Embryos Correct for Genetic Abnormalities

by Dr. Susan Daniel

Early human embryos can contain both genetically normal and abnormal cells. They are said to exhibit mosaicism. At the recent meeting of the European Society for Human Reproduction and Embryology (ESHRE) in Stockholm, Sweden, Drs. William Kearns and Paul Brezina presented results of a study that indicates that embryos containing abnormal cells are capable of relegating those cells to the sidelines where they stop developing while the normal cells continue to grow.

In the study, they re-examined embryos that had been determined to be abnormal after removal of a single cell on the third day after oocyte retrieval and insemination (day 3). The embryos were retested if they reached the blastocyst stage (days 5-6). The scientists found that 16/25 of the embryos diagnosed as abnormal on day 3 were genetically normal blastocysts. Based on these results, Drs. Kearns and Brezina concluded that it is probably common for human embryos to have both normal and abnormal cells in the early stages of development. By some as yet unknown mechanisms, some of these embryos are able to exclude the abnormal cells while promoting the development of the normal ones.

“Early embryos can correct genetic abnormalities during development: findings have significant implications for fertility treatment and stem cell therapies”. 5 July 2011. http://www.ivf.net/ivf/early-embryos-can-correct-genetic-abnormalities-during-development-findings-have-significant-implications-for-fertility-treatment-and-stem-cell-therapies-o6051.html

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Possible Impact of Celiac Disease on Unexplained Infertility

by Dr. Susan Sarajari

Celiac disease is a chronic autoimmune disease of the digestive tract that interferes with the digestion and absorption of nutrients. Patients with celiac disease can not tolerate gluten, which is found in wheat, barley and rye. When people with celiac disease ingest gluten, an immunologically mediated inflammatory response results that damages the mucosa of the intestine resulting in maldigestion and malabsorption.

A recent study published in the Journal of Reproductive Medicine showed increased rates of celiac disease in women with unexplained infertility. The study evaluated 191 patients and found a prevalence rate of 5.9% in women with unexplained infertility. These findings suggest that dietary measures, specifically a gluten-free diet, could improve chances of conception in certain women with unexplained infertility. However, due to the small number of patients who completed the study, these results need to be validated with larger randomized controlled trials.

“Increased Celiac Disease Prevalence In Women With Unexplained Infertility”.
19 Aug 2011. http//:www.medicalnewstoday.com.

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Developments in Embryo Culture Systems

by Dr. Susan Daniel

In the IVF laboratory, embryos are grown in culture medium in plastic dishes. The embryos are moved to fresh medium or to different types media from time-to-time, but the system is static. It is a quite different from the dynamic environment an embryo would encounter in the body.

Dr, Gary Smith at the University of Michigan in Ann Arbor has spent many years working on the development of a new dynamic culture system in which embryos are grown on plastic chips. Fresh medium containing various nutrients and hormones is pulsed over the embryo in regular intervals. Recent work has demonstrated that embryos grow better in the dynamic system when compared to embryos grown under conventional static culture conditions. Dr. Smith hopes that the new system will enhance pregnancy rates in IVF.

“IVF success rates boosted by a bed of nails”. 30 July 2011. http://www.newscientist.com/article/mg21128234.300-ivf-success-rates-boosted-by-a-bed-of-nails.html?DCMP=OTC-rss&nsref=online-news

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Predicting a Woman’s Fertility

by Dr. Susan Sarajari

Predicting how long a woman will remain fertile is becoming more accurate according to researchers from the Universities of St. Andrews in Scotland, who measured Anti-Mullerian Hormone (AMH) levels of 3,200 healthy women and girls to determine what the average AHM level might be. AMH is commonly used to assess ovarian function and AMH changes with a woman’s age.

Low AMH levels predict decreased chances of conceiving. Currently, there is no test that can predict how many eggs a woman still has. Researchers hope that this study might contribute to the development of a test that can reliably predict when menopause will occur and for how long a woman is likely to be able to conceive.

“Predicting How Long A Female Will Remain Fertile Becoming More Accurate”. 08 Aug 2011. http://www.medicalnewstoday.com.

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Non-invasive Test for Chromosome Abnormalities in Oocytes (Eggs)

by Dr. Susan Daniel

Currently there are two methods that can be used to determine whether or not an egg contains the correct number of chromosomes. A small part of the egg called the polar body can be removed and tested or the egg can be fertilized and a cell from the resultant embryo can be taken out and checked. Both procedures are invasive and can result in damage to the egg or embryo.

Scientists at the University of Oxford reasoned that chromosomal abnormalities in eggs might cause changes in the cumulus cells that surround and communicate with them. They studied the activity of genes in cumulus cells from chromosomally normal and abnormal eggs. They found that 729 genes were expressed differently in cumulus cells that had surrounded eggs with abnormal numbers of chromosomes. Dr. Elpida Fragouli, a scientist at the University of Oxford and director of cytogenetics at Reprogenetics, UK explained that they are working to determine whether these genes might be used to develop a non-invasive test for chromosome abnormalities in oocytes.

