"I feel like my stomach will come out of my stomach," Andreotta recalled.
This is the ovarian hyperstimulation syndrome – OHSS in short – a potentially fatal complication described by the U.S. fertility industry. very rare. But the incidence of OHSS and the broader long-term security of hormone-enhancing drugs remains open for debate, even when clinics have developed into multibillion-dollar industries that serve hundreds of thousands of women per year.
Industry critics worry that unregulated providers prescribe drugs, cover potential hazards and fail to report problems correctly when they arise. One study recently published, for example, blamed "increasingly aggressive treatment protocols" for the OHSS incident, while others argued that most cases were truly "avoidable."
Some researchers have theorized that in addition to its relation to OHSS, drugs can potentially cause heart disease, depression, endocrine system disorders, cancer and a number of other conditions. However, several studies published are conflicting or inconclusive. And unlike many developed countries with health care provided by the government, the United States does not seek to track health outcomes in fertility treatments.
"Every fertility doctor says to each fertility patient, & # 39; There is no known risk. Well, there is no known risk because no one sees," said Diane Tober, a medical anthropologist at the University of California at San Francisco who studies reproductive technology.
Industry supporters note that more than 8 million children have been born worldwide through IVF and other fertility treatments since the first "IVF" arrived 40 years ago. Alan Penzias, a professor at Harvard medical school who chairs the practice committee of the American Society for Reproductive Medicine (ASRM), said he had been "quite convinced" that the drugs did not pose a long-term threat to women's health.
"We are at a point in time when, if there is something big, we will see it now," said Penzias, who also serves as surgical director at Boston IVF. "Fortunately, we haven't seen anything negative."
OHSS is an exception. As a complication of the most brutal and immediate fertility treatments, it can strike anyone who takes medication to encourage the ovaries to ripen many eggs – a fundamental step in egg cell freezing, in vitro fertilization (IVF) and egg donation that occurs around 240,000 times a year.
Strategies to identify high-risk patients and treat conditions have increased in recent years. ASRM, which represents most U.S. clinics, calls OHSS "an unusual but serious complication" which is estimated to occur in moderate or severe forms in only 1 to 5 percent of cycles. Fertility doctors often cite studies that show that severe OHSS occurs at 0.03 percent of cycles.
Penzias said hospitalization for the OHSS "almost never happened now" compared to 20 years ago. However, the Washington Post analysis of national emergency room data found that the number remained significant. More than 9,000 women sought help from OHSS in hospitals between 2006 and 2014, the last year providing statistics – around 1,000 women per year.
In Sweden, Canada and the United Kingdom – countries where the government regulates the reproduction of aid and tracks patient outcomes – the medical community notifies patients that about one third of the procedures trigger at least mild OHSS symptoms.
This year, the UK's independent fertility regulator, the Human Fertilization and Embryology Authority, launched an investigation into the differences between OHSS cases reported by fertility clinics and nurseries included in the hospital admission data. While the watchdog group found no systematic evidence that was not reported, the group announced clinical after clinic audits, saying the data increased "significant concerns and questions about the safety of patients undergoing IVF."
Geeta Nargund, a fertility specialist in the UK, urged Parliament to update the reporting requirements to track drugs and doses given during IVF, and to link IVF treatment logs to hospital registrations to enable better tracking of adverse reactions.
"I feel more worried now than before," said Nargund. "It is very important that we do not make healthy women sick from IVF treatment."
Deaths are known to be rare but also difficult to trace, said public health officials. When the ovary is too excessive, the body produces excess fluid that can sink vital organs, which causes a cascade of potentially fatal problems.
In one famous 2005 case, Temilola Akinbolagbe, 33, collapsed at the London bus stop shortly after starting a drug course for IVF. Fluid accumulation from OHSS causes clots in the pelvic vein and, finally, a heart attack.
The coroner records the cause of death as a "misadventure" – the result of voluntary risk – a category more often applied in cases of drug overdoses and blue moon events such as fatal falls while taking selfies.
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& # 39; Miracle medicine & # 39;
When fertility-stimulating drugs entered the market in the late 1960s, they were praised as "miracle drugs" and were initially used to encourage ovulation in women who could not produce their own eggs. When the first commercial fertility clinic opened in 1979 in Norfolk, Virginia, doctors realized that these drugs could be used much more aggressively.
Usually, one egg ripens in a woman's ovary every month and is released into her uterus. Some eggs are destined to become babies; the rest are abnormal or disabled in some cases.
Collecting one egg at a time will be very inefficient for IVF. So the drug is calibrated to trigger a batch of eggs to mature – ideally around 10 to 15, according to the latest research. The less and the chance a woman has to get a baby down. Moreover, the health of the woman herself can be threatened.
However, finding out which drug and how many drugs to use is difficult. Given that IVF can cost $ 15,000 to $ 30,000 per effort, doctors and patients often feel the pressure to produce large numbers of eggs in each round.
The fertility group has developed a standard dosage regimen, but each protocol must be adjusted to fit the size and health of the woman. Meanwhile, there is nothing stopping doctors who want to use larger doses, and there is no systematic way to track doses or results.
Experts have long argued that a brief burst of estrogen, usually 10 days in IVF, is unlikely to have a long-term, profound effect on a woman's body. The researchers argue for further research, noting that estrogen is known to trigger several types of cancer.
