Women in Canada undergoing fertility treatments should be aware of a rare but potentially life-threatening complication, according to new guidelines being issued for the nation’s doctors.
Injectable drugs used to stimulate a woman’s ovaries to produce multiple eggs for fertilization can lead to ovarian hyperstimulation syndrome – a condition in which the ovaries swell and fluid leaks into the abdominal cavity and chest.
Most cases of ovarian hyperstimulation syndrome, or OHSS, are mild. But deaths have been reported in severe cases, according to guidelines published this week by the Society of Obstetricians and Gynaecologists of Canada, and the Canadian Fertility and Andrology Society – the group representing Canada’s fertility specialists.
The goal is to provide doctors who suddenly encounter a case with guidelines on how to quickly recognize and manage the condition, said Dr. Paul Claman, principal co-author and medical director of the Ottawa Fertility Centre.
The syndrome only occurs “about a week after the eggs have been popped,” Claman said. That can create problems when patients live far from the treating fertility clinic.
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“When it comes to the management of OHSS – which, thank God, is quite uncommon nowadays because of the tricks we have – often you’ll have patients come from a small town, have treatment, return to their small town and get sick a week after they return.”
He said he once had a patient who lived a two-hour drive from Ottawa who developed ovarian hyperstimulation syndrome on a weekend. The gynecologist at the local emergency department thought she had an ovarian tumour; he operated and took her ovary out.
Mild forms of ovarian hyperstimulation occur in up to one-third of every cycle of IVF, or in-vitro fertilization, in which a woman’s eggs are retrieved from her uterus, mixed with sperm and the resulting embryos transferred back.
Severe forms occur in about two per cent of IVF cycles. Last year, 11,718 cycles of IVF were performed by Canada’s 28 fertility clinics.
But IVF is only one concern. More infertile Canadians are resorting to a fertility treatment that does not have the success of IVF but that costs thousands of dollars less: ovarian stimulation with artificial insemination.
With intrauterine insemination, or IUI, women inject themselves in the stomach or leg with the same hormonal drugs used in IVF, a class called gonadotropins. Unlike IVF, there is no way of tracking how many cycles of IUI are being performed in Canada, said Dr. Carl Laskin, past president of the Canadian Fertility and Andrology Society and a founding partner of LifeQuest Centre for Reproductive Medicine in Toronto.
Irregular ovulation accounts for one of the most common fertility problems. Sometimes a simple pill called Clomid helps. “But a good 20 to 30 per cent of women who don’t ovulate aren’t going to ovulate on Clomid,” Claman said.
If they don’t, gonadotropins are used. The drugs are prescribed by gynecologists and sometimes by family doctors. Frequent blood tests and ultrasounds are needed to measure the number and size of the egg-containing follicles.
With hyperstimulation, the ovaries keep expanding, growing fat and swollen. They leak fluid into the pelvis and abdomen. Fluid has to be drained via a needle in the abdomen or vaginally. If fluid keeps building up and starts collecting above the diaphragm into the chest, blood clots can form because the red blood cells become concentrated and the blood thickens. Clots can break off and travel to the lung.
Critics have argued that doctors should be less aggressive with ovary-stimulating drugs. The ovaries can go into overdrive, churning out 20, 30 or more eggs. The move has been for milder stimulation using newer medications, so that women produce far fewer eggs.
But it’s controversial. Laskin said pregnancy rates among doctors performing “IVF-lite” are significantly lower than in those doing more standard stimulations.
The risk of hyperstimulation is highest in younger women, who have more egg follicles than older women. “It’s very rare to get 30, 40 follicles to grow in a 40-year-old,” Claman said. “In a 30-year-old that’s very possible.”
The situation can become critical if a woman gets pregnant because the hormones of pregnancy further stimulate the ovaries. In cases of IVF, the embryo transfer is cancelled.
“If we see somebody who had an unusual response, or they just got away from you in terms of the stimulation, we shut them down,” says Laskin. Drugs are used to effectively shut down the woman’s ovaries. “The cycle is cancelled, you emphasize to them how important it is to avoid intercourse, how important it is to avoid pregnancy,” Laskin said.
Even then some women are willing to risk having the embryos transferred.
“When you’ve got couples that are driven by having a baby, all the bad stuff gets minimized or denied,” Laskin said. “And you can understand why.”
But, “You have to keep them safe,” he said. “My response is, ‘You may be willing to take that chance, but I’m not, because I know what you’re in for and you don’t.”
According to the guidelines, “women undergoing gonadotropin ovarian stimulation should be considered at risk for OHSS” and every centre that offers assisted reproduction should provide written information about the potential risks, signs and symptoms, such as bloating, weight gain and less frequent urination.