Subcutaneous Progesterone Versus Vaginal Progesterone Tablets for Luteal Phase Support in In Vitro Fertilization (IVF): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Subcutaneous Progesterone Versus Vaginal Progesterone Tablets for Luteal Phase Support in In Vitro Fertilization (IVF) (NCT00828191), a randomized phase 3 study. The primary outcome is Ongoing Pregnancy Rate.

2. Clinical Question

The trial also listed implantation rate and delivery rate as secondary outcomes. The registry posts numerical results for implantation rate, but delivery-rate values are not reported in the registry record. The available results therefore address only part of the broader question about treatment outcomes.

3. Trial Design

This was a phase 3, randomized, open-label, parallel-group trial of subcutaneous progesterone versus vaginal progesterone tablets for luteal phase support in patients undergoing IVF. The registry describes it as prospective and multicenter. The study was sponsored by IBSA Institut Biochimique SA and is marked completed. The recorded start was 2008-12, and primary completion was 2011-07.

Enrollment was 800. The primary outcome analysis included all randomized patients, with 400 assigned to each treatment group. The registry does not report the randomization sequence method, allocation concealment procedures, or whether any stratification factors were used. Masking is recorded as none, so the treatment assignment was not masked according to the registry. Further details about who knew assignments or how outcome assessment was conducted are not reported in the registry record.

The subcutaneous group received progesterone at 25 mg daily. The comparator group received progesterone tablets intravaginally at 100 mg twice daily, totaling 200 mg daily. The registry describes both interventions as progesterone, with the route and dosing regimen distinguishing the groups. It does not report treatment duration beyond the outcome timeframes, adherence, treatment discontinuation, or details of other IVF procedures.

The primary outcome was ongoing pregnancy rate 10 weeks after treatment start. Implantation rate was listed at 4-5 weeks after treatment start, and delivery rate was also listed as a secondary outcome. Numerical results for delivery rate are not reported in the registry record. The registry identifies three outcome measures and three analyses, but further details of the complete analysis plan, protocol, and endpoint definitions are not reported in the registry record.

The primary comparison is based on the randomized groups. The open-label design and the limited reporting of allocation and follow-up procedures constrain how fully the conduct of the trial can be assessed from the registry record alone.

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: All randomized patients were included in the analysis

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 Ongoing Pregnancy Rate, measured over 10 weeks after treatment start.

Ongoing pregnancy rate is the proportion of randomized patients who had an ongoing pregnancy at the specified assessment. In this trial, the endpoint was assessed 10 weeks after treatment start and expressed as a percentage of randomized patients. The registry states that all randomized patients were included in the analysis. It does not provide a more detailed operational definition of ongoing pregnancy or explain how missing pregnancy assessments were handled.

This endpoint is used to assess a clinically relevant stage of the IVF treatment pathway after implantation and early pregnancy. It captures more than a positive early pregnancy assessment, while remaining an intermediate outcome rather than a delivery outcome. A delivery rate was listed as a secondary outcome, but numerical results for that endpoint are not reported in the registry record. The ongoing pregnancy result therefore cannot be treated as a substitute for the missing delivery results.

The observed rates were 40.8% in the Progesterone SC group and 43.3% in the Progesterone Tablets group. The reported difference in pregnancy rates was -2.5, with a 95% confidence interval from -9.4 to 4.4. These figures describe the posted comparison; they do not, by themselves, establish whether a prespecified non-inferiority or equivalence criterion was met. The registry does not report the endpoint’s detailed definition, a non-inferiority margin, or its justification.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

General: Randomization assigns participants to treatment groups by chance. When implemented appropriately, it can reduce systematic differences between groups at the start of a trial and supports a causal comparison of assigned treatments. The registry identifies this study as randomized and reports 400 patients in each group for the primary analysis. It does not report the sequence-generation method, concealment procedures, or any stratification factors, so those aspects cannot be evaluated from the registry record.

The study was open-label, with masking recorded as none. General: Lack of masking can affect behavior, care, reporting, and assessment, depending on the outcome and trial procedures. The primary endpoint is a pregnancy outcome, but the registry does not describe assessment procedures or safeguards against assessment bias. The record alone does not show whether the open-label design influenced care or outcome ascertainment.

What does the reported difference mean?

