Rescue In Vitro Maturation (R-IVM): A new way to deal with immature eggs

Along with Highly Individualized Egg Retrieval (HIER), a new laboratory procedure for immature eggs gives poor-prognosis patients their best chance of pregnancy with IVF

CHR investigators in 2016 published a paper, where they coined the term rescue in vitro maturation (R-IVM). It describes a circumstance usually encountered in poor prognosis patients who produce small numbers of eggs and embryos and where, therefore, every egg and embryo really counts [Lee et al., Endocrine 2016;52(1):165-171]. This work in CHR’s embryology laboratory has, however, been routine since 2014. What it means is that, if immature eggs are obtained at egg retrieval, a maximal attempt is made to mature those eggs in vitro (i.e., in the laboratory).

In practical terms this meant that embryologists after retrieval, as is routinely done in all IVF laboratories, strip eggs of attached cumulus cells because, as long as those cells remain attached to eggs the maturity grade of eggs cannot be accurately determined. Cumulus cells are, however, the source of the eggs’ nutrition. When we strip them off, eggs continue their in vitro maturation while starving.

Many embryologists, therefore, do not even try to mature immature eggs in vitro because, especially with very premature eggs, so-called GV-stage eggs, maturation only relatively rarely succeeds in leading to pregnancy. Since in such patients every egg truly counts, CHR’s embryologists, who almost exclusively only deal with small numbers of eggs from very poor prognosis patients, however, do not have the luxury of giving up. They, therefore, over the years since starting to routinely use R-IVM, have steadily been searching for ways to improve the results of R-IVM.

We are now pleased to report significant progress on two fronts: CHR’s embryologists have developed an algorithm that allows them to determine which eggs are so immature that they need to undergo R-IVM over night before they can be fertilized (mature eggs are fertilized within hours after retrieval). These eggs, therefore, then can be cultured overnight with their cumulus cells still attached. Though this new approach has only been in used at CHR for ca. six months, we can already see a difference in ultimate egg quality. And since egg quality translates into embryo quality, and embryo quality into pregnancy rates, we are confident that this change in embryology practice at CHR will also improve IVF pregnancy rates.

In combination with Highly Individualized Egg Retrieval (HIER) practice, discussed in detail in the last month’s VOICE, CHR has over the last year radically changed how we approach poor prognosis patients, whether due to age or, simply because of premature ovarian aging (POA), following the center’s motto, “We fight for every egg and embryo.”

We are also very excited to report that, considering the widely acknowledged expertise in imaging of eggs and embryos CHR’s Director of Laboratories, David Albertini, PhD is known for, one of the leading manufacturers of scientific microscopes chose CHR as beta-site for an incredibly sensitive new microscope set-up, which was recently established. CHR is, indeed, currently the only IVF center with such a set up. According to Dr. Albertini, we expect this microscope to see and document details not previously seen and, indeed, are hopeful that this microscope will allow for accurate diagnosis of maturity levels of oocytes without need for prior stripping of cumulus cells.

This is a part of the February 2018 CHR VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.