Paragard

1988-present

Available starting in 1988, the ParaGard had sluggish sales throughout the 1990s. It's more popular now—possibly because it's the only copper IUD sold in the US and it's considerably cheaper than its hormone- releasing competitor.

Photo: Jamie Chung; IUD Courtesy of Teva Women's Health, INC. Gynekoil

1960-early 1970

Also known as the Margulies Spiral or the Perma Spiral, the Gynekoil was the first plastic IUD in the US. The rigid tail was meant to make it easier for women to check that the device was in place, but it also caused pain for male partners.

Photo: Jamie Chung; IUD Courtesy of Dittrick Medical History Center and Museum/Case Western Reserve University Lippes Loop

1964-1986

Before the Dalkon Shield, this was the most popular IUD on the US market. But manufacturer Ortho Pharmaceutical stopped selling it, which inventor Jack Lippes blamed on poor sales and fallout from the Dalkon Shield debacle.

Photo: Jamie Chung; IUD Courtesy of Dittrick Medical History Center and Museum/Case Western Reserve University Cu-7

1974-1986

The Dalkon Shield wasn't the only IUD to spur lawsuits. The Cu-7 ("Cu" is copper), made by Monsanto subsidiary G. D. Searle, caused problems as well. It was linked to ectopic pregnancy, perforation of the uterus, and pelvic inflammation.

Photo: Jamie Chung; IUD Courtesy of Dittrick Medical History Center and Museum/Case Western Reserve University Saf-t-coil

1965-1984

One of the oldest IUDs, the Saf-T-Coil was also one of the least expensive and easiest and safest to insert (a strawlike inserter minimized contamination). But by 1982, the device only had 5 percent of the IUD market and the maker killed it.

Photo: Jamie Chung; IUD Courtesy of Dittrick Medical History Center and Museum/Case Western Reserve University Dalkon Shield

1971-1974

The clawlike appendages that kept the Dalkon Shield in place made removal painful and could perforate the uterus. The Shield also caused cases of pelvic inflammatory disease, infertility, and spontaneous septic abortion.

Photo: Jamie Chung; IUD Courtesy of Dittrick Medical History Center and Museum/Case Western Reserve University Mirena

2001-present

When the Mirena first hit the US market, so few women were using IUDs that many doctors didn't even know how to insert them. Today, the devices are recognized as safe, and 2 million US women have a Mirena.

Photo: Jamie Chung; IUD Courtesy of Dittrick Medical History Center and Museum/Case Western Reserve University

Jeffrey Peipert’s theory about how to prevent unplanned pregnancies isn’t complicated. In 2007, Peipert, an obstetrician-gynecologist at Washington University in St. Louis, began a groundbreaking study of women’s preferences when it comes to birth control. His team began recruiting 10,000 women of childbearing age, counseling them on available contraceptives and offering them whichever form they wanted, free of charge. The goal was twofold: to see whether more women picked contraceptives that they didn’t really have to think about (as opposed to, say, taking a pill every day) and whether those “forgettable” methods in turn reduced unwanted pregnancies and abortions.

Peipert’s hypothesis: The preferred contraceptive would be highly effective and, once activated, require no intervention for years. Forgettable. And in fact, such a device has been around for eight decades, in the form of the intrauterine device, or IUD. But this forgettable contraceptive has been all but forgotten itself. And that’s a shame. While birth control pills fail about 8 percent of the time, less than 1 percent of women with an IUD get pregnant. That’s about the same as the pregnancy rate in women who’ve been surgically sterilized. But when you remove an IUD—boom, fertility rebounds.

The problem is, IUDs have been at the bottom of the contraceptive heap for years, the victim of bad press and a four-decade-old scandal. But Peipert is finding that you can let the past go—of the 8,300 women who have received counseling in his study so far, about 50 percent have chosen an IUD, making it by far the most popular choice.

