From the Guidelines
Letrozole is not recommended over Clomid for ovulation induction in IUI cycles, as the most recent and highest quality evidence shows no benefit in using Letrozole compared to Clomiphene citrate in terms of pregnancy rate per couple 1. The choice between Letrozole and Clomid should be based on individual patient factors, such as the risk of multiple pregnancies and the cost of treatment.
- Clomiphene citrate or tamoxifen are acceptable alternatives to low dose gonadotrophins for low multiple pregnancy and birth rates and with lesser costs, although at a lower live birth rate than with gonadotrophins 1.
- The most common side effects of IUI in cycles with OS are multiple pregnancies and ovarian hyperstimulation syndrome (OHSS), and measures to prevent multiple pregnancies can be divided into primary and secondary measures 1.
- Primary measures include attempting to prevent the growth of more than two to three dominant follicles, and applying the appropriate drug and doses, and to individualize the doses when possible 1.
- High level evidence shows that when gonadotrophins are used in IUI, regiments with 75 IU or lower should be used as higher doses have similar pregnancy rates while increasing MPRs 1.
- Letrozole has been used for ovulation induction in infertility patients, and for the purpose of ovarian stimulation for fertility preservation via oocyte or embryo cryopreservation in women with estrogen-sensitive cancer 1.
- However, in the context of IUI cycles, the evidence does not support the use of Letrozole over Clomid, and the decision should be based on individual patient factors and the risk of multiple pregnancies 1.
From the Research
Comparison of Letrezole and Clomid
- Letrezole has been found to have a higher ovulation rate compared to Clomid in infertile women with polycystic ovary syndrome (PCOS) 2.
- A study found that letrozole was associated with significantly higher clinical pregnancy and live birth rates compared to clomiphene in treatment-naïve infertile women with PCOS 3.
- However, in women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of live birth compared to gonadotropin, but not compared to clomiphene 4.
- An individual participant data meta-analysis found that letrozole improved live birth and clinical pregnancy rates and reduced time-to-pregnancy compared to Clomid in women with PCOS 5.
- A retrospective cohort study found that in patients who failed to conceive with Clomid, gonadotropins had a higher pregnancy rate per cycle than letrozole, but letrozole still had high enough pregnancy rates to justify its use in this population 6.
Efficacy of Letrezole and Clomid
- Letrezole has been found to be a superior ovulation induction agent compared to Clomid in treatment-naïve infertile women with PCOS 3.
- Letrezole improved live birth rates (RR 1.43,95% CI 1.17-1.75) and clinical pregnancy rates (RR 1.45,95% CI 1.23-1.70) compared to Clomid in women with PCOS 5.
- However, Clomid plus metformin may increase clinical pregnancy and reduce time-to-pregnancy compared to Clomid alone, while there is insufficient evidence of a difference on live birth rates 5.