Investigating the effectiveness of a letrozole ‘step-up’ protocol for controlled ovarian stimulation

This study investigated the effect of a letrozole (Femara) step-up protocol (SUP) for controlled ovarian stimulation (COS).

They found that a letrozole-SUP was as effective as standard COS protocol and less costly. 

Unexplained infertility (UI) is increasingly common. Women with UI usually have a normal ovulation pattern. Ovulation is the release of a follicle containing an egg. To treat UI, ovulation can be artificially induced using drugs. This is called controlled ovarian stimulation (COS). Then sperm can be delivered to the uterus by intrauterine insemination (IUI). 

Standard COS involves taking either clomiphene (Clomid) or gonadotrophins (GDTs). GDTs have some disadvantages. They must be injected and they are expensive. Letrozole is a drug that has recently been used for COS. It does not negatively affect the uterus lining (as clomiphene does). Letrozole is taken orally and is less expensive than GDTs. Some studies have shown that letrozole in combination with GDTs is effective. Using increasing doses of letrozole may achieve COS without the need for GDTs. This is called a step-up protocol (SUP). It is unclear if a letrozole-SUP is effective in women with UI.

This study included 58 couples undergoing COS/IUI. Women were randomly assigned to letrozole-SUP (group 1) or letrozole + GDTs (group 2). The treatment for group 1 involved increasing doses of letrozole over 4 days (from 2.5 mg/day to 10 mg/day). In the other group, letrozole was administered at the same dose (5 mg/day) over 5 days. GDT was injected every other day. Pregnancy outcomes were assessed.

Ovulation rates were lower in group 1 compared to group 2 (90.9% vs. 100%). More than one dominant follicle (that turns into an oocyte or egg for fertilization) developed in 68.1% of group 1 and in 72.7% of group 2 patients. Clinical pregnancy rates were similar in both groups. No hyperstimulation (a rare and potentially severe complication of COS) was observed in patients from group 1 compared to one case in group 2. The cost of group 1 treatment was significantly lower than in group 2.

The authors concluded that letrozole-SUP was as effective as letrozole-GDT COS treatment and less costly.

The number of patients in this trial was low. Larger trials are needed to investigate the safety and effectiveness of letrozole-SUP.  

If you have any concerns regarding infertility treatment please consult with your physician.