Artificial Insemination (IUI)
Intrauterine Insemination (IUI) With Ovulation Induction
Intrauterine insemination (IUI), often known as artificial insemination, is recommended for the treatment of infertility unrelated to female organic pelvic disease, for “unexplained” infertility and for infertility due to non-immunologic cervical mucus insufficiency. IUI is often used for treatment of male infertility, though should be limited to those patients with mild to moderate problems. For cases of severe male factor infertility, In Vitro Fertilization and Embryo Transfer (IVF/ET) with Intracytoplasmic Sperm Injection (ICSI), will achieve far greater success and will also afford an opportunity of determining whether a man’s sperm is capable of fertilizing his partner’s eggs. Furthermore, IUI is not the optimal treatment for women over the age of 40, in whom low success rates do little to offset the race against time. IVF/ET is preferable in such cases.
The sperm sample to be used for IUI is collected by masturbation, washed in nutrient culture medium and centrifuged to separate the seminal fluid from the sperm. The sperm is capacitated (see later) and drawn up in a small volume of medium (0.25-0.5 cc) into a thin catheter. The catheter is passed through the cervix into the uterus of the female partner and the sperm are deposited into the uterus as close as possible to the time of ovulation. This often mandates that two inseminations be performed one day apart.
Preparation for the Treatment Cycle
It is important, prior to the performance of IUI, to evaluate both partners to be sure this is the appropriate treatment. The female partner will have a physical examination and blood tests to be sure her hormones are normal. Sperm antibody testing may be performed on a blood sample. If sperm antibodies are present in the female, IUI is not the treatment of choice, as the antibodies are likely present throughout the reproductive tract and may prevent fertilization of the egg by the sperm. If this is the case, IVF is the treatment of choice. The physician may also recommend a hysterosalpingogram or laparoscopy to determine if the fallopian tubes are open and /or to rule out other pelvic pathology such as adhesions or endometriosis.
The male partner will be asked to provide a semen sample for semen analysis and may also have testing done for sperm antibody production (especially if a significant degree of agglutination is seen at the time of semen analysis). If antisperm antibodies are present, the male partner may be asked to ejaculate into a container containing culture medium, to dilute the concentration of antibodies as much as possible before sperm preparation for insemination. In accordance with requirements of the California Tissue Bank law, the male partner must also have blood tests for syphilis, HIV, HTLV-1, hepatitis B surface antigen, and hepatitis C antibody, before inseminations can be initiated.
If the female partner has normal, ovulatory cycles, inseminations may be performed in a natural cycle by timing ovulation with an ovulation predictor kit. However, for unexplained infertility or mild male factor, as well as for women who do not have regular ovulation, pregnancy rates are enhanced by using ovulation induction in conjunction with the intrauterine insemination procedure. Therefore, most women undergoing inseminations with their partner’s sperm are also treated with an ovulation-inducing agent.
Clomiphene citrate (Clomid, Serophene) is the most commonly used medication and is given orally, usually from the third through the seventh day of the menstrual cycle. It increases the output of follicle stimulating hormone (FSH) from the pituitary gland, and may enhance the quality of egg production. Occasionally, more than one egg will mature and ovulate, thus resulting in a small chance (7%) of producing a multiple pregnancy. Insemination is timed by the detection of the luteinizing hormone (LH) surge in the urine (ovulation predictor kit) and by ultrasound. The female is instructed to start urine testing, usually on cycle day 11 or 12 and to call the office when the color change occurs or by cycle day 14. We recommend testing the second morning urine, and calling the office as soon as possible after 9:00 am when the test is positive, to schedule an ultrasound that same day.
