Does progesterone treatment help frozen embryo transfers following a natural cycle?

This review looked at whether luteal phase support (LPS) using progesterone benefitted natural cycle frozen embryo transfers (FETs). It found that FETs with progesterone support had higher pregnancy and birth rates.

Frozen embryo transfer (FET) is an increasingly common infertility treatment. This technique transfers an embryo(s) which was frozen in a previous cycle of in vitro fertilization (IVF). FET is used more frequently since freezing techniques have improved. It is also more common now to transfer only one or two embryos at a time instead of more embryos.

For an embryo to be able to implant, the lining of the uterus needs to be receptive. The uterus is normally receptive during the luteal phase of the menstrual cycle. This is after ovulation. There are several methods to accomplish this for a FET. Natural cycle FET (NC-FET) uses cycle monitoring to time the FET for after ovulation. Alternate methods are to create an artificial cycle using hormones or to use medications to stimulate ovulation.

A fresh IVF cycle typically uses medications to support the luteal phase. This luteal phase support (LPS) can consist of progesterone or human chorionic gonadotropin (hCG). Normally, progesterone rises after ovulation and affects tissues throughout the body, including preparing the uterine lining for an embryo to implant. hCG is secreted by an embryo and is sometimes called the “pregnancy hormone.” Either form of LPS can improve pregnancy rates for a fresh IVF cycle. However, it is not clear whether LPS is beneficial for NC-FET.

This review included 8 studies of LPS following FET. 

Two studies looked at the effect of hCG for LPS in 858 women. One of these studies used patient records. The other study randomly assigned patients to either hCG or to placebo following their FET. Both of the studies found that hCG did not improve pregnancy rates from FET.

Six studies of 1507 patients looked at progesterone for LPS following FET. Three studies used patient records, and three studies compared progesterone to placebo. The review combined data from 5 of these studies. Patients using progesterone had 48% higher odds of a pregnancy confirmed on ultrasound. Data from 3 studies also found patients using progesterone had 67% higher odds of giving birth.

This review found that progesterone luteal phase support improves NC-FET outcomes. It also found no evidence that hCG improves outcomes.

Randomized studies, where patients are assigned to either medication or placebo, are considered the strongest type of evidence. When the researchers only used the randomized studies, it was not clear whether progesterone improves pregnancy rates. Additional studies are needed.

If you are using NC-FET, ask your doctor whether vaginal progesterone is right for you.