Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS) (NCT00805935), a randomized phase 4 study. The primary outcome is Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3.

2. Clinical Question

This is a question about a defined treatment-process outcome, not a direct measure of pregnancy or live birth. The registry lists pregnancy-related measures among secondary outcomes, including biochemical pregnancy, clinical pregnancy, and ongoing pregnancy. Their presence does not establish that results are available or that the study was designed to answer every question about IVF outcomes. The registry record calls the study exploratory and describes a multicenter randomized evaluation. Its primary focus, as registered, is cycle cancellation attributed to OHSS risk in the first weeks of the treatment cycle.

3. Trial Design

The registry describes a phase 4, multicenter, randomized, open-label, parallel study. It lists enrollment as 110 and status as completed. The recorded start is 2009-01, and primary completion is recorded as 2010-07. The brief summary describes the exploratory study as involving approximately 200 participants, which differs from the enrollment value in the record. The registry record does not explain that difference.

Participants were assigned to Menopur or Follistim for ovarian stimulation, with progesterone vaginal insert or progesterone in oil for luteal support. The arm descriptions therefore identify four treatment combinations. The brief summary says each center followed its standard IVF practice within study parameters and describes use of marketed products. It also describes scheduled clinic assessments, including laboratory measurements at specified points in the cycle, and a final study visit after luteal support or a negative serum pregnancy test following embryo transfer.

Open-label means the study was not masked, as confirmed by the registry's masking entry of none. In general, knowledge of treatment assignment can influence care decisions, assessment, or documentation, although the record does not establish that such influence occurred. Random allocation can help balance participant characteristics across groups, but the precise sequence-generation and allocation-concealment methods are not reported in the registry record.

The primary endpoint population is described as randomized participants who received at least one dose of study medication. The record does not provide arm-specific enrollment or explain how participants who did not receive a dose were handled in other analyses. It also does not report the protocol's sample-size justification, the planned statistical model, or whether any interim analyses were conducted.

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.

Before assignment: 127 patients were screened. 120 patients were randomized. Of the randomized patients, 10 did not receive treatment. 110 randomized participants started the study on treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intend-to-treat (ITT) population -- all randomized participants who received at least one dose of study medication

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.

6. Primary Endpoint

The registry lists the primary outcome as Participants With Cycle Cancellation Due to Risk of Ovarian Hyperstimulation Syndrome (OHSS) Between Weeks 1 - 3, measured over weeks 1-3.

The primary endpoint is the number of participants whose cycle was cancelled because of risk of ovarian hyperstimulation syndrome (OHSS) during weeks 1-3. The registry defines an event as a discontinuation clearly documented on a study completion or termination form as cycle cancellation for OHSS risk. This definition ties the count to a specific reason for stopping treatment, rather than to every discontinuation or every occurrence of OHSS.

In general, this kind of endpoint can describe a clinically important treatment-process consequence: a cycle may be stopped when the recorded risk is considered sufficient to cancel it. A count is straightforward to interpret as the number of people meeting the definition, but a count alone does not account for differences in group size. Comparative interpretation generally requires the group denominators and an estimate of the difference or other contrast, with uncertainty described as well.

The endpoint is restricted to the early treatment interval and to cancellations attributed to risk of OHSS. It should not be read as a count of all OHSS diagnoses, all adverse events, or all cycles that did not proceed for any reason. The registry record does not report the primary endpoint counts, group denominators for this endpoint, or a comparative estimate. The size and precision of the registered primary outcome therefore cannot be assessed from the reported record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary count represent?

The endpoint is a binary participant-level event summarized as a count: a participant either meets the recorded definition of cycle cancellation due to OHSS risk during weeks 1-3 or does not. In general, a binary outcome can be summarized with event counts and denominators, and compared using a difference in proportions, a ratio of proportions, or a model-based estimate. The choice depends on the prespecified analysis plan and the scientific question. The registry record does not report which comparative method was planned or used for the primary endpoint.

A count should not be interpreted without its denominator. For example, the same event count can represent different event frequencies in groups of different sizes. When there are few events, estimates can also be imprecise; a confidence interval helps communicate that uncertainty. No primary endpoint event counts, denominators, comparative effect estimate, or confidence interval are reported in the registry record, so none can be interpreted for this outcome.

What does randomization contribute?

In general, random assignment aims to make treatment groups comparable at the start of a trial, on average, for both measured and unmeasured characteristics. It supports a causal comparison when allocation, follow-up, and analysis are conducted appropriately. The record identifies the study as randomized and parallel, but does not report the sequence-generation method, allocation concealment, stratification factors, or specific procedures for maintaining the assigned groups. Those details are not reported in the registry record.

The record describes four combinations: each of the two stimulation treatments appears with each of the two listed luteal-support options. That structure raises distinct possible questions: a comparison of the stimulation drugs, a comparison of progesterone regimens, or an assessment of whether the effects of one treatment depend on the other. Which contrasts were planned, and whether the study was designed to estimate such effects separately, are not reported in the registry record. The existence of four arms does not alone establish a factorial analysis.