IUDs are on the verge of a remarkable return to popularity. Nationally, 5.5 percent of women using contraception choose them. That sounds unimpressive, but it’s the first time in more than 20 years that the number has risen above 2 percent; in 1995, it was 1.3 percent. By that baseline, 5.5 percent represents a sea change. And a few pharmaceutical companies believe that number is poised to grow. Only two IUDs are on the market in the US, but two more are in late-stage clinical trials. Revenue for the Mirena, an IUD made by German drug company Bayer, went from $219 million in 2006 to $714 million in 2010; sales of oral contraceptives fell 2 percent over the same period.

What happened? A small contingent of doctors and researchers never stopped believing in the IUD even when a medical scandal almost erased it from history. The ultimate set-it-and-forget-it contraceptive is finally making a comeback.

When it comes to the intertwined histories of modern birth control and the sexual revolution, the pill gets all the attention. Approved by the FDA in 1960, it obviously did a lot to enable sexual freedom and women’s rights. But hormone levels in early versions of the pill were about 10 times higher than they are today, and newspaper articles and medical journals soon began documenting health risks like breast cancer and heart attacks. The 1969 book The Doctor’s Case Against the Pill argued that safety risks abounded, and in a Senate hearing on the pill’s health risks, women’s rights activist Alice Wolfson jumped up from the audience and demanded to know why there wasn’t a birth control pill for men.

All that controversy primed IUDs for takeoff. Somewhat unbelievably, no one is quite sure how they work, but the theory goes like this: The human uterus has one overriding purpose, which is to protect and sustain a fetus for nine months. If you stick a poker-chip-sized bit of plastic in there, the body reacts the way it does to any foreign object, releasing white blood cells to chase after the invader. Once those white blood cells are set free in the uterus, they start killing foreign cells with efficient zeal. And sperm, it turns out, are very, very foreign. White blood cells scavenge them mercilessly, preventing pregnancy. In copper- containing IUDs, metal ions dissolving from the device add another layer of spermicidal action.

By the early 1970s, 17 IUDs were under development by 15 different companies. The problems started with the fourth one to actually hit the market: the Dalkon Shield. AH Robins (which also made ChapStick and Robitussin) marketed one version of it as a smaller option for women who didn’t have children. Like all medical devices at the time, the Shield wasn’t vetted by the FDA. While drugs got careful screening, safety and efficacy claims on device labels did not. The FDA stepped in only if people started reporting problems.

And report they did. Women with the Shield came to doctors ravaged by infection. Some complained of uterine bleeding or pain during sex. In others, the symptoms were less severe, like vaginal discharge or vague abdominal pain. Doctors diagnosed some of them with a condition called pelvic inflammatory disease—PID—which can be caused by chlamydia and gonorrhea or by normal vaginal bacteria. The women took antibiotics and usually got better, though a few rare cases led to hysterectomies. Furthermore, the Shield had a higher failure rate than originally reported, and some women who became pregnant with the Shield in place experienced spontaneous septic abortion, a miscarriage complicated by infection. At least 18 died. In 1974, faced with a flood of Shield-linked complaints, AH Robins took it off the market.

The fallout persisted for years. Some women who never had symptoms of PID—and others who got treatment and thought they had recovered—later learned that their fallopian tubes were damaged by scar tissue, rendering them infertile. Those users brought more than 400,000 lawsuits against the company. Panic spread; eventually the IUD market cratered. AH Robins went bankrupt in 1985; a year later, public service announcements on TV urged women to have their Dalkon Shields removed. A trust set up to compensate the injured eventually paid out nearly $3 billion.

By 1986 there was just one IUD left on the market, and almost no one was buying it. The devices were commercial losers. But the science of the IUD remained an intriguing puzzle. Women in dozens of countries outside the US were using them in droves. Studies in the 1970s, before the Dalkon Shield panic really took off, gave IUDs glowing reviews. Studies afterward said they were profoundly unsafe. Which were right?

