Poor Responder Definition in IVF
A poor responder in IVF is defined by the Bologna criteria, which require at least two of the following three features: (1) advanced maternal age (≥40 years) or other risk factors for poor ovarian response, (2) a previous poor ovarian response (≤3 oocytes with conventional stimulation), or (3) an abnormal ovarian reserve test (AFC <5-7 follicles or AMH <0.5-1.1 ng/mL). 1
The Bologna Criteria Framework
The European Society of Human Reproduction and Embryology established these standardized criteria to create uniformity in defining poor ovarian response across clinical practice and research 1. This represents the first consensus attempt to define poor response in a simple, reproducible manner.
Core Diagnostic Requirements
At least two of three criteria must be present:
Advanced maternal age (≥40 years) or other risk factors for poor ovarian response, including genetic abnormalities, previous ovarian surgery, chemotherapy, or pelvic radiation 1
Previous poor ovarian response, defined as ≤3 oocytes retrieved with a conventional ovarian stimulation protocol 1
Abnormal ovarian reserve testing, including antral follicle count (AFC) <5-7 follicles or anti-Müllerian hormone (AMH) <0.5-1.1 ng/mL 1
Special Circumstances
Two episodes of poor ovarian response after maximal stimulation are sufficient to define a patient as a poor responder, even without advanced maternal age or abnormal ovarian reserve testing 1. This recognizes that repeated poor response is itself diagnostic, regardless of other factors.
Alternative Definitions in the Literature
While the Bologna criteria represent the consensus standard, earlier definitions focused on different parameters that remain clinically relevant:
Gonadotropin Dose-Based Criteria
Some definitions incorporate the degree of ovarian stimulation required 2:
Cycle cancellation at ≥300 IU FSH/day is associated with significantly worse prognosis and can define poor response 2
Cumulative FSH dose ≥3000 IU per cycle combined with <4 oocytes retrieved indicates poor response with reduced pregnancy rates (7% versus 25% with ≥5 oocytes) 2
When <3000 IU FSH is used, pregnancy rates remain favorable (29%) even with <4 eggs retrieved 2
Traditional Criteria
Historical definitions emphasized 3:
- Small numbers of follicles developed or oocytes retrieved during standard stimulation protocols
- Low estradiol (E2) levels after standard stimulation
- Elevated day 3 FSH and E2 levels or decreased inhibin B levels as predictive markers
The "Expected Poor Responder" Category
Patients with advanced age AND abnormal ovarian reserve testing may be classified as "expected poor responders" without requiring a prior stimulation cycle 1. Both factors indicate reduced ovarian reserve and serve as surrogates for actual cycle outcomes. This allows for preemptive counseling and protocol selection before initiating treatment.
Critical Clinical Pitfalls
The One-Cycle Requirement
By definition, poor ovarian response refers to actual ovarian response, so one stimulated cycle is considered essential for diagnosis 1. The exception is the "expected poor responder" category described above.
Avoiding Premature Pessimism
Cancellation of a first cycle due to poor response does not predict inevitable failure in subsequent cycles 4. In one study of 96 women who continued treatment after a cancelled first cycle, pregnancy rates reached 12.5% per cycle and 16.2% per transfer, with all pregnancies occurring in cycles yielding 2-3 oocytes 4. This demonstrates that continuation of therapy can be a reasonable option despite low success rates.
Protocol Selection Matters
For poor responders, alternative protocols including natural cycle, minimal ovarian stimulation, or luteal phase stimulation should be considered to potentially increase oocyte numbers 5, 6. The evidence suggests that flare-up GnRH agonist protocols produce better results than standard long luteal protocols 3, though high-dose gonadotropin strategies show controversial results with little proven benefit in prospective randomized studies 3.
Practical Application
The Bologna criteria provide the minimal standardized definition needed to select patients for clinical trials and ensure homogeneous study populations 1. By reducing bias from inconsistent definitions, this framework allows meaningful comparison of results across studies and clinical settings. However, clinicians should recognize that no single definition captures all aspects of poor response, and the degree of ovarian stimulation required remains an important consideration in individual patient management 2.