigation of the endocervical canal for 

IUI is by using a semirigid yet flexible catheter that has no 

memory. 42 Pressure is used to force the catheter to follow the 

course of the canal. This technique often requires the use of a 

cervical tenaculum to apply countertraction. Because the diameter 

of some of these types of catheters is usually larger in caliber 

(greater than 3 mm), dilatation is sometimes required in the 

presence of cervical stenosis. 

544 

B 

Figure 36-1 Intrauterine insemination catheters: A, Tefcat catheter 

attached to a syringe (Cook Group, Bloomington, Ind.); B, CryoBioSystem 

catheter (CryoBioSystem, Paris). 

IUI TECHNIQUE 

IUI is performed using one of several commercially available 

intrauterine insemination catheters connected to a 2-mL syringe 

(Fig. 36-1). With the fully awake patient in a dorsal lithotomy 

position, the cervix is visualized with a bivalve vaginal speculum. 

After excess vaginal secretions are wiped from the external 

cervical os, the tip of a thin flexible catheter is passed into the 

uterine cavity, and the sperm sample, suspended in less than 1 mL 

of wash media, is gently expelled high in the uterine cavity. 

Increased resistance during injection suggests that the catheter 

is kinked or the tip might be inadvertently lodged in the endometrium 

or tubal ostia. In this situation, the catheter should be 

withdrawn 1 cm, and injection reattempted. After IUI, the 

catheter is slowly removed and the patient allowed to remain 

supine for 10 minutes after insemination in case she experiences 

a vasovagal reaction. 

Occasionally, there is difficulty navigating the often tortuous 

course of the endocervical canal with the tip of the insemination 

catheter. There are two common approaches to this blind 

procedure. Most commonly, a thin catheter (external diameter 

less than 2 mm) with a “memory” is used so that the tip can be 

bent 20 to 90 degrees , thus allowing angular navigation in 

any direction by carefully twisting the catheter as it is gently 

advanced. Resistance in any direction requires that the catheter 

tip be withdrawn a matter of millimeters, twisted such that the 

FACTORS THAT PREDICT PREGNANCY RATES 

The highest pregnancy rates with IUI are seen within three to 

four cycles. 43 The average live birth rate per cycle is approximately 

10%. 18 Cumulative pregnancy rates depend on the characteristics 

of the couples being treated. In most reports, the 

cumulative pregnancy rate reaches plateau after three to six cycles. 

It is difficult to predict with certainty whether pregnancy will 

occur. Several models have been proposed but have not been 

validated. 44,45 

Male Factors That Predict IUI Success 

Men who have normal seminal characteristics have a higher 

chance of initiating a successful pregnancy as a result of IUI than 

those with abnormal results on semen analysis. This association 

is probably related to two associated factors. First, an abnormal 

semen analysis is often associated with an impaired fertilization 

capacity. Secondly, pregnancy rates positively correlate with the 

total number of motile sperm recovered for IUI, and this number 

is often lower in men with abnormal results on semen analysis. 

Semen Analysis Characteristics 

Semen characteristics clearly affect IUI outcome. 46 IUI is a 

successful treatment for mild male factor infertility, defined as a 

total motile sperm count of more than 5 million and Kruger 

morphology of more than 5%. 47 In a study in patients with mild 

male factor infertility, a live birth rate of 19% per cycle was 

reported. 47 

When prepreparation semen analyses characteristics are 

evaluated, the chances of pregnancy after IUI correlate best with 

morphology. A meta-analysis of six studies using strict morphology 

criteria (Kruger) showed that when the prewashed semen 

specimen had more than 4% normal sperm morphology, the 

chances of pregnancy after IUI were significantly increased. 48 

If the WHO standards were used to evaluate sperm morphology, 

the presence of more than 30% abnormal sperm in the ejaculate 

adversely influenced the pregnancy rate. 49 

Total Motile Sperm Count 

The sperm variable most clearly associated with pregnancy rates 

after IUI is the total motile sperm count after sperm wash or 

swim-up. In a retrospective study of 9963 IUI cycles, the likelihood 

of subsequent pregnancy was maximized when the IUI 

sample contained more than 4 million motile sperm numbers

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Chapter 36 


and sperm motility was greater than 60%. 50 Total motile sperm 

count was reported to affect IUI outcome in 1115 cycles in 332 

infertile couples. 51 No pregnancy occurred in cases where the 

total motile sperm count before semen preparation was less 

than 1 × 10 6 . 

Sperm DNA Damage Tests 

Efforts have been made to find objective assessments of sperm 

quality that will predict pregnancy outcomes in men with abnormal 

results on semen analysis. Three experimental assessments are 

the sperm chromatin structure assay, DNA fragmentation index, 

and terminal deoxynuceotidyl transferase-mediated deoxyuridine 

triphosphate-nick end labeling (TUNEL). 

The sperm chromatin structure assay provides an objective 

assessment of sperm chromatin integrity and can be useful as a 

fertility marker. 52 In a recent study, DNA damage as measured 

using this test was found to predict the outcome of IUI. 