“New, non-invasive test for chromosome abnormalities may also shed light on genetic origins of faulty eggs”. 6 July 2011. http://www.ivf.net/ivf/new-non-invasive-test-for-chromosome-abnormalities-may-also-shed-light-on-genetic-origins-of-faulty-eggs-o6055.html

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Stress and Infertility: A myth?

by Dr. Susan Sarajari

For a very long time infertility has often been blamed on stress and a woman trying to conceive was often told to “just relax” and she will spontaneously conceive or her fertility treatments might work better if stress is reduced. Interestingly, a recently published review in the British Medical Journal of 14 studies examining stress and the ability to conceive concluded that emotional distress was not related to the likelihood of conceiving a pregnancy.

Even though, stress does not cause infertility, infertility itself causes patients a significant level of stress. One study from the Harvard Medical School published in 1993 showed that the psychological symptoms associated with infertility were similar to those associated with other serious medical conditions, such as cancer. Stress might not cause infertility but stress reduction is still an important consideration in patients undergoing infertility treatments.

To learn more about stress and fertility, contact us.

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Sperm Preparation for Intrauterine Insemination (IUI)

by Dr. Susan Daniel

Although some semen may enter the uterus after intercourse, large amounts can cause painful uterine contractions. To avoid inducing contractions, sperm are separated from the liquid portion of the semen before they are used for intrauterine insemination (IUI). In the lab we call this procedure “sperm washing”.

There are two methods that we routinely use. The first method is separation by density gradient. Semen is layered on top of the gradient and centrifuged. Sperm are pulled through the gradient while the semen is left behind. The sperm that make it to the bottom of the gradient tend to be best quality sperm. Because some sperm get stuck and lost in the gradient layers, we prefer to use this method on normal semen specimens.

When the semen parameters are subnormal, we often choose to wash the sperm by resuspending the semen in culture medium and then separating the sperm from the semen by centrifugation. This method generally results in a better recovery of sperm, however, in addition to sperm, the preparation also contains dead sperm, sperm that are not moving, white blood cells, and debris.

Regardless of what method is used, the aim is to produce a preparation with enough motile sperm to optimize the chances of achieving a pregnancy.

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IVF Failure and Immune Response

by Dr. Susan Sarajari

One of the biggest challenges in IVF has been identifying the cause of failed IVF cycles. According to a study by researchers from the Center for Human Reproduction in New York, some failed IVF cycles could be a result of the mother’s immune response to an embryo, similar to an organ rejection that can take place with organ transplants. Implantation is considered an immunologic process and women who have IVF failures are more likely to have autoimmune diseases, the study found. In addition, certain genes were identified, which the researchers believe to be playing a part in embryo rejection. Being able to make a genetic test to identify possible implantation failure, may open up new therapies to improve embryo implantation and IVF success.

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Oral Health and Infertility: A link?

by Dr. Susan Sarajari

According to a study by Professor Roger Hart of the University of Western Australia, which was recently presented at the annual meeting of the European Society of Human Reproduction and Embryology, periodontal disease can delay chances of conceiving by at least two months. The researchers followed a group of over 3,500 women and concluded that the presence of periodontal disease seems to be a modifiable risk factor, which can increase the time to conceive. Women contemplating pregnancy should be encouraged to have any gum disease treated prior to attempting to conceive. Flossing and brushing your teeth regularly should be a part of taking care of yourself pre-conceptionally.

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Male Factor Redefined

by Dr. Susan Daniel

The World Health Organization (WHO) has recently published the results of a large study aimed at developing better reference values for human semen analyses which involved men from eight countries on three different continents. Previous to this study, the accepted “normal” or “reference” values for semen parameters had been derived from poorly defined populations and conducted using methods that may not have been standardized between laboratories.

The following table compares the old (WHO IV) reference values with the new (WHO V).


What does this mean for patients? The semen analysis is an important test and often the only test used for the diagnosis of male factor infertility. Using the old reference values of WHO IV, ICSI (intracytoplasmic sperm injection) was generally recommended when sperm morphology was less than 15% normal forms. With the new reference values of WHO V, ICSI is recommended when morphology falls below 4%. When morphology is 4% or greater, oocytes are inseminated with 50,000-100,000 motile sperm by routine IVF. The fertilization and pregnancy rates have not changed even with less ICSI.

NB Morphology is no the only measurement used to diagnose male factor infertility. Each semen analysis is assessed individually along with the medical history to determine the most appropriate course of treatment.

Cooper, T.G., Noonan, E., von Eckardstein, S., Auger, J., Baker, H.W.G., Behre, H.M. Haugen, T.B., Kruger, T, Wang, C., Mbizvo, M.T., and Vogelsong, K.M. (2010). World Health Organization reference values for human semen characteristics. Human Reprodroduction Update, 16(3): 231-45.

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