Abstract
BackgroundMultiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity. In the past decades the number of multiple pregnancies has increased. This trend is partly due to the fact that women start family planning at an increased age, but also due to the increased use of ART.Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation (IUI COH). The cumulative pregnancy rate is 40%, with a 10% multiple pregnancy rate.This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer (IVF e SET) or Modified Natural Cycle IVF (MNC IVF) can reduce the number of multiple pregnancy rates, but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility. Secondly, the aim is to perform a cost effective analyses and assess treatment preference of these couples.Methods/DesignWe plan a multicentre randomised controlled clinical trial in the Netherlands comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle (MNC) IVF or three cycles with IVF-elective Single Embryo Transfer (eSET) plus cryo-cycles within a time frame of 12 months.Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included. Women with anovulatory cycles, severe endometriosis, double sided tubal pathology or serious endocrine illness will be excluded.Our primary outcome is the birth of a healthy singleton. Secondary outcomes are multiple pregnancy, treatment costs, and patient experiences in each treatment arm. The analysis will be performed according tot the intention to treat principle. We will test for non-inferiority of the three arms with respect to live birth. As we accept a 12.5% loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies, we need 200 couples per arm (600 couples in total).DiscussionDetermining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially diminished perinatal and maternal complications. Should patients find the most cost-effective treatment acceptable or even preferable, this could imply the need for a world wide shift in the primary treatment.Trial registrationCurrent Controlled Trials ISRCTN 52843371
Highlights
Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity
Should patients find the most cost-effective treatment acceptable or even preferable, this could imply the need for a world wide shift in the primary treatment
Of subfertile couples no less than 50% are diagnosed with unexplained infertility or mild male subfertility, and at risk for multiple pregnancy
Summary
Each year about 5000 couples in the Netherlands are diagnosed with unexplained or mild male and an unfavourable prognosis [23]. In these couples there is ambiguity about the preferred first line treatment. The incidence of multiple pregnancies with the standard treatment is substantial. This has far reaching consequences regarding maternal and neonatal morbidity, and with regard to societal costs. Alternative http://www.biomedcentral.com/1472-6874/9/35 treatments need to be considered. To this date no large randomised controlled trials which have compared IUI COH with IVF e SET, and MNC IVF in couples with unexplained or mild male subfertility in order to prevent multiple pregnancies
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