Screening can identify high-risk genes in eggs

Every woman — and man — is at some risk of getting breast cancer, and some of that risk is passed from parent to child. Variants in two genes, known as BRCA1 and BRCA2, greatly increase the risk of developing the disease.

So far, scientists have identified dozens of BRCA mutations that confer an added risk. Children of carriers — either the mother or the father — have a 50% chance of inheriting these mutations.

Enter modern medicine to take chance out of the equation. Embryos created with in vitro fertilization techniques can be screened for these genetic variants before they are implanted in a woman’s uterus. In addition, a Santa Monica fertility doctor is testing an egg screening procedure that would allow women to identify and freeze their lowest-risk eggs until they’re ready to get pregnant.

Practitioners assert that these preimplantation genetic diagnosis technologies, better known as PGD, are sound but still tricky enough that people who choose this route should seek experienced clinics.


“It’s very doable, but PGD is not the stuff for amateurs — you’re dealing with the limits of technology,” says Dr. Joe Simpson of Florida International University in Miami, a leader in the field of prenatal genetic diagnosis.

And yet, for couples who carry one or more of the BRCA mutations, the decision to essentially erase bad genes from their bloodlines is not only very expensive but also rife with medical and moral complexities.

Here’s a closer look at how parents-to-be can avoid passing on their heightened breast cancer risk.

What’s the cancer prognosis for carriers of BRCA mutations?

Women who have one of the known BRCA variants are at five times greater risk of developing breast cancer than women who don’t have those mutations. That is, 60% of women with the genetic variants get breast cancer sometime during their lifetimes, on average, compared with 12.5% of women in the general population, according to data from the National Cancer Institute. Similarly, the risk for ovarian cancer increases from 1.4% in all women to 15% to 40% in women who have a BRCA mutation.

In men, the BRCA variants increase the risk of prostate, colon and breast cancer, but to a lesser degree.

How are embryos and eggs screened for the genetic variants?

Both methods of PGD are done in the context of in vitro fertilization. This means a woman takes hormones to stimulate multiple eggs to mature and undergoes a procedure to withdraw those eggs from her ovaries. The procedure is not risk-free; the hormones can stimulate the ovaries too much and cause pain and bloating.

The eggs are fertilized with sperm in the lab and allowed to grow for three days until they are eight-cell embryos. One of those cells is carefully removed, and the DNA is compared with the mother’s and father’s DNA, which is extracted from a blood sample. The portion of the genome containing the BRCA genes is sequenced using a technique called linkage analysis.

To screen eggs, scientists take advantage of the body’s normal egg-making process. In the final step, the 23 pairs of chromosomes separate — one set goes to the nascent egg and the other set ends up in a tiny sac called the polar body. By comparing the DNA in the polar body and the woman’s DNA, scientists can deduce which versions of the BRCA genes are present in the egg.

How common is PGD?

This method of screening embryos has been around for 20 years and is typically used to prevent childhood diseases that are caused by a single gene, such as cystic fibrosis and muscular dystrophy. Genetic tests for BRCA mutations have been available since 2006.

It’s hard to know exactly how many PGD babies have been born. The Reproductive Genetics Institute in Chicago has performed more than 1,700 embryo-screening procedures alone, and “a number of them have been for BRCA1 and 2,” says Simpson, who serves as the clinic’s medical director. In a review article published this summer in the journal Prenatal Diagnosis, Simpson reported that diagnostic accuracy was greater than 99%.

Dagan Wells, an Oxford University scientist who researches PGD techniques, says that thousands of children have been born using the egg-screening method.

Is PGD safe for the embryo?

Screened embryos appear to grow normally, even though they’re short one cell. A study published in August in the journal Human Reproduction reported that 581 children born after embryo screening did not significantly differ — in terms of birth weight and rate of birth defects — from children conceived in vitro but not screened.

Are there ethical issues with PGD?

Many of the issues are the same as those raised by amniocentesis, a common prenatal test that can identify genetic problems in a fetus about halfway through pregnancy. By screening embryos, couples avoid having to decide whether to terminate a pregnancy; they simply choose not to implant.

Polar body biopsy means screening one step earlier — before fertilization — and therefore skirts the issue of potentially destroying embryos, says Dr. John Jain, a reproductive endocrinologist at Santa Monica Fertility. Jain is now working with Wells to test the viability of eggs after they’ve been screened for BRCA mutations and frozen for a period of time.

Some people argue that genetic screening should be reserved for diseases that are lethal during childhood or cause lifelong problems, such as mental retardation, Simpson says.

Any other considerations with PGD?

It’s expensive. Screening eggs or embryos adds $3,000 to $6,000 to an already expensive procedure — in vitro fertilization runs about $15,000 for a single cycle of treatment.

And it’s fraught with complicated, sometimes angst-inducing decisions, says Gwendolyn Quinn, a health psychologist at the Moffitt Cancer Center in Tampa, Fla., who works with newly diagnosed cancer patients to understand some of the fertility issues they face.

She knows of cancer-free women who had their breasts and ovaries surgically removed to reduce their risk of getting cancer. They also didn’t want to risk bearing children who would face the same dilemma. When they learned about PGD, which would have kept parenthood an option in the future, “they were a little bit devastated,” Quinn says.

Quinn surveyed 962 women who were members of a BRCA carrier community and found that 79% of respondents had never heard of PGD. Once defined, 33% of those surveyed said they would consider PGD, 33% said they would not and 29% couldn’t say one way or the other. The results were published last year in the journal Genetics in Medicine.

Some of the women were disturbed by the technology and told Quinn things like “I wish this test didn’t exist,” and “Thank goodness this wasn’t around when my mother was pregnant with me.” On the other hand, a small group of younger women were glad to know about PGD, she says, “because this is going to impact their decision-making.”