Why does open-label status matter?

In general, masking can reduce the chance that knowledge of assignment affects participant behavior, clinical management, outcome assessment, or recording. This trial is listed as having no masking. The primary endpoint depends on a cancellation decision and documentation of its reason. That makes consistent application of the recorded definition relevant. The registry does not report whether outcome adjudication was independent or whether the decision process was standardized across centers beyond the study parameters described in the brief summary.

How should p-values and confidence intervals be read?

In general, a p-value summarizes how unusual the data would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, nor does it describe the size or importance of an effect. A confidence interval gives a range of estimates compatible with the observed data under the method's assumptions and helps show precision. These measures are most useful alongside the actual group results and the analysis definition. Primary-outcome p-values and confidence intervals are not reported in the registry record.

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. These are assumptions for an illustration, not evidence of the trial's original design choices. The registry record does not report the trial's own sample-size justification. Planning sample sizes are not observed power, and they cannot supply an outcome result that is absent from the record.

What does over-dispersion mean in general?

For count outcomes, a statistical model may assume a particular relationship between the mean and variability of the counts. Over-dispersion occurs when the observed variability exceeds what that model assumes. If ignored, standard errors may be too small and uncertainty may be understated. This concept is relevant to some count-data analyses, but the primary endpoint is described as a participant count with a binary event definition. The registry does not report a model for the primary endpoint, so there is no basis to say that an over-dispersion adjustment was or was not used.

More generally, any analysis depends on how missing outcomes, protocol deviations, and treatment changes are handled. The endpoint population is specified as randomized participants who received at least one dose, but the registry does not describe missing-data methods, sensitivity analyses, or the statistical analysis plan. Those omissions limit assessment of how robust a numerical estimate would be even if one were reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and 4 analyses. It names secondary outcomes spanning ovarian response, laboratory and embryo measures, and pregnancy measures at specified time points. The primary outcome title also includes a defined time interval. The record does not report how the analyses map to individual outcomes, whether multiple comparisons were planned, or whether any adjustment for multiplicity was used.

In general, testing many outcomes or contrasts can increase the chance of at least one apparently unusual result arising by chance. Prespecifying a primary endpoint and distinguishing it from secondary or exploratory outcomes helps readers understand the evidential hierarchy. Here, the primary endpoint is identified, but the statistical plan for the other outcomes and any multiplicity strategy are not reported in the registry record. The study is described as exploratory, which makes clear that the registered study has an exploratory context, but does not specify how its results should be adjusted or interpreted.

The primary population is the ITT population, defined in the record as all randomized participants who received at least one dose of study medication. This definition does not include randomized participants who received no dose, as worded. The record does not state how many such participants there were, whether they were excluded from any other analysis, or whether additional analysis populations were used.

Missing-outcome counts, reasons for missingness, imputation procedures, and sensitivity analyses are not reported in the registry record. Nor are protocol deviations or the handling of participants who discontinued treatment described in enough detail to assess their effect on the analyses. The endpoint definition does specify that cancellation must be clearly documented as due to OHSS risk. The extent of incomplete or ambiguous documentation is not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: conjoined twins (3.7%).

The registry reports serious adverse event counts by treatment combination. For Menotropin/Progesterone Vaginal Insert, 0 of 25 participants were recorded as affected by a serious adverse event. For Menotropin/Progesterone in Oil, 1 of 27 was affected. For Follitropin Beta/Progesterone Vaginal Insert, 0 of 28 were affected. For Follitropin Beta/Progesterone in Oil, 0 of 30 were affected. These are participant counts and the corresponding numbers at risk as recorded; they are not comparative estimates adjusted for other factors.

For other, non-serious adverse events, the registry records 9 of 25, 11 of 27, 15 of 28, and 14 of 30 participants affected, respectively, in those same arm orderings. These counts do not describe event severity beyond the registry's serious versus other categorization, and the record does not provide event-level detail for each group in the information.

The registry lists “Conjoined Twins” among the top serious adverse event terms and gives 3.7%. It does not provide the event count or an arm assignment for that term in the information. Death counts are not reported in the registry record. In general, adverse-event counts describe what was recorded among participants at risk; differences in group size, follow-up, and event ascertainment affect interpretation. These figures alone do not establish that a treatment caused an event or that treatments differ in safety.

12. What the Result Does, and Does Not, Mean

The registry record identifies an exploratory randomized comparison of Menopur and Follistim stimulation regimens in participants with PCOS undergoing IVF. It specifies cycle cancellation due to OHSS risk during weeks 1-3 as the primary endpoint and defines the event in terms of documented cancellation. This describes the question the study set out to address, not the result of that comparison.

The primary endpoint findings are not reported in the registry record. Without group counts and denominators, readers cannot tell how often cancellation occurred in each group. Without a comparative estimate and a measure of uncertainty, readers cannot assess the direction, size, or precision of a difference. The record therefore does not support a conclusion that one stimulation regimen had more or fewer such cancellations than another.

