Blinded rebiopsy and analysis of noneuploid embryos with 2 distinct preimplantation genetic testing platforms for aneuploidy.

OBJECTIVE: To determine how often a noneuploid result from a single trophectoderm (TE) biopsy tested with the next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) is concordant with rebiopsies tested with a single-nucleotide polymorphism (SNP) array-based PGT-A platform. DESIGN: Blinded prospective cohort study. SETTING: University-affiliated fertility center. PATIENT(S): One hundred blastocysts were chosen from donated samples; on TE biopsy with NGS-based PGT-A, 40 had at least one whole chromosome full copy number aneuploidy alone, 20 had a single whole chromosome intermediate copy number ("whole chromosome mosaic"), 20 had a single full segmental aneuploidy (segA), and 20 had a single segmental intermediate copy number ("segmental mosaic"). INTERVENTIONS: Four rebiopsies were collected from each embryo: 3 TE biopsies and the remaining embryo. Each rebiopsy was randomized, blinded, and assessed with an SNP array-based PGT-A platform that combines copy number and allele ratio analyses, without mosaicism reporting. MAIN OUTCOME MEASURE(S): Concordance between the NGS result and rebiopsy results and within each embryo's blinded rebiopsy results. RESULT(S): Next-generation sequencing-diagnosed whole chromosome aneuploidy (WCA) was reconfirmed in 95% (95% confidence interval [CI], 83%-99%) of embryos; 2 embryos with NGS-diagnosed WCA were called euploid on all conclusive rebiopsies. Among embryos with NGS-diagnosed whole chromosome mosaicism, 35% (95% CI, 15%-59%) were called euploid and 15% (95% CI, 3%-38%) were called whole chromosome aneuploid on all conclusive rebiopsies. A total of 30% (95% CI, 12%-54%) of embryos with NGS-diagnosed segA and 65% (95% CI, 41%-85%) of embryos with NGS-diagnosed segmental mosaicism were called euploid on all conclusive rebiopsies. In total, 13% (95% CI, 6%-25%) of embryos with NGS-diagnosed full copy number aneuploidy and 50% (95% CI, 34%-66%) of embryos with NGS-diagnosed mosaicism had uniformly euploid SNP results. Conversely, all embryos with at least one noneuploid SNP result (n = 72) either had SNP-diagnosed aneuploidy on another rebiopsy from the same embryo or NGS-diagnosed aneuploidy/mosaicism involving the same chromosome. CONCLUSION(S): Next-generation sequencing-diagnosed WCA is highly concordant with rebiopsies tested with an SNP array-based PGT-A; however, whole chromosome mosaicism, segA, and segmental mosaicism are less concordant, reinforcing that embryos with these results may have reproductive potential and be suitable for transfer.

Deliveries from trophectoderm biopsied, fresh and vitrified blastocysts derived from polar body biopsied, vitrified oocytes.

This longitudinal study reports preliminary findings of six patients who underwent first polar body biopsy followed by oocyte vitrification. All oocytes were warmed, inseminated by intracytoplasmic sperm injection and cultured to blastocyst. All suitable blastocysts underwent trophectoderm biopsy for aneuploidy screening, and supernumerary blastocysts were vitrified. Euploid blastocysts were transferred either fresh or in a subsequent programmed cycle. Of the 91 metaphase II oocytes, 30 had euploid first polar bodies. Development to blastocyst was more likely in oocytes with a euploid first polar body (66.7% versus 24.6%; P < 0.001). Nineteen euploid blastocysts were produced: 10 from oocytes with a euploid first polar body and nine from oocytes with an aneuploid first polar body. Five out of six patients (83%) had a live birth or ongoing pregnancy at the time of analysis. Eleven euploid blastocysts have been transferred and seven implanted (64%). Although the chromosomal status of the first polar body was poorly predictive of embryonic ploidy, an association was found between chromosomal status of the first polar body and development to blastocyst. Further study is required to characterize these relationships, but proof of concept is provided that twice biopsied, twice cryopreserved oocytes and embryos can lead to viable pregnancies.

