A Trial to Compare the Ovarian Response of REKOVELLE and GONAL-F in Conventional Dosing in Women Undergoing Controlled Ovarian Stimulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Compare the Ovarian Response of REKOVELLE and GONAL-F in Conventional Dosing in Women Undergoing Controlled Ovarian Stimulation (NCT05263388), a randomized phase 3 study. The primary outcome is Number of Oocytes Retrieved.

2. Clinical Question

The clinical question concerns ovarian response during stimulation, not a direct comparison of pregnancy or other later assisted-reproduction outcomes. Oocyte retrieval is the trial’s primary endpoint, and several additional outcomes are listed, including follicle measures, hormone concentrations, fertilized oocytes, fertilization rate, blastocysts, and total gonadotropin dose. Numerical results for those secondary outcomes are not reported in the registry record summarized by these results.

The trial is described as randomized, controlled, assessor-blind, and parallel-group. Random allocation is intended to make treatment groups comparable on average, while assessor blinding can reduce the chance that knowledge of treatment assignment influences outcome assessment. Those design features do not, by themselves, establish that the reported group summaries differ statistically or that any observed difference would be clinically important.

3. Trial Design

This was a phase 3, randomized, controlled, assessor-blind, parallel-group trial. The registry describes it as multicentre and multinational. It compared a conventional starting dose of REKOVELLE (follitropin delta) with a conventional starting dose of GONAL-F (follitropin alfa) in women undergoing controlled ovarian stimulation for an assisted reproductive technology programme. The trial condition is listed as infertility.

The registry reports overall enrollment of 302. The primary-outcome arm summaries list 200.0 participants for REKOVELLE and 100.0 for GONAL-F. These figures are presented as recorded; the registry record does not explain the difference between the overall enrollment figure and the arm counts shown with the primary outcome. It also does not report whether these outcome counts reflect all randomized participants, participants who received treatment, or a defined analysis population.

The trial started on 2022-07-15, reached primary completion on 2024-04-16, and is recorded as completed. The primary outcome is the number of oocytes retrieved, assessed on the day of oocyte retrieval, up to 22 days after stimulation began. The registry describes the reported summary as a median with an interquartile range.

Randomization and an assessor-blind design address different sources of bias: randomization assigns treatment by chance, while assessor blinding limits the influence of treatment knowledge during assessment. The registry does not report the randomization procedure, allocation concealment, which assessors were blinded, or how blinding was maintained. Further details of the protocol and statistical analysis plan are not reported in the registry record. The record lists the sponsor as Ferring Pharmaceuticals.

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

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 Number of Oocytes Retrieved, measured over On day of oocyte retrieval (Up to 22 days after start of stimulation).

The primary endpoint is the number of oocytes retrieved at the oocyte retrieval visit. Oocytes are collected after ovarian stimulation, so this count describes an ovarian response during the treatment cycle. The registry specifies measurement on the retrieval day, up to 22 days after stimulation began.

This endpoint is useful for comparing the ovarian response associated with the two stimulation regimens. A count can be skewed, with some participants having substantially higher or lower values than the middle of the distribution. The registry therefore reports the median and interquartile range rather than a mean and standard deviation. In general, the median is the middle of the ordered observations, and the interquartile range describes the central half of the distribution. These summaries describe the observed groups; they do not alone establish whether the groups differ beyond what might arise from sampling variation.

The median number of oocytes retrieved was 9.0 in each group. The interquartile range was 6.0 to 13.5 for REKOVELLE and 6.5 to 13.0 for GONAL-F. No confidence interval, hypothesis-test result, or adjusted estimate for the primary comparison is reported in the registry record. The primary outcome’s analysis population is also not specified there.

Oocyte count is not the same as fertilization, embryo development, pregnancy, or live birth. Those are different outcomes, and the registry lists some related secondary measures but does not report numerical results for them in this record. The endpoint should therefore be read as a measure of the number of oocytes retrieved, not as a summary of every step or outcome in assisted reproduction.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the median and interquartile range describe?

