Hyaluronic acid (HA) is a gooey, slippery substance that your own body produces naturally throughout the body, especially in eyes, joints and skin. It is widely sought to reduce wrinkles and lines on the face and even to promote wound healing, reduce scars, lubricate joints, reduce acid reflux, treat dry eyes, slow bone loss and relieve bladder pain.
But researchers at the Hebrew University of Jerusalem have found a surprising new use for this substance, which is taken for this variety of uses in the form of pills, liquids mixed with water, gels, shampoos, lotions, creams, patches and eye drops. The new discovery is that it can improve the success of in-vitro fertilization (IVF) for couples suffering from infertility.
HA, a high molecular weight biopolysacharide, was discovered in 1934 by Karl Meyer, a Jew born in 1899 in a German village near Cologne. Myer was drafted into the German Army during World War I and then went to Berlin to study medicine.
After three years as a Rockefeller Fellow in Zurich studying heme-catalyzed oxidation of unsaturated compounds, he was offered a position as assistant professor at the University of California at Berkeley. He developed HA with his assistant, John Palmer, from the vitreous of bovine eyes.
Today, HA is made from ingredients derived from animals, specifically collagen in rooster combs. It is obtained by bio-fermentation, a process using lactic acid bacteria. Then it is collected, purified and dehydrated to form a powder. When added to water, it forms a more or less textured gel. It can also be made in commercial quantities through the application of bacterial expression systems in Streptococcus bacteria.
Worldwide, around 10% to 15% of couples have difficulty conceiving embryos and developing healthy fetuses. Many turn to artificial reproductive technologies (ARTS) – most notably IVF – in the hope of having a baby.
Who are the Israeli researchers?
But this process is fraught with anxiety, as only about one-third of IVF cycles are successful. But a method of improving the success of IVF has now been clearly identified in a systematic review of high-quality clinical trials carried out by a team of researchers at Kaplan Medical Center in Rehovot and Hebrew University. Led by Dr. Devorah Heymann, the team published their findings in the journal Human Reproduction under the title “The effect of hyaluronic acid in embryo transfer media in donor oocyte cycles and autologous oocyte cycles: a systematic review and meta-analysis.”
“We found that exposing an embryo to HA for more than 10 minutes before its transfer to the womb increased the likelihood of a birth from 32% to 39%.”Dr. Devorah Heymann
The trend throughout the world is for couples to delay starting a family until they have launched their careers and achieved greater financial stability. This takes women beyond their years of peak fertility – causing many to rely on processes such as IVF to have a baby.
In IVF, an egg is removed from the woman, fertilized in a dish and then, a few days later, the resulting embryo is implanted in her uterus. While in the dish, the embryo is kept in a liquid, or culture medium, that supports its development. The researchers proved that the addition of HA to this medium improves the ultimate success of IVF.
This significant finding was the result of a detailed systematic review and meta-analysis of the outcome of all high-quality clinical trials in which HA was either added or not added to the culture medium. Fifteen studies totaling 4,686 participants were analyzed.
“We found that exposing an embryo to HA for more than 10 minutes before its transfer to the womb increased the likelihood of a birth from 32% to 39%,” Heymann reported. The most marked success was in cases for women who had a poor prognosis of success.
The increase in birth rate was seen only in cases where a woman was implanted with her own fertilized egg and not in cases where donor eggs were used.
“This could be because donor eggs tend to be of higher quality,” explained Heymann, “as the main benefit was seen in poorer quality eggs.
This study, by Heymann and her colleagues, including IVF experts Prof. Zeev Shoham and Dr. Yuval Or of Kaplan in Rehovot, builds on their work for the Cochrane database of systematic reviews published in 2020 that showed an overall increase in success rate in ARTs when embryos were exposed to HA prior to implantation.
Although HA naturally occurs in the female reproductive tract, its role in improving IVF outcomes is unclear and more research is needed, suggested Heymann. Meanwhile, her prime concern is that IVF clinics act on the findings of this review. But, she concluded, “hyaluronic acid is expensive, and this might mean it is not as widely used as it should be.”