IVF Hyper-responders: Oocyte Vitrification Compared With Embryo Freezing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IVF Hyper-responders: Oocyte Vitrification Compared With Embryo Freezing (NCT02026193), a randomized na study. The primary outcome is Fetal Heart Activity 1 Month Post Embryo Transfer.

2. Clinical Question

The registry summary gives the rationale as concern that pregnancy chances after retrieving >15 oocytes may be affected by the uterine lining. It describes freezing all embryos for later transfer as the usual approach in such cases and presents oocyte vitrification as another option. These statements describe the study’s rationale, not a conclusion established by the posted outcome data.

The primary question is about a clinical outcome after transfer, rather than a laboratory measure of egg or embryo storage. However, the registry does not report details such as how many transfers took place, how transfer decisions were made, or whether participants who did not reach transfer were included in the primary analysis. Those details are not reported in the registry record.

3. Trial Design

The record describes a randomized, parallel-group trial with no masking. It lists an enrollment of 11 and a completed status. The sponsor is Rambam Health Care Campus. The study start is recorded as 2014-01 and primary completion as 2014-11. The phase is listed as NA; further explanation of that designation is not reported in the registry record.

Participants were assigned to one of two procedures: oocyte vitrification or embryo freezing. In the first arm, all retrieved mature oocytes were to be vitrified. In the second, all retrieved oocytes were to be fertilized and the resulting embryos frozen. The registry does not give further information about the randomization sequence, allocation concealment, or procedures used to implement assignment. These aspects of the design are therefore not reported in the registry record.

The primary outcome is fetal heart activity one month after embryo transfer, assessed by vaginal ultrasound. The arm entries report 0 participants with the outcome among 3 in the oocyte vitrification arm, and 4 participants with the outcome among 8 in the embryo freezing arm. These are descriptive counts. The record does not report a two-arm inferential analysis for this binary endpoint.

Only one outcome measure is listed, and no secondary outcomes are posted. No analysis entries are reported. The record does not describe an analysis population, handling of participants without an embryo transfer, or how missing outcome assessments were handled. Those details are not reported in the registry record. The absence of a masking procedure is explicit; other operational details, including follow-up procedures beyond the stated outcome time, are not reported.

The record states that the trial is completed, but it does not provide a detailed participant flow or a narrative account of trial conduct. The listed arm counts should therefore be read as the posted outcome denominators, not as a substitute for a full account of eligibility, assignment, follow-up, and analysis.

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 Fetal Heart Activity 1 Month Post Embryo Transfer, measured over 1 month after embryo transfer.

The primary endpoint is the number of participants with fetal heart activity detected by vaginal ultrasound one month after embryo transfer. Fetal heart activity is a binary outcome: each participant either has the recorded finding or does not. The registry lists the measure in terms of participants with fetal heart activity rather than a continuous measurement or a time-to-event outcome.

This endpoint is used to capture an observed clinical finding after transfer. In this trial, it places the two freezing strategies in the context of a post-transfer outcome, rather than assessing only whether oocytes or embryos were successfully frozen. The registry’s wording specifies the timing as one month after embryo transfer and the assessment method as vaginal ultrasound.

The posted results give the number of participants with fetal heart activity in each arm: 0 in the oocyte vitrification arm and 4 in the embryo freezing arm. The corresponding arm denominators are 3 and 8. The record does not give additional detail on how an absent ultrasound finding was classified, how participants without a transfer were handled, or whether assessments were completed for every assigned participant. These details are not reported in the registry record.

A count at a particular follow-up point does not by itself describe all reproductive outcomes. The registry does not post other clinical outcomes, such as later pregnancy outcomes or birth outcomes, as secondary measures. Thus, the primary endpoint answers a specific question about the recorded ultrasound finding at the specified time; it should not be treated as a measure of every aspect of treatment outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because it records whether fetal heart activity was observed for each participant at the stated assessment. For this kind of endpoint, the basic descriptive information is the number of participants with the event and the number assessed in each arm. The registry posts those counts but does not give a statistical comparison for the two arms.

What would a two-arm comparison estimate?

