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Embryonic Factors

The successful implantation of an embryo not only relies on a receptive uterine environment in the mother but also on the quality of the embryo itself. Embryo quality and probability of implantation can be affected by maternal and paternal genetic abnormalities as well as zona pellucida dysfunction and poor embryo transfer technique.

Male Genetic Abnormalities

The quality of the sperm that fertilizes an egg is a key contributor to the overall quality of the embryo. Abnormalities in DNA fragmentation and chromosomal arrangements are the main source of genetic deviation in males that can affect embryo quality. DNA fragmentation occurs when the strands of DNA are separated to form two separate strands, this disrupts the genetic information that is coded in genes. Depending on the severity of the fragmentation, this can lead to the dysfunction of specific genes which may or may not be essential for embryo survival and in this case the initiation of implantation. DNA fragmentation can happen spontaneously in cells that undergo programmed cell death (apoptosis) where DNA is broken apart by enzymes called endonucleases. However, since the male DNA isn't activated until around day 3 after fertilisation, it is often difficult to diagnose sperm genetic abnormalities because morphological studies could identify a good quality egg when initial transfer occurs, but due to DNA fragmentation in the sperm, the embryo will die after day 3 of growth.

The translocation of chromosomal segments

Female Genetic Abnormalities

Oocyte quality is also a main contributor to overall embryo quality since it is the DNA of the oocyte that is mainly involved in the first 3 days of embryo growth following fertilization. A major source of genetic abnormalities are balanced translocations.

A translocation involves the exchange of segments of chromosomes that are not a homologous pair. In most cases, this leads to balanced translocations, in which no DNA is lost therefore is usually asymptomatic. However, as female gametes are formed, it is probable that 2/3 of embryos produced will have unbalanced translocations within their DNA if fertilised by sperm with a balanced translocation too. Translocation mutations can occur at any point during fertilization or even the first meiotic division that the oocyte undergoes during foetal life.

Zona Pellucida Dysfunction

The zona pellucida surrounds the blastocyst cavity that contains the inner cell mass.

The female egg (oocyte) is surrounded by a layer of glycoproteins called the zona pellucida. Once fertilisation has occurred, this layer will harden to prevent further sperm entering and maintain the shape of the fertilized egg (zygote) as it divides to form a blastocyst. Once the inner cell mass - the group of cells within the blastocyst that go on to form the embryo - starts to expand, lysin enzymes secreted by the inner cell mass will act on the zona pellucida and weaken the hardened structure. Eventually, this will cause the rupture of the zona pellucida, allowing the blastocyst to hatch and begin to implant into the uterine wall.

If the zona pellucida fails to thin in preparation for rupture, this will prevent the blastocyst from hatching and therefore be unable to implant, therefore this is a probable cause of repeated implantation failure (RIF). This is supported by a study which showed that implantation rates in women who received assisted zona pellucida hatching - use of synthetic chemical to artificially weaken the zona pellucida - increased.