TIME health

Three-Parent IVF Deserves a Chance in the U.S.

All new fertility methods sound crazy at first

In a historic vote that rocked the world of fertility medicine Tuesday, British lawmakers approved the use of a controversial IVF practice that would take genetic material from three people to create a single embryo.

The promising technique, which involves replacing the defective cellular material of a woman’s eggs with that from a healthy donor, aims to prevent patients from passing down crippling genetic diseases to their offspring. It also might hold the key to other groundbreaking applications, such as extending women’s fertility by rehabilitating old eggs.

The decision is inspiring because members of Parliament chose science over a firestorm of often ill-informed debate questioning whether we’ve gone too far in experimenting with genetic engineering. Hopefully, they will motivate the U.S. Food and Drug Administration, which held public hearings on the topic last year but declined to move forward with human trials citing lack of safety data, to follow suit. New research published in the New England Journal of Medicine estimated that more than 12,000 women in the U. S. of childbearing age risk passing down such mitochondrial diseases, which have been linked to everything from poor growth, blindness, neurological problems and heart and kidney problems.

The world is right to be cautious about this latest mind-boggling advance in reproductive medicine. It does sound like science fiction: If you’re a woman who suffers from a mutation in her mitochondrial DNA—the part of our cells that generate energy—scientists can take your egg, extract the nucleus—the part containing your most important genetic instructions, such as hair and eye color—and insert it into a new egg that has been provided by another woman. (The nucleus would have already been removed from the donor egg.) This newly renovated egg is then fertilized by your partner’s sperm and implanted into your uterus. You carry on with your pregnancy, just like billions of women before you. (Another version of the technique switches out the nucleus of a newly fertilized egg.)

Have we pushed the boundaries too far in innovative baby-making? Think back to when critics charged that the inventors of in-vitro fertilization recklessly “played God” by daring to combine a sperm and an egg in a lab to create Louise Brown in 1978. Now some 5 million of the world’s babies have been conceived via IVF. But it’s one thing to get used to combining reproductive parts in a lab; it’s a lot less comfortable to imagine tinkering with those parts beforehand. In an open letter to the U.K. Parliament, Paul Knoepfler, stem cell and developmental biology researcher at the University of California Davis School of Medicine, warned that supporters “could well find themselves on the wrong side of history … with horrible consequences.”

Yet it’s important to understand that mitochondrial replacement isn’t genetic engineering run amok, cautions Debra Mathews of the Berman Institute of Bioethics at Johns Hopkins University. The mitochondrial energy-making material of an egg accounts for a mere 37 genes, compared to the nucleus, which contains about 23,000 genes. “No one is messing directly with genes,” she says. “Scientists are replacing damaged mitochondria with healthy mitochondria. It’s a specific technology for a specific application. We’re modifying eggs to avoid serious diseases.” So far, researchers haven’t attempted a pregnancy using the technique, but a study published in 2012 in Nature found that resulting embryos appeared to develop normally with the nucleus intact and did not contain any of the mutated mitochondria from patients’ previous eggs. And scientists at Oregon Health and Science University transferred the mitochondria between rhesus-monkey eggs and created four healthy monkey babies.

Yet determining when a technology is “safe” is especially challenging in fertility medicine because the only way to find out is to create another human. The FDA’s prudence is a welcome change from the early “wild west” days of reproductive medicine when many scientists “implanted and prayed” that their experiments wouldn’t lead to the “horrible consequences” Knoepfler is warning against. So far, we’ve been incredibly lucky.

We don’t want to risk holding up progress by being too cautious, especially when some 1,000 to 4,000 babies are estimated to be born every year with mitochondrial disease, according to the United Mitochondrial Disease Foundation.

Yet what should the threshold be? The FDA shut down other such research being done more than a decade ago. Scientists at several fertility clinics were responsible for 30 pregnancies from eggs that had been injected with donor cytoplasm that contained mitochondria. The kids haven’t been tracked over the long term, and it’s unknown whether the procedure contributed to two cases of chromosomal abnormalities that resulted in one miscarriage and one abortion. And researchers at New York University’s Langone Medical Center tried a similar mitochondrial transfer technique using younger eggs for three women in their 40s suffering from age-related infertility. Although the embryos developed naturally, none got pregnant. A Chinese team later used the NYU method to achieve a triplet pregnancy, but the patient lost the entire pregnancy after she tried to abort one fetus to give the other two a better chance of survival.

Let’s follow the British example and find the right balance between prudence and progress. “We’re at a stage when we can use these technologies to help all kinds of patients, and we have enough reassuring evidence that it’s safe,” says NYU’s Jamie Grifo, and author of the The Whole Life Fertility Plan. “It shouldn’t be taking this long to move forward.”