The median is a measure of location: after observations are ordered, it marks the central observation or the midpoint between central observations. It is less affected by unusually high or low values than the mean. The interquartile range describes the middle half of the observed distribution, bounded by its lower and upper quartiles. In general, reporting both the median and interquartile range gives readers information about a typical value and the spread of central observations, while leaving the tails and individual values unspecified.

For oocytes retrieved, the registry reports a median of 9.0 in each group. The REKOVELLE interquartile range is 6.0 to 13.5, and the GONAL-F interquartile range is 6.5 to 13.0. These summaries are not a complete description of the distributions. They do not tell readers how many participants had values beyond the quartiles, whether the distributions have different shapes, or how uncertain the medians are. Those questions would require additional results or an analysis not reported in the record.

Why is a comparison test important?

A descriptive contrast and an inferential comparison serve different purposes. Descriptive statistics summarize the observed data. An inferential method estimates how compatible an observed contrast is with variation that could arise from sampling, under specified assumptions. A p-value, confidence interval, or estimated effect with uncertainty could contribute to that assessment. None is reported for the primary outcome in the registry record.

In general, a p-value is interpreted in relation to a prespecified hypothesis and analysis; it is not the probability that a treatment is effective or ineffective. A confidence interval conveys uncertainty around an estimate, but its interpretation depends on the model and assumptions used. Neither type of result can be reconstructed from the medians and interquartile ranges alone without making additional assumptions. No such recalculation is reported.

What does randomization contribute?

Randomization assigns participants to treatment groups by chance. In general, this helps limit systematic differences in baseline characteristics between groups and supports a fair comparison, especially when the assignment process is implemented as intended. It does not guarantee identical groups, remove every source of bias, or compensate for missing outcomes or departures from the planned analysis. The registry identifies the trial as randomized but does not report the sequence-generation method or allocation-concealment details.

The record also describes the trial as assessor-blind. Blinding outcome assessors can reduce the influence of knowledge about treatment assignment on assessment. The registry does not specify which assessors were blinded or how the masking was maintained. These details matter when assessing how the design was carried out, but should not be inferred from the label alone.

How should the posted planning illustration be read?

The registry record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustrations use a stated fraction of the observed effect as the effect to detect. In general, such calculations show how a hypothetical future study’s required sample size can vary with the effect chosen, the desired power, and the analysis assumptions.

These are planning illustrations, not observed power and not a description of the actual trial’s design justification. They do not establish that the trial was designed around those assumptions. The registry does not report the trial’s own sample-size justification or statistical plan. No numerical planning estimates are stated in this explanatory text.

Why can count outcomes need special care?

Oocyte counts are nonnegative counts. In general, count data may be skewed and their variability may differ from what a simple normal model assumes. Over-dispersion means the data vary more than a model’s assumed distribution would predict; if ignored, uncertainty estimates can be misleading. This is a general consideration for count outcomes, not a claim that over-dispersion occurred in this trial. The registry does not report a model, diagnostic assessment, or comparison method for the primary endpoint, so the analysis approach cannot be evaluated from the record.

Because the posted summary is a median and interquartile range, it is important not to treat it as a mean difference or to assume a particular model. A suitable comparison could depend on the distribution, the estimand of interest, and the analysis plan. Those details are not reported in the registry record. The descriptive summaries remain interpretable as summaries, but they do not supply a model-based estimate or its precision.

What can be concluded from the available analysis record?

The registry reports zero analysis records. That means the record does not include a documented inferential analysis for this endpoint in the information described. It does not establish that no analysis was performed outside the registry; such an analysis is simply not reported in the registry record. The distinction is important: readers can state the posted medians and interquartile ranges, but should not attach an unreported p-value, confidence interval, adjusted estimate, or conclusion about statistical significance to them.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures in total and 10 secondary outcomes. The secondary outcomes cover follicle number and size, estradiol and progesterone concentrations, fertilized oocytes, fertilization rate, blastocysts and good quality blastocysts, and total gonadotropin dose. Numerical results for these secondary measures are not reported in the registry record.

