What's your approach to implementing dual stimulation protocols for poor responders?

Highlights

• Dual stimulation is most useful for patients needing rapid egg retrieval, such as those undergoing fertility preservation before cancer treatment.
• The protocol involves two stimulation cycles within one month to maximize the number of eggs retrieved from both follicular and luteal phase follicles.
• Consider introducing duo-stim to poor responders after an initial cycle yields a low number of eggs, particularly if PGT is planned.
• The two retrievals in a duo-stim cycle should be viewed as two independent opportunities to collect a viable number of eggs.
• However, some clinicians prefer two consecutive monthly cycles, citing logistical ease and less difficulty distinguishing new from old follicles.

Expert Insights

Defining the Role of Dual Stimulation for Poor Responders

For patients classified as poor responders, the central challenge is often a numbers problem: a diminished ovarian reserve yields fewer oocytes, and with advancing age, each oocyte has a lower probability of resulting in a viable pregnancy. In this context, dual stimulation (duo-stim) protocols have emerged as a strategy to maximize oocyte yield within a single menstrual cycle. This approach involves a standard follicular phase stimulation and retrieval, followed immediately by a second, luteal phase stimulation and subsequent retrieval. While the protocol is gaining traction, expert opinion varies on its ideal application, efficacy compared to alternatives, and practical feasibility.

The Rationale: Maximizing Oocyte Yield Under Time Constraints

The primary argument for duo-stim centers on efficiency and speed. Dr. Joseph Letourneau identifies it as one of the first strategies he considers for poor responders, particularly after an initial cycle yields four or fewer eggs. "We need to get more eggs and we need to get them quickly, because as time elapses they’re less likely to succeed," Dr. Joseph Letourneau explains. The protocol addresses this by initiating a second stimulation approximately five days after the first retrieval, effectively providing two opportunities for oocyte collection in about one month. Similarly, Dr. Randi Goldman finds duo-stim valuable for patients who must complete a cycle quickly, such as those undergoing fertility preservation for cancer. "In my experience, dual stimulation tends to work: you can recruit follicles in both the follicular and luteal phases to maximize the number of eggs obtained in a short period," states Dr. Randi Goldman.

Clinical Application and Expected Outcomes

According to Dr. Joseph Letourneau, the two stimulations within a duo-stim protocol should be viewed as separate opportunities rather than a sequence where the first primes the second. The goal is a rapid accumulation of oocytes to increase the odds of finding a competent one. Dr. Joseph Letourneau notes that while not guaranteed, the combined yield is often roughly double what a single stimulation would produce. This approach is particularly relevant for patients planning preimplantation genetic testing (PGT) or a freeze-all cycle, where a larger cohort of oocytes is advantageous.

"Duo-stim essentially gives you two chances at once." Dr. Joseph Letourneau

However, Dr. Joseph Letourneau also acknowledges the significant commitment required. Duo-stim represents the work and cost of two IVF rounds, a considerable burden that may be mitigated only if a center offers a specific package. Despite this, Dr. Joseph Letourneau asserts there is solid evidence that the protocol can more rapidly improve pregnancy rates for this challenging patient population.

A Counter-Perspective on Efficacy and Logistics

Not all experts are convinced of the protocol's advantages over more conventional approaches. Dr. Molly Moravek expresses skepticism, stating, "I don't think they have an advantage over doing two stimulations two months in a row." In her view, the primary benefit is compressing the timeline, which is most relevant for fertility preservation cases. Dr. Molly Moravek raises significant practical barriers, noting that the rapid turnaround is difficult to accommodate in busy IVF clinics where cycle starts are scheduled well in advance. Beyond logistics, Dr. Molly Moravek points to a clinical challenge: "I've also found that with dual stimulations it's sometimes hard to differentiate between an old follicle and a new follicle." This ambiguity can complicate cycle management.

"For me, unless we're in a time crunch...it's much cleaner to do two months in a row rather than dual stimulation." Dr. Molly Moravek

For these reasons, Dr. Molly Moravek concludes that unless a patient faces a true time crunch, consecutive monthly cycles offer a "cleaner" and more manageable approach.

Synthesis: A Tool for Urgency, Not a Universal Standard

Synthesizing these perspectives, dual stimulation emerges as a specialized tool rather than a universal standard for all poor responders. The decision to implement it hinges on a balance between the clinical urgency for oocyte accumulation and the logistical capacity of the clinic. The consensus among the experts is that its most undisputed indication is for time-sensitive fertility preservation. For other poor responders, its utility is debated. The potential to double the oocyte yield in a single month, as described by Dr. Joseph Letourneau, is a compelling advantage. However, this must be weighed against the significant financial and physical demands on the patient and the practical challenges of clinic scheduling and follicle monitoring highlighted by Dr. Molly Moravek. Ultimately, the choice between a duo-stim protocol and consecutive monthly cycles depends on an individualized assessment of the patient's prognosis, timeline, and resources.