Evaluating IVF and perinatal outcomes following repeat trophectoderm biopsy

Full text

American Society for Reproductive Medicine 2018 Scientific Congress & Expo
October 6 to 10, 2018 Denver, Colorado, USA
Title:
EVALUATING IVF AND PERINATAL OUTCOMES FOLLOWING REPEAT
TROPHECTODERM BIOPSY
Authors:
Sekhon L1,2, McAvey BA1, Lee JA1, Briton-Jones C1, Duke MJ1, Copperman AB1
Affiliations:
1. Reproductive Medicine Associates of New York, 635 Madison Ave 10th Floor New
York, New York, United States, 10022
2. Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount
Sinai, Klingenstein Pavilion 1176 Fifth Avenue 9th Floor New York, New York, United
States, 10029
Objective:
Trophectoderm biopsy (TB) and preimplantation genetic testing (PGT) enable the identification
and selection of euploid embryos for transfer. Occasionally, PGT is limited by failed DNA
amplification, data inconsistency, or other technical limitations, resulting in a non-diagnostic
result. In these situations, patients must choose whether to have these embryos warmed and
transferred “unscreened,” or rebiopsied and reanalyzed, and depending upon the results, then
transferred in a subsequent cycle. While the safety of blastocyst vitrification and TB has been
widely demonstrated in both the literature and clinical practice, there is a paucity of data
regarding the impact of repeated TB. Furthermore, it is not known whether repeat TB could
have downstream effects on placentation. The purpose of our study was to evaluate whether
repeat TB has an impact on IVF and perinatal outcome, while controlling for the effects of
double vitrification-warming.
Design:
Retrospective, cohort study
Materials and Methods:

Patients who underwent euploid frozen embryo transfer (FET) of blastocysts that underwent
double or single TB from October 2013 to March 2018 were included in the analysis.
Quantitative polymerase chain reaction (PCR), array comparative genomic hybridization
(aCGH), and targeted next generation sequencing (NGS) were used to perform preimplantation
genetic testing (PGT). Patients were grouped by the number of TBs performed during treatment.
The double TB group underwent transfer of a euploid frozen-thawed blastocyst after warming,
rebiopsy and re-vitrification due to a non-diagnostic PGT result after initial TB. The single TB
group had previously vitrified unscreened embryos that were warmed, biopsied once and re-
vitrified, prior to FET. The baseline demographics, cycle characteristics, and outcomes were
compared between groups. IVF outcomes included implantation, ongoing pregnancy, early
pregnancy loss (EPL), and live birth. Perinatal outcomes included gestational age, infant
birthweight, and the rates of preterm delivery and low birth weight. Student’s t-test, chi-square,
linear and binary logistic regression analysis were performed.
Result(s):
Eighty-one patients whose embryos underwent double TB to obtain definitive PGT results prior
to ET were compared to 56 controls. Baseline demographics, FET cycle characteristics and
outcomes are shown in Table 1. Controlling for oocyte age, BMI, endometrial thickness,
hatching status, and day of biopsy, the odds of ongoing pregnancy was reduced in the double TB
group (OR 0.37 [95% CI 0.15-0.95], p=0.0382). The odds of EPL were not modified by double
TE biopsy (OR 3.49 [95% CI 0.77-15.8], p=0.11). Controlling for age, gestational age at delivery
was not impacted by the number of TB biopsies (b= 0.70, p=0.21). Controlling for age and
gestational age at delivery, double TB biopsy did not significantly impact infant birthweight (b=
-144.2, p=0.39).
Conclusion(s):
While repeat embryo vitrification and thawing can be safely performed in the modern IVF
laboratory, our findings suggest that performance of a second TB may decrease blastocyst
implantation potential. Once pregnancy is established, patients that undergo transfer of double
biopsied blastocysts can be reassured that they are not at increased risk of pregnancy loss,
preterm delivery or reduced infant birthweight. As the capability of PGT technology expands,
patients may request that their embryos undergo repeat testing for conditions for which these
embryos were not originally tested, warranting further studies to confirm our findings. Our study
design allowed us to isolate the effect of repeat TB, by controlling for embryo exposure to
double vitrification and warming. While there appears to be a 15% decrease in implantation rate
for vitrified embryos that undergo rewarming, biopsy, and refreezing, this risk must be balanced
against the potential benefits gained from obtaining a clinically impactful PGT diagnosis.

Financial Support:
None
References:
None
Table 1:
Single TB
Double TB
p value
Patient age at ET
35.4 ± 4.1 (23.5-43.9)
36.8 ± 4.1 (25.3-44.6)
0.0626
Oocyte age
32.9 ± 4.1 (23.1-40.0)
36.1 ± 4.1 (25.1-42.9)
<0.0001
BMI at ET
22.6 ± 3.8
24.0 ± 4.9
0.0641
Endometrial
thickness at ET (mm)
9.3 ± 1.9
9.7 ± 2.2
0.3797
Proportion of
embryos that
underwent first TE
biopsy on day 5
42.9% (24/56)
53.1% (43/81)
0.239
Proportion of
embryos that
underwent first TE
biopsy on day 6
50.0% (28/56)
43.2% (35/81)
0.433
Proportion of
embryos that
underwent first TE
biopsy on day 7
7.1% (4/56)
3.7% (3/81)
0.369
Proportion of hatched
(expansion grade 6)
embryos
25.0% (14/56)
51.9% (42/81)
0.001673
Implantation rate
66.1% (37/56)
40.7% (33/81)
0.003548
Ongoing pregnancy
rate
62.5% (35/56)
35.8% (29/81)
0.002077
Early pregnancy loss
rate
7.5% (3/40)
18.2% (8/44)
0.14723
Live birth rate
45.9% (17/37)
31.0% (13/42)
0.1706
Gestational age at
delivery
37.8 ± 1.7
38.5 ± 1.1
0.2027
Preterm delivery rate
11.8% (2/17)
7.7% (1/13)
0.8923
Infant birthweight
3400.2 ± 524.6
3365.1 ± 378.5
0.8562

Low birthweight
5.9% (1/17)
0.0% (0/13)
0.392804