Unexplained Infertility

• Controlled ovarian stimulation

• In vitro fertilization

(See also Evidence-based treatments for couples with unexplained infertility: A guideline, from the Practice Committee of the American Society for Reproductive Medicine.)

Controlled ovarian stimulation (COS) can be used to make pregnancy more likely and to achieve it sooner. This procedure stimulates development of multiple follicles; the goal is to induce ovulation of > 1 oocyte (superovulation). However, COS may result in multifetal pregnancy, which has increased risks and morbidity.

COS involves the following:

• Intrauterine insemination within 2 days of hCG administration

• If pregnancy does not result, use of gonadotropins (preparations that contain purified or recombinant follicle-stimulating hormone and variable amounts of luteinizing hormone) with hCG to trigger ovulation, followed by intrauterine insemination (some clinicians begin with gonadotropins rather than clomiphene or letrozole)

A progestogen may be needed during the luteal phase to maximize the chance of implantation. Gonadotropin dosage depends on the patient’s age and ovarian reserve.

Because multifetal pregnancy is a risk, clinicians often proceed directly to in vitro fertilization and avoid COS.

However, when in vitro fertilization is done immediately after unsuccessful treatment with clomiphene plus hCG, women become pregnant more quickly and high-order multifetal pregnancies (≥ 3 fetuses) are much less likely than when gonadotropins are used first. Thus, if clomiphene plus hCG is unsuccessful, more clinicians now recommend in vitro fertilization as the next treatment. Data indicate that women > 38 years with unexplained infertility conceive more quickly and costs are lower when in vitro fertilization is done rather than proceeding to controlled ovarian stimulation (1).