ASRM 2014 · Poster presentation

Comparison of blastocyst morphology and euploidy rates analyzed by SNP and aCGH PGS — 1003 embryos review

O. O. Barash, K. A. Ivani, S. P. Willman, N. Huen, S. C. Lefko, L. N. Weckstein

Reproductive Science Center of the San Francisco Bay Area, USA

ASRM 2014 — Annual Scientific Congress (Honolulu, HI)Fertility and Sterility, 2014; Vol. 102, Issue 3, e182–e183.

173

IVF cycles with PGS

98 SNP · 75 aCGH

1,003

Embryos analyzed

Day 5 or day 6 trophectoderm biopsy

66.9 vs 52.6%

Euploidy: D5 vs D6

± 4.7 / 3.9 % · p < 0.05

≈ NS

SNP vs aCGH overall

52.4 ± 8.1 % vs 55.1 ± 6.1 % · p = 0.16

Background

Why this study

Recent publications have demonstrated significant improvement in IVF treatment outcomes by implementing aCGH or SNP-based preimplantation genetic screening (PGS) (Bisignano et al., 2011; Harper et al., 2010). A correlation between embryo morphology and chromosomal status has been discussed by some authors (Finn et al., 2010; Wells et al., 2010; Alfarawati et al., 2011).

Objective. Identify the relationship between blastocyst morphology and euploidy rates analyzed by SNP- and aCGH-based PGS.

Materials & Methods

Cohort and laboratory workflow

Design. Retrospective review of PGS outcomes for blastocysts biopsied on day 5 or day 6.
Period. January 2013 – March 2014; 173 IVF cycles (98 SNP, 75 aCGH).
Embryo selection. Day 3 hatching; biopsy on day 5 or day 6 with at least 3–7 herniating cells, meeting cryopreservation criteria. Poor-quality blastocysts biopsied only by MD or patient request.
Grading. Gardner classification (Gardner & Schoolcraft, 1999): expansion 1–6; quality good (AA / AB / BA), fair (BB), poor (−C / C−).

Results · Day 5 vs Day 6

Embryos available on day 5 are more often euploid

Euploidy rate was significantly higher for embryos available for biopsy on day 5 than for embryos available on day 6 — 66.9 ± 4.7 % vs 52.6 ± 3.9 %, regardless of blastocyst expansion (p < 0.05). The average number of blastocysts biopsied per case was 5.8 ± 3.3; the day 5 vs day 6 gap widened with advancing patient age.

Among non-expanded blastocysts the day 5 vs day 6 difference was reliable — 57.7 ± 7.1 % vs 35.2 ± 4.9 % (p < 0.05). For expanded blastocysts the difference was not significant — 61.9 ± 8.3 % vs 58.7 ± 6.9 % (p = 0.4591).

Fig. 4 — Euploidy rate by blastocyst expansion category, day 5 vs day 6 biopsy.

Results · Morphology & expansion

Euploidy rises with both quality and degree of expansion

We observed a strong correlation between euploidy rates and embryo quality within the same patient age group: good-quality blastocysts had a much higher rate of euploidy than poor-quality blastocysts. Within each quality group, euploidy also tracked with the degree of blastocyst expansion (Fig. 5).

AB / BA

B− / −B

C− / −C

Expansion 1

50%

n/a

11%

Expansion 2

69%

48%

23%

31%

13%

Expansion 3

60%

48%

32%

23%

Expansion 4

69%

70%

61%

47%

33%

Expansion 5

73%

67%

52%

47%

22%

Expansion 6

79%

66%

70%

47%

Fig. 5 — Euploidy rate by blastocyst expansion (rows) and ICM / trophectoderm quality (columns). Higher rates are darker blue.

Results · SNP vs aCGH

Both platforms produced equivalent euploidy estimates

Overall euploidy rates defined by SNP were very similar to aCGH — 52.4 ± 8.1 % vs 55.1 ± 6.1 % (p = 0.16) — and were not statistically different in any of the study subgroups.

Results · Pregnancy outcomes

Day 5 biopsy is associated with higher pregnancy rates

We observed a statistically significant difference in pregnancy rates between cases where embryos selected for ET were biopsied on day 5 versus day 6 (χ² = 20.2032, p < 0.05). The contrast was even more dramatic for women over 38 years of age (mean age 40.1 ± 1.8 years).

Fig. 6 — Ongoing PR per ET, patients ≥ 38 years.

Conclusion

Summary of findings

Comprehensive chromosome screening provides an opportunity to re-evaluate the correlation between embryo euploidy and embryo morphology in order to design the best treatment strategy for the infertile couple undergoing IVF. There is a significant difference in euploidy rates depending on blastocyst quality and on the day they become available for biopsy; however, our data demonstrated no difference between SNP- and aCGH-based PGS in determining euploidy rates in human blastocysts.

References

Cited works

1.Bisignano A, Wells D, Harton G, Munné S. Reply: PGD and aneuploidy screening for 24 chromosomes by genome-wide SNP analysis: a responsible path towards greater utility. Reprod Biomed Online. 2012 Jan;24(1):4–5. PubMed
2.Harper JC, Harton G. The use of arrays in PGD/PGS. Fertil Steril 2010; 94:1173–1177. PubMed
3.Finn A, Scott L, Davies D, Hill J. Sequential embryo scoring as a predictor of aneuploidy in poor-prognosis patients. Reprod Biomed Online. 2010 Sep;21(3):381–390. PubMed
4.Alfarawati S, Fragouli E, Colls P, et al. The relationship between blastocyst morphology, chromosomal abnormality, and embryo gender. Fertil Steril. 2011 Feb;95(2):520–524. PubMed
5.Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999 Jun;11(3):307–311. PubMed

Reprint requests

Oleksii Barash, Ph.D. · ivfbigdata@gmail.com