ArticleJournal of ovarian research2026
Putative "ovarian awakening" in diminished ovarian reserve: a multicenter analysis demonstrates indistinguishability from regression to the mean.
Article in Journal of ovarian research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Identification of Inflammatory Markers for the Prediction and Diagnosis of Diminished Ovarian Reserve Using Olink Targeted Proteomics.Journal of clinical medicine · 2026Article
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Authors and funding
10 authors.
Funding
Abstract
backgroundIn clinical practice, repeated oocyte retrieval cycles are often necessary for patients with diminished ovarian reserve (DOR). It has been hypothesized that the mechanical stimulation from the initial oocyte pick-up (OPU) procedure might mimic the effect of in vitro activation (IVA), potentially activating dormant follicles and improving outcomes in subsequent cycles. This study aimed to determine whether repeat ovarian stimulation cycles yield superior oocyte and embryological outcomes compared to the initial cycle in patients with DOR.
methodsThis multicenter retrospective cohort study analyzed data from 2,883 DOR patients who underwent at least two ovarian stimulation cycles within 12 months of their initial cycle between 2016 and 2023. Generalized Linear Mixed Models (GLMMs) were employed as the primary analytical method. To formally evaluate the potential impact of regression to the mean (RTM), a simulation-based permutation test was conducted, fitting a null model with only patient-level random intercepts to simulate datasets without any cycle order effect.
resultsGLMM analysis initially indicated that the second and third retrieval cycles yielded significantly more oocytes, 2PN zygotes, transferable embryos, and high-quality embryos compared to the first cycle (all P < 0.05). Mediation analysis suggested that an increase in antral follicle count (AFC) explained over half (51.4%) of the benefit in oocyte yield in the second cycle. However, the formal RTM analysis revealed a consistent numerical trend where the observed “improvement” in oocyte yield was lower than the effect size expected from RTM alone (adjusted effects ranging from − 0.44 to -1.18 oocytes). Crucially, the observed effects were not statistically distinguishable from those generated by the RTM phenomenon (all p-values > 0.49).
conclusionsThe apparent improvement in oocyte yield and embryological outcomes in subsequent cycles for DOR patients, is statistically indistinguishable from the effect expected due to regression to the mean. Caution is warranted in interpreting these outcomes as a genuine biological effect, such as “ovarian awakening”.
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