Which Fertility Drugs Are Used with IUI?

photo of individual preparing to take medication with water

Intrauterine insemination (IUI) can be performed with or without medication.

Natural IUI Cycle

An unmedicated cycle, or a “natural cycle,” is just what it sounds like—no medication is used to induce follicle development.

Sperm is prepared in the lab and delivered through a long thin catheter directly into your uterus when you ovulate.

Even in a “natural cycle,” human chorionic gonadotropin (hCG) medication, including Ovidrel, may be administered to synchronize release of the egg with arrival of the sperm.

Medicated IUI Cycle

A medicated cycle is when IUI is done in conjunction with fertility drugs that stimulate your body to mature and ovulate multiple eggs. This process goes by many names, including superovulation, controlled ovarian hyperstimulation, and ovulation induction by hormone therapy.

Several studies have found that, for couples with unexplained infertility, IUI done along with superovulation offers a slightly greater chance of pregnancy than IUI done in “natural” menstrual cycles. For couples with unexplained infertility, without superovulation, IUI produces similar pregnancy rates as well-timed intercourse.

Research as far back at the late 1990s have looked at the efficacy of medicated IUI cycles. One study from the University of Rochester Medical Center found that superovulation combined with IUI was associated with a three-fold higher chance of pregnancy, compared to no treatment at all. It also resulted in a two-fold higher chance of pregnancy than either IUI or superovulation alone. Over a period of months, couples in the study who used both superovulation and IUI had a 33 percent pregnancy rate, compared with the 10 percent pregnancy rate of infertile couples who used no fertility treatments.

How are Fertility Drugs Used with IUI?

The fertility drugs given during an IUI cycle often include clomiphene citrate (Clomid) and aromatase inhibitors (e.g., Letrozole).

  • You will start on these medications early in your menstrual cycle, on the second, third, fourth, or fifth day after the first day of your period.
  • Your doctor will begin watching for signs of ovulation to know when to schedule the IUI
  • Often, hCG is given to trigger ovulation, and the IUI will be timed to occur between 24 and 36 hours later.

Gonadotropins (e.g,. hMG, brand name Menopur, and FSH, brand names Gonal-f and Follistim) had been used more commonly with IUI, but have largely fallen out of favor due to the unacceptably high risk of multiple gestations and maternal and fetal pregnancy complications.

What Are the Risks of Using Fertility Drugs with IUI?

All ovulation medications increase the risk of twins, and injectible medications increase the risk of triplets and higher order multiple gestations. You should have an in-depth conversation about personalized risk with your physician before starting an IUI cycle, as detection of multiple follicles may be a reason to cancel the IUI cycle.

Dr. Alan Copperman is a board-certified reproductive endocrinologist and infertility specialist with a long history of success in treating infertility and applying fertility preservation technologies. He serves as Medical Director of Progyny, a leading fertility benefits management company, and co-founded and serves as Medical Director of RMA of New York, one of the largest and most prestigious IVF centers in the country.  Dr. Copperman is also the ViceChairman and Director of Infertility for the Icahn School of Medicine at Mount Sinai, and Chief Medical Officer of Sema4, a health information company. Dr. Copperman has been named to New York magazine’s list of Best Doctors 17 years in a row. He has been recognized by his peers and patient advocacy organizations for his commitment to patient-focused and data-driven care. He has published more than 100 original manuscripts and book chapters on reproductive medicine and has co-authored over 300 scientific abstracts on infertility, in vitro fertilization, egg freezing, ovum donation, and reproductive genetics.