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Interventions for unexplained infertility: a systematic review and network meta-analysis.

Rui Wang1, Nora A Danhof, Raissa I Tjon-Kon-Fat

  • 1Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia, 3168.

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Network meta-analysis found insufficient evidence comparing live birth rates for unexplained infertility treatments like ovarian stimulation (OS) and IVF/ICSI versus expectant management. Some treatments may increase multiple pregnancy risks.

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Area of Science:

  • Reproductive Medicine
  • Clinical Epidemiology
  • Biostatistics

Background:

  • Unexplained infertility management includes expectant management and active treatments like ovarian stimulation (OS), intrauterine insemination (IUI), OS-IUI, and in vitro fertilisation (IVF/ICSI).
  • Previous systematic reviews used pairwise meta-analyses, limiting comprehensive comparisons of multiple interventions.
  • Network meta-analysis offers a superior approach by simultaneously comparing multiple treatments using direct and indirect evidence to establish a hierarchy of effectiveness and safety.

Purpose of the Study:

  • To evaluate the effectiveness and safety of various clinical management strategies for unexplained infertility.
  • To compare expectant management, OS, IUI, OS-IUI, and IVF/ICSI using network meta-analysis.

Main Methods:

  • Systematic review and network meta-analysis of randomised controlled trials (RCTs).
  • Searched multiple electronic databases up to September 2018, including trial registers.
  • Included RCTs comparing at least two management options; primary outcomes were live birth/ongoing pregnancy and multiple pregnancy.

Main Results:

  • 27 RCTs (4349 couples) included; 24 RCTs (3983 couples) in network meta-analysis; evidence certainty was low to moderate.
  • Insufficient evidence for live birth differences between OS, IUI, OS-IUI, or IVF/ICSI versus expectant management.
  • OS and OS-IUI increased odds of multiple pregnancy compared to expectant management/IUI; evidence for IVF/ICSI was insufficient.
  • Insufficient evidence for differences in moderate/severe OHSS between IVF/ICSI and OS-IUI.

Conclusions:

  • Insufficient evidence exists to differentiate live birth rates among expectant management, OS, IUI, OS-IUI, and IVF/ICSI for unexplained infertility.
  • Ovarian stimulation (OS) and OS-IUI may increase the risk of multiple pregnancies compared to expectant management or IUI.
  • Further research is needed to clarify the comparative effectiveness and safety of these interventions, particularly regarding OHSS risk.