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Unexplained Infertility Treatment

Advanced treatment with IUI and IVF helps couples with unexplained infertility

The simplest treatment for unexplained infertility consists of intrauterine insemination (IUI) in a natural cycle. In this type of treatment cycle, the woman monitors her follicular development and impending ovulation, typically using an ovulation prediction kit. Intrauterine insemination is performed the day following the detection of the luteinizing hormone (LH) surge, which is the day on which ovulation presumably occurs. The chance for pregnancy with natural cycle/IUI typically ranges from 6% to 10% per cycle. There is no increased risk of multiple pregnancy, nor is there any appreciable increase in the risk of any other types of complications from this treatment.

A slightly more involved form of treatment for unexplained infertility is the combination of IUI with clomiphene citrate.

Clomiphene is a medication that acts directly on the brain and the pituitary gland, typically resulting in more follicular development. This medication comes in a pill form and the typical starting dose is one pill per day for five days, starting on day 3, 4, or 5 of your menstrual cycle. Once we determine that you are responding to the dose of clomiphene that has been selected, we will ask you to use an ovulation prediction kit daily. IUI will be performed on the day following the detection of the LH surge. If you have had problems in the past using or interpreting ovulation prediction kits, or if you do not typically have an LH surge, we may monitor your follicular development with ultrasound and recommend a single injection of Ovidrel® or hCG when your largest follicle is mature in order to cause ovulation to occur.

If you take Ovidrel®, we will typically perform your IUI 24 to 36 hours following the injection. Pregnancy rates following clomiphene/IUI typically range from 8% to 12% per cycle. In addition, there is a 5% to 8% risk of multiple pregnancy, although fortunately almost all of the multiple pregnancies resulting from clomiphene treatment are twins. As noted in other sections of our website, clomiphene can occasionally cause hot flashes, vaginal dryness, headaches, and/or mood swings. In addition, in up to 40% of patients who take clomiphene, there may be a significant decrease in the production of cervical mucus and/or thinning of the uterine lining. In the event that either of these situations occurs, your physician will probably recommend that you move on to an alternative form of therapy.

Injectable fertility medications combined with IUI

The next, more aggressive form of treatment for unexplained infertility combines the use of gonadotropins (follicle stimulating hormone – FSH, or human menopausal gonadotropin – hMG) with IUI. This treatment is more involved, as FSH or hMG are administered via subcutaneous injection (using a little needle just under the skin). Patients will typically start these injections on the second or third day of their cycle and we will see them in the office every two to three days for a blood estrogen level, as well as a vaginal ultrasound to monitor their progress. The gonadotropins are typically administered for 6 to 12 days, and when the largest one or two follicles attain maturity (19 to 20 mm in size), a single injection of Ovidrel® or hCG is administered. We will then typically perform IUI on each of the two subsequent days following your Ovidrel® or hCG injection. This treatment produces pregnancy rates of 20-25% per cycle with a multiple pregnancy rate of approximately 20%. The risk of triplets or more is approximately 2% of all pregnancies produced from this form of treatment.

Therefore, out of every 100 women who conceive following gonadotropin/IUI treatment, approximately 80 will have one baby, 18 will have twins, and 2 will conceive triplets or more. This is why we monitor you very closely during your stimulation – to attempt to minimize this risk. Side effects of gonadotropin therapy include bloating, occasional mood swings, cyst formation, and temporary weight gain. There is also a relatively low risk of developing a condition called ovarian hyperstimulation syndrome (OHSS), which is characterized by significant ovarian enlargement, abdominal swelling, nausea, and occasionally some shortness of breath. While this condition usually resolves on its own, we monitor patients at risk for OHSS very closely to prevent any other complications.

The final, most aggressive form of treatment for unexplained infertility is in vitro fertilization.

This treatment is discussed in great detail in other sections of this web site. Although it is the most aggressive form of therapy for unexplained infertility, it is also the most successful form of therapy. The major advantage of in vitro fertilization over gonadotropin therapy combined with IUI, in addition to a significantly higher pregnancy rate, is a significant reduction in the risk of high order multiple pregnancy.

In summary, unexplained infertility is a relatively common cause of infertility. This diagnosis is only made after a complete basic evaluation for infertility has failed to reveal a definitive cause for the couple’s infertility. Despite the lack of a definitive diagnosis, several effective treatments are available for unexplained infertility, resulting in respectable pregnancy rates with a minimum risk of adverse effects.

For more information

IUI, intrauterine insemination 

IVF, in vitro fertilization


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