Mathematical methodology to obtain and compare different embryo scores

In Vitro Fertilization (IVF) units need to decrease multiple pregnancies without affecting their overall success rate. In this study we propose a mathematical model to evaluate an embryo’s potential ability to implant in the uterus. Embryos are graded by the embryologist based on the number of blastomeres, evenness of growth and degree of fragmentation. Therefore, the following variables were considered: number of blastomeres produced by division of the egg after fertilisation (blastomeres), symmetry and fragmentation of the embryo (grade). This model evaluates the embryos assigning them a score which represents their quality. The main result derived from this model is the estimation of the significant improvement in the implantation rate due to the increase in blastomere values and the decrease in grade factor values. But the increase from two–three to four produces more improvement in the implantation rate than two–three to five–six blastomeres. First, statistical models were used to study embryo traceability from transfer to implantation and to evaluate the effect of the quality of the embryos (embryo score) and women’s age on implantation potential. This score was obtained by making predictions from the fitted model which was used to rank embryos in terms of implantation potential. Then we totalled the scores of embryos that had been transferred to each woman for obtaining the Embryo Quality Index (EQI). In addition, we studied the effects of EQI and women’s age on pregnancy. Finally, statistical techniques such as Receiver Operating Characteristics (ROC) and bootstrap procedures were used to assess the accuracy of this model. This embryo score is a quick, efficient and accurate tool to optimise embryo selection for transfers on the second day after fertilisation. This tool is especially useful for transfers involving non-top embryos.This work was partially supported by a grant from the Generalitat Valenciana (grant no. GVPRE/2008/103). The research of AD and SC was partially supported by a grant from Ministerio de Asuntos Exteriores (grant no. A/023444/09) too. The authors are indebted to the anonymous referee whose comments and suggestions improved the paper considerably.Debón Aucejo, AM.; Molina Botella, MI.; Cabrera García, S.; Pellicer, A. (2013). Mathematical methodology to obtain and compare different embryo scores. Mathematical and Computer Modelling. 57(5-6):1380-1394. https://doi.org/10.1016/j.mcm.2012.11.027S13801394575-

Promising System for Selecting Healthy In Vitro–Fertilized Embryos in Cattle

Conventionally, in vitro–fertilized (IVF) bovine embryos are morphologically evaluated at the time of embryo transfer to select those that are likely to establish a pregnancy. This method is, however, subjective and results in unreliable selection. Here we describe a novel selection system for IVF bovine blastocysts for transfer that traces the development of individual embryos with time-lapse cinematography in our developed microwell culture dish and analyzes embryonic metabolism. The system can noninvasively identify prognostic factors that reflect not only blastocyst qualities detected with histological, cytogenetic, and molecular analysis but also viability after transfer. By assessing a combination of identified prognostic factors—(i) timing of the first cleavage; (ii) number of blastomeres at the end of the first cleavage; (iii) presence or absence of multiple fragments at the end of the first cleavage; (iv) number of blastomeres at the onset of lag-phase, which results in temporary developmental arrest during the fourth or fifth cell cycle; and (v) oxygen consumption at the blastocyst stage—pregnancy success could be accurately predicted (78.9%). The conventional method or individual prognostic factors could not accurately predict pregnancy. No newborn calves showed neonatal overgrowth or death. Our results demonstrate that these five predictors and our system could provide objective and reliable selection of healthy IVF bovine embryos

Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study

<p>Abstract</p> <p>Background</p> <p>Despite the clinical outcomes of ovarian stimulation with either GnRH-agonist or GnRH-antagonist analogues for in vitro fertilization (IVF) being well analysed, the effect of analogues on oocyte/embryo quality and embryo development is still not known in detail. The aim of this case-control study was to compare the efficacy of a multiple-dose GnRH antagonist protocol with that of the GnRH agonist long protocol with a view to oocyte and embryo quality, embryo development and IVF treatment outcome.</p> <p>Methods</p> <p>Between October 2001 and December 2008, 100 patients were stimulated with human menopausal gonadotrophin (HMG) and GnRH antagonist in their first treatment cycle for IVF or intracytoplasmic sperm injection (ICSI). One hundred combined GnRH agonist + HMG (long protocol) cycles were matched to the GnRH antagonist + HMG cycles by age, BMI, baseline FSH levels and by cause of infertility. We determined the number and quality of retrieved oocytes, the rate of early-cleavage embryos, the morphology and development of embryos, as well as clinical pregnancy rates. Statistical analysis was performed using Wilcoxon's matched pairs rank sum test and McNemar's chi-square test. P < 0.05 was considered statistically significant.</p> <p>Results</p> <p>The rate of cytoplasmic abnormalities in retrieved oocytes was significantly higher with the use of GnRH antagonist than in GnRH agonist cycles (62.1% vs. 49.9%; P < 0.01). We observed lower rate of zygotes showing normal pronuclear morphology (49.3% vs. 58.0%; P < 0.01), and higher cell-number of preembryos on day 2 after fertilization (4.28 vs. 4.03; P < 0.01) with the use of GnRH antagonist analogues. The rate of mature oocytes, rate of presence of multinucleated blastomers, amount of fragmentation in embryos and rate of early-cleaved embryos was similar in the two groups. Clinical pregnancy rate per embryo transfer was lower in the antagonist group than in the agonist group (30.8% vs. 40.4%) although this difference did not reach statistical significance (P = 0.17).</p> <p>Conclusion</p> <p>Antagonist seemed to influence favourably some parameters of early embryo development dynamics, while other morphological parameters seemed not to be altered according to GnRH analogue used for ovarian stimulation in IVF cycles.</p

In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages

Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF)1,2,3, its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos4. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis5,6, a high number of embryos containing abnormal cells can pass this strong selection barrier7,8. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages

The long-term fiscal impact of funding cuts to Danish public fertility clinics

This study evaluated the fiscal impact attributed to recent policy changes that limited funding to public fertility clinics in Denmark. Taking into consideration that introducing patient co-payments will influence the numbers of couples treated, the number of children born every year from assisted reproductive technology will be affected. To reflect the government perspective, the model assessed the average life course of a cohort of assisted-conception singletons taking into consideration age-specific, per-capita government transfers (e.g. education, health care, family allowances, education, pensions) and lifetime gross tax contributions to derive the discounted net tax contribution from assisted-conception singletons. An investment of euro11,078 in a mother aged <40 to achieve an assisted-conception singleton was valued at euro154,100 in cumulative discounted net tax revenue when the child reaches age 50. A reduction in the number of live births generated additional savings of euro67-112 million due to reduced government transfers by age 25. However, by age 50, because of fewer children born and consequently fewer tax payers, a euro74-123 million loss to government was estimated. The projected discounted net tax revenue attributed to assisted-conception children suggests that publicly funded treatment provides economic benefits to government over the lifetime of the conceived children. In January 2011, the Danish Parliament introduced a law that limited reimbursement to publicly funded fertility clinics in Denmark. Because reimbursement for fertility services can influence couples' ability to receive treatment, this will consequently result in fewer children being born each year. To inform the policy decision, this study assessed the fiscal consequences of the policy change on the government over many generations. The analytical framework discussed here estimates the net tax revenue of a cohort of assisted-conception children and the discounted net tax revenue that these children pay to the Danish government over their lifetime. The analysis illustrates that the government will save more costs than those directly related to public fertility services because fewer children are likely to be born and consequently to require government services (e.g. education, health care, family allowances). However, over time as the assisted-conception cohort matures and enters the work force. the reduced number of assisted-conception children, attributed to the funding cuts, will negatively impact government accounts due to lost tax revenue. The policy analysis described here suggests that the economic impact of the fertility policy change is dependent on the time frame over which the analysis is considered. In the short term, it is possible to save on assisted reproduction treatment costs; however, taking into consideration the life course of the diminished size of the assisted-conception cohort, this will negatively influence government accounts in the future