In vitro fertilization with preimplantation genetic screening improves implantation and live birth in women age 40 through 43.

PURPOSE: In Vitro Fertilization is an effective treatment for infertility; however, it has relatively low success in women of advanced maternal age (>37) who have a high risk of producing aneuploid embryos, resulting in implantation failure, a higher rate of miscarriage or birth of a child with chromosome abnormalities. The purpose of this study was to compare the implantation, miscarriage and live birth rates with and without preimplantation genetic screening (PGS) of embryos from patients aged 40 through 43 years. METHODS: This is a retrospective cohort study, comparing embryos screened for ploidy using trophectoderm biopsy and array comparative genomic hybridization to embryos that were not screened. We compared pregnancy outcomes for traditional fresh IVF cycles with day 5 embryo transfers, Frozen Embryo Transfer (FET) cycles without PGS and PGS-FET (FET of only euploid embryos) cycles of patients with maternal ages ranging from 40 to 43 years, undergoing oocyte retrievals during the period between 1/1/2011 and 12/31/2012. RESULTS: The implantation rate of euploid embryos transferred in FET cycles (50.9%) was significantly greater than for unscreened embryos transferred in either fresh (23.8%) or FET (25.4%) cycles. The incidence of live birth per transferred embryo for PGS-FET (45.5%) was significantly greater than for No PGS fresh (15.8%) or No PGS FET (19.0 %) cycles. The incidences of live birth per implanted sac for PGS FET cycles (89.3%), No PGS fresh cycles (66.7%) and No PGS FET cycles (75.0%) were not significantly different. CONCLUSIONS: The present data provides evidence of the benefits of PGS with regard to improved implantation and live birth rate per embryo transferred.

Single thawed euploid embryo transfer improves IVF pregnancy, miscarriage, and multiple gestation outcomes and has similar implantation rates as egg donation.

PURPOSE: The objective of our study was to determine if trophectoderm biopsy, vitrification, array-comparative genomic hybridization and single thawed euploid embryo transfer (STEET) can reduce multiple gestations and yield high pregnancy and low miscarriage rates. METHODS: We performed a retrospective observational study comparing single thawed euploid embryo to routine age matched in vitro fertilization (IVF) patients that underwent blastocyst transfer from 2008 to 2011 and to our best prognosis group donor oocyte recipients (Donor). Our main outcome measures were implantation rate, clinical pregnancy rate, spontaneous abortion rate and multiple gestation rate. RESULTS: The STEET group had a significantly higher implantation rate (58 %, 53/91) than the routine IVF group (39 %, 237/613) while the Donor group (57 %, 387/684) had a similar implantation rate. The clinical pregnancy rates were not statistically different between the STEET and IVF groups. However, the multiple gestation rate was significantly lower in the STEET group (STEET 2 % versus IVF 34 %, Donor 47 %). CONCLUSIONS: STEET results in a high pregnancy rate, low multiple gestation rate and miscarriage rates. Despite the older age of STEET patients and transfer of twice as many embryos, the implantation rate for STEET was indistinguishable from that for egg donation. STEET offers an improvement to IVF, lowering risks without compromising pregnancy rate.

Live birth from previously vitrified oocytes, after trophectoderm biopsy, revitrification, and transfer of a euploid blastocyst.

Our objective is to describe a successful live birth from oocyte vitrification followed by thaw, fertilization, blastocyst culture, trophectoderm biopsy, vitrification, and subsequent thaw. Fifteen mature oocytes were frozen from a patient with uterine factor infertility. Thirteen oocytes survived the thaw, and five underwent trophectoderm biopsy and were refrozen. Three euploid embryos were obtained. A single euploid embryo was transferred in the second thaw cycle to a known recipient leading to the delivery of a normal male infant. This case report is proof of the concept that preimplantation screening and diagnosis is an option for fertility preservation patients.