In a way, the answer turned out to be both. Most IUDs were fine; the Shield was bad news. IUDs have a thread dangling down from the uterus into the upper part of the vagina to make them easy to remove. (“You say, ‘Cough,’ and you pull,” one doctor says.) The thread on the Shield was a braid of several strands of nylon-encased filament. Other devices have just a single strand. As cases of pelvic inflammatory disease soared, speculation grew that bacteria from a sexually transmitted disease could migrate up the threads inside the nylon lining and into the uterus. David Hubacher, an epidemiologist at Family Health International who has been studying IUDs for decades, also suspects that because the Shield was marketed to younger, presumably more sexually active women, the users may have had higher disease rates, putting them at greater risk. By the 1990s, researchers were finding that insertion itself pushed vaginal bacteria up into the uterus, causing problems. That’s easy enough to avoid with good sterile procedure.

But that wasn’t enough to erase fears that all IUDs caused infertility, just as the Dalkon Shield had. So in September 1997, Hubacher attempted to disentangle the problems. His team started working in Mexico City public hospitals, recruiting about 1,300 women battling infertility and another 600 who were pregnant. Whether the women had once had an IUD proved irrelevant to whether they could get pregnant. But when the researchers tested the women’s blood for antibodies to the sexually transmitted disease chlamydia, they found a strong correlation. “If you separate all these different factors, what stands out is previous exposure to chlamydia, not an IUD,” Hubacher says. “It’s the bacteria that’s causing the problem.”

Times had also changed. In those heady days of sexual freedom, AIDS was not a worry, and few used condoms. Doctors today speculate that STDs were more widespread than was actually being detected. It also wasn’t possible then to diagnose diseases by testing for tiny bits of DNA; only women who actually showed symptoms got treated. Asymptomatic women still got their IUDs.

The new research and thinking on IUDs had important implications for the future of the device. For one thing, it’s clear that doctors should not put it into women who have an active STD infection. (And even then, it’s only bacterial infections like chlamydia and gonorrhea that are problems; infection with the widespread human papillomavirus doesn’t disqualify anyone.) For another, inserting it under sterile conditions is paramount. To the people running these studies—and the doctors who read them in medical journals—the results were reassuring. There was nothing wrong with IUDs as a technology.

Marie Foegh grew up in Denmark and trained in Copenhagen as an ob-gyn. She came to the US more than 30 years ago, planning to stay just a couple of years, but never left. In 1999, she became director of clinical R&D for female health care at a pharmaceutical company called Berlex. And when she took the job, she found out that her corporate masters at the German pharma giant Schering wanted to bring to the US an IUD called the Mirena. Introduced in Finland in 1990 and then made available in dozens of countries, the device, the company hoped, might have a shot at getting a viable piece of the American market.

Most modern IUDs incorporate copper, which has an assortment of benefits, including increased durability and effectiveness. They’re also free of hormones and can be made cheaply, a boon for women in developing countries. But copper IUDs can cause heavy menstrual bleeding and cramping. The Mirena solves that problem by forgoing the metal for a synthetic version of the hormone progesterone. Here again, the mode of action isn’t completely understood, but researchers suspect that the hormone thickens cervical mucus, which makes it nearly impossible for sperm to swim upstream. It may also thin the uterine lining, rendering it inhospitable to an embryo should fertilization occur. The hormone-based IUD has the opposite side effect of the copper ones: It sometimes leaves women with little uterine lining to shed, so they hardly get any period at all.

As good as it was, the Mirena still faced problems: Few US doctors knew how to insert IUDs. And since the Shield debacle, the FDA had begun regulating IUDs and medical devices far more forcefully. “We knew it would be a big undertaking,” Foegh says. “We couldn’t afford for anything to go wrong, because then people would scream ‘Dalkon Shield!'” European clinical trials would satisfy the FDA, but Foegh knew that having the FDA’s seal of approval wasn’t enough; Berlex would have to invest in educating doctors, and for a time the company would likely lose money as sales were offset by educational costs.

