Triggering of Final Oocyte Maturation With GnRHa (Buserelin) in GnRH Antagonist Cycles: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Triggering of Final Oocyte Maturation With GnRHa (Buserelin) in GnRH Antagonist Cycles (NCT00627406), a randomized phase 4 study. The primary outcome is Frequency of Moderate to Severe OHSS..

2. Clinical Question

The study concerns final oocyte maturation in GnRH antagonist IVF/ICSI cycles. The registry describes the aim as exploring OHSS incidence and possibly improving clinical outcome among patients whose final oocyte maturation was triggered with Buserelin and Pregnyl. The trial separates participants into follicle-count groups, then compares trigger regimens within those groups. This distinction matters: the regimens are not identical across all four arms, and the number of follicles defines which regimen a participant receives.

For participants with more than 14 follicles over 11 mm, one regimen combined 0.5 mg Buserelin with 1500 IU Pregnyl, while the comparator used 5.000 IU Pregnyl. For participants with 14 or fewer follicles over 11 mm, the combined regimen included 0.5 mg Buserelin and 1500 IU Pregnyl at 35 hours, followed by another 1500 IU Pregnyl 7 days after triggering; the comparator used 5000 IU Pregnyl. The registry's arm labels abbreviate these details, so the full arm descriptions are needed to understand the intervention distinction.

The primary endpoint is the number of participants with moderate-to-severe OHSS. Pregnancy rate is the sole posted secondary outcome. These outcomes address different aspects of the study question: the primary endpoint concerns OHSS, while pregnancy rate provides a separate clinical outcome measure. The registry record does not report a formal power calculation, and its description of the primary outcome states that no power calculation was performed.

3. Trial Design

The registry describes a prospective, randomized, parallel-group study with no masking. It lists 384 participants as enrolled and records the study status as completed. The listed phase is Phase 4. The sponsor is Regionshospitalet Viborg, Skive. The recorded study start is 2009-01 and primary completion is 2011-12.

Participants were assigned to one of four arms defined by follicle count and trigger regimen. In the higher-follicle group, arm A used Buserelin plus 1500 IU Pregnyl and arm B used Pregnyl alone. In the lower-follicle group, arm C used Buserelin plus Pregnyl with a further Pregnyl dose after triggering, and arm D used Pregnyl alone. The arm descriptions use the threshold of more than 14 follicles over 11 mm for the higher group and 14 or fewer for the lower group. The results labels use somewhat different shorthand, including “<15 Follicles”; the detailed descriptions clarify the intended grouping.

The posted primary outcome counts are 0 among 60 participants in arm A, 2 among 58 in arm B, 2 among 125 in arm C, and 0 among 141 in arm D. The listed secondary outcome, pregnancy rate, has results for all four arms. These counts should be interpreted in light of the study's allocation structure: the regimen comparisons of clinical interest are within the follicle-count strata, whereas the posted comparison estimates use arm A as the reference for each listed arm. As a result, the displayed comparisons do not all represent a direct comparison between the two trigger regimens within the same follicle-count group.

Allocation is recorded as randomized, but details of sequence generation, concealment, adherence, participant flow, and analysis population are not reported in the registry record. The record also does not report a detailed statistical analysis plan, protocol deviations, or an explanation of how the different trigger schedules were assigned. No assumptions about these matters can be drawn from the posted information.

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

Analysis population for the primary outcome, as defined in the registry: No power calculation was proformed.

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 Frequency of Moderate to Severe OHSS., measured over From the date of triggering ovulation until 2 weeks after pregnancy test. group C and D. 12 days after pregnancy test.

The primary endpoint is the frequency of moderate-to-severe OHSS, expressed as the number of participants with the event. OHSS is the condition named in the study record, and its occurrence is the main safety-related outcome being assessed. Counting affected participants makes the measure directly interpretable as an event count within each arm. It does not, by itself, describe severity beyond the registry's moderate-to-severe classification, duration, treatment, or consequences.

The recorded timeframe begins on the date of triggering ovulation and continues until 2 weeks after the pregnancy test. For groups C and D, the timeframe additionally states 12 days after the pregnancy test. This wording is not fully clear about how the group-specific period relates to the general timeframe, and the registry record does not explain the distinction further.

