Study compares IVF outcomes by follicle size

Researchers in a 2020 study compared IVF outcomes by follicle sizes, and found that larger follicles generally produced mature eggs that were more likely to develop into blastocysts.

This study looked at follicle size by carefully measuring each follicle before aspiration, and separating the resulting egg from the other eggs. These eggs were then inseminated and their development was monitored independently.

Larger follicles are generally believed to be more likely to produce mature and good quality eggs compared to smaller follicles.

Although there have been previous studies that related follicle size with fertilization and embryo quality, there have been no studies that look at euploidy.

Just so everyone’s on the same page, eggs mature from GV –> MI –> MII (MII eggs are mature eggs). So there’s two stages of immaturity before becoming mature (a GV – germinal vesicle, and MI).

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Results

317 eggs were retrieved from 22 egg donors with measured follicle diameters:

• 255 were mature (MII) (80.4%)
• 31 were immature (GV) (9.8%)
• 29 were immature (MI) (9.1%)

These 255 mature eggs were inseminated by ICSI:

• 228 were fertilized (89.4%)
• 94 became blastocysts that were biopsied (36.8%)
• 51 were euploid (20.0% of the mature eggs, or 54.3% of the biopsied blasts)

The size of the follicles were matched to these different eggs. Each egg was cultured individually so they could be followed during embryo culture.

In terms of the average size of follicles and the maturity of the egg inside:

• Immature (GV) eggs had a diameter of 12.5 +/- 1.6 mm (+/- means “plus or minus” so most of the follciles were 10.9 to 14.1 mm in diameter, with the “mean” or average being 12.5).
• Immature (MI) eggs had a diameter of 15.3 +/- 3.2 mm.
• Mature (MII) eggs had a diameter of 18.3 +/- 2.2 mm.

In terms of the proportions of these eggs based on the diamter of the follicle:

• <12 mm: 100% GV
• 12 – 14.6 mm: 48% GV, 29% MI, and 23% MII
• 14.7 – 21.8 mm: 5% MI, 95% MII

So the larger the follicle, the more likely the egg inside is mature!

There were no differences in fertilization based on follicle size.

There were no differences in abnormal fertilization and follicle size. Abnormal fertilization is having more than or less than 2 pronuclei (so 3 PN or 1 PN for example).

Fertilized eggs that came from larger follicles (>18.3 mm) were more likely to develop into blastocysts.

There were no differences in an embryo’s grade for either the ICM or the trophectoderm (good, fair or poor based on standard Gardner grading) and follicle size.

Of the 91 embryos that were biopsied, 51 were found to be euploid (54.3%) and there was no difference in the size of follicles and the chance of getting a euploid.

Conclusions

Follicle sizes are different between GV, MI and MII eggs. Eggs from follicles smaller than 12 mm are more likely to be GV (immature), and eggs from follicles >17 mm are more likely to be MII (mature) eggs.

But there is overlap! So follicle size isn’t an absolute predictor of egg maturity. However, follicles <12 mm are highly likely to be GV (immature).

The “quality” of an egg isn’t necessarily dictated by the size of the follicle, as there are many factors that showed no difference in large vs small follicles, including: fertilization, euploidy, and quality blastocyst formation. Although there was a difference in fertilized eggs from larger follicles compared to fertilized eggs from smaller follicles (the larger follicles were more likely to make blastocysts).

This study was carried out in good prognosis donors. It’s not clear if the results would be different in a different group.

Reference

McCulloh DH, Kutchukhidze N, Charkviani T, Zhorzholadze T, Barbakadze T, Munné S, Chkonia L. Follicle size indicates oocyte maturity and blastocyst formation but not blastocyst euploidy following controlled ovarian hyperstimulation of oocyte donors. Hum Reprod. 2020 Mar 27;35(3):545-556. doi: 10.1093/humrep/dez291. PMID: 32142586.

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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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