TIME Ideas hosts the world's leading voices, providing commentary and expertise on the most compelling events in news, society, and culture. We welcome outside contributions. To submit a piece, email ideas@time.com.

TIME Pregnancy

The Problem With America’s Twin Epidemic

Americans undergoing fertility treatments have gotten used to the prospect of the 'instant family'—but it may carry unnecessary risks.

Remember the days when getting pregnant with twins was a surprise? Now if you’re undergoing fertility treatment, you actually have to decide in advance whether you’re up for double trouble by authorizing how many embryos to have implanted in your uterus. But a new study commissioned by the March of Dimes urges doctors to reduce the health problems caused by multiple births by encouraging patients to get pregnant one embryo at a time.

You don’t have to get mowed down by a double-wide stroller on a city sidewalk to know we’re in the middle of a twin epidemic. Twins account for more than 20 to 30 percent of babies conceived via in-vitro fertilization (IVF), which reached an all-time high with more than 165,000 cycles performed in the U.S. in 2012, according to the latest statistics by the Society for Assisted Reproductive Technology. National data show twin births nearly doubled over the last three decades to 1 in 30 babies born in the United States in 2009, from 1 in every 53 babies in 1980.

“In the old days of IVF, we had such low pregnancy rates that we had to transfer multiple embryos at a time just to have a good chance of creating a successful pregnancy,” explains Robert Anderson, MD, a fertility doctor from Newport Beach, California. Yet as fertility medicine improved over the past few decades, rates of multiples eventually spiked until the American Society for Reproductive Medicine tightened guidelines in 2012 about how many embryos could be transferred at a time to prevent another “Octomom,” whose doctor’s license was revoked after he implanted eight embryos into Nadya Suleman’s uterus. The current rule of thumb: one to two for women under 35 and three to five for women in their early 40s, depending on the quality of the embryos.

Yet doctors like Anderson are making the case that we should rethink the trend of buying our babies in bulk, since a singleton pregnancy is better for the health of the mother and baby. The latest numbers show that nearly 15 percent of women under 35 opted for a single embryo transfer in 2012, which is double the number from three years earlier. “Over the years, we grew to accept a certain percentage of twins, but it’s a big problem,” says Anderson. “They’re born three to four weeks premature on average, and there’s an increased risk of birth defects, not to mention the mother suffering from getting gestational diabetes or preeclampsia. A study last year found that medical costs associated with care for the mother during pregnancy and immediately after birth and for the infants up to one year cost on average about $105,000 for twins, compared to $21,000 for a single baby.

Despite the increasing acceptance of the technique known as elective single embryo transfer,the rates are still low compared to some European countries, where IVF is often covered by national health insurance and doctors prefer to implant just one embryo in the vast majority of cases. The concept has been a hard sell on American patients, since many can’t afford multiple IVF cycles and are thrilled at the idea of getting “two for the price of one.” Or they’re older patients who worry they’ll have a harder time getting pregnant the second time around a few years later. “When I talk to my patients about single embryo transfer, the vast majority of their eyes glaze over,” explains Fady Sharara, M.D., a reproductive endocrinologist in Reston, Virginia. “They’ve already made up their minds. They say, ‘Doctor, I’d rather have twins, and then we’re done.’” This twin mindset has become so entrenched among patients that even in a recent study in which they were offered financial incentives to go for a singleton pregnancy, 40 percent still declined.

Yet the math of “more is more” is misleading, and proponents say success rates can be similar. Anderson’s team at the Southern California Institute for Reproductive Sciences published a study last fall in Fertility & Sterility showing that pregnancy rates involving single embryos that had been genetically tested were equivalent to those with a double transfer. Here’s how it works: Although a woman undergoing IVF might produce enough eggs to create a half-dozen embryos, only a certain percentage will be chromosomally normal and likely to lead to a pregnancy. So doctors boost a patient’s chances of success by transferring one of those good embryos, which has a pregnancy rate of up to nearly 60 percent. (National IVF pregnancy rates involving untested embryos, on the other hand, range from 47 percent in women under 35 and 20 percent for women in their early 40s.) She’ll freeze the extra embryos and come back for another pregnancy attempt later, if they first one fails or she wants another child. “You don’t have to have the whole family at the same time,” explains Sharara, pointing out that even though the first cycle might cost around $20,000, including genetic testing, subsequent transfers of frozen embryos will cost a couple thousand each.

Doctors claim they can boost success rates even more by tinkering with the timing of transfers. During conventional IVF, a woman undergoes weeks of hormone stimulation after which her eggs are retrieved, fertilized with sperm, grown into embryos and implanted into her uterus immediately afterwards. But if a woman chooses genetic testing, her embryos will be frozen while she waits for results, and Anderson says she has a better shot of pregnancy if the embryo is transferred during a later month when her reproductive system isn’t flooded with so many hormones.

