Endometrial Markers and Response of Endometriosis Patients to Prolonged GnRH Agonist Prior to IVF: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Endometrial Markers and Response of Endometriosis Patients to Prolonged GnRH Agonist Prior to IVF (NCT00621179), a randomized phase 4 study. The primary outcome is Patients Who Responded to Controlled Ovarian Hyperstimulation.

2. Clinical Question

The trial asks whether endometrial expression of alpha v, beta 3 vitronectin can help identify which infertile patients with endometriosis undergoing in vitro fertilization might benefit from prolonged pretreatment with leuprolide acetate in depot suspension. The marker was assessed by endometrial biopsy before ovarian stimulation. Participants were grouped according to whether expression was positive or negative and whether they received three months of leuprolide pretreatment or standard controlled ovarian stimulation without intervention.

The primary question is not simply whether implantation occurred in one group more often than another. To establish that the marker predicts different responses to pretreatment, the treatment contrast would need to be evaluated separately among participants with positive and negative marker expression, and those contrasts would need to be compared. The registry record gives participant counts for four marker-and-treatment groups, but does not report a formal analysis of those contrasts or of a treatment-by-marker interaction.

The posted primary outcome is the number of participants who responded to controlled ovarian stimulation as evidenced by embryo implantation, with implantation confirmed by ultrasound at 6 1/2 weeks of pregnancy. The counts are 7 of 12 in Group 1, 5 of 8 in Group 2, 3 of 6 in Group 3, and 5 of 9 in Group 4. Group 1 had positive marker expression and standard therapy; Group 2 had positive expression and leuprolide pretreatment; Group 3 had negative expression and leuprolide pretreatment; Group 4 had negative expression and standard therapy.

These results describe the observed outcomes in the four groups. Without reported comparative estimates and their uncertainty, they do not establish whether the marker predicts a different effect of pretreatment.

3. Trial Design

This was a completed, phase 4, prospective randomized trial with a parallel-group design and no masking. The registry record reports enrollment of 37 participants. The study concerned infertility and endometriosis, and was sponsored by the Colorado Center for Reproductive Medicine. The record lists a start date of 2003-03 and primary completion in 2009-08.

All patients were to undergo endometrial biopsy before ovarian stimulation for IVF. The trial description says participants were randomized to a three-month course of depot leuprolide acetate before ovarian stimulation or to standard therapy. The posted outcome data divide participants into four groups reflecting both marker expression and treatment: positive expression with standard stimulation, positive expression with leuprolide pretreatment, negative expression with leuprolide pretreatment, and negative expression with standard stimulation. No intervention was listed for the standard-therapy groups.

The registry record does not report the randomization procedure, whether allocation was stratified by marker status, or the details of sequence generation and allocation concealment. It also does not report whether the group descriptions represent the full randomized allocation structure or a post-biopsy subgrouping process. These design details matter when interpreting how comparable the groups may be, particularly when assessing differences within each marker category.

Primary outcome counts were posted for 12 participants in Group 1, 8 in Group 2, 6 in Group 3, and 9 in Group 4. The record does not explain why the outcome group counts do not account for the enrollment count. Nor does it report an analysis population, participant flow, or reasons for any difference between enrollment and outcome denominators. Accordingly, the group counts should be read as the denominators accompanying the posted outcome, not as a complete account of all participants enrolled or randomized.

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 Patients Who Responded to Controlled Ovarian Hyperstimulation, measured over Evaluated at 6 1/2 weeks of pregnancy which is 4 weeks post embryo transfer..

The primary endpoint counts participants who responded to controlled ovarian stimulation, with response evidenced by embryo implantation. The registry defines implantation confirmation as ultrasound evidence at 6 1/2 weeks of pregnancy, which is 4 weeks post embryo transfer. The result is therefore a participant count with a binary outcome: each participant is counted as having met or not met the recorded implantation criterion.

Implantation is relevant to the trial question because the study concerns IVF outcomes following stimulation, with or without leuprolide pretreatment, and asks whether a pre-treatment endometrial marker predicts response. An ultrasound-confirmed endpoint also gives the outcome a stated assessment time and confirmation method. It is more specific than an unspecified report of pregnancy, but it is not a measure of every aspect of IVF success or of longer-term pregnancy outcomes.

