Infertility is considered unexplained when semen in the man and ovulation and fallopian tubes in the woman are normal.

When infertility remains unexplained after initial evaluation, empiric treatments are instituted.

Controlled ovarian hyperstimulation (COH) 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, COH may result in multifetal pregnancy, which has increased risks and morbidity. COH involves the following:

• Giving clomiphene, with human chorionic gonadotropin (hCG) to trigger ovulation, for up to 3 menstrual cycles
• Intrauterine insemination within 2 days of hCG administration
• If pregnancy does not result, other assisted reproductive techniques

Alternatively, before trying assisted reproduction, some clinicians use gonadotropins (preparations that contain purified or recombinant follicle-stimulating hormone and variable amounts of luteinizing hormone), followed by hCG as for ovulatory dysfunction, then intrauterine insemination within 2 days of hCG administration. A progestin may be needed during the luteal phase to maximize the chance of implantation. Gonadotropin dosage depends on the patient's age and ovarian reserve.

The pregnancy rate is the same (about 65%) whether in vitro fertilization is used immediately after unsuccessful treatment with clomiphene plus hCG or whether gonadotropins with intrauterine insemination are used next before trying in vitro fertilization. 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.

Last full review/revision January 2013 by Robert W. Rebar, MD