This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Maximal Stimulation and Delayed Fertilization for Diminished Ovarian Reserve: a Randomized Pilot Study (NCT01921166), a randomized phase 4 study. The primary outcome is Oocytes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01921166 |
| Phase | Phase 4 |
| Condition | Infertility |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 23 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Wake Forest University Health Sciences |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns women described in the registry summary as having diminished ovarian reserve and a poor prognosis for IVF. The summary says recruitment was intended for women not eligible for the Carolinas Medical Center Assisted Reproductive Therapy program because of an extremely poor prognosis. The registry record does not report detailed participant characteristics, eligibility thresholds, or the characteristics of those enrolled.
Intervention
The registry lists clomiphene plus gonadotropins and Leuprolide flare as the two study arms. The study description frames these as ovarian stimulation protocols and describes a proposed approach involving retrieval and vitrification of oocytes, followed by fertilization and embryo transfer in a later cycle with endometrial preparation. The record does not report which participants proceeded through each step.
Comparator
This is a comparison between the two listed stimulation protocols, not a comparison with no treatment or with a non-IVF group. The record identifies clomiphene plus gonadotropins and Leuprolide flare as the arms, but it does not report a formal statistical comparison of their primary outcome values.
Primary question
The stated broader purpose includes assessing whether the novel approach improves live birth and determining an optimal stimulation protocol. The posted primary outcome, however, is the number of oocytes retrieved, with a timeframe of up to 24 months. The registry record does not report live-birth results in the posted outcomes summarized for this analysis, nor a formal test comparing oocyte counts between arms.
3. Trial Design
NCT01921166 is registered as a randomized, open-label, parallel-group phase 4 pilot study. The registry lists an enrollment of 23 and identifies Wake Forest University Health Sciences as the sponsor. The study status is completed. The recorded start is 2011-01 and the primary completion is 2011-11.
The two arms are clomiphene plus gonadotropins and Leuprolide flare. The registry lists 8 participants in the clomiphene plus gonadotropins arm and 15 in the Leuprolide flare arm for the primary outcome. Because the study is open-label, masking is listed as none. The registry record does not report details of sequence generation, allocation concealment, or the reasons for the unequal arm sizes.
The study summary describes a proposed approach in which ovarian stimulation is followed by oocyte retrieval and vitrification, then later warming, fertilization, and embryo transfer after endometrial preparation. The record also says the study aimed to consider the stimulation protocol in this setting. It does not report participant-level adherence to these steps or how many proceeded to retrieval, vitrification, fertilization, or transfer.
The registry record lists a primary outcome of number of oocytes retrieved, measured over up to 24 months, and identifies number of oocytes vitrified as a secondary outcome. The record lists three outcome measures, but details for all of them are not reported in the posted results. No outcome analyses are listed. Thus, the design and arm-level outcome values can be described, but the record does not support a complete account of the trial’s analytic plan or all outcomes.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Clomiphene Plus Gonadotropins | Leuprolide Flare |
|---|---|---|
| STARTED | 8 | 15 |
| COMPLETED | 8 | 15 |
| NOT COMPLETED | 0 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Clomiphene Plus Gonadotropins | Leuprolide Flare | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 15 | 23 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 | 15 | 23 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 8 | 15 | 23 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Oocytes, measured over up to 24 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | oocytes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of oocytes retrieved, with the registry giving a timeframe of up to 24 months. This is a count outcome: it records the number of retrieved oocytes rather than a binary event or a time-to-event measure. The registry reports a value of 19 for clomiphene plus gonadotropins and 47 for Leuprolide flare. It does not report a measure of spread, a confidence interval, or an inferential comparison for these values.
Oocyte retrieval is relevant to the study’s stated IVF context because it records an outcome of ovarian stimulation and the retrieval procedure. It is not equivalent to fertilization, embryo transfer, pregnancy, or live birth. The study summary states an interest in live birth, but the posted primary endpoint is oocyte count. The registry record does not report a posted live-birth result among the outcome details.