The registry reports a difference in pregnancy rates of -2.5, with a 95% confidence interval from -9.4 to 4.4 and p = 0.52, using Fisher Exact. General: A difference expresses the contrast between groups according to a specified subtraction order. The sign indicates which group has the larger value under that ordering; the registry’s reported negative estimate is consistent with the lower posted rate in the subcutaneous group. The registry does not provide additional detail about the exact contrast specification.

General: A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the method used. It is not a guarantee that the true effect lies inside the interval, and it does not assign a probability to each possible effect after the data have been observed. The reported interval extends from a difference favoring the subcutaneous group to one favoring the tablets group. Its span signals that the data do not determine a narrow range for the difference.

General: A p-value assesses how compatible the observed data are with a specified null hypothesis under the test’s assumptions. It does not measure the probability that the null hypothesis is true, and a non-significant result does not prove no effect or equivalence. In a non-inferiority or equivalence analysis, interpretation requires a prespecified margin and a comparison of the confidence interval with that margin. The registry labels the analysis as non-inferiority or equivalence, but the margin and protocol rationale are not reported in the registry record.

How should the implantation calculation be read?

The posted implantation-rate means were 33.2 for Progesterone SC and 35.1 for Progesterone Tablets. The unadjusted recalculation gives a mean difference of 1.9 for tablets compared with SC, with a 95% confidence interval from -3.911 to 7.711 and p = 0.522. The reported group standard deviations were 42.0 and 40.9, and the analysis used 392 and 390 participants, respectively. The sponsor-reported ANOVA result is distinct: it reports a mean difference in final values of -1.8, a 95% confidence interval from -7.6 to 4.0, and p = 0.54.

General: A mean difference compares group averages, while the standard deviation describes variation among individual observations within a group. A confidence interval for the mean difference reflects uncertainty in the estimated group contrast, not the range containing most individual outcomes. The registry identifies the implantation measure as a percentage of embryos transferred, but does not report further detail on the distribution, handling of multiple embryos per participant, or any adjustment used in the sponsor analysis. The recalculation is an unadjusted calculation from posted summary statistics, not the trial’s full analysis.

What are the planning illustrations?

The planning illustrations are derived from the observed implantation effect and state participants per arm for 80% power and participants per arm for 90% power. For planning for 100% of the observed effect, the corresponding figures are 7,473 and 10,005. For planning for 75% of the observed effect, they are 13,286 and 17,785. For planning for 50% of the observed effect, they are 29,892 and 40,017.

These are planning illustrations, not observed power and not the actual enrollment target justification for this trial. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrations use the stated fraction of the observed effect. General: Planning based on an observed effect can be unstable because the observed estimate itself is uncertain. A smaller assumed effect generally requires a larger study to detect it under otherwise comparable assumptions. These calculations do not establish the rationale for the trial’s enrollment of 800; that rationale is not reported in the registry record.

Why can variation and endpoint structure matter?

General: Over-dispersion means that observed variability is greater than a model’s assumptions would predict. If a statistical model does not account for extra variation or clustering, standard errors and confidence intervals can be misleading. This is a general consideration for outcomes involving percentages or multiple observations per participant. The registry reports a percentage of embryos transferred for implantation, but does not report enough model detail to determine whether clustering or over-dispersion was considered in the sponsor’s analysis. The unadjusted calculation uses the posted summary statistics and does not resolve those design questions.

For the primary endpoint, the posted comparison uses Fisher Exact. General: Fisher’s exact test evaluates association in a two-group categorical comparison and can be used with counts of outcome and non-outcome observations. The registry does not post the underlying event counts or additional model output for ongoing pregnancy, so it is not possible to independently reproduce the reported test from the posted rates alone. The registry identifies all randomized patients as included in the primary analysis, but does not describe the handling of missing outcome data or provide a participant flow.

10. Analyses Reported by the Sponsor

The registry’s primary result is the sponsor-reported Fisher Exact comparison of pregnancy rates: a difference of -2.5, a 95% confidence interval from -9.4 to 4.4, and p = 0.52. The registry categorizes this as a non-inferiority or equivalence analysis. No independent recalculation of the primary endpoint is posted, and the registry does not provide the event counts needed to reproduce the Fisher Exact result from the percentages alone.

