Nikica Zaninovic used to take embryos out of an incubator each day and photograph them under a microscope to determine which were most likely to produce a baby. He’d inspect the number of cells, the extent to which they’d fragmented, the shell’s thickness and any defects.
Now the embryologist and his colleagues at Weill Cornell Medical College in New York also watch movies of the embryos’ first few days. New equipment takes snapshots inside their incubators every 10 minutes, and replays the frames as a time-lapse film.
The footage captures crucial details about milestones in embryonic growth that were previously missed: how long fertilized eggs take to split into two, three or four cells. Those that are too fast or too slow have less chance of success, and ones that jump directly from one to three cells have almost no chance, Zaninovic said. The technology has the potential to increase pregnancy rates at in-vitro fertilization clinics and reduce the risks of multiple births, he said.
“With time lapse, we have the complete picture,” Zaninovic, an assistant professor and embryology laboratory director at Weill Cornell, said in a telephone interview. “We now can select embryos better and we can put fewer embryos back into the mother, which will reduce the number of twins and triplets.”
Some of the world’s largest and best-known clinics have switched to time-lapse systems made by Unisense Fertilitech A/S of Aarhus, Denmark; Vitrolife AB (VITR) of Gothenburg, Sweden; and Auxogyn Inc. of Menlo Park, California. It’s one of the biggest steps forward in the 35 years since the first IVF baby was born, said Marcos Meseguer, scientific supervisor at IVI in Valencia, Spain, who spoke last month at the European Society of Human Reproduction and Embryology meeting in London.
“It’s definitely a revolution,” Meseguer said in a telephone interview. “In our field, we have had three or four revolutions. This is the latest one.”
While time-lapse cinematography has existed for decades, and scientists have known for about 20 years that there’s a link between the rates at which embryos develop and their viability, only in the past decade has it become practical to commercialize time-lapse equipment for IVF.
The potential market is large. One in six couples has difficulty conceiving a child naturally, according to ESHRE. Less than 10 percent of the world’s estimated 4,500 IVF clinics have adopted the technology since it became commercially available about five years ago, according to Meseguer.
Two business models have emerged. Unisense and Vitrolife sell instruments to clinics. The cost of Unisense’s Embryoscope is estimated by Meseguer at about 80,000 euros ($106,000) in Europe and by Zaninovic at $120,000 in the U.S. Vitrolife sells Primo Vision in Europe at unit prices similar to Embryoscope’s, said Chief Financial Officer Mikael Engblom.
Auxogyn has a fee-based test called early embryo viability assessment, or Eeva, which incorporates proprietary data from research done at Stanford University. The fee is about 800 pounds ($1,255) in the U.K., Chief Executive Officer Lissa Goldenstein said. The company gained European Union clearance to sell Eeva last year and submitted data to the U.S. Food and Drug Administration for approval in June, she said.
Sales doubled last year at closely held Unisense, said Francesca Anne Bahr, the company’s marketing and business development manager. Auxogyn is also closely held and is backed by the venture funds of drugmakers Merck KGaA (MRK)’s Serono unit and GlaxoSmithKline Plc (GSK) and U.S. venture capital firms TPG Biotech and Kleiner Perkins Caufield & Byers, an early investor in Google Inc.
Publicly traded Vitrolife, which sells other products for IVF and cell therapy, has a market capitalization of about 1.4 billion Swedish kronor ($215 million). Its shares have almost doubled in the past 12 months.
Many clinics are hankering for evidence that justifies the additional expense of time-lapse analysis, said Simon Fishel, managing director of Care Fertility Group in Nottingham, England. The clinic charges 750 pounds to monitor and analyze patients’ embryos with the Embryoscope. With it, live birth rates are rising by more than half, he said.
“Not all clinics can buy this equipment because it’s still expensive,” said Natalia Basile, an embryologist at IVI’s clinic in Madrid. IVF costs about 5,000 pounds for one cycle in the U.K., according to the National Health Service, and about $12,400 in the U.S., according to the American Society for Reproductive Medicine.
The companies say they are trying to get data to support their claims. Finding patients willing to enroll in a trial where they may not get the treatment is difficult because everyone wants to have it once they become aware of it, Unisense’s Bahr said.
It’s also unclear if time-lapse imaging is alone responsible for the improved outcomes. One advantage of the systems is that embryos no longer need to be taken out of incubators every day so they can be photographed.
“Embryos don’t like to be changed, but with a regular system you need to take them out,” Basile said.
The technology boosted rates at IVI clinics to 60 percent for 2,000 cycles from 50 percent for 6,000 cycles in which it wasn’t used, Meseguer said. Weill Cornell’s overall rates in time-lapse IVF cycles have risen to about 50 percent from 40 percent, Zaninovic said. Pregnancy rates at Hewitt Fertility Centre in Liverpool, England, improved to 57.3 percent in women under 35 using the Embryoscope from 45 percent, and results with Auxogyn’s device are comparable, said consultant embryologist Karen Schnauffer.
“Those are the data we haven’t seen,” said Andrew LaBarbera, a reproductive physiologist and chief scientific officer of the American Society for Reproductive Medicine. “If time-lapse imaging is shown to be beneficial, then I suspect that it will be adopted almost universally.”
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