Without participant-level counts or a description of how the arm values were summarized, the values cannot establish how oocyte counts varied among participants. In particular, a count reported for an arm does not by itself describe a typical participant’s result or the uncertainty around a between-arm effect. These distinctions matter when interpreting a count endpoint from a small pilot study.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports 19 oocytes for the clomiphene plus gonadotropins arm and 47 for the Leuprolide flare arm. These are the posted primary-outcome values. The record does not report dispersion, confidence intervals, a p-value, or another formal comparison for the two arms. It also does not clarify in the posted outcome details whether these values are totals or another arm-level summary. They should therefore be read as the registry’s reported values, not as a demonstrated difference in an individual participant’s expected outcome.
The arm sizes recorded for the primary outcome are 8 and 15, respectively. Unequal group sizes are relevant context for interpreting raw counts, but the registry record does not provide enough information to standardize or adjust the values. No rate, average per participant, ratio, or difference should be inferred from the posted values alone. A formal comparison would need a clearly specified outcome summary and appropriate information about variability.
The record lists no analyses. Consequently, it does not report whether any statistical model was used, whether the comparison was adjusted, or what inferential approach the investigators intended. It is also not possible from this record to judge whether the apparent arm-level separation is compatible with chance variation or to quantify its precision. The registry record does not report a confidence interval or other uncertainty measure for the primary outcome.
The broader study purpose includes live birth, but the primary result available in this record concerns oocytes retrieved. An oocyte count is an earlier point in the treatment pathway and cannot establish a live-birth effect. The registry also lists number of oocytes vitrified as a secondary outcome, but the posted details do not provide values for that outcome. The record does not report the subsequent treatment steps or outcomes needed to connect retrieval counts to live birth.
This study is identified as a pilot. Its small arm sizes and absence of a reported formal analysis make the posted counts descriptive rather than conclusive evidence about comparative effects. The registry record does not report a sample-size justification, a prespecified hypothesis test, or a confidence interval. Any planning illustration based on an observed effect is a hypothetical design calculation, not observed power and not evidence that a treatment is effective. The sponsor’s own analysis cannot be compared with a recalculation because no sponsor analysis is posted.
9. Statistical Methods Explained
Randomization is a design method intended to allocate participants to study arms by chance. In general, it can reduce systematic differences between groups at enrollment, although it does not guarantee that groups will be balanced, especially in a small study. The registry classifies this study as randomized, but the record does not report the sequence-generation method or allocation concealment. Those details are important for assessing how the random assignment was created and implemented.
The study is listed as open-label, with masking recorded as none. In general, an open-label design means that masking is not used to keep treatment assignment unknown to participants or study personnel. Lack of masking can matter for outcomes shaped by clinical decisions or subjective assessment. Oocyte count is a numerical outcome, but the registry record does not report whether outcome assessment was standardized or whether any protections against assessment bias were used.
The parallel-group model means participants are assigned to one study arm rather than being described as receiving both protocols in sequence. The record lists clomiphene plus gonadotropins and Leuprolide flare as the two arms. It does not report crossover, switching, or adherence information. The phase is recorded as phase 4; this classification alone does not supply details about the study’s analysis plan or the evidence it was designed to establish.
What does the count outcome represent?
A count outcome records how many events or items occur for an observation unit. Here, the endpoint is described as the number of oocytes retrieved. Count data can have a different distribution from measurements that vary continuously. Counts cannot fall below zero, and their variability may change with their average. A statistical method should therefore be suitable for the count’s distribution and the way the endpoint is summarized.
In general, a Poisson model assumes that the mean and variance of a count are linked in a particular way. When observed variability exceeds that assumption, over-dispersion may be present. Over-dispersion matters because a model that understates variability can produce intervals that are too narrow and tests that are too optimistic. Other models or robust uncertainty estimates may be appropriate depending on the data structure. The registry record does not report participant-level counts, a variance estimate, a model, or diagnostics, so it is not possible to assess these issues for this trial.
What can be said about precision?
A confidence interval is a range of values generated by a statistical procedure to express uncertainty about an estimated quantity. Its width depends on the information in the data and the method used. An interval around a between-arm contrast would help show which effect sizes are reasonably compatible with the observed data under the model. No such interval is reported for the primary outcome. Nor does the registry provide the spread needed to reconstruct one responsibly.
A p-value, when reported, describes how incompatible the data are with a specified null model under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. No p-value or test result is listed in the registry record. A formal conclusion about statistical significance is therefore unavailable from these posted results.
