Successful implantation and live birth of a healthy boy after triple biopsy and double vitrification of oocyte-embryo-blastocyst

Abstract

IntroductionPreimplantation genetic diagnosis and/or screening (PGD/PGS) allow the assessment of the genetic health of an embryo before transferring it into the uterus. These techniques require the removal of cellular material (polar bodies, blastomere(s) or trophectoderm cells) in order to perform the proper genetic analysis. We report the implantation and live birth outcome of a vitrified-warmed blastocyst developed after triple biopsy and double vitrification procedures at oocyte, cleavage embryo and blastocyst stage.Case descriptionAn infertile couple, with family history of β-thalassemia, searched for IVF procedure and PGD. First polar bodies biopsy with subsequent vitrification was uninformative due to meiotic crossing-over, so oocytes were inseminated after warming. Two embryos were obtained and blastomere biopsy was performed on day 3 with inconclusive results on their genetic status. Their culture resulted in one expanded blastocyst stage on day 7 that underwent trophectoderm biopsy and vitrification. This embryo showed to be normal. It was then warmed and transferred in an artificial cycle.Discussion and EvaluationPreconception genetic analysis by removal and analysis of the first polar body is technically possible, but the genetic information that we can obtain at this stage may be limited and the oocytes to be inseminated is not predictable. Compared to blastomere biopsy, trophectoderm biopsy has more diagnostic efficiency with respect to both chromosomal mosaicism and PCR accuracy, reducing the problems of amplification failure and allele drop out. Moreover, embryos biopsied at the cleavage stage seem to have lower implantation rate than biopsied blastocyst.ConclusionsThis is the first case report of a live birth obtained from a three step biopsy and double vitrification procedures of a blastocyst. This case report seems also to suggest the harmlessness of all these procedures if carefully performed by a skilled biologist in an IVF lab with quality management system. Finally, our study highlight that blastocyst cryopreserved on day 7 have clinically important potential and embryos that not reach blastocyst stage on day 6 should not to be discharged because they may result in an ongoing pregnancy.

Recent advances in preimplantation genetic diagnosis and screening

“…Blastocyst biopsy has been more widely used than PB biopsy and blastomere biopsy, especially in the past 5 years, due to its low misdiagnosis rate [7,8] and cost-effectiveness [9,10]. Compared to the conventional biopsy methods, the newly developed non-invasive sampling mehtods have many advantages with regard to the ethical, legal, and economic issues.…”

First Case of Successful Implantation and Live Birth after Double Trophectoderm Biopsy before and after Vitrification on the Same Cohort of Blastocyst

“…Case reports of the double biopsy on the same embryo one at cleavage stage followed by trophectoderm biopsy have been reported by Taylor et al 9 and Wininger et al 10 A case of triple biopsy also has been reported where first polar body was biopsied followed by cleavage stage followed by trophectoderm biopsy, which resulted later in live birth. 11 But this case to our knowledge is the first case of trophectoderm biopsy being performed twice on the same embryo before and after vitrification and leading to a successful implantation and birth of a healthy baby boy of 2.7 kg. Effect of cleavage stage biopsy on the embryo in a recent randomized controlled trial demonstrated a lower implantation potential 12 and decrease in embryonic mass by 25%.…”

Cleavage-stage embryo micromanipulation in the clinical setting

“…The high rate of mosaicism in cleavage-stage embryos led to introduce trophectoderm biopsy as an alternative option for PGD-A (Harton et al 2011;Vera-Rodriguez and Rubio 2017). The diagnostic efficacy, regarding chromosomal mosaicism and PCR accuracy, is high in trophectoderm biopsy (Chang et al 2013;Greco et al 2015). Also, technical limitation(s) and FISH interpretation may lead to overstimulation of abnormalities in the blastomere biopsy (Rubio et al 2009; Vera-Rodriguez and Rubio 2017).…”