The widespread academic debate became a public alarm in 2003, when Jessica Grace Wing, a Stanford University graduate and egg donor three times, died of metastatic colon cancer at the age of 32. Ms. Wing, Jennifer Schneider, a doctor who focused on internal medicine, began urging Congress and countries to pass laws requiring better tracking of fertility patients and more funding for research into complications
"As a scientist, I cannot say that I am 100 percent sure it is a fertility drug" that causes cancer, Schneider said in an interview. "All I can say is there is absolutely no other reason for him to get colon cancer as young as this."
Schneider also published works in medical journals that attracted the attention of overseas researchers. A large study soon followed, involving 50,000 women who used fertility drugs in Denmark and 24,000 in Sweden. Research shows there is no relationship between drugs and ovarian cancer.
The latest data, presented in June at a conference in Europe, also showed no increased risk of ovarian cancer. And a study published in July found no increased risk for two other types of cancer – invasive uterus and breasts – among 250,000 British women undergoing fertility treatment.
The current ASRM guidelines say "there does not appear to be a significant increase in risk" from invasive ovarian, breast or endometrial cancer to fertility patients "based on available data." For border ovarian tumors, the group acknowledged that "several studies have shown a small increase in risk."
The guidelines do not mention colon cancer, perhaps because there is no consensus. A study in the Netherlands published in 2016 found – "convincing," the researchers wrote – that women who underwent IVF did not appear to have a higher risk of colon cancer than the general population. However, IVF patients are almost twice as likely to develop colon cancer as women who receive non-IVF fertility treatments, such as tubal surgery or intrauterine insemination, encourage researchers to suggest that "further research is needed."
Schneider notes that research tends not to distinguish between women who use fertility drugs for different reasons. Some are infertile, some are fertile but in treatment because of their partners and some egg freezes and egg donors. Schneider argues that this population is different – and often very different in terms of age and hormone levels.
"The results vary because women in fertility care are a diverse group," Schneider said, adding that no studies have focused solely on elective egg freezing and egg donors.
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Unlike cancer, there is little doubt about the relationship between fertility drugs and OHSS. Complaints about conditions filling fertility blogs and online support groups.
In interviews, a dozen OHSS sufferers described feelings of confusion and chaos when symptoms began. Most say they have never heard of ovarian hyperstimulation syndrome before they become ill.
Asya Ulanova, 22, an egg donor from New York, said she watched television in November when she suddenly felt a "stomach" pain in her stomach and difficulty breathing. An emergency room doctor told him that he had fluid that had accumulated in his stomach and gave him medicine for constipation. Only then did Ulanova learn that she had OHSS.
Emily Ley, 34, an entrepreneur from Pensacola, Florida, is preparing for IVF in 2014 when she rises 22 pounds in 48 hours. He almost died and spent eight days in the hospital with a hose in his stomach to drain fluid.
"Looking back, I don't know how scary my situation is," said Ley, who found out when she was hospitalized that she had twins.
Logan Andreotta said his fertility doctor described the risk of OHSS as "very low." As a result, he was "mentally unprepared" when he woke up one morning in 2014 to find his stomach bulging as if he was suddenly 20 weeks pregnant.
Andreotta was rushed to a fertility clinic, where a doctor used a giant needle to "tap" the fluid in his stomach.
"It's liter and liter and looks like the Coca-Cola you bought in the store – brownish-red liquid," he recalls.
The first day, they filled four to five bottles. They fill two to three subsequent visits. Andreotta said his recovery took almost four weeks.
Apart from a terrible experience, Andreotta, now 29 years old, said he did not regret taking drugs. Of the 50 eggs taken from their ovaries, four of them were normal. One of them produced a daughter, Bonnie, now 4. Two years ago, Bonnie obtained a sister, Audrey, who was conceived without IVF.
But Andreotta said he would advise other women who use fertility drugs to immediately report unusual symptoms.
"I feel very lucky," he said. "They say if I keep waiting, I really can die."
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Effects & # 39; Echo & # 39;
In the early 2000s, so many women came to the hospital's emergency room because of excess fluid and suffered congestive heart failure or other organ closures so that the situation caught the attention of Jacob Udell, a doctor in Canada.
"We are confused. They don't have many risk factors, but the general theme is that they have got fertility drugs," Udell recalled. "They get high doses and try to get pregnant."
Udell and his colleagues wondered whether these ER patients "could be the tip of the iceberg" and whether high levels of estrogen from fertility drugs might hurt the lining of blood vessels. The water that leaks from the wall of the blood vessel that is disrupted can explain the buildup of fluid on the OHSS. Could it also damage the heart?
One study, from Sweden, suggested. This reported a higher level of hypertension and the possibility of stroke among fertility patients. But the Canadian study with the same design showed no connection.
So Udell, now an assistant professor of medicine at the University of Toronto, is working with Natalie Dayan of McGill University in Montreal to do what is believed to be the first major analysis of the relationship between fertility drugs and cardiovascular disease.
Published last year in the Journal of the American College of Cardiology, this study looked at data from 42,000 fertility patients. While treatments don't seem to have an impact on the risk of heart attack, they show potential but not statistically enough to increase the risk of stroke.
Udell said it was impossible to find out whether the difference was caused by fertility drugs or fertility problems that underlie women, age or other factors.
The results, he said, highlighted the need to follow fertility patients more closely.
"We may not see many diseases that are imminent," but "there may be an effect & # 39; echo & # 39; a lighter, long-term," said Udell.
"Sometimes after pregnancy, everyone turns to the baby. But maybe you should also think about it."
This article was written by Ariana Eunjung Cha, a reporter for The Washington Post. The Post's Dan Keating contributed to this report.