IVF Success May Be Dependent on Genetic Factors

An infertility doctor from Ireland presented research at the 25th annual conference of the European Society of Human Reproduction and Embryology in July 2009 that appears to show that IVF success may partly depend on genetic factors.

IVF is a treatment that more couples are trying due to the overall high success rate compared to other treatments. IVF involves stimulating a woman’s ovaries with fertility medications so that multiple eggs mature. The eggs are then extracted from the ovaries and put together with sperm. Those eggs which fertilize are grown in the laboratory for several days. A few embryos are then selected and placed into the woman’s uterus. In the uterus, the embryos must continue to grow and develop and eventually implant into the uterine lining for a pregnancy to be established.

IVF success and IVF failure

There are many factors which determine the success of an IVF cycle. Female age is one of the most important factors. Older women have a lower chance for pregnancy with all treatments including IVF. The impact of age is due to the aging of the eggs. Older eggs develop chromosome and other abnormalities which reduce the chance for the embryos to develop normally and implant into the uterus. Obese women have lower IVF success rates although the reasons are less clear.

However, even when young thin women have apparently nice looking embryos transferred into the uterus, some will fail to become pregnant. Part of this failure is almost certainly due to abnormalities in the embryos that were undetected with current techniques. A large number of research around the world is being conducted to find additional ways to assess embryos. There are several promising methods but none has emerged as yet.

The uterine lining

Some studies have looked at the cells which make up the uterine lining. Proteins on the surface of the uterine lining cells have been identified and some of these seem to be necessary for normal implantation. These surface proteins on the cells of the uterine lining are produced by genes inside the uterine cells.

Chromosomes, genes, DNA and RNA

Like all cells in the body, the cells of the uterine lining are very complex and active. Each cell contains the same chromosomes. Those chromosomes contain genes which are the “blueprints” for producing proteins in the cell.

Genes are composed of DNA. In order to make proteins, the cell “reads” the DNA and produces RNA. The RNA is then used as the template to make proteins. A very important point to understand is that cells in different locations will have different groups of genes that are active. Scientists can tell which genes are active by looking at which types of RNA are present in the cell. Some RNA will “leak” out of cells into the circulation and can be identified and even measured in blood.

Scientists have also attempted to make predictions by comparing the patterns of active genes between individuals.

Recent IVF study

In trying to understand why some IVF cycles work and others don’t, the team from Ireland examined active genes by measuring RNA in the blood, an easily accessible biological sample.

Blood samples from women were taken at eight different stages during the period around conception and the early stages of the IVF cycle. Five of these samples came from women who achieved clinical pregnancies, three from those who had embryos transferred but failed to have any of them implant, and three from women with a history of infertility who managed to conceive on their own without treatment.

Analysis showed that 128 genes were more than twice as active in women with an early pregnancy compared with a non-pregnant state.

The genes were identified as belonging to several different groups. The included genes involved with:

The growth of new blood vessels
Blood vessel constriction
Inflammation
Repair of damage to cell structures
The supply of energy to cells

By looking at the patterns before these women started fertility medication, they found that over 200 genes were active in women who went on to achieve an IVF pregnancy compared with those who did not.

These findings hold out the promise that doctors using these techniques may someday be able to predict women who may not be able to achieve pregnancy using IVF. With a little luck, it may be even be possible to find treatments that could convert a woman with an unfavorable pattern into a favorable one. Of course, these possibilities are a long, long way off.