Fertility medicine has come a long way from throwing a bunch of embryos into a womb and seeing what sticks. Still, the piecemeal approach may not be for everyone, especially older women who want a ready-made family as soon as possible. Also, the insurance companies who do cover IVF, may not cover genetic testing or embryo freezing, which can cost thousands extra. But the growing popularity of the singleton method is a good trend for patients who want more control in shaping the size of their families.

TIME Pregnancy

The Obesity Pregnancy Dilemma

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michele Galli—Getty Images

Doctors' groups are urging ob-gyns to have those difficult conversations with women: lose weight or put your pregnancy at risk

After a third failed attempt at getting pregnant in her late thirties with in-vitro fertilization, Jodi, a pediatric mental health counselor from Chicago, asked her doctor to be straight with her: “Does my weight have anything to do with this?” At 5 feet 5 inches, Jodi weighed close to 300 pounds.

Although studies show that excessive body weight can disrupt obese women’s hormone balance and make it harder for them to ovulate, Jodi’s doctor reassured her that wasn’t her problem. However, he did deliver this sobering news: her weight might make it harder to have a healthy pregnancy and healthy baby.

The latest news about the negative effects of our nation’s obesity epidemic on everything from fertility to pregnancy and maternal mortality recently prompted the American College of Obstetricians and Gynecologists (ACOG) to urge doctors to talk with patients about the benefits of slimming down before trying to conceive. It’s part of an ongoing push to make chats about women’s “reproductive lifespan” as routine as an annual pap smear. Just as doctors have historically shied away from telling women that their eggs are getting too old, many haven’t been eager to point out that a woman’s size might come in between her and her dream of becoming a mother.

“For a woman who’s been trying for a year, the last thing she wants to hear is to take another year off to lose weight,” explains Dr. Jeanne Conry, ACOG president and assistant physician in chief at The Permanente Medical Group in Roseville, California. “But if a woman walks into my office who’s been trying to get pregnant and she has a body mass index of 30 or over [more than 180 pounds for a 5’5” woman] and she’s having an irregular period, the first thing we’re going to do is discuss a healthy diet and exercise program.”

For Jodi, who has been on “hundreds of diets” and struggled with her weight since she was eight years old—topping out at 425 pounds in her early thirties—the pressure to shed pounds felt overwhelming. “I had to worry that I’m not just hurting me when I’m bingeing, but I could be hurting someone else,” she says. Jodi declined to give her full name.

Of course, doctors point out that the majority of the estimated 30% of obese women in the U.S. have no problems conceiving. But there’s a growing body of evidence that’s difficult to ignore. Obesity raises a woman’s risk of gestational diabetes, hypertension, premature delivery, miscarriage, and stillbirth. A mother’s chance of having to undergo a caesarian section is 34% if her BMI is over 30, and 47% if her BMI is over 35—compared to 21% for women with a BMI under 30, according to one study. There’s even evidence that babies born to obese women have a greater chance of suffering neural defects than those whose mothers are normal weight, and will be at greater risk of being obese themselves.

In one recent survey of more than 3,300 women, one-third responded they didn’t believe or were unsure whether a woman’s weight affected her chances of conceiving. The doctors’ organization hopes that encouraging ob-gyns to broach the topic will educate women about that connection, considering that about 6% of infertility is due to obesity (another 6% is due to being too thin), according to statistics by the American Society for Reproductive Medicine. (That goes for men, too, since a recent French study showed their excess poundage contributed to low sperm production.) The good news is that 70% of these women will get pregnant naturally after they lose or gain enough weight to get closer to a healthier BMI.

The other goal is to help patients set and achieve weight-loss goals, or even consider weight loss surgery if they’re severely obese. But adding those expectations on top of conceiving can feel daunting to many women, says Julie Friedman, PhD, a psychologist who directs a weight management program comprised of counseling, workshops, and support groups, at Insight Behavioral Health Centers, a chain of outpatient mental health treatment centers based in Chicago. “They’ve struggled with their weight their whole lives and now they’re going through something so stressful, saying ‘Now you’re telling me to lose weight when I’m this stressed out and trying for a baby?’”

Encouraging obese patients to lose weight before getting pregnant becomes trickier still when they’re racing against a biological clock. “If you have a 42-year-old obese woman who has a low ovarian reserve, you have to try to get her pregnant right away,” explains Dr. Lori Arnold, a fertility specialist in Encinitas, California. “But if she has a normal reserve, then you can take a month or two and try to get her to lose 10 pounds, which can help.”

