Can Reproduction Be Ageless?

It’s well known that more and more women are delaying childbirth until their 30s and 40s to complete their education, pursue careers, or find the right partner. But since a woman’s fertility begins to decline by her late 20s, and even more dramatically after age 35, the result has been an increase in involuntary childlessness.

The options for dealing with this have been limited. Some 61,000 babies were born with the use of in vitro fertilization in 2012 (accounting for 1.5 percent of all babies born in the United States), but IVF success rates also decrease with age—it works about half the time for women under 35, and less than 10 percent of the time for women older than 40.

In the past, a woman unable to get pregnant through IVF had two options: egg or embryo donation, or adoption.

Lately another option has gained some ground: oocyte cryopreservation. Egg freezing is nothing new (the first successful pregnancy with frozen eggs was reported in 1986), but its efficiency has been extremely low—in its first two decades of use, the method would require an average of 100 frozen eggs to result in one baby. But in recent years we’ve seen the breakthrough of flash freezing technology, also known as vitrification. With this technique, the efficiency of egg cryopreservation has improved dramatically—we now need only four to 12 eggs to have a baby. Women can now cryopreserve their eggs during their peak reproductive period (ideally under age 30) and store those eggs until they are ready to have children. A frozen egg maintains its viability at the chronological age when it was obtained—in other words, it stops aging—and the womb itself has no age-related decline in its ability to sustain implantation and carry pregnancy. It is estimated that several tens of thousands babies were born from frozen eggs in the last few years. Some people call oocyte preservation the “second sexual revolution.”

A recently emerged alternative to egg freezing is ovarian tissue cryopreservation. Just last week it was reported that a 24-year-old woman in London had given birth via an ovary that had been removed and frozen when she was nine years old. The woman had been diagnosed with a blood disorder as a girl, and the ovary had been removed and frozen to save it from the damage of chemotherapy.

There’s also promising research aimed at “rejuvenating” aged oocytes. One approach is to replace the cytoplasm (or one of its critical components, the mitochondria) of the “old” egg with cytoplasm or mitochondria extracted either from a young donor egg or from the patient’s own somatic cells (see “Rejuvenating the Chance of Motherhood?”). Yet another line of research takes advantage of induced pluripotent stem cells. In this process an already mature, or “differentiated,” somatic cell from the body can be treated to make it “de-differentiate” (return to its embryonic state). This process is followed by another treatment regimen to stimulate that cell to develop into a functional oocyte. This raises the possibility that we could make human eggs in the lab out of cells taken from a woman’s own skin.

Rejuvenating eggs or making new ones in the lab are both exciting ideas. What’s also true is that the use of these techniques to treat human infertility is likely a very long way off. We’re making progress, but the best current advice for any woman thinking about delaying pregnancy is to freeze your eggs now, while you’re reproductively young, and use them later when you’re ready.

Zsolt Peter Nagy is the scientific and laboratory director of Reproductive Biology Associates and an adjunct assistant professor at Eastern Virginia Medical School.