In general, a comparative analysis of a binary outcome may estimate the event probability in each arm and then express the contrast between arms as a difference, ratio, or another effect measure. These measures answer related but distinct questions. A difference describes the separation between probabilities; a ratio compares them relative to one another. Choosing a measure should be guided by the study question and analysis plan. The registry does not report an effect estimate for this endpoint, and no such estimate is calculated.

The arm counts are 0 with the outcome among 3 in the oocyte vitrification arm and 4 among 8 in the embryo freezing arm. Because the registry marks the two-arm comparison as missing or not estimable, the reported counts should not be mistaken for a completed inferential analysis. In particular, the counts alone do not supply a confidence interval, hypothesis-test result, or model-adjusted comparison.

Why does uncertainty matter?

In general, a confidence interval describes a range of effect values that are reasonably compatible with the observed data under the assumptions of the analysis. It communicates precision as well as direction. When there are few observations, uncertainty is commonly substantial, and a point estimate by itself can give an incomplete impression. No confidence interval is reported for the primary outcome in this record.

Likewise, a p-value, when used, is a measure of how compatible the data are with a specified null hypothesis under the test’s assumptions. It is not the probability that a treatment works, nor does it describe the size or clinical importance of an effect. No p-value for the binary comparison is reported. It would be inappropriate to infer one from the posted counts, especially when the registry indicates that the comparison is not estimable in its results.

What does the analysis record say?

The registry lists one outcome measure and no analysis entries. It does not identify a statistical test, model, covariate adjustment, or analysis population. It also does not report whether the primary analysis was intended to follow assignment regardless of treatment received, or to include only participants who reached embryo transfer. These are important distinctions for a randomized trial, but their handling is not reported in the registry record.

For a binary outcome, analysis choices can matter when events are sparse. General statistical methods may use exact approaches or models designed for binary outcomes, but selecting a method requires knowing the analysis plan and the data structure. The posted record does not name a method or provide an inferential result, so no particular approach can be attributed to this trial.

How should the planning illustrations be read?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They are based on the observed effect, with the effect to detect expressed as a stated fraction of that effect. For time-to-event outcomes, such planning displays concern total events; for other outcomes, they concern participants per arm. These are planning calculations, not observed power and not evidence that the trial had a particular design target. The registry does not report the trial’s own sample-size justification or whether those illustrative assumptions were used when the trial was designed.

More generally, power is a design-stage probability defined under specified assumptions about an effect, variability, significance level, and analysis. It is not a measure of how convincing an observed result is after data collection. A planning calculation based on the observed effect cannot replace a confidence interval or a prespecified sample-size rationale. Numerical planning results and a trial-specific sample-size justification are not reported in the registry record.

The record’s note that the two-arm binary comparison is not estimable is therefore central to interpretation. The descriptive counts remain informative as a record of what was posted, but a formal estimate of comparative effect and its precision are unavailable. Statistical explanations of possible methods are general and should not be read as claims about analyses actually performed in this study.

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("Oocyte Vitrification", "Embryo Freezing")
n      <- c(3, 8)
events <- c(0, 4)
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  Oocyte Vitrification  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Embryo Freezing  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no secondary outcomes. That limits the number of posted endpoints that can be considered, but it does not establish what outcomes may have been collected or examined outside the registry. A prespecified statistical analysis plan and any multiplicity strategy are not reported in the registry record.

Multiplicity arises when several outcomes, time points, or analyses are tested: repeated testing can make chance findings more likely unless the analysis accounts for that process. This is a general statistical concern, not a claim that this trial conducted multiple tests. The record does not report interim analyses, subgroup analyses, or adjustments for multiple comparisons, so none should be assumed.

The registry reports the primary outcome counts by arm, but it does not describe missing outcome data, withdrawals, exclusions, or participants who did not reach embryo transfer. It also does not state whether the posted denominators include all randomized participants or only those with an assessable endpoint. The flow of participants and the analysis population are not reported in the registry record.

In general, missingness can affect interpretation if the likelihood of an outcome being unobserved is related to participant characteristics or outcome status. Statistical approaches depend on how much information is missing and why it is missing. Since the record does not describe missingness or its handling, the effect of any missing data cannot be evaluated from the posted information.

