IVF or IUI as first-line treatment in unexplained subfertility: The conundrum of treatment selection markers

R. I. Tjon-Kon-Fat, P. Tajik, M. H. Zafarmand, A. J. Bensdorp, P. M.M. Bossuyt, G. J.E. Oosterhuis, R. Van Golde, S. Repping, M. D.A. Lambers, E. Slappendel, D. Perquin, M. J. Pelinck, J. Gianotten, J. W.M. Maas, M. J.C. Eijkemans, F. Van Der Veen, B. W. Mol, M. Van Wely

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Study Question Are there treatment selection markers that could aid in identifying couples, with unexplained or mild male subfertility, who would have better chances of a healthy child with IVF with single embryo transfer (IVF-SET) than with IUI with ovarian stimulation (IUI-OS)? Summary Answer We did not find any treatment selection markers that were associated with better chances of a healthy child with IVF-SET instead of IUI-OS in couples with unexplained or mild male subfertility. What is Known Already A recent trial, comparing IVF-SET to IUI-OS, found no evidence of a difference between live birth rates and multiple pregnancy rates. It was suggested that IUI-OS should remain the first-line treatment instead of IVF-SET in couples with unexplained or mild male subfertility and female age between 18 and 38 years. The question remains whether there are some couples that may have higher pregnancy chances if treated with IVF-SET instead of IUI. Study Design, Size, Duration We performed our analyses on data from the INeS trial, where couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception were randomly allocated to IVF-SET, IVF in a modified natural cycle or IUI-OS. In view of the aim of this study, we only used data of the comparison between IVF-SET (201 couples) and IUI-OS (207 couples). Participants/Materials, Setting, Methods We pre-defined the following baseline characteristics as potential treatment selection markers: female age, ethnicity, smoking status, type of subfertility (primary/secondary), duration of subfertility, BMI, pre-wash total motile count and Hunault prediction score. For each potential treatment selection marker, we explored the association with the chances of a healthy child after IVF-SET and IUI-OS and tested if there was an interaction with treatment. Given the exploratory nature of our analysis, we used a P-value of 0.1. Main Results and The Role of chance None of the markers were associated with higher chances of a healthy child from IVF-SET compared to IUI-OS (P-value for interaction >0.10). Limitations, Reasons For Caution Since this is the first large study that looked at potential treatment selection markers for IVF-SET compared to IUI-OS, we had no data on which to base a power calculation. The sample size was limited, making it difficult to detect any smaller associations. Wider Implications of The Findings We could not identify couples with unexplained or mild male subfertility who would have had higher chances of a healthy child from immediate IVF-SET than from IUI-OS. As in the original trial IUI-OS had similar effectiveness and was less costly compared to IVF-SET, IUI-OS should remain the preferred first-line treatment in these couples. Study Funding/Competing Interest(S) The study was supported by a grant from the Netherlands Organization for Health Research and Development, and a grant from the Netherlands' association of health care insurers.

Original languageEnglish
Pages (from-to)1028-1032
Number of pages5
JournalHuman Reproduction
Issue number5
Publication statusPublished or Issued - 1 May 2017


  • IUI
  • IVF
  • marker-treatment interaction
  • treatment selection markers
  • unexplained subfertility

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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