Vaginal Progesterone Gel on Par with Shots for IVF Outcomes

By Megan Brooks

NEW YORK - With modern management of frozen day-five embryos (blastocysts), luteal support with either vaginal progesterone gel or intramuscular progesterone (IMP) results in equivalent pregnancy outcomes, according to a retrospective study.

"Since there is no clinical difference in outcome, the decision about which to use boils down to cost, convenience, and comfort," Dr. Daniel B. Shapiro of Reproductive Biology Associates in Atlanta, Georgia, told Reuters Health by email.

"Progesterone in oil is much less expensive but it is notoriously painful and usually requires that a second person do the injection, while vaginal gel is more expensive but tolerated much better in most patients who can self-administer the drug. I have no specific preference regarding the two drugs and explain the cost and comfort issues to my patients after which I let them decide," Dr. Shapiro said.

He and his colleagues designed their study to answer a simple question: Does the type of luteal support affect pregnancy outcomes of recipients of vitrified blastocytes? The analysis included 920 frozen embryo transfer cycles, 682 using IMP (50 mg once daily) and 238 using vaginal progesterone gel (Crinone 8%, 90 mg). Patient demographics were similar in both groups.

In the journal Human Reproduction online May 20, the researchers say outcomes were not significantly different between IMP and vaginal progesterone gel. Implantation rates were 46.4% with IMP and 45.6% with the gel (p=0.81), clinical pregnancy rates were 61.7% and 60.5% (p= 0.80), respectively, and live birth rates were 49.1% and 48.9% (p>0.99).

The researchers say their study is "limited by its retrospective design and by its lack of randomization to the type of luteal support. In addition, because no a priori expected rates of success could be provided for this retrospective investigation, it was not possible to estimate statistical power associated with the various outcomes presented."

"Even though it's a retrospective study, it shows really for the first time that Crinone replacement in autologous cycles as well as donor egg derived embryo cycles is equivalent to intramuscular progesterone, which is a nice advance in the field and a good study to confirm what we already thought," Dr. Brian M. Berger, who wasn't involved in the study, noted in an interview with Reuters Health.

Yet, vaginal progesterone gel has been slow to catch on in the United States, said Dr. Berger, medical director of the donor egg and gestational carrier program for Boston IVF.

"The rest of the world thinks we are basically barbaric for using IM progesterone because they have largely abandoned it. The United States is probably the last holdout country for using IM progesterone. In Europe it's almost unheard of, but in this country it's still widely used," Dr. Berger said. "Even with fresh embryos where there is ample prospective evidence that for fresh IVF where women are making a lot of their own endogenous progesterone and you don't even need that much progesterone supplementation, people in this country are still stuck on IM progesterone," he added.

Why is that? A variety of reasons, Dr. Berger said, including "perhaps stagnation and inability to change thought processes over time." Some doctors may also be "somewhat immune to the pain and the consequences of IM progesterone because the nurses are doing the shots. So if you're not seeing that part of it but you're seeing good pregnancy outcomes, maybe you stick with it."

At Boston IVF, "we almost exclusively use vaginal progesterone in general," Dr. Berger said. "There are some cycles that still lend themselves to IM and it's not that I think it should never be used. There are some patients, for example, who don't like the idea of placing things vaginally, sometimes it's cultural, sometimes it's personal. There are patients that have a lot of vaginal irritation from Crinone or other vaginal replacement methods. Some patients think if there is no pain there is no gain and they kind of relish the discomfort. But other than those unique circumstances, for the most part we have switched to vaginal progesterone," Dr. Berger said.

Actavis provided funds for the study. Several of the authors have financial relationships with the company. One author is an employee of the company. Dr. Berger is on the advisory boards of Actavis and Merck.

SOURCE: https://bit.ly/1ttAFKR

Hum Reprod 2014.

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