Trophectoderm biopsy is associated with lower risks of moderate to extreme prematurity and low birthweights: a national registry cohort study of singleton livebirths from frozen-thawed blastocyst transfers

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BackgroundTrophectoderm biopsy has become the mainstay assisted reproductive technique performed for preimplantation genetic testing, accounting for 43.8% of embryo transfer cycles in the US in 2019 alone. Despite its prevalence, data on the obstetric and perinatal outcomes post trophectoderm biopsy remains sparse and mixed. ObjectiveThis study aimed to examine the risks of adverse perinatal outcomes in birth weights and prematurity after transfers of vitrified-thawed blastocyst with trophectoderm biopsy for preimplantation genetic testing. Study DesignThis was a retrospective observational cohort study of 45,712 singleton live births resulting from autologous vitrified-thawed blastocyst transfer cycles with or without trophectoderm biopsy for preimplantation genetic testing, reported by participating member clinics to the Society for Assisted Reproductive Technology national registry between 2014 and 2017. Adverse perinatal outcomes of preterm births and low birth weights were analyzed. Multivariable regression analyses were performed to control for covariates. Comparing the trophectoderm biopsy (n=21,584) and no trophectoderm biopsy (n=24,128) groups, adjusted odds ratios were calculated for the outcomes of small for gestational age, large for gestational age, low birth weight < 2,500 g, very low birth weight < 1,500 g, extremely low birth weight < 1,000 g, late preterm births < 37 weeks, moderate preterm births < 34 weeks, and extremely preterm births < 28 weeks. ResultsWomen in the trophectoderm biopsy group were older and more likely to have prior pregnancies, deliveries, and history of spontaneous abortions. Tobacco use, diminished ovarian reserve, and recurrent pregnancy loss were also more prevalent in the trophectoderm biopsy group. Trophectoderm biopsy was not associated with small-for-gestational-age (aOR 0.97, 95% CI 0.85-1.12, p-value 0.72) or large-for-gestational-age newborns (aOR 1.10, 95% CI 0.99-1.22, p-value 0.09). Risks of preterm births < 37 weeks gestation were similar between the biopsy and non-biopsy groups (aOR 0.93, 95% CI 0.85-1.02, p-value 0.11). Trophectoderm biopsy was associated with a significantly lower risk of low birthweight < 2,500 g (aOR 0.80, 95% CI 0.70-0.92, p-value <0.001), very low birthweight < 1,500 g (aOR 0.62, 95% CI 0.46-0.83, p-value <0.001), extremely low birthweight < 1,000 g (aOR 0.48, 95% CI 0.31-0.74, p-value <0.001), moderate preterm birth < 34 weeks (aOR 0.76, 95% CI 0.64-0.91, p-value 0.003), and extreme preterm birth < 28 weeks (aOR 0.63, 95% CI 0.43-0.92, p-value 0.017). ConclusionTrophectoderm biopsy is not associated with increased risks of small for gestational age, large for gestational age, or late preterm birth. Risks of low birthweight, very low birthweight, and extremely low birthweight from moderate and extreme preterm births are lower after trophectoderm biopsy, possibly by selecting against confined placental mosaicism or inducing placental epigenetic changes, the mechanisms of which warrant further investigation.