Letrozole Co-treatment not better for Infertile Women Over 40

Dr. Randy Morris

Letrozole Co-treatment not better for Infertile Women Over 40

Dr. Randy Morris

Unfortunately, a significant decline in reproduction success occurs as women get older. This includes poor egg quality, reduction in recruitment of eggs, and a reduction in response to internal and external hormones. In some cases, there have been advances in fertility treatments to compensate for these losses in reproductive success. One commonly used treatment is the use of fertility medications to stimulate multiple egg development (also known as controlled ovarian hyperstimulation (COH)) combined with intrauterine insemination (IUI) . This infertility treatment is often used for unexplained infertility , early stage endometriosis , and mild male factor infertility .

Aromatase Inhibitors to Reduce E2 Levels

Fertility drugs containing reproductive hormones called gonadotropins are used to help multiple eggs to develop and mature in the ovaries. There are some problems with the use of these medications. First, they can be very expensive. Second, when successful, the stimulation of multiple eggs can produce higher levels of estrogen. Some experts have expressed concern that high estrogen levels could adversely affect the chance for embryos to implant in the uterus. High estrogen levels have also been associated with the development of ovarian hyperstimulaion syndrome (OHSS) or multiple pregnancies. There is a class of medications called aromatase inhibitors which block the production of estrogen and therefore result in lower estrogen levels. Aromatase inhibitors have been used to treat a variety of diseases in which having lower estrogen would be a benefit. These include breast cancer and endometriosis. Studies have shown that aromatase inhibitors could be used as a fertility medication to stimulate multiple egg development. Recently, a study was performed to see if one of these aromatase inhibitors, known as Letrozole , in conjunction with gonadotropins, would have any effect on the pregnancy rates of infertile women over 40.


For this study, infertile women were recruited who were 40 years old or older. The women were then separated into two groups:Group 1- received Letrozole in combination with gonadotropin fertility drugs Group 2- received gonadotropins alone In both groups, if the women developed eggs and ovulated, then they had an IUI performed. The researchers looked at how often pregnancy occurred in each group as well as how many eggs developed in the ovaries, the levels of estrogen measured in the blood, and the thickness of the uterine lining. The development of eggs in the ovaries is monitored in part with ultrasound. The eggs frown inside of small cysts called follicles. These follicles can be seen and measured on ultrasound. Both groups had comparable baseline features such as age as well as hormonal profile and ultrasound assessment.


Advantages for the Letrozole Group:

  • Fewer cancelled cycles
  • Less fertility medication used
  • Lower cost
  • Lower estrogen levels

Advantages for Group 2 (No letrozole):

  • Thicker uterine lining
  • Fewer miscarriages
  • Higher implantation potential

However, the chance for pregnancy was similar between the letrozole group and the non- letrozole group. A treatment was canceled if there was a lack of follicle development, excessive follicular development (>6 large follicles), the couple requested cycle cancellation for personal reasons, or other causes such as the presence of ovarian cysts, abnormal baseline hormones, and failure to obtain a semen sample adequate for insemination. However, the reasons for cancellations were not significantly different between the two groups.


Pregnancy Rates were the same

There has been much information on the internet suggesting that Letrozole co-treatment is superior to treatment with fertility drugs alone. The present results showed that letrozole failed to improve the chance for pregnancy when given alongside of the other fertility drugs. In addition, the patients who had letrozole co-treatment had lower estrogen levels. Theoretically, this might be useful in decreasing the risk of ovarian hyperstimulation syndrome (OHSS). However, since the risk for OHSS is very low, this study couldn’t prove that the risk was decreased.


A reduction of the dose of FSH, the most expensive among the ovarian stimulation drugs, also translated into reduction in the overall cost of medication paid by the patient. For advanced reproductive age women, this would be of particular relevance, as they often require high doses of gonadotropins to overcome the poor ovarian response common at this age.


Co – treatment with letrozole wasn’t any worse than treatment without letrozole in terms of how many women were getting pregnant. More study is needed to determine whether the miscarriage rate with letrozole is higher. Decrease in fertility with age can’t be compensated by all current methods and women should be made aware of this for their future reproductive lives.