Prognostic profiles and the effectiveness of assisted conception: secondary analyses of individual patient data

N M Van den Boogaard, A. J. Bensdorp, K. Oude Rengerink, K Barnhart, S Bhattacharya, I M Custers, C Coutifaris, A J Goverede, D S Guzick, E C Hughes, P F Litvak, P Steures, P G A Hompes, F Van der Veen, Ben Mol, P Bossuyt

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Abstract

BACKGROUND At present, it is unclear which treatment strategy is best for couples with unexplained or mild male subfertility. We hypothesized that the prognostic profile influences the effectiveness of assisted conception. We addressed this issue by analysing individual patient data (IPD) from randomized controlled trials (RCTs).

METHODS We performed an IPD analysis of published RCTs on treatment strategies for subfertile couples. Eligible studies were identified from Cochrane systematic reviews and we also searched Medline and EMBASE. The authors of RCTs that compared expectant management (EM), intracervical insemination (ICI), intrauterine insemination (IUI), all three with or without controlled ovarian stimulation (COS) and IVF in couples with unexplained or male subfertility, and had reported live birth or ongoing pregnancy as an outcome measure, were invited to share their data. For each individual patient the chance of natural conception was calculated with a validated prognostic model. We constructed prognosis-by-treatment curves and tested whether there was a significant interaction between treatment and prognosis.

RESULTS We acquired data from 8 RCTs, including 2550 couples. In three studies (n = 954) the more invasive treatment strategies tended to be less effective in couples with a high chance of natural conception but this difference did not reach statistical significance (P-value for interaction between prognosis and treatment outcome were 0.71, 0.31 and 0.19). In one study (n = 932 couples) the strategies with COS (ICI and IUI) led to higher pregnancy rates than unstimulated strategies (ICI 8% versus 15%, IUI 13% versus 22%), regardless of prognosis (P-value for interaction in all comparisons >0.5), but at the expense of a high twin rate in the COS strategies (ICI 6% versus 23% and IUI 3% versus 30%, respectively). In two studies (n = 373 couples), the more invasive treatment strategies tended to be more effective in couples with a good prognosis but this difference did not reach statistical significance (P-value for interaction: 0.38 and 0.68). In one study (n = 253 couples) the differential effect of prognosis on treatment effect was limited (P-value for interaction 0.52), perhaps because prognosis was incorporated in the inclusion criteria. The only study that compared EM with IVF included 38 couples, too small for a precise estimate.

CONCLUSIONS In this IPD analysis of couples with unexplained or male subfertility, we did not find a large differential effect of prognosis on the effectiveness of fertility treatment with IUI, COS or IVF.
Original languageEnglish
Pages (from-to)141-151
Number of pages11
JournalHuman Reproduction Update
Volume20
Issue number1
Early online date30 Oct 2013
DOIs
Publication statusPublished - Jan 2014

Keywords

  • individual patient data
  • assisted reproduction
  • assisted conception
  • prognosis
  • RCT

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    Van den Boogaard, N. M., Bensdorp, A. J., Rengerink, K. O., Barnhart, K., Bhattacharya, S., Custers, I. M., Coutifaris, C., Goverede, A. J., Guzick, D. S., Hughes, E. C., Litvak, P. F., Steures, P., Hompes, P. G. A., Van der Veen, F., Mol, B., & Bossuyt, P. (2014). Prognostic profiles and the effectiveness of assisted conception: secondary analyses of individual patient data. Human Reproduction Update, 20(1), 141-151. https://doi.org/10.1093/humupd/dmt035