Egg quality is central – and arguably the most important variable – in both natural and assisted human reproduction. For decades, we viewed “poor egg quality” through a fatalistic lens, often treating it as an inevitable diagnosis of age or an intrinsic female pathology. However, the latest understanding of reproductive science reveals that poor egg quality is merely an observation, not a diagnosis – and it is frequently manageable.
Therefore, it should not be generalized. Instead, it must be investigated within the context of a patient’s unique circumstances and the latest understanding of the reproductive cycle. This site is dedicated to a new, non-empirical approach to the analysis and management of poor egg quality, based on the Dozortsev–Diamond paradigm.
Scientific Recognition: The Dozortsev–Diamond paradigm was featured in the Fertility and Sterility series in 2020 as part of the landmark “Sea Changes in Reproductive Physiology“.
Correct ovulation paradigm is crucial for managing egg quality
Egg quality has three possible origins. One is intrinsic and cannot be changed. Every woman, at any age, has a mix of good- and poor-quality eggs in her ovaries.
The second and third sources – pathophysiological and iatrogenic – occur during the follicular phase and therefore can be influenced.
Egg quality is therefore not solely an intrinsic property of the oocyte, but the result of how that oocyte is allowed to mature during the follicular phase.
Pathophysiological factors arise when otherwise good-quality eggs are prevented from achieving developmental competence during the follicular phase by a woman’s own physiology. Examples include age-related loss of collagen in the ovarian cortex or elevated FSH levels, which can force follicles to rupture prematurely, effectively transforming good eggs into poor-quality eggs.
Iatrogenic factors occur when otherwise good-quality eggs degrade under the influence of medications or other external factors introduced during ovarian cycle management:
The clinical practice of managing egg quality is based on the foundation of reproductive physiology. Inconsistent or erroneous ovulation paradigm hinders clinical opportunities or renders them empirical. Therefore, correct understanding of ovulation and of the events leading up to ovulation during the final two weeks of follicular development is directly connected to egg quality.
Legacy ovulation paradigm
The legacy ovulation paradigm positions estradiol (E2) as the physiological trigger of ovulation. It suggests that E2 triggers the LH surge from the pituitary after reaching a specific threshold, typically between 200 and 500 pg/mL. In turn, the LH surge restarts meiosis, ruptures the follicle, and luteinizes the granulosa cells—signaling them to switch to progesterone production to prepare the uterus for implantation. A common refinement to this idea, introduced by Leyendecker et al in 70s, suggests that E2 triggers LH not when it reaches its peak, but specifically when levels begin to decline.
- This legacy paradigm has left many questions unanswered, or at least failed to provide intellectually satisfying and actionable explanations. Here is an incomplete list of these gaps:
- If estradiol is a trigger, why does it only work in experimental settings on post-menopausal females? Why no one has been able to use it as a trigger in normally cycling females?
- If E2 cannot trigger ovulation in practice, is that why assisted reproduction relies on hCG or GnRH agonists (like Lupron) instead?
- Why would estradiol, which is well known to suppress LH and FSH at almost any concentration switch into an LH and FSH releaser as it continues to rise or falls?
- Why does ovulation timing remain unchanged even when estradiol is suppressed with letrozole to levels as low as 50 pg/mL throughout the follicular phase?
- If estradiol is the trigger, how can cycle duration remain constant despite wide month-to-month variations in peak E2 levels?
- How can estradiol levels accurately reflect a follicle’s readiness to rupture if those levels vary so significantly from cycle to cycle?
- The list could continue, but it is clear that the legacy paradigm suffers from multiple well-known inconsistencies.
Dozortsev-Diamond – New Ovulation Paradigm
The Dozortsev–Diamond Paradigm does not rely on a single, isolated experimental breakthrough; rather, it is a re-evaluation and synthesis of over 50 years of accumulated physiological data, which were all valid on their own merits but due to a variety of circumstances where entangled and often even contradictory. The new paradigm resolves long-standing inconsistencies and presents the mechanics of human reproduction in a compellingly logical way making it actionable and creating new entry points to tackle poor egg quality.
The Dozortsev–Diamond Ovulation Paradigm: Rethinking the LH Surge
For decades, reproductive medicine has taught that a peak in estradiol (estrogen) is the primary trigger of the LH surge. However, this model leaves many clinical observations unexplained, including cycle shortening with age, variable egg quality, vanishing follicles, and inconsistent responses to ovarian stimulation.
The Dozortsev–Diamond paradigm re-examines the physiology of ovulation to offer a consistent explanation of what triggers the LH surge, how ovulation is coordinated with follicle readiness, and why ovulation mechanics are directly linked to egg quality.
The Key Point: Ovulation is Triggered by Ovarian Cortex
The paradigm proposes that ovulation is physically triggered when the ovarian cortex reaches its capacity to accommodate continued follicular expansion just like any comedo somewhere else on the skin. They propose that as follicles expand, mechanical stress leads to local inflammation and compromises follicular integrity. Granulosa cells begin switching from estradiol production to progesterone production in an LH-independent manner.
This rise in progesterone signals physiological readiness of the follicle, tightly linking the timing of the LH surge to the actual maturity of the egg.
