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6. Sperm Factorsto "Why does IVF fail?" main page a. Balanced translocationsMen have 46 chromosomes, 46, XY, 22 sets of autosomes and 1 set of sex chromosomes. The sperm will have 23 with either an X or Y chromosome. Translocations occur when a piece of one chromosome is moved to another chromosome. The carrier has basically all of the genetic material they need, but their gametes (i.e. sperm) carry only ½ which will combine with the normal complement of the spouse to create an ‘unbalanced conception’ which may miscarry. Thus, the male may carry a chromosome translocation that may be responsible for the low sperm count and increase the risk of miscarriage ( see Figure 14). Figure 14. Balanced chromosome translocation showing production of gametes and embryos
b. Y-Chromosome microdeletionsThe Y chromosome has genes important for Y chromosome function and has been extensively studies in male factor infertility (Figure 15). There are very few genes on the Y chromosome and many other genes on different chromosomes contribute to male development. Testing for deletions of the Y chromosome has been done in specialized laboratories. A number of studies have shown that the outcomes of IVF with respect to pregnancy rates and delivery rates and no different when a Y chromosome microdeletion is present or not. This may be due to the few number of genes that are present on the Y chromosome. Of course, it is possible that the offspring male children would have the same deletion and infertility problems and this should be discussed with the patients at the time of consent of IVF-ICSI. Figure 15. Diagram of Y Chromosome
c. Cystic fibrosis mutation screeningCystic fibrosis is the most common inherited condition in the Caucasian
population with 1 in 20 people as carriers. There are over 800 mutations
know to affect the gene for the cystic fibrosis transmembrane conductance
receptor (CFTR), which is associated with Congenital Bilateral Absence of
the Vas Deferens (CBAVD) in > 95% of men with cystic fibrosis. CF accounts
for only about 1% of all infertility, but studies have shown that patients
without CF may have mutations in the large gene. Some studies showed that
the CFTR gene product may affect the sperm capacitation reaction by its
influence on intracellular chloride, bicarbonate and cell charge. The risk
of a CF mutation in patients with non-obstructive azoospermia is about
10%, thus it is important to test the male and female partner. If both
were to have mutations, their child would have a ¼ chance of being
affected by CF. Figure 16. Diagram of DNA packaging in sperm and other cells.
Once the sperm is in
the oocyte, the protamines are exchanged for histone proteins that can
then interact with the maternal DNA. In fertile males, sperm integrity is
high. In some infertile males studies have shown more damage. Factors that
might lead to sperm damage include intrinsic and extrinsic factors that
might be reactive oxygen species, heat, tobacco, varicocoels, infections
or chemotherapy. |
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