OHSS is used as the primary endpoint because the study's stated purpose includes exploring its incidence under the different trigger approaches. An endpoint should be considered in the context of its definition and observation period: events outside the stated period, or events not meeting the moderate-to-severe classification, are not represented by the posted primary counts. The registry gives no further diagnostic criteria, adjudication procedure, or detail on how severity was determined. It therefore supports interpretation of the reported event counts, but not a more detailed assessment of event ascertainment.

The primary results contain few events: the recorded counts are 0, 2, 2, and 0 across the four arms. Sparse events limit the amount of information available for comparing event frequencies. In particular, an arm with no recorded events does not establish that the underlying event risk is zero; it indicates only that no events were recorded among the participants listed for that arm during the specified follow-up.

7. Results Posted in the Registry

• B: >14 Follicles; hCG Trigger: 3.4% (2/58) versus 0.0% (0/60) on control; risk difference 3.4 percentage points (95% CI -1.2 to 8.1); unadjusted two-proportion z-test p = 0.147.
• C:<15 Follicles; GnRHa Trigger + 1500 hCG x 2: 1.6% (2/125) versus 0.0% (0/60) on control; risk difference 1.6 percentage points (95% CI -0.6 to 3.8); unadjusted two-proportion z-test p = 0.325.
• D: <15 Follicles; hCG Trigger: 0.0% (0/141) versus 0.0% (0/60) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Pregnancy Rate

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • B: >14 Follicles; hCG Trigger: 25.9% (15/58) versus 28.3% (17/60) on control; risk difference -2.5 percentage points (95% CI -18.5 to 13.6), risk ratio 0.91 (0.50–1.65); unadjusted two-proportion z-test p = 0.763.
  • C:<15 Follicles; GnRHa Trigger + 1500 hCG x 2: 29.6% (37/125) versus 28.3% (17/60) on control; risk difference 1.3 percentage points (95% CI -12.7 to 15.2), risk ratio 1.04 (0.64–1.70); unadjusted two-proportion z-test p = 0.859.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B: >14 Follicles; hCG Trigger and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C:<15 Follicles; GnRHa Trigger + 1500 hCG x 2 and the control. The interval gives the range of effects that remain compatible with the data.

Pregnancy rate is the one posted secondary endpoint. Across the arm comparisons, the estimated directions are not uniform: the comparison with arm B points one way relative to arm A, while the comparison with arm C points the other way. The registry's posted intervals are broad and include no difference. The overall pattern therefore does not provide a stable or precise signal that can resolve the primary OHSS question.

The secondary outcome is relevant because the registry describes a broader interest in clinical outcome as well as OHSS incidence. However, pregnancy rate and moderate-to-severe OHSS are distinct outcomes. A pattern in pregnancy estimates cannot be used as a substitute for the primary safety-related endpoint, and the primary event counts do not determine the pregnancy findings. The results should be considered separately, with attention to the fact that pregnancy rate was designated secondary.

Unadjusted secondary results carry less weight for confirmatory interpretation for several reasons. Multiple outcomes and comparisons create opportunities for apparently notable findings to arise by chance. The registry does not report a multiplicity strategy, a hierarchy of secondary hypotheses, or a confirmatory analysis plan. The posted p-values are unadjusted, and the registry lists no reported analyses. Accordingly, a nominal result from an individual secondary comparison would not, on its own, establish a reliable treatment effect.

The registry record also does not report missing-data methods, analysis populations, or covariate adjustments for pregnancy rate. The observed counts remain descriptive of the participants included in the posted results, but the record does not explain whether every randomized participant contributed to the endpoint. The most appropriate reading is that the secondary outcome adds context, while its imprecise comparisons and unreported analysis details prevent strong conclusions or a reinterpretation of the primary result.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Pregnancy Rate

9. Statistical Interpretation

10. Statistical Methods Explained

Several statistical ideas help put the reported counts and comparisons in context. The outcome is binary at the participant level: each person either had a recorded moderate-to-severe OHSS event during the stated follow-up or did not. The registry reports numbers of participants with the event, rather than a continuous measurement such as a laboratory value. For this kind of outcome, a risk difference expresses the difference between the event proportions in two groups. Positive and negative values indicate opposite directions according to the comparison's reference ordering; a value of zero represents no estimated difference.