Progesterone is the primary trigger of LH
According to the Dozortsev–Diamond paradigm, the most upstream event leading to the LH surge is not a peak in estradiol. Instead, ovulation is initiated by a small, early rise in progesterone that occurs before the LH surge as granulose begins to luteinize spontaneously. This rise typically reaches approximately 0.5–1.0 ng/mL. It occurs during the late follicular phase and activates the GnRH–LH signaling pathway in the hypothalamus. Estradiol remains important, but its primary role is suppressing LH release—allowing LH to accumulate in the pituitary—rather than triggering the surge itself.
Why Progesterone Can Both Trigger and Block Ovulation
The Dozortsev–Diamond paradigm resolves the long-standing “progesterone paradox” – why progesterone is used in birth control yet can also trigger ovulation -through receptor sensitivity.
During the follicular phase, very low progesterone levels sensitize progesterone receptors, so a modest rise acts as a trigger. With prolonged or high exposure, such as during pregnancy or hormonal contraception, receptors become desensitized and progesterone acts as a blocker. This behavior is analogous to GnRH agonists such as Lupron, which trigger an LH surge when administered acutely but suppress the system when given continuously.
Reinterpreting the Classic Leyendecker Experiment
The traditional estrogen-trigger model relies heavily on a classic experiment showing an LH surge after estradiol administration in post-menopausal women. Dozortsev and Diamond propose that this observation represents a pathological artifact rather than a physiological mechanism.
Estradiol suppresses LH release, but not LH synthesis. In post-menopausal women, LH production is extremely high, causing LH to accumulate in the pituitary under estradiol’s influence. When estradiol levels subsequently fall, this stored LH is released all at once, creating a false “surge” that does not occur in normally cycling women.
How Ovulation Physiology Explains Poor Egg Quality
By placing control of ovulation in the ovarian cortex rather than relying solely on hormone thresholds, this paradigm explains several clinically important phenomena.
Loss of cortical elasticity with age causes follicles to rupture earlier, before optimal egg maturation, leading to age-related cycle shortening. In IVF, mechanical, LH-independent ruptures explain vanishing follicles.
Why This Matters for Fertility
A correct understanding of ovulation is crucial for managing egg quality. When ovulation is triggered at the wrong time or through non-physiological mechanisms, otherwise healthy eggs may lose developmental competence. This framework provides the foundation for Term Stimulation, a strategy designed to ensure that eggs are allowed to reach their full developmental potential.
Ramifications for Infertility Management
By restoring physiological coherence to the ovulation process, the Dozortsev–Diamond Paradigm opens new possibilities for addressing poor egg quality:
For Age-Related Decline: Explains how the loss of elasticity in the ovarian cortex leads to premature triggering and “under-cooked” eggs.
For Cycle Management: Provides a rationale for extending the follicular phase using anti-inflammatory interventions to reach Term Maturation.
These are just very general statements and real clinical management has to take into account many nuances unique for every patient with poor egg quality.
Besides new approaches to egg quality management, Dozortsev-Diamond paradigm solved numerous other decades old puzzles, such as randomness of ovulations on right an left side, mono-ovulation, explained why PCOS and very young patients may have worse outcomes, introduced a new theory for origin of PCOS and importantly, finally made available a new clinical ovulation trigger.
New Natural Ovulation Trigger: Introduces progesterone as a physiological, inexpensive, and ubiquitous trigger for natural and frozen embryo transfer cycles.
A Dozortsev-Diamond Framework for Egg Quality
Dozortsev-Diamond ovulation paradigm point to very specific and quantifiable hormonal imbalances, ovarian tissue factors, and inflammatory markers that directly impact the follicle during its most critical phase: the final two weeks of development. Because this window is accessible to clinical intervention, we can strategically influence egg quality by addressing the following:
Endocrine Environment: LH and FSH levels directly impact oocyte maturation, while Estradiol and Progesterone serve as critical biomarkers of the egg’s developmental trajectory.
Follicular Phase Duration: A follicular phase that is either accelerated or excessively prolonged can significantly compromise egg quality.
The Ovarian Cortex: The physical and biochemical properties of the ovarian cortex determine length of the follicular phase. It ends when cortex can no longer accommodate the expansion of the follicle without losing its integrity.
Inflammation: Inflammatory factors, interacting with the ovarian cortex, act as key determinants of the duration of follicular phase.
The Diagnostic Cycle
A rational approach to managing poor egg quality must move beyond trial and error. Before attempting a new IVF cycle, it is essential to conduct a diagnostic cycle. This allows for a granular, patient-specific understanding of reproductive physiology, ensuring that subsequent treatments are tailored to the individual’s unique hormonal and ovarian profile.
This site is a public service of Dmitri Dozortsev, MD, PhD – physician-scientist, President of the American College of Embryology, and expert in translational fertility. It serves as an independent knowledge base dedicated to revising reproductive physiology through the lens of the Dozortsev–Diamond Paradigm.
As long as there are eggs, there is hope. This is not mere a comforting phrase; it is a statement grounded in the new science of reproductive history.