INFERTILITY

Many couples have difficulty in conceiving. The emotional suffering and despair which childlessness may bring to an otherwise fulfilling relationship is substantial. Couples who are unable to conceive turn to their physician for advice and guidance and may need referral to a subspecialist for very sophisticated treatment.

The choice of one particular procedure will depend on the type (or cause) of infertility which investigations reveal. This booklet tells you more about intrauterine insemination (IUI) which is just one of several treatment techniques which may be recommended.

THE SCALE OF THE PROBLEM
A normal fertile couple in their mid-20s, having regular intercourse, has between a one-in-five or one-in-six chance of conceiving each month when not using contraception. This means that around 85-90% of the couples trying for a baby will conceive within a year of attempting pregnancy. However, 10-15% of the "fertile" population are those couples who will ultimately be diagnosed as infertile or, more accurately, "subfertile". The accepted definition of infertility is the inability to conceive after at least one year of trying.

Intrauterine insemination may be considered for couples thought suitable. Usually, IUI will only be performed in couples whose infertility investigation has failed to detect a specific cause of infertility and who have been trying for a baby for at least two years. This technique should not be undertaken until a thorough investigation has been performed to try and determine the reason for the inability to conceive.

ASSESSING THE CAUSES
Investigations into the cause of the inability to conceive can provide the likely cause of infertility in most cases. Around 15 percent of couples will not have a cause for their infertility identified and studies have shown that intrauterine insemination can be a useful treatment for these unexplained cases.

The tests required to determine a specific cause of infertility will assess ovulation, the quality of the fallopian tubes (by laparoscope and/or hysterosalpingogram), and hormone levels in women and sperm production (numbers, movement, and shape) in men. Following intercourse, only a small number of the sperm ascend the female genital tract. The goal of IUI is to increase the number of sperm at the site of fertilization in the fallopian tubes.

INTRAUTERINE INSEMINATION

The objective of IUI is to introduce a quantity of sperm into the female partner's uterus, and thereby encourage fertilization.

For IUI, sperm are first washed and placed into a sterile medium. The sperm are then concentrated in a small volume of medium and are injected directly into the uterus.

WHICH COUPLES BENEFIT?
Because sperm (separated from the liquid portion of the semen) are inseminated into the uterus, it is important that the female partner has no other obvious fertility problems. Investigations should ideally show that the female is ovulating normally, has open fallopian tubes, and has a normal uterine cavity. Indeed, infertility tests are often normal in both partners, since IUI has been found useful in couples with no obvious cause of infertility.

IUI is also effective in women with ovulatory disorders, provided they respond adequately to fertility drugs. In such cases ovulation is stimulated by a course of hormone treatment, such that intrauterine insemination is timed to take place shortly after the day of ovulation. Indeed, this technique of stimulating ovulation with hormones and introducing the sperm (commonly referred to as "washed sperm") just after ovulation has proven very effective in a variety of cases and is now the preferred method in couples with or without ovulatory disorder.

Because IUI relies on the natural ability of sperm to fertilize an egg within the reproductive tract, it is important that tests for male infertility indicate reasonable sperm function (numbers, movement, and shape).

Normal Sperm Morphology (left), and various abnormal forms of sperm

There has been some success with IUI in cases where the female partner has endometriosis in the absence of mechanical distortion of the pelvic structures. This is a very common disorder, particularly in women in their thirties who have had no children, and may be associated with as many as one-in-four cases of infertility. The condition occurs when tissue from the womb lining (endometrium) is spilled through the fallopian tubes, into the pelvis, and implants on the surface of the pelvic cavity and often the ovaries. Women with mild endometriosis are usually treated similarly to women with unexplained infertility.

Studies show that IUI will not be effective in cases where the male has low sperm counts or poor sperm shape. Similarly, women with severely damaged or blocked tubes will not be helped by IUI.

