Do fertility medications improve fertility outcomes for women with PCOS?

This study compared letrozole (Femara), clomiphene (Clomid), or no ovarian stimulation for women with polycystic ovarian syndrome (PCOS). It found that letrozole led to the uterus being more receptive to an embryo, and to higher pregnancy rates.

Women with PCOS do not ovulate frequently or at all. Patients who want to become pregnant are often given medications which stimulate ovulation, such as clomiphene or letrozole. Both medications affect the hypothalamus in the brain. When this gland senses that the level of estrogen is low, it releases hormones that lead to ovulation.

Clomiphene blocks the hypothalamus from sensing estrogen. However, it also blocks the cervix and uterus from sensing estrogen. Thus clomiphene prevents the lining of the uterus from thickening to prepare for a pregnancy. Clomiphene also dries up the cervical fluid which is necessary for sperm to survive. Letrozole works in a slightly different way, by reducing the amount of estrogen in the body. Letrozole does not have the same impact on the uterus and the cervix.

It is not clear which method of conception leads to the best embryo implantation for women with PCOS.

This study included 270 patients with PCOS who were trying to conceive. Patients were randomly assigned to 3 different groups. Group 1 received clomiphene at the beginning of the cycle, group 2 was assigned to letrozole, and group 3 did not receive any medications for ovulation stimulation (natural cycles). When ultrasound imaging showed that one of the ovarian follicles was mature, medication was used to trigger ovulation.

Patients were similarly likely to ovulate using either medication (63.3% – letrozole and 61.1% – clomiphene). Significantly fewer patients in group 3 ovulated (12.2%). The authors did not report how long they monitored cycles in the control group before determining they did not have ovulation.

In patients who ovulated, an ultrasound of their uterus was performed 7 to 9 days later. Ultrasound showed that patients who took letrozole had a thicker uterine lining and better blood flow to the uterus than the other patients. Patients who had more blood vessels into the uterine lining were more likely to become pregnant and stay pregnant. This was true regardless of which group they were in.

There was a significantly higher pregnancy rate for letrozole than for clomiphene (25.6% vs. 13.3%). The pregnancy rate of patients in group 3 was lower than for either medication (4.4%). Also, more patients taking letrozole reached 12 weeks of pregnancy (23.3%) than either of the other groups.

This study found that letrozole led to a more receptive uterine lining and higher pregnancy rates than other options for patients with PCOS.

Because the natural cycles group received ovulation triggering medication, it is not clear whether their uterine characteristics are the same as in an actual natural cycle.