The registry reports counts rather than adjusted estimates, confidence intervals, or a formal comparison. The counts are 7 participants in Group 1, 5 in Group 2, 3 in Group 3, and 5 in Group 4. Those values identify the number meeting the endpoint within each reported group; they do not by themselves quantify uncertainty or show whether differences are compatible with chance variation. The registry record does not report a separate definition of non-response, handling of participants without an ultrasound assessment, or details of endpoint adjudication.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a randomized, parallel-group trial, but it does not report the methods used to analyze the primary endpoint. No formal analyses are posted. The endpoint is binary at the participant level: the reported count is the number meeting the ultrasound-confirmed implantation criterion in each group. The following concepts describe how such data are generally analyzed; they are not claims about methods used in this trial.

What does a group count tell us?

A count tells how many participants in a reported group experienced the endpoint. It is a basic descriptive result. A count should be interpreted alongside its group denominator, because the same count can have different meaning in groups of different sizes. For this trial, both the count and denominator are posted for each group, but no comparative estimate or uncertainty interval accompanies them.

For a binary endpoint, a comparison between two groups can be expressed using an absolute difference in event probabilities, a relative measure, or another model-based contrast. Each summarizes a different aspect of the comparison. General statistical explanation: an absolute difference describes how far apart the group probabilities are, while a relative measure describes their relationship as a ratio. Neither is automatically more informative in every clinical setting. The registry record does not report such estimates for this endpoint, and no new estimate is calculated.

Why is a confidence interval useful?

A confidence interval communicates uncertainty around an estimated contrast. It helps readers distinguish a point estimate from the range of values that remain compatible with the data under the analysis assumptions. In a small trial, uncertainty can be substantial even when the observed counts appear different. The registry record does not report confidence intervals for the primary outcome, so the precision of any group contrast cannot be assessed from the posted results.

A p-value, when reported, addresses how compatible the observed data are with a specified null hypothesis under the statistical model. It does not measure the probability that a treatment works, nor does it quantify the clinical importance of an effect. No p-value or test result for the primary endpoint is reported in the registry record.

What would the predictive-marker question require?

A marker is predictive when the treatment effect differs across marker-defined groups. In this trial, the relevant structure is the pair of treatment comparisons: leuprolide pretreatment versus standard therapy among participants with positive expression, and the same treatment comparison among participants with negative expression. A predictive claim depends on whether those treatment contrasts differ from one another. Comparing marker-positive and marker-negative participants without accounting for treatment would not answer that question, because marker groups may differ for reasons unrelated to treatment response.

A statistical model could represent this question with treatment, marker status, and a treatment-by-marker interaction. The interaction term evaluates whether the treatment contrast changes with marker status. This is a general description of an approach, not a statement that such a model was fitted. The registry record reports no interaction estimate, interaction test, or analysis plan.

How does randomization contribute?

Randomization is intended to reduce systematic differences between treatment groups, on average, by using chance to assign treatment. It does not guarantee that small groups will be balanced on every characteristic. The registry record identifies the trial as randomized but does not report the allocation procedure or whether randomization was conducted separately within marker categories. Those details affect how directly the four posted groups can support the predictive question.

Masking is listed as none. This describes the trial as unmasked in the registry record, but the record does not specify which people knew treatment assignments or whether outcome assessment was independently blinded. The endpoint includes ultrasound confirmation, but no further assessment procedures are reported.

What can planning calculations tell us?

Planning sample-size illustrations are not evidence that a trial had a particular probability of detecting an effect after it was conducted. The stated planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm. These are planning illustrations based on the observed effect, not the trial's own design justification or observed power.

The registry record does not report a sample-size justification, the target effect used in the original design, interim analyses, or a prespecified statistical analysis plan. A planning calculation based on an observed effect is especially dependent on the observed estimate and should not be treated as an independently validated design target. It also cannot substitute for a reported estimate with an uncertainty interval.