HOW THE TECHNIQUE WORKS
The most recent studies of intrauterine insemination suggest that the best results are achieved when insemination is coupled with ovulation induced by fertility drugs. For this reason, doctors refer to "controlled ovarian hyperstimulation" or "superovulation and IUI" to describe the technique.

Because fertility drugs can produce several eggs, monitoring is important during this drug treatment phase in order to ensure that any side effects of treatment and/or the risk of multiple pregnancy are reduced. Monitoring of treatment is carried out by measuring estrogen concentrations in blood samples, and by tracking the development of follicles by ultrasound. If too many follicles develop, too many eggs may be released and thus, increase the risk of multiple pregnancy. Therefore, the usual aim in IUI is to generate at most two to three eggs. (Superovulation and IUI differs from IVF in that the former aims to stimulate just one dominant follicle, while the latter aims to produce as many eggs as possible for laboratory fertilization).

When two or three follicles have reached their target size, ovulation is induced with a further hormone injection (hCG). Then, shortly after the time of ovulation, a sample of fresh semen is collected by the male, washed, inserted through the cervix and placed high into the uterus of the female partner through a fine catheter. This is a quite painless procedure, comparable to a Pap test.

Through the process IUI, sperm are placed high in the female reproductive tract to enhance the chance of successful fertilization.

WHOSE SEMEN?
Under normal circumstances, IUI uses sperm from the male partner. However, another insemination technique, artificial insemination by donor (AID) or therapeutic donor insemination (TDI), uses screened sperm samples from anonymous donors. This treatment is reserved for cases of male infertility where the male partner's own sperm is severely abnormal - perhaps very low (or zero) sperm counts or poor shape and movement. Around one-in-eight infertile couples are treated this way.

STEP BY STEP IUI TREATMENT

1. Drug Treatment, to encourage two or three eggs to mature.
   • Usually gonadotropins are used to stimulate the growth of follicles and cause ovulation.
2. Monitoring of treatment, to measure the growth of follicles, individualize drug doses, and prevent serious side effects.
   • By transvaginal ultrasound scanning (two or three times during a treatment cycle)
   • Sometimes by measuring estrogen in a blood sample
3. Sperm sample, provided on morning of ovulation, is prepared and inseminated later that day.
4. Pregnancy testing and early ultrasound monitoring.

New "micromanipulation" techniques of treating these difficult cases of male infertility are considered very exciting. One of these microtechniques, known as intracytoplasmic sperm injection (ICSI), allows doctors to inject a single sperm into the center of an egg to bring about fertilization. The success of this technique seems likely to make TDI less frequently used. IUI as a treatment differs from AID or TDI in that the male partner has better quality sperm and usually provides his own sample. The treatment, therefore, poses none of the emotional difficulties of AID or TDI, because no third party is involved.

THE RISKS OF TREATMENT
While complications of IUI are infrequent, they can include infection, brief uterine cramping, or transmission of venereal disease (with AID/TDI unless appropriately screened). Risks of the controlled ovarian hyperstimulation include multiple pregnancy and the Ovarian Hyperstimulation Syndrome (large ovaries and collection of fluid in the abdomen). In cases where more than three follicles develop to a size greater than 14 millimeters, there is a weighed risk of multiple pregnancy which could warrant abandoning treatment. Multiple pregnancies are associated with higher rates of pregnancy loss and lower birth-weight babies, as well as, with greater social difficulties. Cycles would also be canceled if there was any hint of a rare condition known as Ovarian Hyperstimulation Syndrome, which is why drug treatment is always monitored. Too high a dose of drug can cause excessive stimulation of the ovaries, which may be noticed as pain in the abdomen.

THE CHANCE OF SUCCESS
The success rates of superovulation and IUI are between 10 and 20 percent per cycle provided that the male partner's sperm count is within normal limits and the female's tubes are healthy.

Doctors might try four cycles of IUI and if these are not successful, then recommend other methods like IVF or GIFT. Unlike IVF or GIFT IUI involves no difficult egg collection or general anesthetic and is currently a popular and quite successful treatment method of infertility.

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