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Increase in IVF complications raises concerns over use of fertility drugs

by Hannah DevlinThe Guardian [US]
November 13th, 2016

A person is laying with their shirt lifted, so that the stomach is visible. Gripping a syringe full of hormone medication, the needle is pointed towards the pelvic area.

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Stronger fertility drugs could be linked to last year’s increase in cases of potentially life-threatening ovarian hyperstimulation syndrome, warn doctors

Increased numbers of women suffered from a serious complication of IVF last year, according to official figures that raise concerns about the use of powerful fertility drugs.

In 2015, 60 women were admitted to hospital with severe ovarian hyperstimulation syndrome (OHSS), a 40% increase on the previous year. The condition, which is triggered when the ovaries swell up and leak fluid, is potentially life-threatening. Symptoms include abdominal swelling and pain, nausea, dehydration and blood clots in the legs.

Leading fertility doctors warned that the trend could be driven by doctors giving women stronger drugs to harvest more of their eggs, with a view to boosting the chances of a successful pregnancy.

Professor Geeta Nargund, a senior consultant at St George’s Hospital in London and medical director of Create Fertility, said: “OHSS is a preventable condition. The number should never go up, it should always go down in modern fertility practice.”

In the past decade the numbers of OHSS cases have been steadily falling as clinics have shifted towards milder treatments, but the latest figures suggest a reversal of this trend.

Nick Macklon, professor of obstetrics and gynaecology at the University of Southampton, believes the increase could be linked to recent improvements in embryo and egg freezing technology.

In theory, the ability to freeze eggs and delay transferring embryos until the ovaries have settled down should help avoid serious cases of OHSS, which can be worsened by pregnancy. However, it also provides a greater incentive for clinicians to obtain as many eggs as possible to maximise a couple’s chances of success, he said.

“This escape route may have encouraged clinicians to return to harder stimulation regimens,” said Macklon, adding that recent Human Fertilisation and Embryology Authority (HFEA) figures showing higher pregnancy rates when around 15 eggs are obtained may also have played a role.

During IVF, a woman is typically given injections of drugs designed to stimulate the ovaries into releasing eggs, which are then harvested, fertilised and either transferred back to the patient or frozen for future use. Some women are more sensitive to the drugs, however, and their ovaries are sent into overdrive, causing them to enlarge and release chemicals into the bloodstream.

Fluid from the blood vessels leaks into the abdomen, and in severe cases, into the space around the heart and lungs. Mild OHSS is common, affecting about one in three women, but the condition can result in serious health problems and -extremely rarely - women have died.

Blood tests are now used by clinics to predict who is at risk of OHSS, based on their natural levels of a hormone called AMH. “We might reasonably expect that the trend in incidence should therefore be down rather than up, so I think there is likely to be a real cause rather than statistical artefact behind the rise,” said Macklon. “The overall numbers remain very low compared with the past, but I think there is a message in these data to remain vigilant about preventing OHSS by avoiding high dose stimulation where possible.”

According to HFEA data, in 2014, 42 cases of severe OHSS were recorded, compared to 46 the previous year, but last year the figure rose to 60 cases.

The regulator classifies severe OHSS as a grade B adverse incident, one level below the most serious category, which includes the death of a patient or an embryo being transferred to the wrong woman.

Professor Adam Balen, chairman of the British Fertility Society and a spokesman for the Royal College of Obstetricians and Gynaecologists, said: “OHSS is a potentially serious complication of fertility treatment, particularly IVF. Most women will recover with pain relief; however, for severe cases, women may need to be admitted to hospital and given treatment to reduce their risk of developing blood clots, which is a serious complication of the condition.”

HFEA figures show a steady upward trend in the number of IVF cycles carried out annually, rising from 68,000 in 2014 to around 72,000 in 2015 (roughly a 6% increase), which might explain part of the increase in adverse incidents last year.

A decade ago, Lee Cowden, a primary school teacher from Surrey, was newly married and lying in bed with her husband, Iain, after a weekend away in Norfolk. “I remember sitting up in bed gasping and saying to my husband ‘I can’t breathe.’” she said. “We hadn’t been married that long and I said ‘call my mum,’ and then ‘no, call an ambulance.’”

Lee later discovered she had suffered a heart attack as a result of OHSS.

At 25 she had decided to start trying for a baby, because her diagnosis of polycystic ovary syndrome meant she would need fertility treatment. She had been prescribed stimulation drugs to induce ovulation, but when it hadn’t worked the clinic had doubled the dose.

The first sign that she was suffering OHSS was abdominal pains, but the clinic told her this was probably due to a benign ovarian cyst. In fact, her ovaries had become severely over-stimulated and this eventually led to a blood clot forming that travelled to her heart.

“I felt a stabbing pain between my shoulder blades, which I knew was a sign of a heart attack, but I thought: don’t be ridiculous, you’re 25,” she recalls.

Since then, she said, she has met many others who have suffered from milder forms of OHSS. “So many women ... think overstimulation is part and parcel of treatment,” she said. “It’s not acceptable.”

Lee, now 37, made a good recovery - although she will take daily heart medication for the rest of her life - and went on to have IVF treatment using milder drugs. She conceived her daughter, Molly, who is now nearly ten. Two years later, she conceived naturally, and her second daughter, Ruby, is eight.

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