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April 15, 2026The Obstetrician & Gynaecologist0 citationsOpen Access

Unexplained Infertility: An Update

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CRClaudia RaperportRFRosa Ferguson‐LoboGLGidon Lieberman

Key Points

  • To review definitions, hypotheses, and management strategies for unexplained infertility.
  • Reviewed definitions and hypotheses for unexplained infertility.
  • Summarized best practices for investigating subfertile couples.
  • Analyzed recent evidence on treatments like IUI and IVF.
  • Unexplained infertility accounts for up to 30% of infertility cases.
  • Predictive models like the Hunault model aid in predicting natural conception likelihood.
  • IUI is supported as a first-line treatment according to recent ESHRE guidance.

Abstract

ABSTRACT Key Content Unexplained infertility accounts for up to 30% of cases of infertility. Potential causes for unexplained infertility have been proposed including reduced oocyte quality, poor endometrial receptivity, ovulatory PCOS, subclinical endometriosis and low semen quality. Investigations for the diagnosis of infertility include assessment of ovulation, tubal patency, semen quality and uterine structure. Predictive models such as the Hunault model can predict the likelihood of natural conception in those with unexplained infertility and can help guide management options which include expectant management, intrauterine insemination (IUI) (with or without ovarian stimulation) or in vitro fertilisation (IVF). Current NICE guidance advises that couples with unexplained infertility are referred for IVF after 2 years of trying to conceive naturally. The recent ESHRE guidance supports IUI as a first‐line treatment for those with unexplained infertility. There is some evidence that both IUI and IVF confer a benefit in those with a poor prognosis to natural conception; however, further good‐quality research is required. Learning Objectives To review current definitions and potential hypotheses for the causes of unexplained infertility. To summarise the best practice for the investigation of the subfertile couple. To summarise and review recent evidence on the treatment of unexplained infertility.

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Cite This Study

Raperport et al. (2026) studied this question.

synapsesocial.com/papers/69df2bcae4eeef8a2a6b0b96https://doi.org/10.1111/tog.70037
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Unraveling infertility - most frequent causes and essential predictors of assisted reproductive technologies outcomes2025
  2. 2Investigating the Genetic Basis of Unexplained Infertility and Potential Chromosomal Abnormalities2024
  3. 3PREDICTORS OF INTRA CYTOPLASMIC SPERM INJECTION SUCCESS IN COUPLES WITH UNEXPLAINED SUB-FERTILITY2024
  4. 4A Decade of Data from an IVF Center: Factors Contributing to Infertility, Their Prevalence, and Impact on Live Birth Rates2026
  5. 5P-488 The importance of identifying and addressing sexual functioning in couples with unexplained infertility2024