The EX IUI study
What is the effectiveness of IUI-OH in couples with unexplained or mild male subfertility and a poor prognosis for natural conception?
Of the 20,000 couples who yearly seek fertility treatment, more than 50% are diagnosed with unexplained or mild male factor subfertility. In The Netherlands, the first line treatment for these women is intrauterine insemination with ovarian hyperstimulation (IUI-OH) if the probability of a natural conception within the following year is less than 30% according to the validated model of Hunault. An estimated 28,500 cycles are conducted every year in the Netherlands, costing approximately 20 million euros, without any valid evidence that IUI-OH increases live birth rate compared to expectant management. Besides the costs, IUI-OH bears a risk of multiple pregnancies. Women with a multiple pregnancy have an increased risk of premature birth, with associated neonatal mortality and morbidity.
To evaluate whether expectant management for 6 months does not lead to a decrease in ongoing pregnancy rate leading to a live birth compared to 6 months IUI-OH.
Randomised multicentre, non-inferiority trial with cost-effectiveness analysis.
Couples of all ethnicities, with a female age between 18 and 42 years, diagnosed with unexplained or mild male subfertility and an unfavourable prognosis for natural conception.
Six months expectant management (experimental arm) and six months IUI-OH (standard or control arm).
The primary outcome is ongoing pregnancy leading to a live birth, conceived within 6 months after randomisation.
We expect a 30% live birth rate after 6 months IUI-OH. To evaluate whether 6 months expectant management does not result in a decrease of an ongoing pregnancy rate of 7%, we need 982 patients. (power 80%, alpha error 0.05). Anticipating 10% lost to follow up, we need to randomise 1,091 women (calculated with STATA 14.1). CEA/ BIA: In case expectant management does not lead to a decrease of more than 7% in efficiency, de-implementation of IUI-OH will follow, leading to annual cost savings of 20 million Euros.
The economic evaluation will be designed as a cost-effectiveness analysis. The time horizon will be 6 months or until an ongoing pregnancy. Longer-term costs, i.e. costs of delivery and perinatal costs, will be determined as well. Cost-effectiveness of each strategy will be presented as cost per ongoing pregnancy and costs per live birth.
A total of 48 months will be needed.
Dr. F. Mol
Dr. M. van Wely
ZonMW (no 837004023)