The ultrasound will confirm the presence of a preovulatory follicle(s), and will evaluate the uterine lining. If a follicle is present, the first insemination will be scheduled for the following day, the most likely time for ovulation to occur. An ultrasound will be repeated with the first insemination, and if follicle rupture is confirmed, only one insemination is necessary. If ovulation has not yet occurred, a second insemination will be recommended for the following day. In this way, we try to ensure that sperm are in the uterus and tubes as close as possible to the time of ovulation. Pregnancy testing will be performed 14 to 15 days later if menses have not ensued. The combination of Clomiphene and intrauterine insemination has a 15% per cycle pregnancy rate with a cumulative pregnancy rate of approximately 40% in three cycles in women under the age of 40. If conception has not occurred within 3 to 4 cycles (or if the woman is over the age of 40), it is often recommended that the couple consider moving on to more aggressive therapy, such as ovulation induction with gonadotropin therapy in combination with IUI.
Human gonadotropin preparations are the medications that contain FSH, the primary hormone responsible for follicular development. In a natural cycle, usually one egg reaches maturity and is released from the ovary; however, in an FSH stimulated cycle, there is usually maturation and release of several eggs, and egg quality may also be improved. These medications are often prescribed when Clomiphene has failed to work, or in women of older reproductive age. Gonadotropins have been administered as intramuscular injections (Pergonal, Humegon, Metrodin) for many years, but more highly purified forms of FSH (Fertinex) and recombinant forms of FSH (Gonal-F, Follistim) are now widely used. These have the advantage of being able to be self-administered as easier, subcutaneous injections, and have the same efficacy as their predecessors.
Injections are initiated on the second day of a menstrual cycle, after a baseline ultrasound has confirmed that there are no ovarian cysts present. Injections are administered daily (or occasionally twice daily) until one or more follicles have reached maturation (approximately 10 days). Monitoring with serial blood estradiol levels and transvaginal ultrasounds begins on the seventh or eighth day of the cycle. Follicles usually grow 2 mm/day and an intramuscular injection of Human Chorionic Gonadotropin (HCG) is given to trigger ovulation when the largest follicle reaches 18 mm in diameter. Since several follicles may reach maturity, and more that one egg may be released at different times, inseminations are performed twice, once on the day after HCG administration and again the following day. This regimen results in a pregnancy rate of approximately 20% per cycle in women under age 40, with a 25% chance of multiple pregnancy. Three attempts of gonadotropin ovulation induction with IUI will result in a cumulative chance of pregnancy of 50%. The luteal phase of the cycle is usually supported with progesterone suppositories placed intravaginally twice daily and pregnancy testing is performed two weeks after the second insemination. If pregnancy is achieved, an ultrasound is performed four weeks after insemination (6 weeks gestation) to document the viability of the pregnancy by detection of a fetal heartbeat.
If a couple with unexplained or male factor infertility has not conceived after three attempts of gonadotropin therapy and IUI, it is our general recommendation that the couple move on to in vitro fertilization to provide a better opportunity for conception.
Sperm Preparation and Insemination
On the specified day, the male partner will collect a semen specimen by masturbation into a sterile container. The sperm are separated from the seminal fluid by washing and centrifugation in culture medium, which also initiates the process of capacitation. Capacitation is a series of enzymatic changes that occur in the head of the sperm, which give the sperm the capacity to fertilize an egg. The sperm are also centrifuged through a density gradient, which separates dead sperm and debris from the actively motile sperm. The motile sperm are then resuspended into a small volume (0.3 cc) of medium, which concentrates them for the insemination. The preparation procedure takes approximately 2 hours to complete.
The sperm are then loaded into a tiny teflon catheter, which is threaded through the female partner’s cervix to the top of the uterine cavity, where the sperm are deposited. This places the sperm in close proximity to the tubal openings and maximizes the number of motile sperm reaching the egg(s). After the insemination is completed, the female partner reclines on the examining table for 10 minutes and thereafter has no restrictions on physical activity.
Intrauterine insemination is a very safe procedure, although there is a small risk of transmission of infection to the genital tract of the female partner if the male partner has an infection (bacterial, viral, or chlamydial) present in his semen. It is also important to understand that there is a 2% risk of congenital abnormalities in all children born, including those from intrauterine insemination. Ovulation induction, sperm washing and insemination do not change this risk.
Estimated cost for Clomiphene IUI cycles are approximately $1,620. Estimated cost for IUI cycles with injectable medications (COH IUI) are approximately $2,690. No cycle cost information includes medications and are subject to change.