Two of the commonest therapies for infertility offered to hundreds of thousands of women each year are worthless and may cause unpleasant side effects, a study has shown.
The first treatment is clomifene citrate, a drug believed to correct dysfunction of the ovaries. The second is intra-uterine insemination (IUI), in which a sample of semen is introduced directly into the womb.
Both have been offered for decades as the initial treatment for infertility because they are less invasive and cheaper than IVF and are recommended by the National Institute for Clinical Effectiveness (Nice). However they have never been tested in a major trial – until now.
One in seven couples has difficulty conceiving and, in a quarter, the infertility is unexplained, following initial tests to confirm that sperm are healthy and eggs are being produced and reaching the womb.
A team of researchers led by Professor Siladitya Bhattacharya of the department of Obstetrics and Gynaecology at the University of Aberdeen, recruited almost 600 women in Scotland who had experienced unexplained infertility for more than two years.
They were divided into three groups, one of which was encouraged to try for a baby in the usual way without medical help, one which took oral clomifene citrate, and one which had IUI.
After six months, 101 of the women were pregnant and went on to have live births. The results, published in BMJ, showed that those women who had no treatment had a higher live birth rate of 17 per cent than those who took clomifene citrate (14 per cent).
In addition, up to one in five women on the drug suffered side-effects including abdominal pain, bloating, hot flushes, nausea and headaches.
The highest birth rate was seen among women who had IUI – at 23 per cent. But the researchers say that to have a "meaningful and significant effect", the benefit of IUI over natural reproduction would have to be much higher than the 6 per cent recorded in the trial.
However, women who had the treatments, even though they did not work, were more satisfied than those who had no treatment, demonstrating the difficulty doctors face in persuading patients they are better off without intervention.
"Because these treatments are relatively inexpensive and non-invasive, doctors feel morally obliged to offer them and couples are very keen to accept anything that might help," Professor Bhattacharya said.
Many couples with unexplained infertility attend private clinics where they may be charged hundreds of pounds for exploratory tests and initial treatments, which are offered on a trial and error basis. Professor Bhattacharya added: "If you don't know what's broken it is difficult to know how to fix it. All the treatments have come in mostly by intuition. It is difficult to do trials [in this field] because patients don't like being allocated to a "no treatment" group. It is counter-intuitive to come to hospital and get no treatment."
In a commentary published with the study, specialists from the Assisted Conception Unit at Guy's and St Thomas' Hospital, said: "As a direct result of the lack of evidence, many couples with unexplained infertility endure (even request) expensive, potentially hazardous, and often unnecessary treatments."
Nice guidance, issued four years ago, recommending clomifene citrate and up to six cycles of IUI, was based on the limited evidence then available. Nice is due to update its guidance shortly.Reuse content