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Can Phytoestrogens Boost IVF Success Rates?

Naturally-occurring hormones found in certain plants may be the key to improve outcomes of in-vitro fertilization, say doctors in Italy who tested their use in a group of women in a new study.1

"Phytoestrogens continue to be of increasing interest because of their possible influence on the physiology of the reproductive tract," wrote Vittorio Unfer, MD, of the Obstetrics and Gynecology Center in Rome, and his colleagues.

Estrogen-Like Substances
Phytoestrogens are compounds found in some plants, and are available in a wide range of foods and supplements. Their effect in the body is similar to estradiol, the most powerful naturally-occurring estrogen. Some of the most common plants in which phytoestrogens are found include herbs, grains and fruits.2

While some previous studies suggested that higher levels of estradiol in women tended to boost the odds that an embryo would successfully implant in the uterus prior to pregnancy, Unfer and his fellow investigators noted that many of them were contradictory. To help set the record straight, they tested the effect of phytoestrogen supplementation on IVF results, compared to the effect of a treatment plan that did not include phytoestrogens.

Are Phytoestrogens Helpful in IVF?
More than 200 women who were being treated over a 2-year period at the researchers' IVF centers took part in the trial. Each of them was similar in age and weight, and had been infertile for a relatively similar length of time. As part of a standard treatment protocol, patients were divided at random into two groups and were given either 50 mg of daily progesterone plus a non-therapeutic placebo, or the same dose of progesterone combined with 1,500 mg of phytoestrogens in tablet form.  Progesterone is a standard treatment used as a supportive therapy during a woman's luteal phase of her cycle. That's the phase after ovulation and before uterine implantation in which the body produces natural hormones that, in turn, cause the uterus' lining to produce substances that help promote successful embryo implantation. Supplemental progesterone is used in this case as a replacement for potentially low levels of natural progesterone that could result in an unsuccessful implantation.

Each patient underwent controlled ovarian hyperstimulation to retrieve eggs for eventual in-vitro fertilization. Up to 36 hours after the injection of human chorionic gonadotropin (hCG)—a medication used to trigger ovulation—eggs were retrieved from each patient and the two treatment plans (phytoestrogens or no phytoestrogens) were administered. Eggs were fertilized using IVF, and up to 3 resulting embryos were later transferred to begin pregnancy in each patient. 

Treatment with phytoestrogens or without was stopped when either pregnancy or no pregnancy was confirmed. All told, the physicians performed 155 IVF cycles in the group of women who had received progesterone combined with phytoestrogens, and 129 cycles in women who were given progesterone combined with placebo.

More Benefits Found with Phytoestrogens
At the end of the study, Unfer's team learned that there were significant differences in the number of pregnancies, the number of successful embryo implantations in the uterus, and the number of ongoing pregnancies combined with the number of deliveries between the two groups. Those women who had been given the phytoestrogen treatment tended to have these successful IVF outcomes more often, the researchers noted.

The implantation rate for those given phytoestrogens was about 25% compared to 20% for those given a placebo. Approximately 39 percent of those given phytoestrogens had a confirmed pregnancy, compared to just 21 percent of those given progesterone alone. Nearly a third of those who had taken phytoestrogens had a successful ongoing pregnancy and later delivery compared to about 16 percent of those who didn't receive phytoestrogens in the study.

Similar Embryo Quality
"Considering that the quality of the embryo transferred was similar in both groups, the beneficial effect of phytoestrogens must be attributed to a positive effect on endometrial receptivity," the researchers wrote. (The endometrium is the medical term for the uterine lining.)

In terms of how it works, Unfer and his colleagues theorize that phytoestrogens somehow compete with very high levels of naturally-produced estradiol in the body by softening estradiol's blow to the uterus prior to implantation due directly to its high concentration. "As far as we know, this is the first study performed in women undergoing [IVF] cycles in which high doses of phytoestrogens have been administered when high levels of [natural] estrogens are present," they wrote.

There is a need for larger studies to better evaluate the effect of phytoestrogens on IVF outcomes, the researchers reported. "Nevertheless, our findings suggest new avenues for future fertility research and treatment with phytoestrogens, and strengthen the importance of investigating the features of estrogenic action on endometrium before implantation."

1. Unfer V, Casini ML, Gerli S, Costabile L, Mignosa M, Di Renzo GC. Phytoestrogens may improve the pregnancy rate in in vitro fertilization-embryo transfer cycles: A prospective, controlled, randomized trial. Fertil Steril 2004 Dec;82(6):1509-13.
2. National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health (NIH). Phytoestrogens and Bone Health. Available at: http://www.osteo.org/newfile.asp?
=HTML+Fact+Sheet. Accessed December 30, 2004.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications. 

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