When a study examines multiple outcomes or performs multiple comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control that risk or prioritize a smaller set of prespecified questions. The registry record does not report whether a multiplicity adjustment was planned or used, how outcome priority was handled, or which comparisons were included in any inferential analysis. No inferential analysis records are listed, so the record does not permit an assessment of multiplicity in the results.

Missing-data handling is not reported in the registry record. The primary outcome’s population field is blank, and the record does not state whether participants with no recorded retrieval outcome were excluded, how missing outcomes were treated, or whether any sensitivity analyses were conducted. The arm counts attached to the primary summaries are 200.0 for REKOVELLE and 100.0 for GONAL-F; the registry does not explain how those counts relate to overall enrollment of 302 or define the analysis population.

The registry also does not report whether the primary comparison was based on intention-to-treat, per-protocol, or another analysis population. These are not interchangeable choices: in general, an analysis population defines which participants contribute to an estimate and can affect its interpretation. Without the population definition, missing-data approach, and statistical plan, the completeness and robustness of the primary comparison cannot be assessed from the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: haemoperitoneum (2.0%).

The registry reports serious adverse events affecting 0 participants in the REKOVELLE group, with 200 at risk, and 2 participants in the GONAL-F group, with 100 at risk. It records 0 deaths in each group. The listed top serious adverse event term is haemoperitoneum, reported as 2.0%. The registry does not identify that term’s group in the information, so it should not be assigned to either group on that basis.

These are event counts and recorded denominators, not an adjusted comparison. In general, counts need to be interpreted in light of the number at risk, how events were defined and collected, and the period of observation. A difference in raw counts does not by itself show that the underlying risks differ. The registry record does not report a statistical comparison, confidence interval, or detailed timing for the serious adverse event results.

The record separately reports other adverse events affecting 24 participants in the REKOVELLE group, with 200 at risk, and 11 in the GONAL-F group, with 100 at risk. These figures should not be conflated with serious adverse events. The registry does not provide enough detail in this record to interpret event severity beyond the categories reported or to determine whether events were related to treatment.

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

The primary result describes the number of oocytes retrieved in the two trial groups. Both groups have a reported median of 9.0. The interquartile range is 6.0 to 13.5 for REKOVELLE and 6.5 to 13.0 for GONAL-F. Those values provide a concise account of the central outcome distributions, but they do not show every participant’s result or describe the full distribution.

The result does not establish that the treatments are equivalent. Equivalence is a specific statistical question that requires an appropriate margin and analysis; neither is reported in the registry record. Nor does an equal median establish non-inferiority, superiority, or the absence of a meaningful difference. A formal comparison with an estimate and its uncertainty would be needed to evaluate such claims, and none is reported for the primary outcome.

The registry record also does not report numerical findings for the listed secondary outcomes. Therefore, the primary oocyte-count summaries cannot answer questions about follicle measures, hormones, fertilization, blastocysts, or total gonadotropin dose. Oocyte retrieval is an intermediate measure in an assisted reproductive technology programme, not a direct report of pregnancy or live birth. The record’s stated outcome should not be interpreted as evidence about those later outcomes.

The trial’s randomized and assessor-blind design describes intended features that can support a comparison, but the registry record does not provide enough detail to assess all implementation issues. It does not report the primary analysis method, the analysis population, missing-data handling, or inferential results. Overall enrollment is reported as 302, while primary-outcome arm counts are 200.0 and 100.0; the relationship between these figures is not explained.

The careful conclusion is descriptive: the posted medians are the same, and the posted interquartile ranges are as stated. The record does not quantify uncertainty around a treatment contrast or support a claim that the regimens produce identical responses. It also does not provide the additional outcome or safety analyses needed to address broader clinical questions. This interpretation concerns the registry record and should not be extended beyond the outcomes and details it reports.

