Skip to content
IVF BIG DATA

ESHRE 2015 · Poster presentation

Association between blastocyst morphology and euploidy rates in different age groups analyzed by aCGH and SNP PGD

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

Reproductive Science Center of the San Francisco Bay Area, USA

ESHRE 2015 Annual Meeting

535

IVF PGD cycles

364 SNP · 171 aCGH · Jan 2013 – Mar 2015

2,715

Embryos analyzed

Good 1,057 · Fair 962 · Poor 696

71.8 %

Euploidy · good < 38 y.o.

vs 58.9 % fair · 48.9 % poor

59.6 → 47.4 %

Day 5 vs Day 6 euploidy

± 4.1 / 3.8 · p < 0.05

Background

Why this study

The vast majority of aneuploidies in preimplantation embryos are of maternal origin (meiotic or mitotic); the proportion of aneuploid embryos rises with age. Previous studies have shown that aCGH- and SNP-based PGT are the most reliable techniques to determine genetic status of embryos in vitro.

Objective. Identify the association between blastocyst morphology and euploidy rates in different age groups in PGT cycles.

Materials & Methods

Cohort and grouping

  • Design. Retrospective comparative study, January 2013 – March 2015. 535 IVF PGT cycles — 364 SNP, 171 aCGH.
  • Embryos. 2,715 analyzed. Morphology graded by two embryologists (Gardner classification) before trophectoderm biopsy.
  • Groups. Quality — good (AA/AB/BA, 1,057), fair (BB, 962), poor (C−/−C, 696). Age — SART age groups.

Results · Age vs cohort yield

Euploidy and blastulation both fall sharply with advancing age

Average maternal age was 38.03 ± 3.56 (51 % ≥ 38 y.o.). Blastulation rate in donor- egg PGT was 68.08 %; in autologous cycles it fell from 70.42 % in patients < 35 y.o. to 35.81 % in patients > 45 y.o.

Euploidy rates decreased gradually with age. The combined drop in blastulation and euploidy caused a rapid reduction in the number of euploid embryos available for transfer.

Results · Morphology by age

The morphology–euploidy gap is largest in younger patients and narrows with age

Statistically significant difference in euploidy between good, fair, and poor quality embryos in all age groups (p < 0.05, χ² = 9.72). In patients < 38 y.o.: 71.84 % (421/586), 58.89 % (298/506), 48.87 % (173/354) — good / fair / poor.

Regression coefficients of euploidy vs age: good y = −5.356x + 89.82, fair y = −4.777x + 71.64, poor y = −2.746x + 32.04. In patients > 40 y.o., good / fair / poor fell to 38.96 % / 31.25 % / 11.56 % (p < 0.05, χ² = 6.08).

The proportion of good / fair / poor embryos remained roughly stable across age groups, with only a small decrease in good-quality share (linear regression: y = −0.865x + 42.57).

Results · Day 5 vs Day 6 × morphology

Euploidy tracks both expansion and ICM/TE quality on both biopsy days

Day-5 embryos are more often euploid than day-6 — 59.62 ± 4.1 % vs 47.41 ± 3.8 %, p < 0.05. The pattern held in every morphology class (Fig. 6).

AA
AB/BA
BB
B−/−B
C−/−C
Exp. 1
n/a
0%
n/a
n/a
n/a
Exp. 2
81%
46%
41%
27%
0%
Exp. 3
63%
59%
51%
47%
33%
Exp. 4
61%
74%
61%
75%
n/a
Exp. 5
71%
72%
58%
50%
n/a
Exp. 6
86%
85%
67%
33%
n/a
Fig. 7 (top) — Euploidy rate · day 5 biopsy, by expansion × ICM/TE quality.
AA
AB/BA
BB
B−/−B
C−/−C
Exp. 1
0%
100%
0%
n/a
8%
Exp. 2
50%
33%
28%
29%
14%
Exp. 3
57%
48%
41%
25%
22%
Exp. 4
50%
39%
52%
36%
33%
Exp. 5
68%
57%
48%
44%
18%
Exp. 6
81%
67%
64%
48%
75%
Fig. 7 (bottom) — Euploidy rate · day 6 biopsy.

Results · Pregnancy outcomes

Ongoing PR is significantly higher when a good-quality euploid embryo is transferred

Analysis of ongoing PR after single euploid ET showed euploid good-quality embryos have a higher chance of implantation. Regardless of oocyte source, ongoing PR was significantly higher when good-quality embryos were available for ET in PGT cycles (Fig. 8).

Conclusion

Summary of findings

Reliable data about the correlation between morphology and euploidy will help clinicians create the best treatment strategy and help patients make informed decisions about the necessity of PGT based on maternal age, quality, and number of embryos.

References

Cited works

  1. 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;24(1):4–5. PubMed
  2. 2.Fragouli E, Alfarawati S, Spath K, et al. The origin and impact of embryonic aneuploidy. Hum Genet. 2013;132:1001–1013. PubMed
  3. 3.Schoolcraft WB, Katz-Jaffe MG. Comprehensive chromosome screening of trophectoderm with vitrification facilitates elective single-embryo transfer for infertile women with advanced maternal age. Fertil Steril. 2013;100:615–619. PubMed
  4. 4.Harper JC, Harton G. The use of arrays in PGD/PGS. Fertil Steril. 2010;94:1173–1177. PubMed
  5. 5.Handyside AH. 24-chromosome copy number analysis: a comparison of available technologies. Fertil Steril. 2013;100:595–602. PubMed
  6. 6.Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11(3):307–311. PubMed

Reprint requests

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