Researchers in a 2022 meta-analysis found that hyaluronic acid, the active ingredient in “embryo glue,” increases live birth and clinical pregnancy rates in women using their own eggs, but not in women using donor eggs.
Hyaluronic acid (HA) is a common add-on for IVF cycles. It works by forming a viscous solution for the embryo to be suspended in, which may prevent expulsion from the uterus, or in mixing with the uterine fluid after transfer. It may also help in promoting contact of the embryo with other cells, including the endometrium.
The impact of HA on IVF cycle outcomes has been studied thoroughly, and a 2020 Cochrane review (reviewed here) has found a positive benefit in using HA, in terms of live birth rates for fresh (not frozen) transfers.
It’s not clear if donor cycles perform better with HA or if this is only limited to autologous (self) cycles using a patient’s own eggs. It’s possible that donor eggs might not benefit from HA, as they are typically higher quality than autologous eggs, and HA may only have an impact on autologous cycles with a poorer prognosis.
So this meta-analysis updates the previous 2020 Cochrane review, as well as addresses the effect of HA on donor egg cycles.
🔗 Original studies are referenced in this post or within the linked Remembryo posts.
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Heymann et al. (2022) performed a meta-analysis that compared RCTs that made use of high HA (at least 0.5 mg/ml) vs no or low concentrations of HA (<0.125 mg/ml). They only included studies where the egg source was known (donor or self).
For live birth rates, they included 2 studies involving donor eggs and 9 using autologous eggs. The donor egg group showed no significant differences in live birth rates with HA vs no/low HA (46.5% vs 41.8%, 317 participants, risk ratio [95% CI]: 1.12 [0.86, 1.44]), while the autologous egg group did find a difference (39.2% vs 32.1%, 3215 participants, risk ratio [95% CI]: 1.22 [1.11, 1.34]). Because these studies included a mix of blastocyst and cleavage stage embryo transfers, they also did a subgroup analysis and found a similar benefit.
For miscarriage rates, they only included 1 study for donor cycles (which didn’t find any differences) and 4 studies using autologous cycles that found a significant decrease between HA and no/low HA (7% vs 11%, 2094 participants, risk ratio [95% CI]: 0.63 [0.48, 0.84]). The authors point out that this significant result was not seen when one study, which was an abstract that contained outlier data, was removed.
For clinical pregnancy rates, they looked at 3 studies from donor cycles and 13 studies from autologous cycles. The donor cycles found no significant difference in clinical pregnancy between HA and no/low HA, while the autologous group found an increase with HA (47% vs 42%, 4014 participants, risk ratio [95% CI]: 1.11 [1.04, 1.18]).
For multiple pregnancy rates, they only reported on autologous cycles which showed an increase with HA vs no/low HA in 5 studies (23% vs 16%, 2400 participants, risk ratio [95% CI]: 1.49 [1.27, 1.76]).
In terms of adverse effects, there was one study that reported on ectopic pregnancies that found no difference with HA or no/low HA (550 participants).
Overall this study found a benefit of HA over no/low HA in terms of live birth rate and clinical pregnancy rate. Miscarriage rates may decrease, however this isn’t clear. In terms of the higher multiple pregnancy rate, the authors point out that this may be a natural consequence of higher implantation rates with HA as well as the policy of clinics transferring more than one embryo. Transferring one embryo with HA may be best to avoid risks of multiples.
In terms of donor cycles, the available evidence suggests that HA doesn’t provide a benefit. The authors explain that this may be due to the small number of studies examined here, or may reflect higher quality embryos that are typically seen in donor cycles. Therefore, HA may provide a clearer benefit to those with a poorer prognosis.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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