Monday, September 10, 2007

Infertility Can Be Devastating, But Science Can Offer A Helping Hand

Stephanie M. Caballero

By Karen Lindell

The drop begins even before she is born.

A woman has the most eggs stored in her ovaries when she's growing inside her mother.

As a 20-week-old fetus, she's got 4 million to 6 million. As a newborn, she's down to 1 million. As an adolescent, she's holding on to 400,000. At menopause, she's left with 1,000.

But the eggs start to fray around her 35th birthday — long before menopause. Their chromosomes no longer divide properly. Response to pregnancy hormones is sluggish.

Despite all the stories about wonders worked on eggs, sperm and embryos in science labs, no one has discovered a drug or procedure that can prod a human egg into being young again.

But scientists have found other ways to overcome the body's limitations and help infertile couples bring a baby into the world. Fertility technology has advanced considerably since Louise Brown, the first "test tube baby," was born in England in 1978.

From 1996, when the Centers for Disease Control and Prevention started officially keeping track of fertility-clinic birth rates, through 2004, the number of live births in the U.S. as a result of assisted reproductive technology (ART) more than doubled, from 14,507 to 36,760.

In 2004, 37 percent of ART cycles started by women younger than 35 who used their own eggs resulted in live births. The numbers are lower for older women who use their own eggs, dropping to 4 percent for those older than 42.

Using donated eggs or embryos, however, boosts the percentages for moms-to-be who are 35 and older.

According to the American Society for Reproductive Medicine, the majority of infertility cases are treated with medication, such as fertility drugs or surgery on the reproductive organs.

Assisted reproductive technology accounts for less than 3 percent of infertility services. But ART grabs the most hearts, especially when a celebrity like Brooke Shields is splashed across the cover of People magazine, marveling at her "miracle" baby.

The ART of in vitro

The most common form of ART is in vitro fertilization, or IVF. Here's the condensed version of how it's done, minus the many delicate and meticulous in-between steps and monitoring: A woman's eggs are removed from her ovaries, then fertilized with her partner's sperm in vitro (Latin for "in glass") in a laboratory. Three to five days later, the fertilized eggs are placed directly into the uterus. If all goes well, nine months later.

Other ART techniques, which we won't delve into in great detail here because in vitro fertilization comprises more than 99 percent of treatments, are gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT). ART, alas, is an acronym-heavy field.

Variations include implanting embryos that have been frozen and thawed from a previous ART cycle or, as Star reporter Anna Chang-Yen relates in the accompanying first-person article, using a donor's eggs.

Chang-Yen, 28, has premature ovarian failure, meaning she has run out of viable eggs before age 40. She and her husband, David, have asked Chang-Yen's older sister, Shanna Brittian, to donate eggs that will be fertilized with David's sperm and implanted into Anna's uterus.

Dr. Ashim Kumar and his team at the Fertility and Surgical Associates of California clinic in Thousand Oaks are leading Anna, David and Shanna through IVF.

During a recent interview at his office, Kumar discussed the most recent advancements in IVF.

ICSI: one egg, one sperm

A breakthrough that's actually been around for more than 10 years, but "a lot of people don't know is available," Kumar said, is intracytoplasmic sperm injection, or ICSI (pronounced IK-see).

During in vitro fertilization, eggs can be fertilized "naturally" by placing 50,000 to 100,000 sperm around each egg; or with ICSI, by injecting a single sperm into a mature egg. ICSI is used when a woman's partner has severe infertility problems or has undergone a vasectomy but wants to use his own sperm, not a donor's. Fertility doctors can surgically extract the man's sperm, even if he has had a vasectomy.

PGD: genetic screening

Preimplantation genetic diagnosis, or PGD, tests embryos for genetic disorders before the embryos are transferred to the uterus.

PGD, not yet offered widely (it was used in 4 percent of ART cycles in 2005), is for potential parents with inherited genetic disorders such as cystic fibrosis or muscular dystrophy. In the lab, doctors can determine which embryos are carriers and transfer only those without the defect.
"Unfortunately, when people run out of choices, they can go to the fringes of medicine. That's where a third or second opinion comes in." Dr. Ashim Kumar, of Fertility and Surgical Associates of California clinic in Thousand Oaks.

Photo by Joseph Garcia

"Unfortunately, when people run out of choices, they can go to the fringes of medicine. That's where a third or second opinion comes in." Dr. Ashim Kumar, of Fertility and Surgical Associates of California clinic in Thousand Oaks.

Other candidates for PGD, Kumar said, are women who have had repeated miscarriages. Recurring pregnancy loss, he said, might occur "because part of one chromosome in the egg or sperm breaks off and attaches to another, so there's missing material on one chromosome and additional (material) on another."

