Controlled ovarian stimulation and intrauterine insemination vs in vitro fertilisation as the first line treatment for unexplained subfertility - a randomised controlled trial

Abstract

Background: This thesis is based on a randomised controlled trial comparing the effectiveness of intrauterine insemination (IUI) plus Controlled Ovarian Hyperstimulation (COH) versus in vitro fertilisation (IVF) as the first line treatment option for couples with unexplained subfertility. Subfertility of a couple is classed as unexplained when they fail to conceive after one year of regular unprotected intercourse and when all the standard investigations for ovulation, tubal patency and semen analysis have been found to be normal. It affects 30-40% of couples. The age-old methods of treating these couples have included the empirical use of clomiphene or gonadotrophins to correct any possible subtle defects in ovulation with or without IUI (to overcome any existing cervical barrier to natural conception) or IVF. However, the best treatment options for these couples have yet to be determined. The matter has been made even more controversial by the issue of NICE (National Institute for Health and Care Excellence) guidelines in the UK that suggest IUI be abandoned completely for these women in favour of IVF after 2 years of expectant management. A systematic review of the available literature comparing IUI + COH versus IVF for unexplained subfertility revealed limited numbers of available studies and high clinical and statistical heterogeneity among them. An online survey was also conducted among fertility specialists to establish the general consensus regarding management of such couples. The results revealed a lack of agreement among fertility specialists with regards to the first line treatment of couples with unexplained subfertility. The mixed 8 response to this survey demonstrated the ongoing dilemma among practitioners, much of which was due to the lack of robust evidence. A randomised controlled trial was then designed to examine the effectiveness of COH with gonadotrophins + IUI versus IVF as the first line approach to the treatment of unexplained subfertility (Figure 1). This was the first UK-based randomised controlled trial comparing these two first-line management options for unexplained subfertility.