For implantation rate, the sponsor-reported ANOVA analysis gives a mean difference in final values of -1.8, a 95% confidence interval from -7.6 to 4.0, and p = 0.54. The unadjusted recalculation from posted summary statistics gives a mean difference of 1.9 for tablets compared with SC, with a 95% confidence interval from -3.911 to 7.711 and p = 0.522. These estimates are not identical. The reported contrast direction, adjustment details, and analysis specification are not sufficiently described to reconcile the estimates. The recalculation is a simple unadjusted comparison, not a replacement for the sponsor’s analysis.

The registry record does not identify a discrepancy flag for these results. The available information supports reporting both analyses with their methods and uncertainty, while avoiding an unsupported explanation for the differences between them.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies ongoing pregnancy rate as the primary outcome and lists implantation rate and delivery rate as secondary outcomes. However, a complete prespecified analysis plan is not reported in the registry record. The record does not describe whether the secondary outcomes were tested in a hierarchy, whether any adjustment for multiple comparisons was planned, or whether there were additional endpoints or subgroup analyses. Without those details, the evidential status of each reported comparison cannot be fully assessed.

General: Multiplicity arises when several outcomes, comparisons, time points, or subgroups are examined. The more analyses undertaken, the more likely it is that at least one result may appear notable by chance, even when there is no underlying effect. Prespecification and appropriate statistical adjustment can help clarify how much weight to give individual results. The registry’s designation of primary and secondary outcomes provides some hierarchy, but does not establish the full testing strategy.

The primary analysis states that all randomized patients were included. That description identifies the analysis population, but does not explain whether every randomized patient had an observed outcome, how missing outcomes were handled, or whether imputation or sensitivity analyses were used. Participant flow, withdrawal counts, and reasons for missing data are not reported in the registry record. The posted arm sizes match the stated randomized group sizes, but that alone does not establish complete outcome ascertainment.

General: Missing outcome data can affect an estimate if the chance of being missing is related to treatment assignment or outcome status. Sensitivity analyses can explore how conclusions change under different assumptions about missing results. The registry does not report such analyses for ongoing pregnancy or implantation.

The record also does not report a protocol or statistical analysis plan, sample-size justification, interim analyses, or a detailed account of deviations from planned methods. These details are important for distinguishing prespecified analyses from analyses selected after seeing the results. Their absence limits evaluation of multiplicity, missing-data assumptions, and the robustness of the reported conclusions.

12. 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.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 400 patients at risk in each group. It also records 156 other adverse events in the Progesterone SC group and 161 in the Progesterone Tablets group, with 400 patients at risk in each. The registry does not list any top serious adverse-event terms. These counts describe what is recorded in the registry; they do not provide detail about event types, severity within the non-serious category, timing, or attribution.

Deaths are not reported in the registry record. The record also does not provide further information about how adverse events were collected, how long participants were monitored for safety, or whether the adverse-event categories were defined identically across groups. As the trial was open-label, the registry does not clarify whether knowledge of treatment assignment could have affected event reporting.

General: A recorded count of zero serious events does not prove that a treatment has no serious risks. The amount of information about uncommon events depends on the number of participants, duration of observation, and completeness of reporting. Likewise, counts of other adverse events alone do not establish comparative safety without details about event definitions, exposure, and analysis. These figures should be read as registry-recorded counts, not as a comprehensive safety assessment.

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

The primary result describes ongoing pregnancy rates of 40.8% for Progesterone SC and 43.3% for Progesterone Tablets. The reported difference was -2.5, with a 95% confidence interval from -9.4 to 4.4 and p = 0.52. The estimate is compatible with differences in either direction, and the interval does not establish that the groups are equivalent. The registry labels the analysis as non-inferiority or equivalence, but the margin required to interpret that framework is not reported in the registry record.

The result does not show that the regimens are identical. Nor does the p-value establish that any difference is absent. General: Evidence of equivalence or non-inferiority requires a prespecified clinical margin and an analysis demonstrating that the relevant uncertainty bound meets that criterion. A non-significant test of difference is not a substitute for that assessment. The record does not report the margin or its justification, so a formal conclusion about the stated analysis category cannot be independently evaluated.

The implantation outcome offers additional but limited information. Its sponsor-reported and unadjusted analyses are not identical, and the registry does not provide enough methodological detail to reconcile them fully. Delivery-rate values are not reported in the registry record. Consequently, the posted outcomes do not provide a complete account across the pregnancy-to-delivery pathway.