In December 2000, the FDA gave Berlex the green light to start selling the Mirena in the US. The company began educating doctors aggressively, starting with those in large practices or hospitals, where their skills could spread to other physicians. The pharmaceutical company taught them to use a speculum to help guide the insertion, to rinse the cervix and the vagina with an antibacterial solution, to use a tenaculum (a kind of forceps) to keep the cervix steady, and to measure the depth of the uterus with a thin rod called a sound to ensure that the IUD would be put in the right spot. Once it’s there, the doctor flips open the arms of the IUD, wedging it in place.

Berlex also made a clever decision about marketing: It sought FDA approval only for women who already had children, skirting concerns about fertility. The education program continued for about four years, Foegh estimates, and sales grew slowly during that time. In 2006, Bayer bought out Schering, and it continues to manufacture the Mirena—but without Foegh. She left a couple of years later to become chief medical officer at Agile Therapeutics, where she works on new contraceptives.

Meanwhile, a competitor to the Mirena experienced a similar resurgence. In the early 2000s, US venture capitalists looking for sleepy, underperforming products with big sales potential had come across the ParaGard, a copper IUD approved in 1984 that never had any marketing heft behind it. They formed a company called FEI Women’s Health, purchased marketing rights to the ParaGard, and hired a New York ob-gyn named Laura MacIsaac—who happened to have a copper IUD herself—to be their chief medical officer. “It was a big title for a small job,” MacIsaac says, since the company had only one product.

FEI trained a small sales force, modernized the ParaGard literature, and sought FDA approval for updated, less-restrictive labeling; the ParaGard is approved for women with and without children. It didn’t take long for sales to grow enough that other companies took notice. Even after a series of corporate acquisitions, the ParaGard is still on sale today.

What was still missing was broad support from the medical community. Eve Espey, an ob-gyn at the University of New Mexico, helped change that, not because of her training so much as her unusual life story: Her freshman year at Harvard, Espey got pregnant accidentally and dropped out. In 1979, right after giving birth to a baby boy whom she would raise alone, she had a copper IUD inserted. She subsequently finished college and medical school, and when her son was 12 they moved to a rural area of New Mexico, where she worked at the Gallup Indian Medical Center. At the time, the county had one of the highest teen-pregnancy rates in the US. It became clear to Espey that short-term methods like the pill just weren’t doing the job for her patients. They required too much consistent effort on a woman’s part. “There’s such a huge gap between perfect and typical use,” she says.

In the late 1990s, Espey was researching her master’s project on the attitudes of Navajo-area medical providers toward IUDs when she came across guidelines issued by the American College of Obstetricians and Gynecologists. The document was woefully out-of-date. Crafted in 1992, it recommended IUDs for older women who’d already had children, and discussed liability for products that had been discontinued. In 2001, Espey emailed a friend on an ACOG committee and offered to rewrite the guidelines herself.

As it happened, ACOG was already reviewing the evidence. Espey’s enthusiasm fit right in. “She made this a very competitive priority,” says Janet Chapin, director of ACOG’s division of women’s health issues. “You need a stimulus half the time, like any organization.” Espey wrote a first draft, which then was filtered through layers of bureaucracy. In 2005, ACOG released a practice bulletin urging greater use of IUDs, and in 2007, it suggested that IUDs “should be considered as first-line choices” for teenagers. The IUD was out of intensive care and on its way to recovery.

One of the places IUDs are already making inroads is on American college campuses—thanks to physicians like Melanie Gold, who treats students at the University of Pittsburgh. Now 48, Gold grew up in Paterson, New Jersey, and in the 1970s often hung around Greenwich Village with her father, an ophthalmologist. He wore leather pants, a leather vest, and a leather hat with chains on it and had several attractive male friends. One day when Gold was 14, out walking the family’s black standard poodle with her dad, she asked him if he was gay. “He’s like, ‘Oh thank God you finally asked me.'” He told her he was, and that her mother was, too.

Gay Pride Day became a family holiday. Gold’s parents (who then slept in separate bedrooms and are now in same-sex relationships) spoke openly with her and her younger twin sisters about everything from anal sex to orgasms. After Gold completed her training in pediatrics and adolescent medicine, she briefly performed abortions before moving to Children’s Hospital of Pittsburgh. There she studied emergency contraception in teenagers and focused on the bread and butter of adolescent medicine: acne, eating disorders, and contraception.