What does randomization contribute?

Random assignment can make groups comparable on average with respect to both measured and unmeasured characteristics, supporting a causal comparison when the randomized groups are analyzed as assigned and other design requirements are met. Randomization does not guarantee that every group will be identical, especially when event counts are sparse. The registry identifies the study as randomized but does not report sequence generation, allocation concealment, adherence, or a detailed analysis population. Those details are therefore not available for evaluating how fully the randomized design was implemented or preserved.

There are four arms because the intended trigger regimen depends on the follicle-count group. The natural regimen comparisons are within each stratum: A versus B for the group with more than 14 follicles over 11 mm, and C versus D for the group with 14 or fewer. This is a stratified clinical question, not simply a comparison of all participants receiving one broad treatment versus all participants receiving another. The posted comparison estimates instead use arm A as the reference for B, C, and D. That choice means the estimates involving C and D combine differences in follicle group with differences in regimen. They are not equivalent to a direct randomized comparison between C and D.

What do the p-values and confidence intervals convey?

A p-value measures how incompatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it quantify the size or clinical importance of a difference. The posted p-values are unadjusted. They are therefore individual comparison results and do not account for the possibility of examining multiple outcomes or comparisons.

A confidence interval describes a range of estimates that are reasonably compatible with the data and the method used, under repeated-sampling assumptions. A broad interval reflects limited precision. For rare binary events, few observed events can make comparisons particularly uncertain. When an interval includes zero for a risk difference, the data are compatible with no difference as well as with differences on either side of zero. This does not prove equivalence. A formal equivalence conclusion would require an appropriate design and a prespecified margin, neither of which is reported in the registry record.

Arm D has no recorded primary events, as does reference arm A. The posted difference is consequently zero, and its interval is also given as zero. A zero-width interval in this setting should not be read as certainty about the underlying event risks. It reflects the posted calculation for two groups with zero recorded events; the registry does not provide methodological detail explaining this handling. The event counts themselves show that the comparison has little direct event information.

How should the secondary-outcome results be read?

Pregnancy rate is a binary secondary outcome, reported as participant counts. Its comparison estimates include risk differences, confidence intervals, risk ratios, odds ratios, and unadjusted p-values. These are alternative ways to express an association between groups, not separate independent outcomes. A risk ratio compares event proportions as a ratio; an odds ratio compares event odds. Both may be less intuitive than a risk difference, and neither removes uncertainty arising from the observed sample and event counts.

The registry reports no formal analyses for the primary or secondary outcome. Thus the posted estimates should not be assumed to be adjusted for baseline characteristics, stratification factors, or other covariates. The record does not describe imputation, missing-data handling, a per-protocol analysis, or an intention-to-treat analysis. It also does not report whether all randomized participants were included in each endpoint analysis. These omissions limit assessment of the validity and reproducibility of the estimates.

What do the planning illustrations mean?

The registry explicitly states that no power calculation was performed for the trial. The separate sample-size illustrations are planning calculations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For example, for the pregnancy comparison between arm A and arm B, the illustration gives 5,077 participants per arm for 80% power when planning for 100% of the observed effect, and 9,091 participants per arm for 80% power when planning for 75% of the observed effect. These are hypothetical planning values, not the size or power of the completed trial. They are sensitive to the observed effect used as the starting point, and they do not supply a retrospective measure of what the trial could detect. The record's own statement that no power calculation was performed remains distinct from these later planning illustrations.

For both outcomes, statistical interpretation should therefore start with the observed counts and the exact comparison definition, then consider interval width and analysis limitations. General statistical principles cannot substitute for unreported protocol details or for an analysis that directly answers the within-stratum randomized comparisons.

11. Confidence Intervals and Precision

Precision is limited for the primary endpoint because only four moderate-to-severe OHSS events are recorded across all arms. The nonzero risk-difference estimates are accompanied by confidence intervals that include zero. For arm B versus arm A, the interval runs from -0.013 to 0.081; for arm C versus arm A, it runs from -0.006 to 0.038. These ranges are compatible with no estimated difference and with effects in either direction. They do not identify a narrow range of plausible values.

