Frontiers of Fertility

Better IVF. Cutting-edge ways to size up embryos. For couples struggling to conceive, the options are expanding—and the outlook is improving

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A baby in utero. New techniques can improve the odds of conception.

Not all sperm are created equal either. The average male produces 76 million sperm per ejaculation; the lower limit for conception is 18 million. For IVF, the quality of sperm is judged in the lowest-tech way possible: a lab technician looks at them through a microscope. This method has just the limitations you might expect.

“A sperm has a head, a midpiece and a tail,” says Niederberger, “and there’s a lot you can find that looks wrong. You would think if you can find the best-looking sperm, it would also be the healthiest one, but that is absolutely not correct. The vast majority of sperm—up to 96%—look abnormal, and the exact shape of a sperm doesn’t necessarily equate to its success.”

This is increasingly problematic as doctors turn away from the original IVF method of simply mixing an egg and a semen sample in a dish and adopt a more exacting approach known as intracytoplasmic sperm injection (ICSI), in which a single, especially handsome sperm is selected, lifted by the tail and injected directly into the egg. That practically guarantees fertilization, but if the technician was fooled by looks and rejected more viable candidates—what fertility experts dub “overcalling” sperm—it may doom a pregnancy before it can even get started.

All of this explains the growing interest in an approach called mini IVF, which Zhang’s and other clinics are promoting. As its name suggests, mini IVF strips the familiar in vitro regimen down in a way that makes it both less arduous and, its proponents say, more effective. Rather than endure a month of hormonal carpet bombing, women take a 12-day course of Clomid, an oral drug that blocks the body’s estrogen receptors and promotes egg maturation. This causes the ovaries to produce only three to five comparatively viable eggs rather than a dozen often immature ones. In the final day or two of the cycle, the women also use a nasal-spray version of Synarel, a drug that’s usually used to treat endometriosis but in this case helps trigger egg release. Eggs are then retrieved and fertilized as in traditional IVF.

“The physiologic changes the body experiences in mini IVF are close to the natural cycle, without excessive drugs,” says Zhang. Starting with fewer embryos can also help mitigate the ethical issues raised when unused ones are frozen and stored in clinics, with little or no prospect of ever being implanted but little or no appetite on the part of anyone involved to destroy them.

Not everyone is sold on the promise of mini IVF. Some critics suggest that the odds of producing a successful pregnancy with mini IVF are actually lower than with traditional IVF, but so far there have been few long-term studies to crunch the numbers. And though the drug regimen is less intensive, for some women Clomid brings on physical and emotional side effects similar to standard IVF hormone treatment. Zhang just completed a five-year look at mini-IVF success rates that he is submitting for publication and promises will be a “time bomb”—presumably the good kind—in the field. But he’s one of the method’s pioneers. Other, more disinterested experts may offer a more measured assessment when they see his data.

The job of selecting the best sperm for conception in any type of IVF is also seeing some advances. The trick is to look not just at the sperm cells but inside them to get a sense of how their DNA is packaged—and to do that without destroying them in the process. One method is to use something called Raman spectroscopy, which involves beaming laser energy of a particular frequency at the head of the sperm; the beam scatters back in readable patterns that reveal clues to the interior structure. The technique isn’t quite ready for wide use, but it’s getting close. “People are studying various frequencies along the electromagnetic spectrum to interrogate the sperm in a nondestructive way,” says Niederberger. “This holds a lot of promise.”

Even assuming the very best sperm can be matched with the very best egg, doctors still have to determine which of the several embryos that are often created in any one IVF cycle is the most viable one to transfer to the womb. That remains a highly subjective matter that depends, again, simply on which one looks the best. “Identifying the single best embryo for implantation is one of the challenges of the last decades in assisted reproduction,” says Dr. Zev Rosenwaks, director of the Center for Reproductive Medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center.

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