For the posted endpoint, the record offers descriptive counts in four groups but no reported comparative analysis. That distinction is central: the existence of randomized allocation does not itself supply the missing effect estimates, uncertainty, or interaction test needed to answer the trial's predictive-marker question.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group 1", "Group 2", "Group 3", "Group 4")
n      <- c(12, 8, 6, 9)
events <- c(7, 5, 3, 5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group 1  12  7  58.3  27.7  84.8  32.0  80.7  31.6  80.8
ARM  Group 2  8  5  62.5  24.5  91.5  30.6  86.3  29.9  86.3
ARM  Group 3  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Group 4  9  5  55.6  21.2  86.3  26.7  81.1  26.2  81.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no secondary outcomes. It reports zero analyses. It does not report a statistical analysis plan, a prespecified hierarchy of hypotheses, or any adjustment for multiple comparisons. The record also does not describe interim analyses or stopping rules. As a result, it is not possible to determine which comparisons were planned in advance or whether the posted outcome was the only analysis considered.

Multiplicity arises when several outcomes, groups, or hypotheses are tested. Repeated testing can increase the chance of a nominally unusual result under a setting where none of the tested effects is real. General statistical practice may address this through prespecified primary hypotheses or multiplicity adjustments, but the registry record does not say whether either approach was used. The four marker-and-treatment groups make the choice of comparison particularly important: separate within-marker comparisons and a direct interaction analysis answer related but distinct questions.

The record does not report missing-outcome counts, reasons for missingness, imputation, or a complete analysis population. Primary outcome denominators are 12, 8, 6, and 9 in Groups 1 through 4, while overall enrollment is 37. No participant-flow accounting explains the relationship between enrollment and those denominators. The registry record also does not state whether the primary outcome was analyzed according to randomized assignment or according to another population definition.

These omissions leave uncertainty about the scope of the analysis and whether outcome availability could have affected the group results. They do not establish that missing data or multiplicity affected the findings; rather, those issues are not reported in the registry record and cannot be evaluated from the posted results.

12. 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.

The serious adverse event figures report zero affected participants in every group: 0 of 12 in Group 1, 0 of 8 in Group 2, 0 of 7 in Group 3, and 0 of 9 in Group 4. The registry also reports zero deaths in each group. These are recorded counts within the listed safety denominators; they are not comparative estimates of safety.

The safety denominators are not identical to the primary outcome denominators. In particular, the safety record lists 7 participants at risk in Group 3, while the primary outcome lists 6 participants in that group. The registry record does not explain this difference. The adverse-event record reports zero other adverse events in the listed groups as well as zero serious events, but the record gives no serious adverse event terms.

Zero reported events means none were recorded in those denominators during the registry's safety reporting. It does not demonstrate that an event could not occur, and it does not establish equivalence between treatment groups. General statistical interpretation: when event counts are sparse or absent, estimates of comparative risk are limited, and uncertainty can remain despite a zero count. The registry record does not report follow-up duration or additional detail about adverse-event collection, so the safety figures should be read as the posted counts rather than as a complete account of all possible harms.

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

The posted results establish that the registry records ultrasound-confirmed embryo implantation counts for four groups defined by marker expression and treatment. The counts are 7 of 12 for positive expression with standard therapy, 5 of 8 for positive expression with leuprolide pretreatment, 3 of 6 for negative expression with leuprolide pretreatment, and 5 of 9 for negative expression with standard therapy. They are descriptive observations from this trial.

Those observations do not, on their own, show whether leuprolide pretreatment changed the outcome, whether any apparent difference is precise, or whether marker expression predicts a different response to treatment. The latter question requires comparing treatment effects across marker groups. The registry record does not report those effect estimates or an interaction analysis. It also does not report confidence intervals or p-values, so the statistical uncertainty of the comparisons is not quantified.

The endpoint is an ultrasound-confirmed implantation outcome at a specified assessment time. It is not a report of all pregnancy outcomes, live birth, or longer-term follow-up. The registry record does not report additional reproductive outcomes in the posted results. Therefore, conclusions should remain limited to the endpoint definition and time point recorded.

The trial is identified as randomized and parallel-group, but the registry record does not provide the randomization details, a participant-flow account, or the primary analysis population. Overall enrollment is 37, whereas the primary outcome denominators are reported separately by group and do not account for that enrollment. This unresolved accounting limits interpretation of who contributed to the outcome counts.

