Animal models sharpen the case for tailored ovarian stimulation
Bottom line
Version 1
A new review in Frontiers in Endocrinology argues that random-start ovarian stimulation and DuoStim in women should be understood through a more nuanced physiologic lens, and that domestic animal models, especially cattle and mares, can help explain why ovarian response varies even when stimulation begins in the same menstrual-cycle phase. Author DR Don Rick Bergfelt of Lincoln Memorial University says the key issue is that cycle phase alone may not capture the ovarian environment at stimulation start, because dominant follicle status, follicular-wave stage, and corpus luteum maturity can differ meaningfully. The paper positions cattle and mares as useful comparative models because those variables can be measured and manipulated more directly than in women. (frontiersin.org)
Why it matters: For veterinary professionals, the review is a reminder that domestic animal reproduction research continues to inform human assisted reproduction in concrete ways. Bergfelt’s synthesis suggests that findings from monovulatory species may help refine prediction of ovarian responsiveness, not just support the biologic rationale for random-start protocols and DuoStim. That translational link matters as human fertility societies continue to endorse random-start stimulation for urgent fertility preservation, while the evidence base for broader DuoStim use, particularly in poor responders, remains debated. (frontiersin.org)
What to watch: Watch for prospective human studies that test whether measurable follicular and luteal markers, drawn from animal-model insights, can better predict who benefits from random-start stimulation or DuoStim. (frontiersin.org)
Key facts
- Article type
- Review
- Journal
- Frontiers in Endocrinology
- Topic
- Random-start ovarian stimulation and DuoStim in women
- Main argument
- Cycle phase alone may not capture the ovarian environment at stimulation start
- Comparative models
- Cattle and mares
- Key variables
- Dominant follicle status, follicular-wave stage, and corpus luteum maturity
- Why the models matter
- They can be measured and manipulated more directly than in women
- Clinical context
- Random-start stimulation is used for urgent fertility preservation
- DuoStim context
- The evidence base for broader DuoStim use, especially in poor responders, remains debated
A newly published review in Frontiers in Endocrinology makes a translational case for looking to domestic animal models to better understand ovarian responsiveness during random-start stimulation and DuoStim in women. In the paper, DR Don Rick Bergfelt argues that the ovarian environment at the moment stimulation begins is more heterogeneous than menstrual-cycle phase alone suggests, and that this may help explain uneven response to these increasingly used protocols. (frontiersin.org)
The review builds on a shift in reproductive biology that followed recognition of sequential follicular waves during the menstrual cycle. That concept helped support random-start ovarian stimulation, which allows treatment to begin outside the conventional early follicular window, and DuoStim, which uses two stimulation rounds in a single cycle to shorten time to oocyte retrieval. Bergfelt’s article says those strategies are especially relevant for fertility preservation and other time-sensitive situations. (frontiersin.org)
What Bergfelt adds is a comparative framework. According to the review, cattle and mares offer a way to study follicular-wave emergence, dominant follicle effects, luteal function, and endocrine conditions with more control than is possible in women. The article argues that those models provide direct evidence that dominant follicle status and corpus luteum maturity influence follicular recruitment and ovarian response to gonadotropin stimulation, even if those findings can’t be mapped one-to-one onto human physiology. (frontiersin.org)
That matters because random-start stimulation and DuoStim are not interchangeable physiologic states. Bergfelt distinguishes spontaneous-cycle random-start stimulation from the second stimulation in DuoStim, which begins after prior follicular-phase stimulation, final oocyte maturation triggering, and oocyte retrieval, in what the paper describes as a treatment-modified post-retrieval luteal environment. The review’s central hypothesis is that cycle phase alone is too blunt a descriptor, and that measurable follicular, luteal, and endocrine variables may better explain response variability. (frontiersin.org)
Outside the paper, current guidance and commentary show why that framing is timely. The 2025 ESHRE ovarian stimulation guideline update recommends that, for patients facing gonadotoxic treatment, ovarian stimulation for fertility preservation should start regardless of menstrual-cycle phase, reflecting growing acceptance of random-start approaches in urgent settings. ASRM’s 2026 committee opinion on fertility preservation likewise discusses random-start stimulation in cancer patients and emphasizes multidisciplinary planning in time-sensitive care. (pmc.ncbi.nlm.nih.gov)
DuoStim, though, remains more contested. A recent Frontiers paper reporting 10 years of real-world experience described increasing clinical use from 2015 to 2024 and argued that DuoStim can increase total oocyte yield in time-sensitive, poor-prognosis patients. But a commentary in Human Reproduction has argued that routine DuoStim in poor responders lacks adequate rationale and strong outcome evidence, particularly outside urgent fertility-preservation scenarios. Taken together, those sources suggest that the field agrees on the biologic plausibility of flexible-start stimulation, but not on how far DuoStim should extend into routine practice. (frontiersin.org)
For veterinary professionals, this is a useful example of how animal reproduction research continues to shape human clinical thinking. The review doesn’t just cite domestic species as analogies; it treats them as mechanistic models that can help define the ovarian variables worth measuring in women. That has implications for comparative endocrinology, assisted reproduction research, and the broader case for veterinary science as a contributor to human reproductive medicine. (frontiersin.org)
What to watch: The next step is likely better stratification, not just broader use. If future prospective studies show that dominant follicle status, luteal maturity, or related endocrine markers can predict response, clinicians may be able to tailor random-start stimulation and DuoStim more precisely, and the veterinary-human translational bridge outlined in this review could become more clinically actionable. That’s an inference from the paper’s framework and the current guideline debate, rather than a stated near-term policy change. (frontiersin.org)