Now 45, with few viable eggs left, Jodi is trying to get pregnant again using donor eggs fertilized with her husband’s sperm. Since her last attempt, she has lost and regained 40 pounds. Last fall, she enrolled in Insight’s program on managing eating disorders. They also offer sessions about coping with the emotional challenges of infertility.

“There’s so much shame when you’re struggling with your weight. There’s so much shame when you’re struggling with infertility. Imagine the intensity of those two forces combined,” Jodi says. “It does feel insurmountable sometimes.”

TIME psychology

Facebook’s Gender Labeling Revolution

William Andrew—Getty Images

The pressure to choose a public identity can be harmful for people who haven’t decided on a private one, but at the very least seeing that long list can make you feel less isolated

At age 8, Eli Erlick wanted to be treated as a girl. But teachers denied the child’s request to join the girls’ gymnastic team or play on the girl’s side in the “Battle of the Sexes” academic competition. “That’s impossible, Eli,” they said. “You’re a boy.” Still, Eli persisted in wearing lip gloss and skirts, and spent the rest of elementary school eating lunch alone to escape the daily harassment of classmates.

By 13, Eli’s parents allowed their child to begin the transition from male to female, which meant adopting a feminine appearance, changing school records, and starting hormone treatment a few years later. That’s also when she learned about the concept of transgender, an umbrella term used to describe people whose gender identity differs from the sex they were assigned at birth. “It was such a relief. I found a word to finally describe who I was,” says Erlick, 18, a freshman at Pitzer College in Claremont, California, who founded the national advocacy organization Trans Student Equality Resources.

She also found joy in Facebook’s announcement last week that the social media giant has added 58 new options to the binary “male” and “female” choices in the user profile gender question. They include everything from androgynous to gender questioning to pangender. Erlick checked three boxes she felt represented her: Trans Woman, Trans Person, and Trans Feminine (because that’s how she presents herself to the world). “Being able to identify as a trans woman is so powerful,” she said. “I want to be among people like me.”

Mental health professionals who serve the transgender community overwhelmingly praise the decision for giving a voice to the more than 700,000 transgender people living in the U.S. who have long felt invisible. In 2012, the term “gender identity disorder” was stricken from the The Diagnostic and Statistical Manual of Mental Disorders (DSM-V) in 2012, though gender dysphoria is recognized and describes those who experience emotional distress over “a marked incongruence between one’s experienced/expressed gender and assigned gender,” which can lead to depression, post-traumatic stress, suicide, and other mental health disorders.

But “for people who are clear about who they are and want to be visible and have people mirror their identity back to them, this is a tremendous movement forward,” says Diane Ehrensaft, PhD, a clinical psychologist and director of the Mental Health Child and Adolescent Gender Center in Oakland, California.

But what if you’re 15 and not sure who you are? The sheer number of choices can be overwhelming, cautions Ehrensaft. The pressure to choose a public identity can actually be harmful for people who haven’t yet decided on a private one.

Many transgender people like Erlick knew who they were from a young age, but others need years – even decades – before they’re ready to check a box (or several). While the “coming out” experience is widely varied, there is a common sequence. “There’s a coming to consciousness that there’s something going on inside me that doesn’t match how the world sees me. One child told me ‘I shouldn’t have a penis. I’m a girl,’” says Ehrensaft. Then there’s a period of exploration. “You try a lot of things on for size. The expansive Facebook categories give you lots of choices. You’re swimming around in them. You might just grab a pole. You can always change it,” she says. (The last two stages involve disclosing your identity and then resolving to live in your gender.)

But jumping around from “gender nonconforming” to “gender fluid” to “transsexual” may be harder in a forum like Facebook after making a public statement, especially to an audience of family and friends who don’t understand their nuances, she says. (Parents of some of Ehrensaft’s clients learned about their children’s gender identity this way.) Also, even though the act of declaring who you are to the Internet can feel liberating, it’s also anxiety-producing. “Every time they make themselves public, they open themselves up for possible pushback from hostile people,” she says.

Yet there is an upside to so many choices. For those people who are wrestling with their identity, the existence of something other than the generic “transgender” is educational, adds Ruben Hopwood, PhD, trans health program coordinator at Fenway Health in Boston. “I see people who tell me ‘I don’t like my gender.’ Now this will push them to think more thoroughly about what they’re feeling,” he says.

Even if you refuse to check any gender box (just like you don’t have to advertise your relationship status or political views), seeing that long list can make you feel less isolated. “People going through this often think they’re the only ones like this in the world,” Hopwood says. “This is a message that you’re not alone.”

A previous version of this story stated that Eli learned about the concept of transgender at age 16. It has been corrected.

Sarah Elizabeth Richards is the author of Motherhood, Rescheduled: The New Frontier of Egg Freezing and the Women Who Tried It.

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