During in vitro fertilization, he said, "we can make a window in the shell of the embryo, extract one cell, fix it onto a slide and stain the slide to see what part of the chromosomes are present."

More controversial is using PGD for a nonmedical reason: choosing the sex of a baby.

Injuring without harm

Kumar also described a technique for women who can't get pregnant because embryos won't take hold in their uterus. Fibroids or polyps, which are often the cause, can be removed surgically.

But for cases when fibroids or polyps aren't the culprit, Israeli researchers have had success with "injuring the endometrium," a procedure that "sounds more invasive than it is," Kumar said.

The technique involves taking a biopsy of the uterus using an instrument called a pipelle before an IVF cycle. "It supposedly increases implantation rates by 50 percent," Kumar said. Researchers aren't sure why the pipelle treatment works. The technique is experimental, because only one group of researchers has studied it. Still, he said, his clinic offers the procedure because "the risk is minimal — maybe five seconds of discomfort — and the benefit is pretty significant. It holds promise for someone who's gone through failed IVF cycles."

Multiples, not by choice

Sometimes, baby makes two or three or more. One of the downsides (or upsides, depending on how you look at it) of ART, which offers the opportunity to implant more than one embryo, is the associated rise in multiple births (twins, triplets and beyond). Multiple gestation is more dangerous for the mom and babies, potentially leading to premature birth, low birth weight and other problems.

The ASRM has issued guidelines about the number of embryos that should be implanted, Kumar said, so patients should ask the clinic whether it follows those recommendations.

Multiple gestation raises an inherent conflict of interest, however.

"How we're graded (by the CDC) is our pregnancy rates, and it's easy to increase rates by replacing more embryos," Kumar explained. "But if you have a good IVF lab and do things carefully, you're going to get good pregnancy rates even by putting in fewer embryos," Kumar said, noting that his clinic follows a two-embryo guideline.

Many European countries, he said, will transfer only one embryo. But those countries pay for every cycle of IVF, unlike the U.S., where most insurance plans don't cover even one cycle. If a couple are spending their life savings on IVF, Kumar said, "it's unfair to say they have to accept a lower pregnancy rate by only putting one embryo back."

Freeze embryos, not eggs

Kumar also described a new ART procedure that hasn't had a high success rate: oocyte cryopreservation, or freezing unfertilized eggs for later use.
The micro manipulator attached to an inverted compound microscope is used in the IVF lab at Fertility and Surgical Associates of California for in vitro fertilization procedures.

Photo by Joseph Garcia

The micro manipulator attached to an inverted compound microscope is used in the IVF lab at Fertility and Surgical Associates of California for in vitro fertilization procedures.

Oocyte cryopreservation is not the same as embryo cryopreservation, a more reliable freezing procedure.

Embryos created through IVF can be preserved in liquid nitrogen, "and when we thaw them they have a very good chance of survival," Kumar said. Eggs, Kumar said, "have relatively high water content and are difficult to thaw and freeze effectively."

Freezing embryos lets women implant another embryo if a previous IVF cycle fails. The goal of freezing eggs is to preserve her fertility. For example, an unmarried woman in her 30s who wants to have a baby someday can freeze her eggs until she finds the right partner. "She'll then have the eggs of somebody who's younger and can conceive a baby with her own eggs," Kumar said. Or a woman going through chemotherapy can freeze her eggs before starting the treatment.

Yes, Kumar said, babies have been born from eggs that were frozen, but the chance of that happening is extremely low.

"Unfortunately, when people run out of choices, they can go to the fringes of medicine," Kumar said. "That's where a second or third opinion comes in. If somebody tells you they're one of five centers in the world or country offering this, you should think, Why is everyone else not offering this?'"

Despite all the fancy genetic work, Kumar said much of the increase in success rates for infertility treatment is "about improvements in the IVF laboratory. There's constant attention to what's happening in the lab — the culture medium, the air quality. Every little thing helps. If you leave an embryo on a countertop unheated for 15 seconds, it's not going to do well."

And he reminds patients who balk at what they perceive as low pregnancy rates for IVF (below 40 percent): "If you look at conception that occurs naturally in a young healthy couple, you don't have implantation rates of 60, 70 or 80 percent. It's just not true even in nature, a perfect system. I think we're trying to beat nature at its game, and it's fraught with complications. We shouldn't overestimate our abilities."

1 comment:

Melanie said...

I have been doing some research online about egg freezing and based on what I have read, the success rates of egg freezing has gone up considerably since it first started and the data to date seems to suggest that the children born from frozen eggs are healthy. In my travels I have found a company called Extend Fertility Their website has an informative and empowering outlook of women and their choices when it comes to their reproductive health.