The zero estimate and zero-width interval reported for arm D versus arm A need special caution. Both arms had zero recorded events, so the data contain no observed event contrast. A reported point estimate of zero in this circumstance should not be interpreted as precise knowledge that the underlying risks are equal. The registry record does not describe the interval method or provide an alternative estimate for this sparse-event comparison.

Confidence intervals convey uncertainty about the estimate, not the chance that an individual participant will experience an event. Nor do they account automatically for all sources of uncertainty, such as missing outcome data, deviations from assigned treatment, or differences in endpoint ascertainment. The registry record does not report enough detail to assess those issues.

For pregnancy rate, the posted comparison intervals are also broad, and the risk-difference intervals include zero. The size of the enrollment alone does not guarantee precision for every outcome: precision depends on the number of events, the comparison being made, and the method used. Overall, the estimates should be read as uncertain rather than as evidence of equivalence or a definitive difference.

12. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a strategy for controlling multiplicity across the primary endpoint, the secondary endpoint, or the several arm comparisons. When multiple hypotheses are examined, the chance of at least one apparently unusual result can increase. General methods for addressing this include defining a primary contrast in advance, specifying a testing hierarchy, or adjusting significance criteria; the record does not say that any of these approaches was used. The posted p-values are unadjusted, so they should be treated as exploratory rather than as a familywise confirmatory set.

Missing-data handling is not reported in the registry record. There is no description of whether missing outcome values occurred, how they were handled, or whether any sensitivity analyses were performed. Participant flow, withdrawals, exclusions, and the number analyzed for each endpoint are also not reported beyond the arm counts associated with the posted outcome results. It is therefore not possible to establish from this record whether the endpoint counts include all randomized participants.

The analysis population is likewise not described. The registry does not report whether analyses followed intention-to-treat, per-protocol, or another population definition. It gives no account of treatment adherence, crossover, or deviations from the assigned regimen. These details matter because excluding participants or analyzing them according to treatment received can affect the protection offered by randomization.

The record identifies random allocation but does not report the method of sequence generation or allocation concealment. It also does not describe adjustment for the follicle-count strata. The posted comparisons use arm A as the reference, while the clinical regimen contrasts appear to be within follicle strata. A prespecified stratified analysis or direct C-versus-D estimate is not reported. These gaps do not show that the analyses were inappropriate; they mean the registry record does not permit their evaluation. As a result, the posted findings should be interpreted as limited descriptive evidence rather than as a fully documented confirmatory analysis.

13. 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 5% reporting threshold.

The serious adverse event summary lists 0 serious events in each of the four groups: among 60 participants in arm A, 58 in arm B, 125 in arm C, and 141 in arm D. The other adverse event counts are also listed as 0 in each group. No serious adverse event terms are listed. These figures describe the safety information recorded in the registry; they do not establish that no adverse events occurred outside the categories or reporting period represented by these fields.

The primary endpoint is moderate-to-severe OHSS, while the adverse-event summary is presented separately. The registry record does not explain how these safety categories relate, whether adverse events were actively solicited, or the period and criteria used for their collection. The death fields are not populated with a count, so no inference about deaths should be drawn from them.

Zero recorded serious events is not equivalent to proof of zero risk. The total participant numbers and the way events were collected affect how much can be inferred from an absence of reports. The registry record does not provide sufficient detail to assess completeness of adverse-event ascertainment or to compare the safety profiles beyond the counts posted.

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

The results establish what was recorded among the participants represented in the registry outcome counts: few moderate-to-severe OHSS events, with different observed counts across the four arms, and pregnancy outcomes reported as a secondary measure. They do not establish that any trigger regimen works, fails, or is equivalent to another. Sparse events and wide intervals leave substantial uncertainty about the underlying differences.

The study was randomized, which is an important design feature for comparisons, but the registry's posted estimates do not directly present both within-stratum regimen contrasts. The comparison of arms A and B corresponds to the higher-follicle group; the posted comparisons of C and D against A do not isolate the lower-follicle regimen contrast. The record does not report a direct estimate for C versus D. Consequently, some of the available comparisons do not align cleanly with the clinical question implied by the four-arm design.

The absence of a statistically significant unadjusted result should not be interpreted as evidence that regimens have the same effect. Conversely, observed differences in counts are not, by themselves, evidence of a reliable treatment effect. Both statements follow from the uncertainty in the estimates and the limited number of primary events, rather than from a judgment about clinical benefit.

