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So you’ve just had an egg retrieval and the results are in! You got 10 mature eggs, and 6 immature eggs. Good news on the 10 mature eggs, but what about the 6 immature eggs? Can't they be used for anything?
Some research is showing that they can be used, after applying a technique known as "rescue in vitro maturation," or "rescue IVM."
Essentially, rescue IVM involves culturing the immature eggs a bit longer until they mature, and then inseminating them. But before we discuss this, let’s back up and talk about what it means to have a mature vs. immature egg.
What’s the difference between mature and immature eggs?
As an egg develops in the follicle, it goes through several stages to become mature and ready for fertilization.
Without getting into too much detail, the stages an egg goes through as it matures are different steps of meiosis. Meiosis is a special type of cell division that our bodies use to make our sex cells, like egg and sperm cells.
When the egg is immature, there are two stages: the earlier immature stage, called the germinal vesicle (GV) stage, and the later immature stage, called the metaphase 1 (M1) stage. Metaphase refers to a specific step of meiosis.
Once the egg matures, it’s called a metaphase 2, or an M2 egg. The embryologist can tell that an egg is mature because they can see a tiny sac called a polar body that’s released by the egg. You can see an M2 with its polar body below:
Source: Remembryo
Whether or not an egg is mature is usually only determined in preparation for ICSI (when an egg is injected with a sperm cell). When an egg is first retrieved from a follicle, the egg itself is covered in cells and these cells need to be removed (or “stripped”) in order to tell if the egg is mature or not. Only mature eggs are used for ICSI.
In summary, the egg goes from a GV to an M1 to an M2. A mature egg, or an M2 egg, is one that’s ready to be fertilized and is what we hope to get during an egg retrieval. However, sometimes immature M1 and GV eggs are retrieved.
In many labs, these immature eggs are discarded, but with rescue IVM they can potentially be used to make more mature eggs!
How does rescue in vitro maturation work?
Rescue IVM is a special type of in vitro maturation.
Traditional IVM involves a special type of IVF cycle where immature eggs are retrieved and then matured in the lab with a specific protocol.
In a regular IVF cycle, immature eggs can be retrieved along with mature eggs. Rescue IVM is a type of IVM that’s used to “rescue” these immature eggs so they can be used along with the other mature eggs from the same IVF cycle.
Rescue IVM often doesn’t require any specialized culture media or equipment and can be performed in most labs. Once immature eggs are identified, they can be left to develop in a culture dish for a few hours or overnight. After this period, the embryologist checks the immature eggs to see if they’ve matured and can then perform ICSI on them.
Some labs are overworked, and may not be able to accommodate rescue IVM cycles. This is because there are basically two rounds of ICSI being done (one round on the first set of M2 eggs, and another round on the rescue IVM mature eggs). If rescue IVM is done overnight, then the embryologist may need to perform ICSI in the morning when retrievals typically occur, which might be difficult if the clinic is understaffed.
How successful is rescue IVM?
A number of studies have investigated rescue IVM to see how well it works, let’s look at a couple of them.
This study cultured immature M1 eggs for 2-6 hours and any matured eggs were used for ICSI. For the rescue IVM eggs, they found lower fertilization rates, blastocyst conversion rates (fewer of them became blastocysts), and euploid rates. However, the pregnancy and live birth rates were similar.
Another study used rescue IVM to culture immature eggs (GV and M1) overnight and found that 89% of M1 eggs and 54% of GV eggs became mature over this time. Compared to M2 eggs from the same IVF cycle, these eggs had similar fertilization and euploid rates, but lower blastocyst conversion rates.
You can see the data for this last study below (note that p-values below 0.05 are statistically significant, and in this case, only the blastocyst conversion rates are statistically significant).
Source: Remembryo
Unfortunately, pregnancy outcomes are a bit limited when it comes to rescue IVM. This is because IVF clinics prioritize transferring embryos from normally mature M2 eggs over immature eggs made mature by rescue IVM. Still, there are reports of live births.
Should you do rescue IVM?
Rescue IVM may be a great method to increase the number of usable eggs in a cycle, particularly for those with a lot of immature eggs or with low numbers of eggs retrieved.
While there has been success in generating more eggs to make embryos for transfer, there is limited evidence regarding pregnancy outcomes. It’s possible that these embryos may miscarry more often, for example, but because of the limited data, it’s hard to say for sure. To overcome this, testing the rescue IVM embryos by PGT-A and only transferring euploids might be a good strategy!
Regardless, it’s definitely something that needs to be discussed with your doctor. Many labs may not feel comfortable doing rescue IVM, either because of limited data or because of limited staffing to handle the additional work, but it's still worth having the conversation!
Sean Lauber a.k.a. "Embryoman" is a former embryologist and creator of Remembryo.com, where he provides weekly summaries of the latest IVF research. You can also follow him on Facebook, Instagram and TikTok.