Why have four decades of research into decreased ovarian reserve (DOR) failed to improve live birth rates?
- 1Department of Obstetrics and Gynecology and IVF, Laniado Medical Center, Netanya, Israel.
- 2Chaim Sheba Medical Center, Ramat- Gan. The Tarnesby-Tarnowski Chair for Family Planning and Fertility Regulation,the Gray Faculty of Medical and Health Science, Tel-Aviv University, Tel-Aviv, Israel. [email protected].
Abstract
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.
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BibTeX
@article{rafael2026have,
title = {{Why have four decades of research into decreased ovarian reserve (DOR) failed to improve live birth rates?}},
author = {Zion Ben Rafael and Raoul Orvieto},
journal = {Archives of gynecology and obstetrics},
year = {2026},
month = aug,
doi = {10.1007/s00404-026-08550-9},
url = {https://europepmc.org/article/MED/42970091},
note = {CC BY},
}
RIS
TY - JOUR
TI - Why have four decades of research into decreased ovarian reserve (DOR) failed to improve live birth rates?
AU - Zion Ben Rafael
AU - Raoul Orvieto
PY - 2026
DA - 2026/08/05
JO - Archives of gynecology and obstetrics
DO - 10.1007/s00404-026-08550-9
UR - https://europepmc.org/article/MED/42970091
AB - 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.
SN - 0932-0067
SN - 1432-0711
ER -