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<p>Despite forty years of intense research and multitudinous clinical innovations, live birth rates (LBR) among women diagnosed with decreased ovarian reserve (DOR) remain disappointingly poor. Is this because a solution has not yet been discovered, or are we searching in the wrong way? This persistent failure is probably the product of both undisputable biological realities, the exponential decline in oocyte euploidy with advanced maternal age, and persistent methodological flaws, most notably the inclusion of highly heterogeneous cohorts in clinical trials and inadequate stratification by critical variables, such as age. No ovarian stimulation protocol, adjuvant therapy, or laboratory add-on has consistently improved outcomes. The grouping of young and older DOR women in clinical studies, the focus on surrogate endpoints over live birth, and failure to account for cycle-to-cycle and operator variability further obscure valid conclusions and mislead both clinicians and patients. In this review, we delineate the evolution of DOR research, drilling down to the biological, technical, and methodological roots of failed progress. We argue that only by rigorously stratifying study populations by narrow age bands, repeated response criteria and prioritizing true endpoints, can future research genuinely advance the field and provide realistic, evidence based counseling. Clinical humility and research rigor are prerequisites for sparing patients needless interventions and false hope.</p>

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Why have four decades of research into decreased ovarian reserve (DOR) failed to improve live birth rates?

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Zion Ben Rafael,
  • Raoul Orvieto

摘要

Despite forty years of intense research and multitudinous clinical innovations, live birth rates (LBR) among women diagnosed with decreased ovarian reserve (DOR) remain disappointingly poor. Is this because a solution has not yet been discovered, or are we searching in the wrong way? This persistent failure is probably the product of both undisputable biological realities, the exponential decline in oocyte euploidy with advanced maternal age, and persistent methodological flaws, most notably the inclusion of highly heterogeneous cohorts in clinical trials and inadequate stratification by critical variables, such as age. No ovarian stimulation protocol, adjuvant therapy, or laboratory add-on has consistently improved outcomes. The grouping of young and older DOR women in clinical studies, the focus on surrogate endpoints over live birth, and failure to account for cycle-to-cycle and operator variability further obscure valid conclusions and mislead both clinicians and patients. In this review, we delineate the evolution of DOR research, drilling down to the biological, technical, and methodological roots of failed progress. We argue that only by rigorously stratifying study populations by narrow age bands, repeated response criteria and prioritizing true endpoints, can future research genuinely advance the field and provide realistic, evidence based counseling. Clinical humility and research rigor are prerequisites for sparing patients needless interventions and false hope.