The record also leaves important methods details unreported, including the power calculation, analysis populations, missing-data handling, multiplicity strategy, and endpoint ascertainment procedures. The sample-size figures are planning illustrations based on observed effects, not an indication that the completed study had a particular power. Taken together, the posted evidence is best understood as a limited description of outcomes in this trial, not a definitive answer about the comparative effects of the trigger regimens.

15. Why This Trial Matters Statistically

This study illustrates why design structure and statistical comparison must be read together. The four arms are organized around two follicle-count strata, with a different regimen contrast in each stratum. Although randomized assignment is recorded, a comparison against one common reference arm does not automatically answer each within-stratum treatment question. The relevant contrast needs to match the way the clinical regimens were assigned.

It also demonstrates how sparse outcomes constrain interpretation. The primary endpoint has few recorded events, and estimates from such data can be uncertain even when the study has hundreds of enrolled participants. A zero count in an arm is a feature of the observed sample, not proof that the underlying event risk is zero. Confidence intervals help make this uncertainty visible, but their usefulness depends on the calculation method, which the registry does not describe for these results.

Finally, the record distinguishes trial design from later planning illustrations. It states that no power calculation was performed, while separate hypothetical sample-size estimates use observed effects and specified assumptions. Keeping those concepts separate prevents planning calculations from being mistaken for a justification of the completed enrollment or a measure of the trial's observed power.

For researchers, the central statistical lesson is that conclusions depend not only on counts and p-values but also on estimand, comparison group, endpoint definition, follow-up, and analysis transparency. The registry contains useful descriptive outcome information, but its unreported analysis details and comparison structure limit how far those findings can be taken.

16. 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 main trial-specific limitation is the scarcity of primary endpoint events: the recorded moderate-to-severe OHSS counts are 0, 2, 2, and 0. This leaves little event information for estimating between-group differences. The uncertainty is reflected in the posted intervals for the nonzero comparisons, while the zero-versus-zero comparison has a reported zero-width interval that should not be read as certainty.

A second limitation is the mismatch between the four-arm structure and the posted comparison set. The interventions are organized as regimen contrasts within follicle-count strata, but the reported estimates compare each non-reference arm with arm A. In particular, comparisons of arms C and D with A combine differences in follicle stratum and regimen. A direct C-versus-D estimate is not reported in the registry record.

The outcome timing is not fully clear. The primary endpoint description gives a period from triggering until 2 weeks after the pregnancy test and then specifies 12 days after the pregnancy test for groups C and D. The record does not explain this distinction. Diagnostic criteria, event ascertainment, and severity classification procedures are also not reported.

Important design and analysis details are absent, including the randomization method, allocation concealment, analysis populations, adherence, missing-data handling, and multiplicity strategy. The record states that no power calculation was performed and lists no reported analyses. These gaps make it difficult to assess bias, completeness, and the prespecification of comparisons. The secondary pregnancy outcome has broad uncertainty and should not compensate for the limited primary-event information.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Triggering of Final Oocyte Maturation With GnRHa (Buserelin) in GnRH Antagonist Cycles — NCT00627406.
• Registry record last updated 2013-11-27; status last verified 2013-09.
• Results first posted 2013-11-27.
• 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.

20. Record Summary

NCT00627406 is a completed, randomized, unmasked, parallel-group Phase 4 study of final oocyte maturation triggers in GnRH antagonist IVF/ICSI cycles. The registry lists 384 participants enrolled. The four arms combine follicle-count strata with Buserelin-plus-Pregnyl or Pregnyl trigger regimens.

The primary outcome is the number of participants with moderate-to-severe OHSS. The posted counts are 0 of 60, 2 of 58, 2 of 125, and 0 of 141 across arms A through D. Pregnancy rate is the only posted secondary outcome. The primary comparisons are sparse and uncertain, and the displayed comparison structure does not provide a direct estimate for every within-stratum regimen contrast.

The registry states that no power calculation was performed. It does not report a detailed statistical analysis plan, missing-data approach, analysis population, or multiplicity procedure. The outcome counts are informative as a record of what was observed, but they do not support a definitive claim of benefit, harm, or equivalence between regimens.