How should planning calculations be read?
Sample-size planning uses assumptions about an effect worth detecting, outcome variability, significance level, allocation, and the statistical method. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a chosen fraction of the observed effect. These are planning assumptions, not observed trial outcomes. Sample-size illustrations are hypothetical and should be described as participants per arm for a stated power, not as power achieved by this completed study.
Planning calculations depend on the effect estimate used as their starting point. When the underlying outcome comparison is not reported as an estimable two-arm analysis, those calculations cannot be treated as a reliable account of the evidence. The registry record does not report an analysis for the primary count outcome or a sample-size justification from the trial’s own design. A planning illustration cannot repair that absence, and it cannot establish that the study had adequate precision.
In general, recalculations from posted summary statistics are unadjusted and depend on the assumptions of the recalculation. They do not replace the investigators’ analysis, which could account for design details or prespecified methods not visible in the registry. No recalculated two-arm inference is reported for this endpoint. The registry record also lists zero analyses, so there is no sponsor-reported statistical analysis to set alongside the descriptive arm values.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures and identifies number of oocytes retrieved as primary and number of oocytes vitrified as secondary. The record does not report all outcome details in the posted results summarized for this analysis. It also does not report a multiplicity plan describing how inference across outcomes or other comparisons was to be handled. When several outcomes or tests are considered, the chance of at least one apparently unusual result can increase; methods for controlling or interpreting that issue depend on the prespecified analysis strategy. No such strategy is reported.
The registry record lists no analyses. It does not report a statistical analysis plan, a prespecified model, a hierarchy of secondary outcomes, or whether any interim analyses were planned or performed. These items are not reported in the registry record, so their absence from the record should not be interpreted as proof that investigators did not make such plans elsewhere.
The record does not report missing-data counts or how missing outcomes were handled. It does not identify an analysis population, such as an intention-to-treat or per-protocol population, and does not describe exclusions after randomization. Without those details, it is not possible to determine which participants contributed to each outcome or whether the posted arm values include all randomized participants.
The outcome timeframe is up to 24 months, but the registry does not report participant-level follow-up or whether all participants had complete observation through that timeframe. These omissions limit interpretation of the posted values and make it impossible to assess whether missingness could have affected a comparison. No assumptions about missing observations should be substituted for information that the registry does not report.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Clomiphene Plus Gonadotropins | 0 | 8 | 0.0% |
| Leuprolide Flare | 0 | 15 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Clomiphene Plus Gonadotropins | 0 of 8 |
| Leuprolide Flare | 0 of 15 |
The registry records zero serious adverse events in the clomiphene plus gonadotropins group, among 8 participants at risk, and zero in the Leuprolide flare group, among 15 participants at risk. It also records zero other adverse events in the respective groups. These are the posted event counts for the registry’s recorded risk groups. They describe what was entered in the record; they do not establish that no adverse events occurred outside the registry’s definitions, collection period, or reporting process.
The record does not report death counts. It also lists no serious adverse-event terms, so no event-specific description is available. Zero reported events in a small study does not establish that an event is impossible or that the treatments have equivalent safety. A comparison of safety would require adequate follow-up and a clear account of event definitions, ascertainment, and completeness, none of which is reported in the registry record.
These figures should be read as registry reporting, not as medical advice or a general safety conclusion. The registry record does not describe the duration of adverse-event monitoring or provide a detailed safety analysis.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry records oocyte-count values of 19 for clomiphene plus gonadotropins and 47 for Leuprolide flare, with primary-outcome group sizes of 8 and 15. They also establish that the registry lists the study as randomized, open-label, parallel-group, and completed. These statements describe the record, not a verified causal effect.
The results do not establish which protocol produces a higher number of oocytes for an individual participant. The registry does not clarify the arm-level summary represented by the values, provide variation among participants, or report a formal comparison. Without those details, the values cannot support an estimate of the size or precision of a between-arm effect. They should not be converted into a rate, mean, ratio, or difference.
The posted endpoint is oocyte retrieval, not live birth. Although the study summary describes live birth as a broader objective, the record does not report a live-birth result in the outcomes. Nor does the listed retrieval endpoint establish successful vitrification, fertilization, embryo transfer, pregnancy, or any later outcome. The registry lists oocytes vitrified as a secondary outcome, but its result is not reported in the posted outcome details.