The DNA fragmentation index (DFI) has been shown to be 

negatively correlated with the overall pregnancy rate in women 

undergoing IUI, IVF, or ICSI. 53 The chances of achieving pregnancy 

are significantly lower when the sperm DFI is greater than 

27% after IUI processing. 54 

TUNEL evaluates the degree of sperm DNA fragmentation 

and stability. 55 In one study, lower degrees of DNA 

fragmentation after IUI sperm preparation correlated with 

higher pregnancy rates, and no pregnancy occurred when 

more than 12% of sperm in an IUI specimen were TUNELpositive. 

Hypo-osmotic Swelling Test 

The hypo-osmotic swelling test evaluates the membrane integrity 

of the sperm tail, detects the differences on the sperm surface, 

and detects subtle damage in membrane properties, which 

reduces the ability of spermatozoa to induce a viable embryo. 56 

A sample “passes” the hypo-osmotic swelling test when at least 

50% of sperm in an IUI sample swell. 57 Sperm specimens that 

fail the hypo-osmotic swelling test appear to have decreased 

fertilizing ability, and thus pregnancy rates after IUI are lower. 

The miscarriage rate was also higher when result of hypo-osmotic 

swelling test was less than 50%. 


Both IUI and IVF appear to be effective in treating subfertility 

in men with antisperm antibodies, although IVF/ICSI appears 

to have higher pregnancy rates per cycle than IUI. 58 However, 

to date no large prospective, randomized, controlled trial has 

compared IUI to IVF/ICSI in men with antisperm antibodies. 

In severe cases of antisperm antibodies, especially when the 

sperm head is involved, IVF/ICSI will often be required to 

achieve pregnancy. 59,60 

Female Factors That Predict IUI Success 

Many studies have examined the different variables affecting 

pregnancy rates after IUI. 25,61–64 The influence of lifestyle habits 

(e.g., smoking, caffeine consumption, and weight) is unclear but 

is most probably significant. There appear to be several important 

female factors that are useful in predicting pregnancy rates after 

IUI. These factors are maternal age, duration of infertility, and 

fenale infertility factors. 65 

Maternal Age 

A woman’s age is an indirect indicator for oocyte quality, and it 

has a significant effect on the pregnancy rates. An age-related 

decline in female fecundity has been documented in women 

undergoing IUI. 43,64 Successful pregnancy rates decrease after 

age 35 and reduce dramatically after age 40. However, pregnancies 

can occur at relatively advanced maternal ages, and satisfactory 

pregnancy rates can be obtained with IUI among women 

age 40 to 42. 66,67 

Duration of Infertility 

The longer the duration of infertility, the lower the pregnancy 

rates are after IUI. 25,43,65 Although the precise limits of infertility 

duration for recommending IUI have not been clearly established, 

the pregnancy rate may be seriously compromised when infertility 

has lasted 3 or more years. 

Female Fertility Factors 

The success of artificial insemination depends not only on the 

quality of oocytes and spermatozoa, but also on the receptivity 

of the endometrium. In a retrospective study, the presence of 

uterine anomalies negatively affected the success of IUI. 65 

Endometrial thickness and pattern is also predictive of IUI 

success. In a study on women undergoing controlled ovarian 

hyperstimulation and IUI, a trilaminar endometrium on the day 

of IUI provided a favorable prediction of pregnancy. However, 

endometrial thickness and Doppler surveys of the spiral and 

uterine arteries and dominant follicle gave no useful predictive 

value. 68 A study evaluated the role of endometrial volume 

measurement in predicting the pregnancy rate in women receiving 

controlled ovarian hyperstimulation and IUI. 69 An endometrial 

volume of less than 2 mL on three-dimensional ultrasound on 

the day of insemination was associated with a poor likelihood of 

pregnancy. 

Pregnancy rates after IUI are dependent on ovum pickup and 

transport. It follows that pregnancy rates after IUI are decreased 

by other causes of female infertility, including tubal factor and 

endometriosis. 

RISKS AND COMPLICATIONS 

Complications associated with IUI are extremely uncommon. 

Most of the complications that occur are related to the 

medications used to recruit multiple follicles before IUI. 

Pelvic Infections 

Limited cramping during or after an IUI procedure from the 

catheter or cervical tenaculum is common. These symptoms are 

self-limiting and should resolve within hours of the procedure. 

Continued discomfort can be an indication of a developing pelvic 

infection, which has been estimated to occur in less than 2 per 

1000 IUI procedures. 63 Early diagnosis and treatment are 

essential in these rare cases to minimize the risk to the patient, 

particularly that of subsequent decreased fertility. 

Vasovagal Reaction 

Vasovagal reactions can occur as a result of manipulation of the 

cervix. The resulting vasodilation and decreased heart rate can 

lead to hypotension, most commonly manifest by diaphoresis in 

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546 

a supine patient. Sitting or standing increases the risk of syncope, 

which is unlikely to occur supine. Persistent symptomatic vasovagal 

reactions in a supine patient will often respond to the 

patient crossing her legs. 70 More severe cases might require 

treatment with intramuscular atropine injection (0.5 mg). 