The same distinction applies to the registered secondary outcomes. Their names indicate that the study considered follicular response, oocyte and embryo outcomes, and pregnancy measures. The registry record does not report those results here, so their relative patterns cannot be characterized. The adverse-event counts are available, but they are descriptive counts across four treatment combinations; they do not, by themselves, establish causation or a treatment advantage.

In general, a trial result is most informative when the outcome definition, analysis population, group denominators, effect estimate, and uncertainty are considered together. A statistically detectable difference would not automatically establish that the difference is important, and a result that is not statistically detectable would not establish equivalence. No such comparative result is reported for the primary endpoint in this record.

The appropriate conclusion is narrow: the registry describes the design, treatment combinations, primary endpoint, and some safety counts, but does not report the primary efficacy result needed to answer its central comparative question. The record also does not report the statistical analysis plan, so it cannot clarify the methods used to produce a primary comparison.

13. Why This Trial Matters Statistically

This trial is statistically notable for its combination of a randomized comparison and a decision-based primary endpoint. Randomization can support a fair treatment comparison, while the endpoint depends on a clinical decision and its documentation. In general, that makes the endpoint definition, consistency of decisions across centers, and completeness of records important to interpreting any observed count. The registry provides a definition centered on clearly documented cancellation for OHSS risk, but does not report further adjudication or analysis details.

The four listed treatment combinations also create more than one possible comparison. Menopur and Follistim are each paired with two luteal-support options. Statistically, comparisons across those combinations can address different questions, and the number of outcomes and analyses raises questions about which contrasts were primary and how multiplicity was handled. The registry identifies the primary endpoint but does not report the planned contrast structure or multiplicity approach.

The study is described as exploratory, and the registry contains a mismatch between enrollment of 110 and the brief summary's approximately 200 participants. Such differences highlight why denominators and participant flow matter in clinical trial interpretation. The record does not explain the mismatch or provide the primary endpoint results needed to connect enrollment to the analysis population.

More broadly, this record illustrates a key distinction in biostatistical reporting: a defined design and endpoint are not substitutes for outcome estimates. Without group-specific primary outcome data and uncertainty, the central treatment comparison cannot be evaluated. That limitation is especially important when readers might otherwise infer a result from the trial title or from the presence of registered outcomes.

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 most consequential limitation for interpreting this study is that the primary endpoint results are not reported in the registry record. The record gives neither group-specific counts nor denominators for cycle cancellation due to OHSS risk, and it does not give an effect estimate or measure of uncertainty. The trial's central comparison therefore cannot be evaluated from the reported primary outcome information.

There is a discrepancy between the registry's enrollment value of 110 and the brief summary's description of approximately 200 participants. The registry record does not explain whether these figures refer to different stages or definitions of enrollment. Arm-specific enrollment and participant flow are not reported in the information, limiting assessment of how the recorded safety counts relate to the primary analysis population.

The study is open-label, and the primary endpoint depends on a cancellation decision and documentation of its reason. In general, an unmasked decision-based outcome can be susceptible to variation in management or recording. The record does not report blinded adjudication, center-level consistency checks, or further safeguards that would clarify this concern.

The statistical analysis plan, sample-size justification, missing-data procedures, interim analyses, and multiplicity strategy are not reported in the registry record. The record lists 14 outcome measures and 4 analyses, but does not explain the analysis-to-outcome mapping or how multiple comparisons were handled. As a result, the planned inferential framework cannot be reconstructed from the registry information.

The brief summary describes center-specific standard IVF practice within study parameters. The record does not provide detailed center-level procedures or results, so variation across centers cannot be assessed. The treatment descriptions also have truncated details for some luteal-support regimens. These gaps constrain interpretation of the precise treatment implementation. They do not establish that these limitations affected outcomes, but they prevent a fuller assessment of design and analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Menopur® Versus Follistim® in Polycystic Ovarian Syndrome (PCOS) — NCT00805935.
• Registry record last updated 2012-01-27; status last verified 2012-01.
• Results first posted 2012-01-25.
• 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.

18. Record Summary

The registry describes NCT00805935 as a completed, multicenter, randomized, open-label phase 4 parallel study comparing Menopur and Follistim stimulation strategies in participants with PCOS undergoing IVF. The treatment combinations include progesterone vaginal insert or progesterone in oil for luteal support. Enrollment is listed as 110; the brief summary describes approximately 200 participants, and the record does not explain the difference.

The primary endpoint is the number of participants with cycle cancellation due to OHSS risk during weeks 1-3, in an ITT population defined as randomized participants who received at least one study-medication dose. The primary endpoint results and comparative statistical estimates are not reported in the registry record. Safety counts are reported for serious and other adverse events across four arm combinations; death counts are not reported. The statistical analysis plan, missing-data methods, and multiplicity strategy are also not reported.