Non-invasive cell-free DNA-based approach for the diagnosis of clinical miscarriage: A retrospective study.

Objective: To evaluate cell-free DNA (cfDNA) testing as a non-invasive approach to detecting aneuploidies in clinical miscarriages.

Design: A retrospective cohort study of women with pregnancy loss.

Setting: Hospitals and genetic analysis laboratories.

Inherited unbalanced reciprocal translocation with 3q duplication and 5p deletion in a foetus revealed by cell-free foetal DNA (cffDNA) testing: a case report.

Background: Since 2011, screening maternal blood for cell-free foetal DNA (cffDNA) fragments has offered a robust clinical tool to classify pregnancy as low or high-risk for Down, Edwards, and Patau syndromes. With recent advances in molecular biology and improvements in data analysis algorithms, the screening's scope of analysis continues to expand. Indeed, screening now encompassess additional conditions, including aneuploidies for sex chromosomes, microdeletions and microduplications, rare autosomal trisomies, and, more recently, segmental deletions and duplications called copy number variations (CNVs).

The morphokinetic signature of mosaic embryos: evidence in support of their own genetic identity.

Objective: To provide full morphokinetic characterization of embryos ranked with different degrees of chromosomal mosaicism.

Design: Retrospective cohort study.

Setting: University-affiliated private in vitro fertilization clinic.

The impact of patient, embryo, and translocation characteristics on the ploidy status of young couples undergoing preimplantation genetic testing for structural rearrangements (PGT-SR) by next generation sequencing (NGS).

Purpose: To evaluate the factors that affect the incidence of euploid balanced embryos and interchromosomal effect (ICE) in carriers of different structural rearrangements.

Methods: This retrospective study includes 95 couples with reciprocal translocations (RecT) and 36 couples with Robertsonian translocations (RobT) undergoing Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) between March 2016 and July 2019. Next-generation sequencing (NGS) was the technique used coupled with trophectoderm (TE) biopsy.

Sperm genetic abnormalities and their contribution to embryo aneuploidy & miscarriage.

Sperm genetic testing has been proposed for clinical diagnosis of possible causes of male infertility. We reviewed the most remarkable publications of sperm DNA integrity and sperm aneuploidy as they relate to clinical outcomes, and the relationship between both genetic defects, and its association to embryo aneuploidy and recurrent pregnancy loss.

Characteristics of the IVF Cycle that Contribute to the Incidence of Mosaicism.

Highly sensitive next-generation sequencing (NGS) platforms applied to preimplantation genetic testing for aneuploidy (PGT-A) allow the classification of mosaicism in trophectoderm biopsies. However, the incidence of mosaicism reported by these tests can be affected by a wide number of analytical, biological, and clinical factors. With the use of a proprietary algorithm for automated diagnosis of aneuploidy and mosaicism, we retrospectively analyzed a large series of 115,368 trophectoderm biopsies from 27,436 PGT-A cycles to determine whether certain biological factors and fertilization (IVF) practices influence the incidence of overall aneuploidy, whole uniform aneuploidy, mosaicism, and TE biopsies with only segmental aneuploidy.

Optimized NGS Approach for Detection of Aneuploidies and Mosaicism in PGT-A and Imbalances in PGT-SR.

The detection of chromosomal aneuploidies and mosaicism degree in preimplantation embryos may be essential for achieving pregnancy. The aim of this study was to determine the robustness of diagnosing homogenous and mosaic aneuploidies using a validated algorithm and the minimal resolution for de novo and inherited deletions and duplications (Del/Dup). Two workflows were developed and validated: (a,b) preimplantation genetic testing for uniform whole and segmental aneuploidies, plus mixtures of euploid/aneuploid genomic DNA to develop an algorithm for detecting mosaicism; and (c) preimplantation genetic testing for structural rearrangements for detecting Del/Dup ≥ 6 Mb.

Clinical application of embryo aneuploidy testing by next-generation sequencing.

We review here the evolution in the field of embryo aneuploidy testing over the last 20 years, from the analysis of a subset of chromosomes by fluorescence in situ hybridisation to the transition toward a more comprehensive analysis of all 24 chromosomes. This current comprehensive aneuploidy testing most commonly employs next-generation sequencing (NGS). We present our experience in over 130 000 embryo biopsies using this technology.

In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study.

Objective: To determine the clinical value of preimplantation genetic diagnosis for aneuploidy screening (PGD-A) in women of advanced maternal age (AMA; between 38 and 41 years).

Design: This was a multicenter, randomized trial with two arms: a PGD-A group with blastocyst transfer, and a control group with blastocyst transfer without PGD-A.