Allergic Reaction 

Allergic reactions, including anaphylaxis, can occur after IUI in 

response to potential allergens in the wash media. Reactions 

have been reported to both the bovine serum albumin and 

antibiotics (penicillin and streptomycin) commonly used in the 

wash media. 71,72 Of these, penicillin allergies are the most 

common in the general population. Allergic reactions after IUI 

can range from a mild skin rash to life-threatening anaphylaxis 

with laryngeal edema, bronchospasm, and hypotension. For the 

rare patient experiencing an allergic reaction after IUI, the use 

of wash media free of albumin and antibiotics is advised. 


When IUI was first introduced, there was a concern that the 

procedure could result in the development of serum antisperm 

antibodies. Fortunately, after 40 years of experience, it appears 

that exposure of the upper reproductive tract to washed 

spermatozoa during IUI does not stimulate the appearance of 

clinically significant female antisperm antibodies. 73 

Pregnancy-Related Complications 

Multiple Pregnancies 

The risk of multiple pregnancies is not increased by IUI. 

However, medications used to recruit multiple follicles before 

IUI do increase this risk. Clomiphene citrate is associated with 

a twin risk of 5% to 10% and rare higher-order multiples. 

Injectable gonadotropins are associated with multiple pregnancy 

rates of 14% to 39%. 74–76 Careful monitoring of the number of 

periovulatory follicles and peak estradiol levels might decrease 

the rate of multiple pregnancies. 61,74,77 In general, women are at 

high risk if they are younger than age 30, have more than six 

preovulatory follicles, and a peak serum estradiol level greater 

than 1000 pg/mL. 

Spontaneous Abortion and Ectopic Pregnancy 

The risk of spontaneous abortion appears to be increased after 

IUI compared to the fertile population and is in the range of 

20% to 25%. 1,78 The increased risk is probably not directly 

attributed to IUI but is most likely due to the underlying infertility 

problem. Likewise, ectopic pregnancy rates depend largely on 

the presence of predisposing factors such as tubal disease and do 

not appear to be attributed to the IUI procedure. 79 

PSYCHOLOGICAL, ETHICAL, AND LEGAL 

ISSUES OF DONOR INSEMINATION 

Parents 

Donor insemination has more psychological implications than 

partner insemination. Before donor insemination, several issues 

should be discussed in detail, including the couple’s desire or 

need to start a family, the alternatives that the male partner has 

to procreate his own genetic children, and financial factors. 

It is recommended that the couple undergo counseling before 

the procedure so that they can both face their feelings concerning 

infertility, donor insemination, and other concerns. The 

male partner may experience a loss of self-esteem and fear 

losing his partner because of infertility. Both partners may feel 

guilty or angry toward each other for having an infertility problem. 

Infertility tends to separate the couple, especially when one side 

is uncooperative. Support groups or professional counseling can 

be helpful. 

Offspring 

There are expert opinions both for and against disclosing to the 

child that he or she is the product of donor insemination. Before 

undergoing donor IUI, the couple should decide if they plan to 

disclose the nature of the procedure and the biologic implications 

to their friends, relatives and, ultimately, their child. If 

knowledge of the procedure is shared with friends and relatives, 

there is always the risk that the truth will be disclosed to the 

child by someone other than the parents. These sometimesunderappreciated 

issues can cause unnecessary grief if not 

adequately addressed prior to therapy. 

Legal Issues 

It is imperative that both partners understand the legal issues 

concerning donor insemination. Before donor insemination, both 

partners should sign an informed consent that clearly states the 

rights and obligations of the parties involved and those of the 

child. Although laws vary from state to state, when sperm is 

obtained from a sperm bank, the donor universally has no legal 

access to the couple’s identity. In cases where couples elect to 

use a donor known to them, an attorney should be obtained to 

draft the appropriate papers to terminate any parental rights of 

the donor and give the couple full custody of any subsequent 

child. In some states, the child conceived from donor sperm 

may have the right to obtain identifying information about the 

donor once they reach adulthood. 

● 

● 

● 

● 

● 

● 

● 

PEARLS 

Artificial insemination is a useful and cost-effective treatment 

option in selected groups of infertile couples. 

Infertility due to cervical factor and mild male factor (without 

any associated female factor) can be treated with intrauterine 

insemination without ovarian stimulation. 

Artificial insemination appears to be more cost-effective and 

simple compared to the IVF/ICSI if the couples are selected 

appropriately. 

In spite of extensive research, we are still not able to predict 

the success of artificial insemination in a specific couple. 

Duration of the infertility negatively impacts the artificial 

insemination success. 

Couples with unexplained infertility have better success with 

artificial insemination than natural intercourse. 

Couples with unexplained infertility should use controlled 

ovarian hyperstimulation along with the artificial insemination.

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Chapter 36 


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