In-vitro fertilization (IVF)
With advances in the assisted reproductive techniques, IVF has emerged as a safe and successful treatment option. However, debate continues as to whether it should be the sole treatment for these couples.
The first randomised controlled trial by Goverde et al in 2000, compared six cycles of IUI in a natural cycle vs six cycles of IUI + COH versus six cycles of IVF in 258 couples with unexplained subfertility and mild male factor. They found that though pregnancy rate per cycle was better with IVF compared to IUI in a natural cycle or IUI + COH (12.2% vs 7.45 and 8.7% respectively), there was no difference in the cumulative pregnancy rates (38% vs 31% vs 37% respectively) [Ref]. However over the years, pregnancy rates from IVF continued to improve and with the current UK IVF figures being 27%–32% for women under 37 years of age (http://www.hfea.gov.uk/ivf-figures-2006.html), one might argue that the pregnancy rate reported by Goverede et al is outdated.
Reindollar et. al 2010 [Ref] showed in a large randomised controlled trial, the effectiveness of moving to IVF after a course of clomiphene citrate and IUI compared to conventional treatments of clomiphene citrate and IUI and FSH and IUI and then IVF. Not only pregnancy rates were higher but IVF allowed women to conceive 3 months faster. However, the use of clomiphene citrate and IUI prior to IVF in this trial can be questioned as evidence against the use of clomiphene citrate is replete67. The same group compared two cycles of clomiphene citrate and IUI vs two cycles of FSH and IUI vs immediate IVF in 154 couples with older women (38 – 42 years) and demonstrated superior pregnancy rates and fewer treatment cycles with immediate IVF [Ref].
Custers et al in 2011, randomized 116 couples with unexplained subfertility and mild male factors and unfavorable prognosis of natural conception, to one cycle of IVF-eSET (elective single embryo transfer) and three cycles of IUI + COH and showed similar live birth rates, 24% in the IVF-eSET group and 21% in the IUI + COH group (relative ratio 1.17; 95% CI 0.60–2.30) [Ref].
In 2015 a Cochrane review summarised these trials and failed to prove the effectiveness of IVF over IUI. They did not find any significant differences in multiple pregnancies or ovarian hyperstimulation syndrome rate between the two treatments [Ref].
The most recent study by Bensdorp et al 2015, sheds new light on the effectiveness of IUI and IVF for these couples. In this multicenter randomised controlled trial involving 17 centres in The Netherlands, 602 couples with unexplained subfertility and mild male factors and unfavourable prognosis for natural conception, were randomised to three cycles of IVF and single embryo transfer, six cycles of IVF in a modified natural cycle and six cycles of IUI and COH. They found comparable singleton live birth rates (52% vs 43% vs 47% respectively) and comparable multiple pregnancy rates (6% vs 5% vs 7% respectively) between the treatment arms [Ref].
From the existing literature it appears that though the per-cycle success rate of IUI is lower compared to IVF (9% vs 22%), cumulative success rates are comparable to IVF [Ref]. From the couple’s perspective IUI remains less invasive, less stressful and less time consuming than IVF. The perinatal outcome for singletons is better with IUI compared to IVF [Ref]. Hence IUI + COH remains a very realistic treatment option.