13. Why This Trial Matters Statistically

This trial illustrates why descriptive summaries and comparative inference should be kept distinct. The primary outcome is presented with medians and interquartile ranges, which describe the observed center and spread. The two medians are both 9.0, but that fact alone is not a test of whether the groups differ. Without an estimated contrast and a measure of uncertainty, readers cannot judge how precisely the group comparison has been made.

It also illustrates the importance of matching an analysis to an outcome. Oocyte retrieval is a count, and count outcomes can have distributions that differ from a simple bell-shaped pattern. In general, analysts consider the outcome’s distribution, the target comparison, and the assumptions of candidate methods before selecting an approach. The registry does not report the analysis method, so readers cannot assess those choices or the robustness of the result to them.

Transparent reporting of analysis populations and missing-data procedures is also important. The record gives an overall enrollment figure and arm counts for the primary summary but does not explain their relationship or identify the analyzed population. Without that information, the scope of the descriptive result is less clear. Reporting the planned population, outcome availability, and handling of missing values would help readers understand precisely which data underlie a comparison.

Finally, the record lists multiple outcomes but does not report numerical secondary results or a multiplicity approach. In general, a clear hierarchy of outcomes and a prespecified analysis plan help readers distinguish confirmatory questions from exploratory ones. The planning assumptions described in the record are explicitly an illustration based on an observed effect; they are not evidence of the trial’s original design rationale or observed power.

The statistical lesson is not that a particular treatment should be selected. It is that a trial’s design labels and descriptive summaries do not replace an interpretable analysis with defined populations, methods, estimates, and uncertainty. Those details are necessary to move from describing observed data to evaluating a comparative claim.

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 primary outcome is reported only through a median and interquartile range. No inferential comparison, confidence interval, or model-based estimate is reported in the registry record. This prevents an assessment of the precision of the between-group comparison and does not support a conclusion about statistical significance, equivalence, or non-inferiority.

The primary analysis population is not specified. The record gives overall enrollment of 302 and primary-outcome arm counts of 200.0 for REKOVELLE and 100.0 for GONAL-F, but does not explain how those figures relate or identify who contributed data. Missing outcome handling, exclusions, and sensitivity analyses are not reported. These gaps limit assessment of how representative the summaries are of the randomized groups.

The registry does not report the statistical method used for the primary outcome, the analysis plan, randomization details, allocation concealment, or the specific arrangements for assessor blinding. It also does not report a sample-size justification for the trial. Planning illustrations based on an observed effect are not a substitute for the trial’s own design rationale.

Although several secondary outcomes are listed, their numerical results are not reported in this registry record. The record also does not describe how multiplicity was addressed. Safety results are given as counts, but the record does not provide an inferential comparison or enough detail to interpret the timing and treatment relationship of events. These limitations are specific to what the registry record reports; they do not establish what may be available in other trial documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Trial to Compare the Ovarian Response of REKOVELLE and GONAL-F in Conventional Dosing in Women Undergoing Controlled Ovarian Stimulation — NCT05263388.
• Registry record last updated 2025-04-02; status last verified 2025-03.
• Results first posted 2025-04-02.
• 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

NCT05263388 is a completed phase 3 randomized, controlled, assessor-blind, parallel-group trial sponsored by Ferring Pharmaceuticals. It studied women with infertility undergoing controlled ovarian stimulation for an assisted reproductive technology programme, comparing REKOVELLE (follitropin delta) starting at 15 µg with GONAL-F (follitropin alfa) starting at 225 IU.

The registry reports enrollment of 302. The primary outcome was number of oocytes retrieved on the retrieval day, up to 22 days after stimulation began. The median was 9.0 in each group; the interquartile ranges were 6.0 to 13.5 for REKOVELLE and 6.5 to 13.0 for GONAL-F. No inferential comparison or confidence interval is reported for this outcome.

The trial started on 2022-07-15 and reached primary completion on 2024-04-16. The registry lists secondary outcomes but does not report their numerical results in this record. Analysis population, missing-data handling, and the statistical plan are not reported.