Vaginal Progesterone or Progesterone Injections for IVF?

Vaginal Progesterone or Progesterone Injections for IVF?

There are many different methods for administering progesterone in IVF and frozen embryo transfer cycles. The two most common methods used by IVF clinics today are vaginal progesterone and progesterone injections. Which method of giving progesterone results in the highest success rates?

Progesterone is needed to prepare the uterus

In order for an embryo to implant in the uterus the uterine lining must be prepared first. Estrogen makes the uterine lining thicker, but it is progesterone that causes the changes necessary to allow an embryo to implant. Progesterone injections are the most painful method for giving progesterone and are really the most painful part of the entire IVF process.

Why are progesterone injections so painful?

Progesterone injections come in an oil base. Because of this, it must be injected directly into the muscle. This requires a longer needle to reach the muscle and a larger diameter needle to allow injection of the thick progesterone oil. Ouch!

Is it necessary to use progesterone injections?

My patients tell me that they will do whatever they have to do if it will help them to have a baby. Is it really necessary to use progesterone injections? Couldn't you just use vaginal progesterone and skip the injections? Let's look at the data.

progesterone shot ivf

A 2018 study compared three different protocols for preparing the uterus for a frozen embryo transfer. Embryo transfer was at the blastocyst stage.

  • Group 1 was given vaginal progesterone only.
  • Group 2 received vaginal progesterone every day and progesterone injections every day
  • Group 3 received vaginal progesterone every day and progesterone injections once every three days

A total of 645 frozen embryo transfer cycles were studied. The results may surprise you. The vaginal progesterone only group did so poorly compared to the other two injection groups that they stopped enrolling patients in that group early.

The ongoing pregnancy rate was 30% which was about 15% to 20% lower than the other two groups which saw ongoing pregnancy rates of 47% to 50%.

On the other hand, there was no difference between the groups that took progesterone injections every day compared to every three days. Remember, these groups were also taking vaginal progesterone every day.

Our bottom line

First, for frozen embryo transfer, vaginal progesterone alone results in a significantly lower success rate compared to combined vaginal progesterone and injections.

fet frozen embryo transfer progesterone

Second, if you are already taking vaginal progesterone every day, then taking progesterone injections every three days was just as successful as taking injections every day.

Based on this data, I recommend using the combined approach but taking progesterone injections every 3 days to reduce the total number of those awful painful intramuscular injections.