Table 9 Studies examining the relationship between cytoplasmic fragmentation and chromosomal abnormalities in human embryos
Author | Year | Title of Paper | Type of study | No. of study participants | Embryo stage | PGT-A platform | Age | Intervention (stim protocol) | Outcome measure |
|---|---|---|---|---|---|---|---|---|---|
Findikli et al. | 2004 | Assessment of DNA fragmentation and aneuploidy on poor quality human embryos | Experimental | 57 embryos. | Different developmental stages. | FISH | Female mean age: 30.4 +/- 5.9 years. Male mean age: 37.8 +/- 8.0 years. | Pituitary downregulation with GnRH analogue and follicular development stimulated with injection of FSH, HMG, and HCG. | Assess the extent of DNA fragmentation and aneuploidy in spare slow growing or arrested human embryos. |
Munne et al. | 1995 | Embryo morphology, developmental rates and maternal age are correlated with chromosome abnormalities | Prospective | 524 monospermic embryos; 283 analyzed with X, Y, 18, 13/21 probes and remainder with X, Y, and 18 probes. | Cleavage-stage embryos. | FISH | Maternal age groups used: 20 – 34, 35 – 39, 40 - 47 years. | Per protocol at Center for Reproductive Medicine and Infertility, The New York Hospital- Cornel University Medical College. | Detection of maternal age effect, complete assessment of mosaicism (by analysis of all cells), relationship with embryonic dysmorphism. |
Almeida and Bolton | 1996 | The relationship between chromosomal abnormality in the human preimplantation embryo and development in vitro | Prospective | Total of 103 patients, 410 embryos. | Pronucleate to 8-cell stage. | Cytogenetic | Patient median age 33 years (range, 23-40 years). | Ovarian stimulation, ultrasound-directed follicle aspiration and IVF performed as described previously by Bolton et al., 1989.1 | Preimplantation development rate of chromosomally-abnormal embryos. Association between chromosomal abnormalities and embryo morphology. |
Magli et al. | 2001 | Chromosomal abnormalities in embryos | Retrospective | 256 patients from S.I.S.M.E.R. Reproductive Medicine Unit; 1620 embryos biopsied. | Embryos at the 7-8 cell stage exhibited the lower frequency of abnormalities (55%) compared to embryos with a slower rate of cleavage (74%) at 3-4 cell stage. | FISH | Maternal age > 36 years. | PGD cycles following induction of multiple follicular growth as described by Ferraretti et al., 1996.2 Oocytes were transvaginally collected via ultrasound guidance 34-36 h after HCG administration. | Rate of development to expanded blastocysts. |
Moayeri er al. | 2008 | Day-3 embryo morphology predicts euploidy among older subjects | Retrospective | 1,043 biopsied blastomeres. | Day-3 embryos. | FISH | Mean age 37.7 years. AMA group mean age 40.1 +/- 2 years. Young group mean age 34.2 +/- 1 years. | Controlled ovarian hyperstimulation using a GnRH antagonist protocol with Follistim. Ovulation was triggered with 10,000 IU hCG given SC followed by transvaginal ultrasound–guided egg retrieval 34–36 hours later. | Day-3 embryo morphology score and PGD fluorescence in situ hybridization results for chromosomes: 13, 15, 16, 17, 18, 21, 22, X, and Y. |
Baltaci et al. | 2006 | Relationship between embryo quality and aneuploidies | Retrospective | 132 patients; 1107 embryos. | Day-3 embryos. | FISH | Mean age 35.45 +/- 5.6 years. | GnRH agonist given to assist flare-up effect. Tryptorelin acetate 0.1 mg subcutaneous daily or nafarelin acetate 200 µg intranasally 3x/day was administered for each patient. Stimulation with 300 IU follitropin alpha i.m. HCG 10,000 IU i.m. adminstered 36 h before oocyte retrieval. | Detect correlation between embryo quality and genetic status. |
Pellestor et al. | 1994 | Relationship between morphology and chromosomal constitution in human preimplantation embryo | Prospective | 462 preimplantation embryos analyzed (426 poor quality and 36 good quality embryos); chromosomal analysis successful in 153 cases. | Embryos examined 24 hrs and 48 hrs after insemination. | Cytogenetic | Â | Â | Chromosomal status and morphologic quality of preimplantation eggs. |
Pellestor et al. | 1994 | Direct assessment of the rate of chromosomal abnormalities in grade IV human embryos produced by in-vitro fertilization procedure | Prospective | 411 grade IV embryos from 327 couples participating in IVF. | Cleaved embryos classified 48 hrs after insemination. | Cytogenetic | Female age range 24 - 43 years. Male age range 25 - 52 years. | Stimulation protocol previously described by Audibert et al., 1989.3 | Karyotype of grade IV embryos. |
Chavez et al. | 2012 | Dynamic blastomere behavior reflects human embryo ploidy by the four-cell stage | Retrospective | 85 two pronuclear and 25 cleavage-stage supernumerary human embryos. | Cleavage stage embryos; 4-cell stage. | aCGH | Average maternal age 33.5 years. | Â | Karyotype of all blastomeres in 4-cell human embryos. |
Ziebe et al. | 2003 | FISH analysis for chromosomes 13, 16, 18, 21, 22, X and Y in all blastomeres of IVF pre-embryos from 144 randomly selected donated human oocytes and impact on pre-embryo morphology | Retrospective | 103 day 1 to day 3 embryos | Cleavage stage embryos | FISH, | Female age 25-37 years | Long or short protocols | Relationship between chromosomal status (13, 16, 21, 22, X and Y) and embryo morphology |
Delimitreva et al. | 2005 | Chromosomal disorders and nuclear and cell destruction in cleaving human embryos | Retrospective | 169 day 1 to day 3 | Cleavage stage embryos | FISH | Mean maternal age: 33 years (range 23 - 38) | Long protocol | Relationship between chromosomal status (1, 5, 19 and X or 18, 21, X and Y) and blastomere fragmentation, nuclear apoptotic changes |
Magli et al. | 2007 | Embryo morphology and development are dependent on the chromosomal complement | Retrospective | 5227, 62 h after insemination | Cleavage stage embryos | FISH | maternal age ≥36 years | Long protocol | Relationship between embryo morphology and chromosomal competent |
Vera-Rodriguez et al. | 2015 | Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis | Retrospective | 57 | Day 3 | aCGH | maternal age: 33.7±4.3 years | - | Using time-lapse, complete chromosomal assessment and single-cell RT–qPCR to simultaneously obtain a prediction model for aneuploidy |
Minasi et al. | 2016 | Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study | Case series study | 1730 | Day 5 | aCGH | Maternal age: 36.8±4.24 | Recombinant FSH and a GnRH agonist suppression protocol (short or long) or GnRH antagonist flexible protocol | Correlations among human blastocyst ploidy status, standard morphology evaluation and time-lapse kinetics |