Gold had kept up with the literature on IUDs and came to believe they were a good option for adolescents. But she knew the contraceptive wasn’t making its way to young women. She spent a year trying to bring the device to her hospital, but despite initial encouragement, officials told her they couldn’t figure out how to bill insurance companies for IUDs. When she moved to the university in 2008, Gold was at last able to set up an IUD program, bringing in a colleague from San Francisco to help train the staff.

Despite Gold’s efforts, getting an IUD at Pitt today can be a lonely experience. The same is true on other campuses. “Everybody who has hormonal birth control can talk to each other,” says Kate Schnuriger, who got an IUD from Gold in 2009, at the start of her senior year. “But with an IUD, there’s really nobody. Nobody I knew had it. Nobody was there to hold my hand and help me through this.” Her mother, who works as a secretary in a medical office, told her IUDs weren’t safe for childless women.

As much as Schnuriger loves her IUD now, the first day wasn’t easy. The insertion was traumatic: For many women it feels like bad menstrual cramps. It was worse for Schnuriger, who was tense going into the appointment and says she almost passed out from the pain. But once her IUD was in place she felt fine, even making it to her job in the anthropology museum that afternoon.

Despite ACOG guidelines, despite FDA approval of the Mirena, misconceptions abound. Jeff Peipert recalls one of his study participants who received an IUD three years ago, when she was 16. Later, her mother told her she wouldn’t be able have children if she kept it in. “We told her we didn’t think there was an increased risk,” Peipert says. “She said, ‘I just want it out.’ So we took out this 19-year-old’s IUD.”

The comeback, in other words, could still be derailed. Even though many more doctors are comfortable with the IUD, a generation of doctors didn’t get practice inserting it. And if they don’t know how to put one in, they’re less likely to recommend it as an option. Also, the devices are expensive—the ParaGard costs $500, the Mirena $850. “It’s absolute highway robbery that these companies charge so much,” Espey says. “If you went to Home Depot and got the raw materials for a copper IUD, it would cost less than 5 cents.” And the hormones don’t contribute much more to the cost, she adds.

In fact, amortized over years of use—10 for the ParaGard and five for the Mirena—an IUD is far cheaper than birth control pills, which can cost $30 or more a month. But the initial outlay is difficult for some women to manage, and it’s not always covered by insurance. Schnuriger, who comes from a working-class St. Louis family, split the $450 cost of her IUD with her boyfriend. She used money earned from a work-study job to pay her half. If she keeps the ParaGard the full 10 years, it will end up having cost $3.75 a month.

With new IUDs in clinical trials, the US market is almost certain to expand. A hormone-based IUD “should be available to lots and lots of women on the planet, and it’s just not” because it costs so much, says Victoria Hale, CEO of Medicines 360, one of the new IUD developers. The company hopes that by selling its IUD for pennies in poor countries and more in the developed world, it can make the IUD far more accessible while still turning a profit.

Likewise, Bayer is convinced that there’s a market for a second- generation Mirena—this one smaller, with slightly lower hormone levels. The company has been guarded about its new product. Full results of completed trials aren’t available, but a synopsis posted on the Bayer clinical trials database reported “a trend” toward less painful insertion. A wider test on nearly 3,000 women will presumably offer clearer results. Leo Plouffe, vice president of medical affairs for women’s health care at Bayer, acknowledged the desire among doctors for an IUD with data backing its safety among young, childless women. “It has been an area of concern among clinicians, not having the data for the Mirena label,” he says.

Back in St. Louis, Peipert says it will be a few years before his study shows whether IUDs are driving a drop in unplanned pregnancies. “The best method of contraception is being completely underutilized,” Peipert says. We’re using methods that are inferior, he says, even though a better one is out there. He makes it sound so simple.

Jennifer Couzin-Frankel (jcouzin@gmail.com) is a writer for Science.