In practical statistical terms, the record supports a description of the observed groups, not a definitive claim about treatment benefit or the predictive performance of the marker. The absence of a reported comparative analysis should not be mistaken for evidence of no effect; equally, the group counts should not be treated as proof of a treatment effect or a useful marker.

14. Why This Trial Matters Statistically

This trial addresses a statistical question that is more demanding than asking whether two treatment groups have different observed outcomes. A predictive biomarker claim concerns whether a treatment contrast changes according to marker status. That requires attention to the interaction between treatment and marker, rather than an isolated comparison of marker-positive and marker-negative participants.

The four reported groups make this distinction visible: each marker category has a leuprolide pretreatment group and a standard-therapy group. Such a layout can describe the outcome pattern across marker and treatment combinations, but a pattern of counts is not itself an interaction estimate. The registry record reports no formal comparative analyses, leaving the central predictive question unanswered by the posted analysis results.

The trial also illustrates why denominators and analysis populations matter. Enrollment is reported as 37, while the primary outcome is reported using group denominators of 12, 8, 6, and 9. The safety record has a different denominator for Group 3. Without participant-flow information and an explanation of these denominators, readers cannot fully assess the relationship between enrollment, treatment assignment, endpoint observation, and safety reporting.

Finally, the endpoint is clearly tied to an assessment time and ultrasound confirmation, but the registry record provides only counts. Statistical interpretation requires both an estimate of the comparison and an account of its uncertainty. Here, no such comparative estimate, interval, or test is reported. The case underscores that descriptive outcomes can be informative about what was recorded while remaining insufficient for a causal or predictive conclusion.

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.

The primary limitation is that the registry record posts group outcome counts but no inferential analysis. No treatment-effect estimates, confidence intervals, p-values, or treatment-by-marker interaction results are reported. As a result, the magnitude and precision of the comparisons, and the evidence for predictive value, cannot be assessed from the record.

The relationship between enrollment and outcome denominators is not explained. Enrollment is 37, while the primary outcome counts are reported for groups of 12, 8, 6, and 9. The record does not report participant flow, exclusions, withdrawals, missing outcome data, or the population used in analysis. Safety denominators also differ from primary outcome denominators for Group 3, with no explanation recorded.

Important design and analysis details are absent, including the randomization procedure, whether allocation was stratified by marker status, the original sample-size justification, the analysis plan, and whether interim analyses were conducted. Masking is listed as none, but the registry does not say who knew the assignments or how outcome assessment was conducted. These omissions limit assessment of bias and the intended statistical comparisons.

The reported endpoint is implantation confirmed by ultrasound at 6 1/2 weeks of pregnancy, 4 weeks post embryo transfer. The registry does not report longer-term reproductive outcomes or additional endpoint details such as handling of participants without an assessment. Thus, the posted result applies only to the specified endpoint and time point. These record-level limitations do not establish that the trial was conducted improperly; they define what can and cannot be evaluated from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Endometrial Markers and Response of Endometriosis Patients to Prolonged GnRH Agonist Prior to IVF — NCT00621179.
• Registry record last updated 2021-08-10; status last verified 2021-08.
• Results first posted 2020-10-05.
• 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

NCT00621179 is a completed phase 4 randomized parallel-group trial with no masking, sponsored by the Colorado Center for Reproductive Medicine. It enrolled 37 participants with endometriosis and infertility. The study examined endometrial alpha v, beta 3 vitronectin expression in relation to leuprolide acetate pretreatment before controlled ovarian stimulation and IVF.

The primary outcome was the number of participants with embryo implantation confirmed by ultrasound at 6 1/2 weeks of pregnancy, 4 weeks post embryo transfer. Counts were 7 of 12 in Group 1, 5 of 8 in Group 2, 3 of 6 in Group 3, and 5 of 9 in Group 4. The registry record reports zero serious adverse events and zero deaths in the listed safety groups.

No formal primary outcome analyses, comparative estimates, or uncertainty intervals are reported. The record also does not explain the participant denominators or provide a complete analysis population. The posted counts therefore describe observed outcomes by group but do not establish whether the marker predicts a different treatment response.