UNiTY logo showing a couples hands and a healthcare scientists hands surrounding a sperm and egg. 

Funded by NIHR National Institute for Health and Care Research

One third of all infertile couples have a diagnosis of unexplained infertility with no clear reason identified despite tests. This has a major emotional impact and results in couples considering in vitro fertilisation (IVF) which is an intense and expensive route.

In a woman’s normal monthly cycle usually only one egg develops to a stage where it may be fertilised by sperm to form an embryo (earliest stage of a baby). IVF treatment involves daily self-injection of hormones to boost the egg supply. This is monitored with vaginal ultrasound scanning. Eggs are collected by passing a needle through the vaginal wall into the ovaries. The eggs are mixed with the sperm to achieve fertilisation before they are transferred back into the womb days later. There are risks with IVF such as infection, bleeding during the egg collection and risk of ovarian hyperstimulation syndrome. This is where an unpredictable excessive response to injections leads to many eggs developing in the ovaries. This can result in the ovaries releasing chemicals which cause liquid to leak into the abdomen and in severe cases, the lungs. This can be serious and require hospitalisation.

Intrauterine insemination (IUI) is simpler with a much lower dose of hormones. Sperm are introduced directly into the womb. This increases the chance of fertilising the egg and there are data suggesting healthier babies with this approach. Current UK (NICE) guidance only recommends IVF for unexplained infertility, but this is based on weak evidence. Recent research suggests that three cycles of IUI may offer the same chance of a healthy baby as one cycle of IVF and may be more cost effective and less invasive.

To answer the question of which approach is best for unexplained infertility we would like to carry out a study called a randomised controlled trial where couples (NHS or Private) will be randomly allocated to either three cycles of IUI or directly to an IVF cycle. Those couples having IUI first, if unsuccessful, will still be able to follow through to IVF.

During the initial stage of the trial, we will ask how couples feel about each treatment option; this will not change the treatment they are offered. We will evaluate other important patient outcomes such as quality of life, work disruption, and emotional/physical burden, as well as examine cost-effectiveness. Our research has been developed (and implemented) with members of the fertility patient treatment co-design group at the Birmingham Women’s Hospital, local commissioners and interested lay people. We have incorporated patient voices from questionnaires and focus group and have a patient as a coapplicant. A UK leading Infertility Counsellor will help ensure all views and quieter patient voices are represented.

We aim to recruit an ethnically, economically and socially diverse patient population and have engaged with patient ambassadors within the hospital and community to maximise opportunities for recruitment. We have a comprehensive plan to share the results of the trial with relevant stakeholders including GPs, hospital doctors, professional societies, patient support groups, NHS policy makers and patients. The findings will be published in major medical journals, presented at UK and international scientific meetings and made freely available through relevant patient and professional websites – we will focus on this being inclusive and accessible through use of infographics and multi-language verbal summaries.