Setting: Private reproductive centers.

Type of chromosome abnormality affects embryo morphology dynamics.

Objective: To study the differences in the cleavage time between types of embryo chromosomal abnormalities and elaborate algorithm to exclude aneuploid embryos according to the likelihood to be euploid.

Design: Retrospective cohort study.

Setting: University affiliated private center.

Distribution patterns of segmental aneuploidies in human blastocysts identified by next-generation sequencing.

Objective: To evaluate the ability of next-generation sequencing (NGS) to detect pure and mosaic segmental aneuploidies in trophectoderm biopsies and to identify distribution patterns in whole blastocysts.

Design: Validation study.

Setting: Reference laboratory.

New tools for embryo selection: comprehensive chromosome screening by array comparative genomic hybridization.

The objective of this study was to evaluate the usefulness of comprehensive chromosome screening (CCS) using array comparative genomic hybridization (aCGH). The study included 1420 CCS cycles for recurrent miscarriage (n = 203); repetitive implantation failure (n = 188); severe male factor (n = 116); previous trisomic pregnancy (n = 33); and advanced maternal age (n = 880). CCS was performed in cycles with fresh oocytes and embryos (n = 774); mixed cycles with fresh and vitrified oocytes (n = 320); mixed cycles with fresh and vitrified day-2 embryos (n = 235); and mixed cycles with fresh and vitrified day-3 embryos (n = 91).

Increasing the probability of selecting chromosomally normal embryos by time-lapse morphokinetics analysis.

Objective: To study the differences in the cleavage time between chromosomally normal and abnormal embryos and to elaborate an algorithm to increase the probability of noninvasively selecting chromosomally normal embryos.

Design: Retrospective cohort study.

Setting: University-affiliated infertility center.

Use of array comparative genomic hybridization (array-CGH) for embryo assessment: clinical results.

Objective: To review clinical outcomes after preimplantation genetic screening. Most methods of embryo viability assessment involve morphologic evaluation at different preimplantation developmental stages. A weak association between blastocyst morphology and aneuploidy has been described, supporting the basis for preimplantation genetic screening (PGS) for assessment of embryo viability.

Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles.

Context: A high chromosomal abnormalities rate has been observed in human embryos derived from in vitro fertilization (IVF) treatments. The real incidence in natural cycles has been poorly studied, so whether this frequency may be induced by external factors, such as use of gonadotropins for ovarian stimulation, remains unknown.

Design: We conducted a prospective cohort study in a University-affiliated private infertility clinic with a comparison between unstimulated and stimulated ovarian cycles in the same women.

Testicular sperm from patients with obstructive and nonobstructive azoospermia: aneuploidy risk and reproductive prognosis using testicular sperm from fertile donors as control samples.

Objective: To establish a baseline incidence of chromosomal abnormalities in testicular sperm of fertile men and to determine the best control sample for comparisons with azoospermic males to estimate their reproductive prognosis.

Design: Prospective study.

Setting: Infertility clinic.

Redefining advanced maternal age as an indication for preimplantation genetic screening.

In this retrospective study, the utility of preimplantation genetic screening (PGS) in patients with advanced maternal age is evaluated. The patient population consisted of women aged 38-44years and included in a regular IVF programme with or without PGS analysis. Transfer rate, ongoing implantation rate and ongoing pregnancy rate were the main outcome parameters measured.

Aneuploidies in embryos and spermatozoa from patients with Y chromosome microdeletions.

In patients with Y chromosome microdeletions and high percentage of numeric chromosome abnormalities detected by fluorescence in situ hybridization on sperm, a high percentage of abnormal embryos was observed compared with oligozoospermic patients without Y chromosome microdeletions, with a significant increase in the percentage of embryos with monosomy X. Differences in fertilization rates between the different patient groups were not observed; however, blastocyst rates were significantly impaired in patients with Y chromosome microdeletions.

Prospective cohort study in high responder oocyte donors using two hormonal stimulation protocols: impact on embryo aneuploidy and development.

Background: Ovarian stimulation regimens for in vitro fertilization seem to have a deleterious effect on oocyte quality and embryo aneuploidy in a dose-dependent manner. This study aims to test the influence of gonadotrophin doses on embryo aneuploidy rates.

Methods: A total of 32 young oocyte donors with a high response to ovarian stimulation, were included in the study.

Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos.

Objective: To evaluate the effect of sperm chromosome abnormalities--disomy for sex chromosomes and diploidy--in the chromosomal constitution of preimplantation embryos.

Design: Retrospective cohort study.

Setting: Infertility clinic.