A new method for picking the ‘right’ egg in IVF

In a groundbreaking study, Yale School of Medicine researchers and colleagues at the University of Oxford have identified the chromosomal make-up of a human egg. This discovery may soon allow them to avoid using abnormal - or aneuploid - eggs during infertility treatments, and instead to pick eggs that are healthy enough for a successful in vitro fertilization (IVF) cycle.

The results are published in the May issue of the journal Human Reproduction.

Only a few oocytes (eggs) per IVF treatment cycle are able to produce a pregnancy because many eggs have the wrong number of chromosomes. If the egg is missing a chromosome or has an extra chromosome, this is referred to as aneuploidy. This problem increases as women age.

Oocytes are surrounded by cells, called cumulus cells, which regulate and assist the process of egg maturation. In this study, Yale Fertility Center director Pasquale Patrizio, M.D., and Dagan Wells of the University of Oxford studied genes expressed in the cumulus cells. They were able to identify a set of genes that are less active in cells that are associated with abnormal eggs.

They characterized two genes - SPSB2 and TP5313 - and found that the expression of these genes was consistently underrepresented in cumulus cells that surrounded abnormal eggs, while these same genes were normally expressed in eggs with the correct number of chromosomes.

“The identification of these genes in cumulus cells can serve as a novel, non-invasive marker to identify abnormal oocytes and thus ultimately improve IVF success rates,” said Patrizio, professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale. “We can use cumulus cells surrounding the eggs to gain insight into the health of an egg. These cells are now able to inform us about the chromosomal makeup of an egg. This can help us know if it is the ‘right egg’ to be fertilized and produce a baby.”

Primary infertility affects about 6.1 million people in the United States, about 10% of men and women of reproductive age. Assisted reproductive technologies (ARTs) are techniques to help a woman become pregnant, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other similar procedures.

IVF was used successfully for the first time in the United States in 1981. More than 4 million babies have been born worldwide as a result of using the in vitro fertilization technique. IVF offers infertile couples a chance to have a child who is biologically related to them. Today, over 1% of infants born in the US are a result of a pregnancy conceived by ARTs.

With IVF, a method of assisted reproduction, a man’s sperm and the woman’s egg are combined in a laboratory dish, where fertilization occurs. The resulting embryo or embryos is/are then transferred to the woman’s uterus (womb) to implant and develop naturally. Usually, two to four embryos are placed in the woman’s uterus at one time. Each attempt is called a cycle.

The term test tube baby has been used in the past to refer to children conceived with this technique. The first so-called test tube baby, Louise Brown, reached age 25 years in 2003. She was born in England.

Less than 5% of infertile couples actually use IVF. IVF is usually the treatment of choice for a woman with blocked, severely damaged, or no Fallopian tubes. IVF is also used to overcome infertility caused by endometriosis or problems with the man’s sperm (such as low sperm count). Couples who simply can’t conceive and have tried other infertility methods (such as intrauterine insemination) that have not worked for them can also try IVF.

“This finding opens up the possibility of a safe, effective, and inexpensive way of identifying healthy eggs, potentially lowering the risks of miscarriage and Down syndrome,” said Wells. “By conducting these tests before eggs are fertilized, ethical concerns about analysis of human embryos are avoided.”

What Causes of Infertility Can IVF Treat?

When it comes to infertility, IVF may be an option if you or your partner have been diagnosed with:

- Endometriosis
- Low sperm counts
- Problems with the uterus or fallopian tubes
- Problems with ovulation
- Antibody problems that harm sperm or eggs
- The inability of sperm to penetrate or survive in the cervical mucus
- An unexplained fertility problem

IVF is never the first step in the treatment of infertility. Instead, it’s reserved for cases in which other methods such as fertility drugs, surgery, and artificial insemination haven’t worked.

If you think that IVF might make sense for you, carefully assess any treatment center before undergoing the procedure. Here are some questions to ask the staff at the fertility clinic:

- What is your pregnancy ratio per embryo transfer?
- What is your pregnancy rate for couples in our age group and with our fertility problem?
- What is the live birth rate for all couples who undergo this procedure each year at your facility?
- How many of those deliveries are twins or other multiple births?
- How much will the procedure cost, including the cost of the hormone treatments?
- How much does it cost to store embryos and how long can we store them?
- Do you participate in an egg donation program?

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Other authors on the study include Elpida Fragouli, Amy E. Lager, and Umit A. Kayisli.

Wells is supported by the National Institute for Health Research Biomedical Research Centre, Oxford; the work was also supported by a grant from Gema Diagnostics, Inc.

Citation: Human Reproduction doi: 10.1093/humrep/des170

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Karen N. Peart
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203-432-1326
Yale University

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