The record does not report analyses, a statistical plan, confidence intervals, p-values, missing-data methods, or analysis populations. Consequently, the evidence available from the registry is descriptive and incomplete for judging comparative efficacy or precision. The trial’s pilot designation is consistent with treating the posted counts cautiously, but the registry record does not report the investigators’ specific rationale for the study size. No claim that either protocol works or does not work follows from these values alone.
13. Why This Trial Matters Statistically
This trial illustrates why a randomized design and a reported outcome value are not enough, by themselves, to support a comparative statistical conclusion. Randomization can help make arm comparisons interpretable, but readers also need a clear definition of the outcome summary, information about variability, and an analysis appropriate to the data. The registry identifies the design and posts arm-level values, yet does not report the comparison or its uncertainty.
The endpoint is a count, making the way its distribution is handled important. Count outcomes can show variability that is not captured by a simple normal approximation, and over-dispersion can affect standard errors and confidence intervals. Without participant-level results or a reported model, readers cannot evaluate whether the analysis addressed these features. The issue is not that one particular model must have been used; the registry record does not report which, if any, was used.
The difference between the study’s broader purpose and the posted primary endpoint also matters. The summary describes an interest in live birth, while the primary outcome listed in the registry is number of oocytes retrieved. These outcomes occupy different stages in the described IVF pathway and answer different questions. A result for retrieval cannot substitute for a result on live birth.
Finally, the record shows how incomplete reporting constrains secondary interpretation. The registry identifies a secondary outcome and lists safety event counts, but it does not provide a full analysis, uncertainty estimates, or detailed follow-up information. For biostatisticians and clinical researchers, this is a reminder to separate descriptive reporting from inferential evidence and to distinguish what a registry entry records from what it does not report.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The central limitation for statistical interpretation is that the registry reports primary-outcome values without a formal comparison or a measure of variability. It does not clarify the exact arm-level summary represented by 19 and 47. This prevents assessment of the distribution of participant-level counts and of the precision of any between-arm estimate.
The arm sizes are limited, with 8 participants recorded for clomiphene plus gonadotropins and 15 for Leuprolide flare. In a pilot study, such group sizes may leave estimates imprecise, but the registry does not report a confidence interval or a design justification that would quantify precision or explain the intended purpose of the enrollment. The record also does not report why allocation resulted in unequal arm sizes.
The registry lists no analyses and does not report methods for random sequence generation, allocation concealment, missing data, outcome assessment, or analysis populations. It does not report whether participants followed the described retrieval and vitrification pathway or whether subsequent treatment steps were completed. These gaps limit evaluation of both internal validity and the relationship between the primary outcome and the broader study objective.
The study summary discusses live birth, but the primary outcome posted is oocyte retrieval. The registry record does not provide a live-birth result among the outcome details. It also lists oocytes vitrified as a secondary outcome without reporting its result in those details. Safety reporting is limited to the recorded event counts, with no death counts or event terms reported. These limitations concern the information in the registry record and do not establish what may or may not have been collected elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Maximal Stimulation and Delayed Fertilization for Diminished Ovarian Reserve: a Randomized Pilot Study — NCT01921166.
- Registry record last updated 2024-08-02; status last verified 2021-06.
- Results first posted 2018-02-23.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT01921166 is a completed, randomized, open-label, parallel-group phase 4 pilot study sponsored by Wake Forest University Health Sciences. The registry records a start of 2011-01, primary completion of 2011-11, and enrollment of 23. The arms are clomiphene plus gonadotropins and Leuprolide flare.
The primary outcome is number of oocytes retrieved over up to 24 months. The registry reports values of 19 and 47 for the respective arms, with recorded primary-outcome group sizes of 8 and 15. It does not report dispersion or a formal comparison. Number of oocytes vitrified is listed as a secondary outcome, but its result is not reported in the posted outcome details. No analyses are listed.
Recorded serious and other adverse-event counts are zero in both groups; death counts are not reported. The registry record does not report a statistical analysis plan, missing-data methods, or analysis populations. The posted information supports a descriptive account of the study, not a precise estimate of comparative effects.