SETTING EXPECTATIONS FOR COUPLES UNDERGOING PREIMPLANTATION GENETIC TESTING (PGT) FOR TWO SEPARATE INHERITED SINGLE GENE DISORDERS WITH CONCURRENT 24 CHROMOSOME ANEUPLOIDY SCREENING

Abstract STUDY QUESTION Does the reproductive potential of embryos change when blastocyst development takes longer than the traditionally accepted 5 days when accounting for aneuploidy and endometrial-embryo asynchrony? SUMMARY ANSWER Aneuploidy increases with increasing duration of blastulation, but if blastocyst morphologic quality and endometrial-embryo asynchrony are controlled for, euploid Day 7 embryos have similar sustained implantation as compared to Days 5 and 6 euploid blastocysts. WHAT IS KNOWN ALREADY The relative contributions of diminished embryo quality versus endometrial and embryo asynchrony to poor outcomes associated with embryos cultured past Day 6 are not clear. Asynchrony can be eliminated by embryo vitrification with transfer in a subsequent month after retrieval. STUDY DESIGN, SIZE, DURATION Retrospective cohort study of patients from a single center attempting conception through ICSI and utilizing preimplantation genetic testing for aneuploidy screening (PGT-A) from January 2017 to September 2018. Cycles were excluded if they utilized surgical sperm or preimplantation genetic testing for monogenetic/single gene defects. ICSI cycle outcomes from 2586 patients were evaluated for ploidy status of embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS Only patients undergoing single, euploid frozen embryo transfer were included when analyzing cycle outcomes by day of blastocyst expansion of the transferred embryo (n = 2130). Ploidy rates by the day upon which an embryo was considered to be usable (denoted, ‘usable blastulation day’) were determined so as to assess the contribution of aneuploidy to slow embryo development. Outcomes of euploid frozen single embryo transfers (SET) of Day 7 embryos were evaluated to assess the reproductive potential associated with embryos that were slowly developing for reasons other than aneuploidy. Analyses were adjusted by maternal age and blastocyst morphology. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 67.7% (n = 3508) of usable Day 5 blastocysts were euploid, 52.1% (n = 5560) of usable Day 6 blastocysts were euploid and 43.1% (n = 229) of usable Day 7 embryos were euploid (Day 5 versus Day 6: odds ratio (OR) 0.7 (95% CI, 0.64–0.76), P < 0.001; Day 5 versus Day 7: OR 0.56 (95% CI, 0.46–0.69), P < 0.001; Day 6 versus Day 7: OR 0.81 (95% CI, 0.67–0.99), P = 0.036). Stratified by Society for Assisted Reproductive Technology maternal age groups, a reduction in the prevalence of euploidy by increasing time to embryo blastulation was still seen. The sustained implantation rate (SIR) was similar after euploid SET of Days 5 and 6 embryos (overall, 68.9% (95% CI, 66.0–71.6) and 66.8% (95% CI, 63.8–69.7), respectively; P = 0.81). SIR after euploid Day 7 SET appeared slightly lower than that of Days 5 and 6 embryos (52.6% (95% CI, 35.8–69.0); (Day 5 versus Day 7: OR, 0.67 (95% CI, 0.32–1.41), P = 0.29; Day 6 versus Day 7: OR 0.58 (95% CI, 0.28–1.2), P = 0.14)) but did not achieve statistical significance. LIMITATIONS, REASONS FOR CAUTION The primary limitation is the low number of Day 7 blastocyst transfers that limits statistical power. Additionally, the retrospective nature of this study may prevent full elucidation of potential biases with respect to culture, morphologic assessment and selection of Day 7 embryos for transfer. WIDER IMPLICATIONS OF THE FINDINGS Routine culture through Day 7 may successfully increase the pool of transferrable embryos for patients who would otherwise have no usable embryos if culture terminated on Day 6. This is particularly true for older patients (i.e. greater than 35 years of age), whose embryos take longer to blastulate and, therefore, are more susceptible to cycle cancelation. Additionally, as evidenced by an adequate overall SIR of 52.6% after euploid SET of Day 7 blastocysts, embryos developing to a usable blastocyst on Day 7 are likely within the ‘window of blastulation.’ STUDY FUNDING/COMPETING INTEREST(S) None.

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Spontaneous Conception during In Vitro Fertilization prior to Embryo Transfer without the Opportunity for Preimplantation Genetic Testing

Case Reports in Obstetrics and Gynecology ◽

10.1155/2019/1804948 ◽

2019 ◽

Vol 2019 ◽

pp. 1-3

Author(s):

Brindha Bavan ◽

Amin A. Milki

Keyword(s):

Genetic Testing ◽

In Vitro Fertilization ◽

Embryo Transfer ◽

Single Gene ◽

Multiple Pregnancy ◽

Preimplantation Genetic Testing ◽

Vitro Fertilization ◽

Spontaneous Conception ◽

Single Gene Disorders

In addition to the potential for multiple pregnancy, spontaneous conception during in vitro fertilization (IVF) can lead to undesired genetic outcomes. We present a case of a patient undergoing IVF with the intention of subsequent frozen embryo transfer after preimplantation genetic testing (PGT). Unprotected intercourse 6 days prior to egg retrieval resulted in a spontaneous pregnancy before the opportunity for embryo transfer. This case report highlights that spontaneous conception during IVF compromises the ability to transfer embryos that are euploid, unaffected by single gene disorders, or intended for gender balancing within a family when desired.

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PREIMPLANTATION GENETIC TESTING: Non-invasive prenatal testing for aneuploidy, copy-number variants and single-gene disorders

Reproduction ◽

10.1530/rep-19-0591 ◽

2020 ◽

Vol 160 (5) ◽

pp. A1-A11

Author(s):

J Shaw ◽

E Scotchman ◽

N Chandler ◽

L S Chitty

Keyword(s):

Copy Number ◽

Sex Chromosome ◽

Single Gene ◽

Copy Number Variants ◽

Prenatal Testing ◽

Aneuploidy Screening ◽

Preimplantation Genetic Testing ◽

Non Invasive ◽

Single Gene Disorders ◽

Cell Free Fetal Dna

The discovery of cell-free fetal DNA (cffDNA) in maternal plasma has enabled a paradigm shift in prenatal testing, allowing for safer, earlier detection of genetic conditions of the fetus. Non-invasive prenatal testing (NIPT) for fetal aneuploidies has provided an alternative, highly efficient approach to first-trimester aneuploidy screening, and since its inception has been rapidly adopted worldwide. Due to the genome-wide nature of some NIPT protocols, the commercial sector has widened the scope of cell-free DNA (cfDNA) screening to include sex chromosome aneuploidies, rare autosomal trisomies and sub-microscopic copy-number variants. These developments may be marketed as ‘expanded NIPT’ or ‘NIPT Plus’ and bring with them a plethora of ethical and practical considerations. Concurrently, cfDNA tests for single-gene disorders, termed non-invasive prenatal diagnosis (NIPD), have been developed for an increasing array of conditions but are less widely available. Despite the fact that all these tests utilise the same biomarker, cfDNA, there is considerable variation in key parameters such as sensitivity, specificity and positive predictive value depending on what the test is for. The distinction between diagnostics and screening has become blurred, and there is a clear need for the education of physicians and patients regarding the technical capabilities and limitations of these different forms of testing. Furthermore, there is a requirement for consistent guidelines that apply across health sectors, both public and commercial, to ensure that tests are validated and robust and that careful and appropriate pre-test and post-test counselling is provided by professionals who understand the tests offered.

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