4.6 Review

Polygenic embryo screening: are there potential maternal and fetal harms?

Related references

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Summary: This review examines the impact of embryo biopsy on obstetric and neonatal outcomes. Limited evidence suggests that embryo biopsy may increase the risk of preterm delivery, low birthweight, and hypertensive disorders of pregnancy. However, more research is needed to fully understand the potential consequences of this procedure and develop alternative non-invasive approaches for preimplantation genetic testing (PGT).

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PGT-A is associated with reduced cumulative live birth rate in first reported IVF stimulation cycles age ≤ 40: an analysis of 133,494 autologous cycles reported to SART CORS

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Summary: This retrospective cohort study evaluates the impact of preimplantation genetic testing for aneuploidy (PGT-A) on cumulative live birth rate (CLBR) in IVF cycles using autologous oocytes. The study finds that PGT-A is associated with decreased CLBR for patients with blastocysts available for either embryo transfer or PGT-A, except for patients aged > 40. Furthermore, the use of PGT-A is associated with significantly higher CLBR in patients undergoing PGT-A and subsequent frozen embryo transfer. The non-PGT-A group has higher rates of multiple gestations, preterm birth, early pregnancy loss, and low birth weight.

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Summary: This study compared the perinatal outcomes of singleton babies conceived through blastocyst transfer versus cleavage-stage embryo transfer in frozen-thawed embryo transfer cycles. The results showed that infants born after blastocyst transfer had a higher risk of preterm birth, large for gestational age, and very large for gestational age compared to infants born after cleavage-stage embryo transfer.

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Cancer in children born after frozen-thawed embryo transfer: A cohort study

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Summary: Private companies have started offering services for parents undergoing in-vitro fertilisation to screen embryos for genetic risk of complex diseases, including psychiatric disorders. This raises difficult scientific and ethical issues, and the implications of polygenic embryo screening have not been adequately discussed. The International Society of Psychiatric Genetics is the first biomedical organization to issue a statement urging caution and further research on the use of polygenic embryo screening.

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Is Preimplantation Genetic Testing Associated with Increased Risk of Abnormal Placentation After Frozen Embryo Transfer?

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A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy

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Summary: The study aimed to determine the predictive value of PGT-A testing in forecasting the failure of successful delivery, finding high accuracy in predicting delivery failure with aneuploid results. Additionally, trophectoderm biopsy did not have a detectable adverse impact on sustained implantation.

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Greater fetal crown-rump length growth with the use of in vitro fertilization or intracytoplasmic sperm injection conceptions after thawed versus fresh blastocyst transfers: secondary analysis of a prospective cohort study

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Do assisted reproductive technologies and in vitro embryo culture influence the epigenetic control of imprinted genes and transposable elements in children?

J. Barberet et al.

Summary: This study compared the epigenetic profiles of children conceived through ART and naturally conceived children, finding significant differences in DNA methylation levels of IGs between the two groups. While there were no differences found in the culture media, specific IG regions related to development showed methylation changes between children conceived through ART and naturally conceived children.

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Impact of trophectoderm biopsy on obstetric and perinatal outcomes following frozen-thawed embryo transfer cycles

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Summary: The study suggests that trophectoderm biopsy may increase the risk of hypertensive disorders of pregnancy in frozen-thawed embryo transfer cycles, but does not have a significant impact on fetal growth restriction. Further research is needed to confirm these findings.

HUMAN REPRODUCTION (2021)

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Sonographic abnormalities in pregnancies conceived following IVF with and without preimplantation genetic testing for aneuploidy (PGT-A)

Carrie K. Riestenberg et al.

Summary: There was no significant difference in the rate of fetal anomalies between patients who underwent IVF with PGT-A, those who conceived following IVF with unscreened embryos, and age-matched patients with natural conceptions. However, IVF patients had higher rates of abnormal placental ultrasound findings and abnormal second trimester serum analytes compared to natural conception controls. The study emphasizes the importance of improved patient counseling regarding the limitations of PGT-A and providing standard prenatal care for pregnancies conceived through ART.

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS (2021)

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Lower risk of adverse perinatal outcomes in natural versus artificial frozen-thawed embryo transfer cycles: a systematic review and meta-analysis

Jose Moreno-Sepulveda et al.

