2015 Group Project 1

2015 Student Projects
2015 Projects: Three Person Embryos | Ovarian Hyper-stimulation Syndrome | Polycystic Ovarian Syndrome | Male Infertility | Oncofertility | Preimplantation Genetic Diagnosis | Students
2015 Group Project Topic - Assisted Reproductive Technology
This page is an undergraduate science embryology student and may contain inaccuracies in either description or acknowledgements.

Three Person Embryos

(intro) Here is a good source for overview and status of 3 Person IVF. http://www.geneticsandsociety.org/article.php?id=6527

History

Case of Alana Saarinen???

The girl with three biological parents

Benefits

PMID 25629662 Mitochondrial donation--how many women could benefit? This is a statistical analysis of the prevalence of women of child bearing age that have pathogenic mutation to their mitochondria that could benefit from mitochondrial donation in the UK. And the affects of the mitochondrial mutation on fertility as compared to background natural birth rate. They found no difference in fertility rates and 4% of women at risk of passing on symptomatic mitochondrial disease.

PMID 18674747 Pathogenic mitochondrial DNA mutations are common in the general population. Another on the prevalence of mitochondrial mutations in the populous. This time via mtDNA sequencing from umbilical samples from live births, looking for ten specific mt-DNA mutations. It found a frequency rate of 0.54% for these mutations. Although they had limited data on the prevalence of these mutations maternally.

Technical Progression

PMID 23103867 Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases This is a review paper of current technicals in 3 person embryo, in other words, replacement of the mitochondrial DNA. 1. the nuclear genome from the pronuclear stage zygote of an affected woman is transferred to an enucleated donor zygote 2. transfer of the metaphase II spindle from the unfertilized oocyte of an affected woman to an enucleated donor oocyte the authur's group works on spindle transfer between human oocytes, resulting in blastocyst development and embryonic stem cell derivation, with very low levels of heteroplasmy

PMID 25229667

Spindle-chromosome transfer

PMID 23103867 Towards germline gene therapy of inherited mitochondrial diseases. the authur investigates the spindle-chromosomal (ST) complex transfer on human oocytes. they concluded that the mtDNA can be efficiently replaced in human oocytes, although some ST oocytes displayed abnormal fertilization.

PMID 25973765 Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans extreme-high depth mtDNA re-sequencing up to ~1.2 million-fold coverage, the author has proved the dogma that mammalian mitochondrial DNA (mtDNA) is strictly maternally inherited. It also indicated that an active mechanism eliminates paternal mtDNA which likely acts at the molecular level.

Pronuclear transfer

PMID 20393463 Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease As the name suggest this paper looks at pronuclear transfer as way to remove donor mitochondria measured by mt-DNA. And it effectiveness in doing so. And the processes that occur in the oocyte when this method is used.

Polar body transfer

PMID 24949971 Polar body genome transfer for preventing the transmission of inherited mitochondrial diseases The authur adopts polar body transfer to prevent the transmission of mtDNA variants. they also compare the effects of different types of germline genome transfer, including spindle-chromosome transfer, pronuclear transfer, and first and second polar body transfer, in mice. Their pre-clinical model indicate that polar body transfer has better potential in preventing the inheritance of mitochondrial diseases.

Ethics

1.PMID 26239841 The ethical challenges of the clinical introduction of mitochondrial replacement techniques. The first part of the paper evaluates the three concerns about the safety of mitochondrial replacement techniques including whether it is ethical; persons with three genetic contributors and the trust of society. And then, two recommendations are made.

2.PMID 21059727 Ethics of mitochondrial gene replacement: from bench to bedside. Both of the risks and benefits are accessed in this paper after the briefly introduction of mitochondrial replacement techniques. And then the question of when are enough safeguards made to justify introducing mitochondrial gene replacement into the clinic is discussed.

3.PMID 25888328 Mitochondrial replacement to prevent the transmission of mitochondrial DNA disease. This paper discussed about the ethics and feasibility of mitochondrial replacement techniques. The possibility of preventing the transmission of mtDNA disease by MRT is first discussed. Moreover, the four big challenges mainly ethics are discussed.

Further Reading

useful publications:

PMID 23608245 The ethics of creating children with three genetic parents.

PMID 24382342 Three-Parent IVF: Gene Replacement for the Prevention of Inherited Mitochondrial Diseases.

PMID 20933103 Mitochondrial function in the human oocyte and embryo and their role in developmental competence.

PMID 26020522 Mitochondrial reshaping accompanies neural differentiation in the developing spinal cord.

PMID 25421171 The impact of mitochondrial function/dysfunction on IVF and new treatment possibilities for infertility.

PMID 25807984 Risks inherent to mitochondrial replacement.