Culturing immature eggs overnight by rescue IVM increases number of euploids in cycle

Researchers in a 2023 study used rescue IVM and found that many immature eggs became mature and had comparable fertilization and euploid rates to sibling mature eggs, although there was a decrease in blastocyst formation rates.

Many IVF cycles result in immature eggs, which are normally discarded, but continued culture of these immature eggs by rescue in vitro maturation (rescue IVM), may be a viable way to maximize the number of mature eggs in an IVF cycle.

Elkhatib et al. (2023) compared embryology outcomes of normally matured eggs and rescue IVM eggs, which were immature at retrieval but matured overnight. This study involved 390 patients and 5,449 retrieved eggs, and took place between 2019 and 2021 at a fertility clinic in the United Arab Emirates.

Key information:

Rescue IVM eggs: Eggs that weren’t mature at the time of retrieval that matured overnight after 20-28 hours since the eggs were stripped/denuded following retrieval.
Sibling eggs: Eggs that were mature at the time of retrieval. These are eggs from the same IVF cycle (sibling eggs) as the rescue IVM eggs.
Only PGT-A cycles were included to evaluate euploid rates. Day 5-7 blastocysts, with a quality of 3CC or higher, were eligible for biopsy.
This IVF center had a policy where IVF was used on 25-50% of retrieved eggs in non-male factor cases, while the rest were inseminated by ICSI.
The average female age was 36.45.

As a reminder, immature eggs come as two types: germinal vesicle (GV) or metaphase 1 (M1). Eggs mature starting from a GV, then to M1, then to M2. So a GV is less mature than an M1. For more background on egg quality and maturity, check out my Complete guide to egg quality.

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Rescue IVM eggs have similar fertilization, euploid rates, but are less likely to become blastocysts

In total, there were 5,449 eggs that were collected among the 390 patients.

A total of 4,751 eggs were used for ICSI, with 1,840 that were immature (38.7%). After rescue IVM, 910 matured (49.5%) and 930 didn’t. So half of the immature eggs on the day of retrieval became mature after rescue IVM.

The rescue IVM eggs were compared to normally matured eggs from the same IVF cycle (sibling eggs).

You can see the embryology outcomes for the rescue IVM eggs and the sibling eggs below. The blastocyst biopsy rate refers to blastocysts that were eligible for biopsy (quality 3CC or higher on day 5-7). There were statistically significant differences between the fertilization and blastocyst biopsy rates (p< 0.001), but not for the euploidy rates.

Just to give a better idea of the sample size here…There were 367 rescue-M1 mature eggs, 208 fertilized, 42 were biopsied and 16 were euploid. There were 543 rescue-GV mature eggs, 301 fertilized, 52 were biopsied and 21 were euploid. Approximately the same proportions of day 5-7 embryos were biopsied, for sibling eggs (33%, 60% and 7%) and rescue IVM eggs (32%, 57% and 11%).

So immature eggs (M1 or GV) that were matured overnight by rescue IVM had a lower fertilization rate compared to sibling eggs. Rescue IVM eggs were less likely to produce blastocysts, but the blastocysts that were produced had the same chance as the sibling eggs as being euploid.

The big thing that they’re finding here is that rescue IVM eggs are less likely to produce blastocysts.

They performed another analysis and found that the odds of having a blastocyst biopsied from rescue IVM eggs decreased by 4% for every year of increased age (odds ratio [95% CI]: 0.96 [0.92-1.0]). Another analysis found that patients with 50% or more of their blastocysts from rescue IVM eggs were generally older (average age 37.76), had <10 eggs retrieved, had <34% mature eggs, and/or had <60% fertilization.

Using rescue IVM on immature eggs increases the number of euploids available for transfer

The researchers found that the chance of getting a euploid increased with the number of rescue IVM eggs the patient had. In this study, rescue-GV eggs had a higher chance of being euploid.

Rescue IVM pregnancy outcomes

Now for the pregnancy outcomes!

Unfortunately, as is the case with these rescue IVM studies, there isn’t much data to work from. This is because euploids from rescue IVM eggs are generally considered secondary to euploids from normally matured eggs.

There were a total of 17 euploids from rescue IVM eggs transferred in this study:

3 single embryo transfers: 1 live birth, 1 miscarriage
2 double embryo transfers: 1 ongoing pregnancy
9 double embryo transfers, with a euploid from a rescue IVM egg and a euploid from a normally matured egg: 5 singletons; 1 twin; 1 miscarriage. One of the singletons was confirmed to be from rescue IVM, 2 were from normally matured eggs, and the other 2 are ongoing.

This adds up to 16, not 17, but that’s the information they provided!

Conclusion

Rescue IVM eggs had a lower fertilization rate compared to sibling eggs, and were less likely to produce blastocysts. However, the blastocysts produced from rescue IVM eggs or sibling eggs had the same chance of being a euploid.

The chance of getting a euploid increased with the number of rescue IVM eggs the patient had, from about 2% with 1 egg to up to 86% with 12, depending on whether it was a GV or M1 immature egg.

There were limited pregnancy outcomes to compare, since euploids from rescue IVM eggs are generally prioritized after euploids from mature eggs. In total, there were 16 euploids from rescue IVM eggs transferred, with most being combined with a sibling euploid, and 5 from a single/double euploid transfer from rescue IVM eggs (1 live birth, 1 ongoing, 1 miscarriage)

They found that patients that benefited most from rescue IVM were older, had lower egg maturity rates, and/or had low fertilization.

This study comes after another one that found similar outcomes, and if you’d like to read about that study check out my post Immature eggs cultured overnight by rescue IVM show promising IVF outcomes.

Reference

Elkhatib I, Nogueira D, Bayram A, Abdala A, Del Gallego R, Melado L, De Munck N, Lawrenz B, Fatemi H. How to identify patients who would benefit from delayed-matured oocytes insemination: a sibling oocyte and ploidy outcome study. Hum Reprod. 2023 Aug 1;38(8):1473-1483. doi: 10.1093/humrep/dead129. PMID: 37344149.

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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.