It all began for us in 2011 with a female patient trying everything to conceive and a doctor who would not give up hope.
"I have to tell you a secret"
After more than a quarter century researching and treating fertility, Dr. Norbert Gleicher thought he had seen it all. That is, until Dwyn Harben walked into his office at the Center for Human Reproduction in New York City.
Forty-two years old and single at the time, Harben knew that one day she would want to have children. "Well I have always known that I wanted to have children on my own; I'm really not interested in having a partner," says Harben, who is a banker. "I guess there were things I got busy with and I didn't get around to doing things as early as I should have, but finances were also a concern. But from the time I was eight or nine years old I always pictured myself with daughters." So she asked Gleicher to either harvest her eggs and freeze them for when she is ready; or to fertilize those eggs with donated sperm, and freeze the embryos.
"I actually advised her against both of these options, because to freeze eggs and/or embryos at age 43 is not a very good option," says Gleicher, who has published dozens of papers on reproduction and is the editor of the Journal of Assisted Reproduction and Genetics. "As [a woman's] eggs get older, their ability to lead to normal pregnancy greatly declines. And that is a steady decline, but after age 37 or 38 that decline becomes very, very rapid. And after age 40 it's what I call a waterfall."
Gleicher advised Harben to wait until she felt ready to become pregnant, and to use donated eggs from another, younger woman when that time came. But Harben was insistent, and Gleicher's doubts were confirmed: "As I had predicted the first cycle went very poorly. We had only one egg and one embryo," he says. "We froze it, because she wanted to accumulate embryos for future use at some time."
Harben wanted to try again. "He tried to talk me out of it, but I persuaded him that I'd really feel better if I tried at least one more round," she says. "And meanwhile I did what any modern woman does, and I went to the Internet and started doing some research."
She came across a small study published in 2000 in the journal Human Reproduction, which showed that five women taking a combination of fertility drugs and a supplement called dehydroepiandrosterone (DHEA) showed a slightly improved response in ovarian stimulation i.e., release of eggs during fertility treatment after two months. The study's results were not strong enough for any other fertility researchers to follow up on it. But it was enough to cause Harben to go out and buy some DHEA, which is widely available and typically touted as an anti-aging supplement. She started taking it twice a day without Gleicher's knowledge.
"To cut a long story short, her second cycle was a little better, her third cycle was yet a little better," recalls Gleicher. "And to my big surprise, having expected that as this woman gets older things would get even worse, she really improved from cycle to cycle to cycle. Every cycle she gave us more eggs, and more good-looking embryos for freezing purposes. I was astonished. And after she had done six cycles, she comes in here one day before starting her seventh cycle and says, 'Dr. Gleicher, I have to tell you a secret.'"
Gleicher was skeptical that DHEA could cause such a huge effect (Harben produced 13 eggs during her sixth cycle), but he let her continue taking it and continue her egg retrieval cycles.
"And so then I did another round and I produced 16 eggs," says Harben. "And I did another round and I produced 19."
"Apparently as we learned from this patient, the maximum effect of this DHEA kicks in only after about four months," says Gleicher (which may be why no one took note of the previous study, which only lasted two months). "And indeed if somebody takes it for that long the effect is almost unbelievable. This patient has by now done 11 cycles with us, and in her last two cycles we had to step her [fertility] medication down because she was over-stimulating. In other words, her ovaries were behaving like those of 20-year-old or 25-year-old."
As for Harben, she plans to do one more round of egg retrieval and embryo freezing. All told she figures to have about 100 embryos to choose from when she feels ready, and she thinks that time might come in about four years. And even if things don't work out, she says she'll have few regrets: "Even if something goes wrong and I still, after the tremendous number of embryos I've produced, I still don't end up giving birth to at least one daughter that's genetically my own, at least I know that a lot of other women are going to benefit from it."