Summary: This study found that in singleton pregnancies following IVF, natural cycle frozen embryo transfer (NC-FET) was associated with a lower risk of hypertensive disorders, preeclampsia, large for gestational age, and macrosomia compared to artificial cycle frozen embryo transfer (AC-FET), with no significant difference in the risk of gestational hypertension and small for gestational age. Additionally, NC-FET significantly decreased the risk of various other adverse perinatal outcomes such as preterm birth, post-term birth, low birth weight, cesarean section, postpartum hemorrhage, placental abruption, and placenta accreta.

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Does fresh or frozen embryo transfer affect imprinted gene expressions in human term placenta?

Asli Ozmen et al.

Summary: This study aimed to compare epigenetic alterations in placentae between IVF patients and spontaneous pregnancies, revealing that IVF techniques influence imprinted gene expressions in placentae, potentially impacting glucose transport and cell proliferation.

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Embryo biopsy and maternal and neonatal outcomes following cryopreserved-thawed single embryo transfer

Cynthia K. Sites et al.

Summary: The removal of cells for preimplantation genetic testing from embryos before frozen-thawed single embryo transfer does not increase the risk of adverse obstetrical or neonatal outcomes, including preeclampsia, pregnancy-related hypertension, placental disorders, preterm birth, low birthweight, cesarean delivery, gestational diabetes mellitus, or prolonged hospital stays for mothers and infants.

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Embryo biopsy and perinatal outcomes of singleton pregnancies: an analysis of 16,246 frozen embryo transfer cycles reported in the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System

Mengmeng Li et al.

Summary: The study compared perinatal outcomes in singleton pregnancies conceived following frozen embryo transfer with or without preimplantation genetic testing. The findings suggested a slightly increased risk of preterm birth with preimplantation genetic testing, while other outcomes such as birthweight showed no significant differences. Further investigation is warranted to fully understand the implications.

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY (2021)

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Utility of polygenic embryo screening for disease depends on the selection strategy

Todd Lencz et al.

Summary: This study predicts the expected reduction in complex disease risk following polygenic embryo screening for a single disease based on the liability threshold model. Selecting embryos with the lowest PRS can lead to substantial risk reductions, highlighting the importance of selection strategy. Various factors such as variance explained by the PRS and the number of embryos impact the utility of screening.

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Influence of Trophectoderm Biopsy Prior to Frozen Blastocyst Transfer on Obstetrical Outcomes

Michael S. Awadalla et al.

Summary: The study found that trophectoderm biopsy before frozen blastocyst transfer in programmed cycles was not associated with adverse obstetric outcomes related to gestational age at delivery, birth weight, or cesarean rate.

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Impact of preimplantation genetic testing on obstetric and neonatal outcomes: a systematic review and meta-analysis

Wenhui Hou et al.

Summary: The study found that preimplantation genetic testing (PGT) does not increase the risk of adverse obstetric outcomes, but is associated with a higher risk of hypertensive disorders of pregnancy and further investigation is needed for the risk of IUGR.

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Cardiac remodeling in fetuses conceived by ARTs: fresh versus frozen embryo transfer

M. L. Boutet et al.

Summary: The study found that embryos transfer impacts fetal cardiac remodeling and suboptimal function, with more pronounced changes after fresh embryo transfer compared to frozen embryo transfer. Fetuses conceived by assisted reproductive technologies showed larger atria, more globular ventricles, and thicker myocardial walls, as well as signs of suboptimal systolic and diastolic function as compared to spontaneously conceived pregnancies.

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Obstetric and neonatal outcomes of pregnancies resulting from preimplantation genetic testing: a systematic review and meta-analysis

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Summary: Pregnancies conceived after PGT show a higher risk of LBW, PTD, and HDP compared to spontaneously conceived pregnancies, but have overall more favorable obstetric and neonatal outcomes than IVF/ICSI pregnancies. Further studies are needed to confirm these conclusions.

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PGT-A: who and when? Α systematic review and network meta-analysis of RCTs

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Summary: Preimplantation genetic testing for aneuploidy (PGT-A) did not improve clinical outcomes for the general population, however it improved live-birth rates strictly when performed on blastocyst stage embryos of women over the 35-year-old mark.

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Problems with Using Polygenic Scores to Select Embryos

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