Table 6 Studies examining the effect of cytoplasmic fragmentation on embryo development
Author | Year | Title of Paper | Type of study | No. of study participants | Embryo stage | Age | Intervention (stim protocol) | Outcome measure |
|---|---|---|---|---|---|---|---|---|
Van Blerkom et al. | 2001 | A microscopic and biochemical study of fragmentation phenotypes in stage-appropriate human embryos | Observational | 91 embryos (50 monospermic, 41 dispermic). | Fragmented monospermic and dispermic pronuclear to early cleavage stages human embryos classified as stage-appropriate during the first 3.5 days of culture. | Female age range 28 - 37 years. | Ovarian stimulation protocol previously described by Van Blerkom et al., 1995.1 | Temporal, spatial, fine structural, and biochemical aspects of fragmentation were examined. |
Sathananthan et al. | 1990 | Ultrastructure of preimplantation human embryos co-cultured with human ampullary cells | Observational | 15 embryos. | 2-cell stage to blastocyst hatching. | Ultrastructure evaluation. | ||
Antczak and Van Blerkom | 1999 | Temporal and spatial aspects of developmental potential of the embryo itself. In-vitro study of fragmentation in early human embryos: possible effects on developmental competence and association with the differential elimination of regulatory FP and developmental events, such as ability to blastulate, proteins from polarized domains | Prospective | 2293 fertilized eggs from 257 IVF cycles. | First 72 hrs of human embryo culture. | Female mean age 36 years (range, 23 - 41 years). | Stimulation protocol previously described by Van Blerkom et al., 1995.1 | Effect of fragmentation on the distribution of the following eight regulatory proteins found to be: (i) localized in the mature oocyte in subplasmalemmal, polarized domains; and (ii) unequally inherited by the blastomeres during cleavage: leptin, signal transducer and activator of transcription 3 (STAT3), Bax, Bcl-x, transforming growth factor beta 2 (TGF beta 2), vascular endothelial growth factor (VEGF), c-kit and epidermal growth factor R (EGF-R). |
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. | Female age range 24 - 43 years. Male age range 25 - 52 years. | Stimulation protocol previously described by Audibert et al., 1989.2 | Karyotype of grade IV embryos. |
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. | Chromosomal status and morphologic quality of preimplantation eggs. | ||
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. | 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. |
Morgan et al. | 1995 | Use of videocinematography to assess morphological qualities of conventionally cultured and cocultured embryos | Prospective | 24-30 h of in-vitro development. | Stimulation protocols previously described by Wiemer et al., 1993.3 | Effect of conventional and coculture methodologies on morphological parameters in human embryos and to examine clinical pregnancy rate. | ||
Alikani et al. | 2000 | Cleavage anomalies in early human embryos and survival after prolonged culture in-vitro | Prospective | 102 patients who were elected to have a day-5 embryo transfer. | Day-5 embryos. | Mean ages of regular patients 33.89 +/- 3.7 years. Mean ages of oocyte recipients 40.06 +/- 4.21 years. | Standard down-regulation protocol including 1 mg Lupron. Stimulation with recombinant FSH and HCG administration when lead follicle reached 16-17 mm. Oocyte retrieval 36 h after hCG. | Normal blastocyst development in vitro; impact of cleavage rate, fragmentation, and multinucleation on compaction, cavitation, and inner cell mas and trophectoderm formation was assessed. |
Hardy et al. | 2003 | Maintenance of inner cell mass in human blastocysts from fragmented embryos | Retrospective | 363 embryos from donated infertile couples undergoing IVF. | Day-2 to day-6 embryos. | Superovulation induced with human menopausal gonadotropin after pituitary suppression by an LH-releasing hormone agonist. 10,000 u of hCG 36 hrs before egg retrieval. | Rates of development and blastocyst formation. The number of cells in the trophectoderm and inner cell mass and the incidence of apoptosis. | |
Guerif et al. | 2007 | Limited value of morphological assessment at days 1 and 2 to predict blastocyst development potential: a prospective study based on 4042 embryos | Prospective | 4042 embryos | Assessment of day-1 (zygote stage) to day-5/6 (blastocyst stage). | Mean female age 33.9 +/- 4.0 years (range, 25-43 years). | Ovarian stimulation protocol previously described by Guerif et al., 2004.4 | Pronuclear morphology on day 1, and early cleavage, cell number and fragmentation rate on day 2 were evaluated for each zygote. Blastocyst transfers were analyzed to their implantation ability and early embryo development parameters. |
Ivec et al. | 2011 | Prediction of human blastocyst development from morulas with delayed and/or incomplete compaction | Prospective | Day-4 embryos (n=329); Day 5 embryos (n=256). | Day-4 or day-5 embryos. | Females < 37 years. | Stim protocols used combination of GnRH agonist/GnRH antagonist and recombinant FSH/hMG. Egg retrieval carried at 35-36 hrs after hCG injection. | Blastocyst development rate, blastocoel expansion rate, and optimal blastocyst rate. In an optimal blastocyst: surface area, trophectoderm cell number, inner cell mass (ICM) surface area, ICM volume and ICM shape. |
Hnida et al. | 2004 | Computer‐controlled, multilevel, morphometric analysis of blastomere size as biomarker of fragmentation and multinuclearity in human embryos | Prospective | 63 ICSI patients. Consecutive cohort of 232 human 2-, 3- and 4-cell embryos from patients referred for ICSI treatment. | Cleavage stage embryos. | Mean female age 32.1 years (range, 24 – 39 years). | Long protocol using GnRH agonist for down-regulation and recombinant FSH for ovarian stimulation. HCG was given 36h before oocyte retrieval. | Mean blastomere size, embryonic fragmentation, and multinuclearity. |
Sjoblom et al. | 2006 | Prediction of embryo developmental potential and pregnancy based on early stage morphological characteristics | Retrospective audit of data | 268 patients, 357 treatment cycles IVF (n=170) and ICSI (n=187). | Days 0-2 embryos. | Hormonal treatment regimen, OCP-Long protocol was used: OCPs for 21 days, administration of GnRH agonists (with nafarelin 200 μg intranasal spray twice a day or leuprolide acetate injections 1 mg SC daily for 14 days. Stimulation with recombinant FSH 150-225 IU injected SC daily. 10,000 hCG given when one or more follicles reached size >18 mm, oocyte pickup 36 h later. | The association of blastocyst development and pregnancy with morphological characteristics. |