Evaluating outcomes for frozen embryo transfer with irregular cycles

This study compared two methods of preparing for frozen embryo transfer (FET) for women who do not ovulate regularly. It found that letrozole (Femara) led to fewer miscarriages and higher birth rates than hormone replacement therapy (HRT).

FET is an increasingly common infertility treatment. FET uses additional embryos that have been frozen after a previous in vitro fertilization (IVF). This can increase the overall pregnancy rate per IVF cycle. By reducing the number of embryos transferred at one time, FET also reduces the health risks of twin or multiple pregnancies.

For a FET to be successful, the lining of the uterus needs to be receptive to an embryo implanting. The uterus is naturally receptive after ovulation. FET can be done during a natural menstrual cycle, after monitoring shows ovulation has already occurred.

However, not all women ovulate regularly. This includes women with polycystic ovarian syndrome (PCOS), a common hormonal condition which can reduce fertility. For women who do not ovulate regularly, there are a few options to prepare for FET. Letrozole is a medication that encourages ovulation. It causes hormone glands in the brain to release hormones that stimulate the ovaries. Alternately, HRT uses synthetic estrogen and progesterone to prepare the uterus. HRT is also referred to as artificial cycle FET.

Studies have found that HRT-FET has lower birth rates than FET methods involving ovulation. However, most of these studies look at all types of patients with infertility. It is not clear which FET method is best for patients who do not ovulate regularly.

This study used records from 2782 FET cycles. All of the cycles were from women who ovulated infrequently or never. 502 cycles used letrozole, and 2280 cycles used HRT.

The uterine lining was significantly thicker in letrozole-FET cycles compared to HRT (9.72 vs. 8.99 mm). In general, a thick uterine lining is better able to support a pregnancy.

The two FET methods had no clear difference in pregnancy rates (letrozole: 58.4% vs HRT: 54.5%). However, significantly fewer pregnancies using letrozole ended in miscarriage (14.3% vs. 21.7%). 

Cycles using letrozole led to a live birth more often (49.6% vs. 41.7%). The researchers statistically adjusted for other factors which can affect pregnancy rates. These factors included the woman’s body weight, ovarian reserve, and how long she had been trying to conceive. After adjustment, they found using letrozole increased the odds of birth by 30%.

Babies conceived through FET had similar outcomes with both letrozole and HRT. This included birth weight and the rate of preterm birth. Also, the two methods led to similar rates of twin pregnancies. Pregnancies of twins can have more complications.

This study found that letrozole FET leads to higher birth rates than HRT FET for women with infrequent ovulation.

This study used hospital records. The patients who selected letrozole may have had differences from those who used HRT.

If you have irregular menstrual cycles and are using FET, ask your doctor whether letrozole is right for you.