The findings should not be interpreted as medical advice or as a basis for choosing a treatment. They describe the results recorded for this randomized trial, with uncertainty and reporting limitations. Assessing the broader evidence would require information beyond this record, including a fully specified protocol, outcome definitions, missing-data handling, and the complete results for secondary outcomes.

14. Why This Trial Matters Statistically

This trial is statistically notable because its registry categorizes the primary comparison as non-inferiority or equivalence, yet does not report the margin that gives that analysis its meaning. A difference estimate and confidence interval can be presented, but a claim of non-inferiority or equivalence depends on whether the interval satisfies a prespecified threshold. Without the threshold, the reader cannot determine from the registry record whether the stated criterion was met.

The example also illustrates why a p-value alone is not an adequate summary. The reported p = 0.52 does not demonstrate that the two regimens have the same effect. The confidence interval communicates uncertainty more directly, while its span across values favoring either group signals that the comparison is not precise enough to establish a narrow effect range.

The secondary implantation result further shows why an unadjusted recalculation should be distinguished from the sponsor’s analysis. Both estimates are reported with their own methods, and the registry does not provide the contrast or adjustment details needed to reconcile them fully. Preserving that distinction avoids treating a simple calculation from summary statistics as if it were the trial’s complete analysis.

Finally, the record demonstrates that a trial’s randomized design does not by itself answer every methodological question. Allocation procedures, endpoint definitions, missing-data handling, multiplicity, sample-size justification, and interim analyses are not reported in the registry record. Identifying these omissions is part of interpreting the evidence: it clarifies what the posted estimates can support and where conclusions must remain limited.

15. 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.

Several trial-specific details needed to assess conduct and interpretation are not reported in the registry record. These include eligibility criteria, participant characteristics, randomization sequence generation, allocation concealment, treatment adherence, discontinuations, and participant flow. The record identifies the study as open-label but does not explain how pregnancy outcomes were assessed or whether assessment procedures were standardized.

The ongoing pregnancy endpoint is named and timed at 10 weeks after treatment start, but its detailed definition and rules for handling missing assessments are not reported. Although all randomized patients are described as included in the primary analysis, the record does not provide outcome counts or explain whether all participants had an observed endpoint. No missing-data or sensitivity analyses are reported.

The non-inferiority or equivalence margin, its rationale, and the underlying sample-size justification are not reported in the registry record. The record also does not describe interim analyses or a complete statistical analysis plan. These omissions prevent independent assessment of whether the enrollment target was based on a suitable margin and whether the reported analysis followed a prespecified plan.

For the secondary outcomes, implantation rate is reported, but the details of the sponsor’s ANOVA contrast and any adjustment are insufficient to reconcile its estimate with the unadjusted recalculation. Delivery-rate values are not reported. The registry does not describe multiplicity procedures or whether all planned outcomes and analyses are represented.

The safety record gives counts but does not report detailed event definitions, monitoring duration, attribution, or death counts. These limitations restrict interpretation of comparative safety. The registry record is therefore informative about the listed design and posted results, but does not supply the full methodological and outcome detail needed for a comprehensive evaluation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Subcutaneous Progesterone Versus Vaginal Progesterone Tablets for Luteal Phase Support in In Vitro Fertilization (IVF) — NCT00828191.
• Registry record last updated 2013-01-31; status last verified 2013-01.
• Results first posted 2012-12-26.
• 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.

19. Record Summary

NCT00828191 is a completed phase 3 randomized, open-label, parallel-group, multicenter trial sponsored by IBSA Institut Biochimique SA. It compared progesterone administered subcutaneously at 25 mg daily with vaginal progesterone tablets at 100 mg twice daily for luteal phase support during IVF. Enrollment was 800, with 400 randomized patients in each group.

The primary endpoint was ongoing pregnancy rate 10 weeks after treatment start. Rates were 40.8% for Progesterone SC and 43.3% for Progesterone Tablets. The reported difference was -2.5, with a 95% confidence interval from -9.4 to 4.4 and p = 0.52. The registry categorizes the analysis as non-inferiority or equivalence, but does not report the margin.

Implantation rate was listed as a secondary outcome and has posted results; delivery rate was also listed, but numerical results are not reported in the registry record. The record reports zero serious adverse events in both groups and counts of other adverse events. Important details about missing data, multiplicity, analysis planning, and endpoint definitions are not reported.