Shortly before 10:30 on a recent evening, with a nearly full moon luminous through mile-high air, Jonathan Van Blerkom climbed into his car, eased out of his driveway, and threaded his way through a quiet Denver neighborhood to check on the fate of some precious human eggs. They had been inseminated that morning, and some of them should be one-celled embryos by now. Van Blerkom’s day had begun more than 16 hours earlier, but human development works the night shift, so Van Blerkom does too. Every evening, weekends included, he sets out on this five-minute drive to do one of the things he does best: look at very early embryos, only hours after fertilization, to decide if they are likely to become babies.

Courtesy of S. Makabe and Jonathan Van Blerkom, “An Atlas of Human Female Reproductive Function,” Taylor & Francis Books LTD., 2004.




A mature egg, ready for fertilization, is covered with clusters of granulosa cells. From the time an egg begins to develop in one of a woman’s ovaries, the granulosa cells serve as a communication system—signaling, for example, when the egg needs nutrients and proteins.

The embryos had been incubating all day in a small laboratory at Colorado Reproductive Endocrinology, a private fertility clinic where Van Blerkom, a professor at the University of Colorado, collaborates with in vitro fertilization doctors to help increase the chances that infertile couples can have children. He himself is not an “IVF doc.” He is a scientist with a passionate, if not obsessive, curiosity about the biological factors that allow an egg to create a human. Ironically, that interest has also made him an expert in all the things that can go wrong with an egg and doom a pregnancy—even before it begins.

On this particular night, Van Blerkom dropped in to check on the status of eight eggs that were harvested that morning from a persistently infertile woman and soon afterward mixed with her husband’s sperm. The woman had undergone several previous cycles of IVF at another clinic without a pregnancy, and Van Blerkom wasn’t particularly hopeful about this round, either. “She’s maybe a problem,” he said in his low, urgent voice as he moved quickly about the lab.

Van Blerkom—dressed in blue jeans and a blue button-down shirt, a fringe of long graying hair sticking out like a worn-down but beloved brush—took great pains to keep the eggs warm during this nocturnal assessment. He turned on special heaters and waited about 15 minutes until the filtered air under a protective hood—where he would inspect the nascent embryos under a microscope—had reached 95 degrees Fahrenheit. Then he removed several small plastic dishes from the incubator and began to peruse the eggs.

For the better part of the past two decades, human embryologists have been staring at eggs and early embryos trying to decide which are “good” and which are not, which embryos seem most likely to yield a viable infant after implanting and which are destined to fail. These judgments have traditionally involved more art than science, as befits a procedure with an overall success rate of less than 34 percent. Van Blerkom has spent the last 25 years trying to inject scientific logic into these snap visual judgments, which last no more than 30 seconds.

Under the microscope, these eggs appeared like dark dots in a field of cellular clutter. “She has a couple fertilized,” he remarked, removing the debris with a sharply pointed pipette. Then he moved to a second, more powerful Leica microscope attached to a video monitor. One by one, eight human egg cells, as big as the moon that Colorado night, loomed on the screen.

“This is at 10 hours after insemination,” Van Blerkom said. “There, you can see the pronuclei.” There on the screen was the huge, rotund universe of the female egg cell, its internal jelly, or cytoplasm, smooth and evenly grained, and there, just below the equator, two ghostly yolklike circles around the male and female DNA, mere mirages of genetic material, in close proximity, nearly nuzzling. Each gamete—egg and sperm—prepares its half packet of genetic material, known as the pronucleus, and one of the first organizational tasks of human development is to bring these two packets together. The glancing proximity of the male and female pronuclei on the screen represented the final stage of a daylong dance—a long latitudinal migration by the sperm’s DNA to the site of the female pronucleus, so that the male and female chromosomes can “approach each other and melt into one,” as a 19th-century embryologist poetically put it. That produces a complete set of human chromosomes and leads to the first division of the cell.

Even though the first several embryos looked smooth and even, Van Blerkom wasn’t optimistic. “She doesn’t have great stuff,” he said. When asked how he could tell, he replied, “Just by looking at the quality of the cytoplasm in the unfertilized eggs. This is in pretty bad shape. These are not normal eggs.

“Look at this one,” he continued. “This one has a lot of disorganization in the cytoplasm.” And indeed, as more of the eggs filled the screen of the monitor—some fertilized, most not—the cells frequently had large vacuoles, or fluid-filled bubbles, in their interior. From experience, Van Blerkom knew that, although such eggs may become fertilized, they rarely produce a successful pregnancy. There is even a hint of evidence that normal-looking eggs from a woman who also has these abnormal eggs may fail to yield offspring.

“You look at these eggs, and you know they’re telling a story,” Van Blerkom said later. “But you only know bits of the story. If it were an abstract notion, who’d care? But around the world, thousands of people are looking down microscopes at thousands of eggs and asking, ‘Should I keep this?’ So life-or-death decisions for the one-celled embryo are made every day. My argument is, let’s make those decisions based on biology.”