Progesterone treatment: Injections and vaginal administration compared

This study compared progesterone injections with vaginal administration in women undergoing assisted reproductive techniques. Authors reported no significant differences across modes of administration in pregnancy rates, live birth rates, or complications.

The hormone progesterone is important for the successful implantation and development of an embryo. Progesterone supplements are often recommended for women undergoing in vitro fertilization (in which the sperm fertilizes an egg in a dish outside of the body, and the embryo is implanted in the uterus) to increase the likelihood of pregnancy. Progesterone treatment typically takes place during the luteal phase (second half) of the menstrual cycle. It can be administered in a number of different ways.

Oral supplements and vaginal suppositories or gels are the most common modes of administration. Oral supplements have the disadvantage that they have to be metabolized by the digestive system and the liver. This can reduce the effectiveness of treatment. More recently, progesterone injections have become available as another alternative. How progesterone injections compare to vaginal administration has not been fully studied.

This study analyzed the findings of two late-phase trials comparing the two modes of progesterone administration. 1,435 women undergoing in vitro fertilization were included in the analysis. All embryos transferred were fresh (not frozen). All women received progesterone treatment for a maximum of 10 weeks. 714 women received progesterone via injection under the skin. 721 women received vaginally administered progesterone. Pregnancy rates after 10 weeks of treatment were compared between the two groups.

The mode of progesterone administration did not significantly affect pregnancy rates. 52.1% of women that received progesterone vaginally were clinically pregnant after 10 weeks of treatment. This was similar to 47.9% of women that received progesterone via injection. Overall, younger women had higher odds of pregnancy than older women.  

There was also no difference noted in live birth rates across modes of progesterone administration. About half of clinically pregnant women had live births, regardless of mode of administration. Younger age, larger number of eggs received, and thicker uterus lining all increased the likelihood of live births.

Ovarian hyperstimulation syndrome (OHSS; painful, swollen ovaries, considered a serious complication) occurred in about half of women. There was no significant difference in OHSS rates between progesterone injections (48.2%) and vaginal administration (51.2%). Incidence of severe OHSS were rare (less than 1%) and not significantly different between the two groups studied. However, younger age and larger number of eggs received increased OHSS risk.

Authors concluded that there were no significant differences between progesterone injections and vaginal progesterone administration.