The randomization is reported, but the analysis approach for preserving the benefits of random assignment is not. Whether analyses followed assigned groups, actual procedures received, or another population is not reported in the registry record. These gaps matter when interpreting a comparison based on a post-transfer endpoint.

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 0% reporting threshold.

The registry’s adverse-event entries report 0 serious adverse events in the oocyte vitrification arm among 3 participants at risk, and 0 in the embryo freezing arm among 8 participants at risk. The entries also report 0 other adverse events in the respective groups, using the same at-risk counts. These figures describe the adverse-event information posted for the trial.

Zero reported events should be read as an observation in the listed groups, not as proof that an event is impossible or that there is no safety risk. The numbers at risk are small, and the registry does not provide a detailed description of safety surveillance, event definitions, collection methods, or follow-up duration for adverse events. Those details are not reported in the registry record.

Deaths are not reported in the adverse-event entries. The record lists no serious adverse-event terms. The posted entries do not establish that every possible harm was assessed or that the two approaches have equivalent safety. They are limited to the adverse-event counts and categories recorded in the registry.

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

The registry records a randomized comparison of two freezing strategies for IVF hyper-responders and reports fetal heart activity one month after embryo transfer as the primary outcome. It lists 0 participants with the finding in the oocyte vitrification arm and 4 in the embryo freezing arm. The corresponding arm counts are 3 and 8. This is a description of the posted outcome data, not a complete statistical comparison.

The record does not provide an estimated between-arm effect, confidence interval, or test result. It also marks the binary two-arm comparison as missing or not estimable. As a result, the precision of any comparative effect cannot be assessed from the registry entry. The observed counts should not be interpreted as establishing that one strategy performs better or worse.

The endpoint is specific: fetal heart activity by vaginal ultrasound one month after transfer. It is not a report of every outcome relevant to IVF, and the registry lists no secondary outcomes. Later pregnancy outcomes, births, and other measures are not reported as outcomes in the record. It is also unclear from the entry how participants without a transfer or without an outcome assessment were treated.

The trial’s randomized design is relevant, but design labels alone do not resolve uncertainty from small arm counts or missing analysis details. The registry does not report the randomization implementation, analysis population, missing-data handling, or statistical method. These limitations prevent a more complete assessment of how assignment and follow-up relate to the posted endpoint counts.

The record also reports no serious or other adverse events in the listed arms, while providing no detailed safety methods or longer-term safety account. This should be interpreted as no events recorded in these entries, rather than proof of an absence of risk. Taken together, the registry offers a limited descriptive account of one primary outcome and adverse-event counts. It does not establish comparative efficacy, safety equivalence, or outcomes beyond those specifically recorded.

14. Why This Trial Matters Statistically

This trial illustrates the difference between having a randomized design and having a precise, interpretable treatment-effect estimate. Random assignment is a useful design principle for comparing interventions, but the posted primary outcome counts are based on small arm sizes, and the registry does not report a comparative estimate or its uncertainty. Without those elements, a reader cannot gauge how compatible the observed pattern is with a wide range of underlying effects.

It also highlights why outcome definition and analysis population matter. Fetal heart activity is assessed one month after embryo transfer, while the intervention assignment occurs at the earlier egg or embryo freezing stage. The registry does not report the path from assignment to transfer or how participants without a transfer were handled. A post-transfer outcome can therefore leave important questions about who contributed to the endpoint counts.

The record is useful for distinguishing descriptive reporting from inferential analysis. It posts event counts and arm denominators, yet identifies the binary comparison as not estimable. Avoiding an unsupported calculation is important: an apparent difference in raw counts does not account for the distinct denominators or quantify uncertainty.

Finally, the trial provides a setting in which planning calculations must be kept separate from evidence generated by the trial. The stated sample-size assumptions describe planning illustrations based on an observed effect; they are not observed power and are not a substitute for a trial-specific design justification. The registry record does not report that justification. These features make the study a concise example of why complete reporting of outcomes, participant flow, analysis methods, and uncertainty is needed for readers to interpret clinical trial results.

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 posted enrollment is 11, with arm outcome counts based on 3 participants in the oocyte vitrification group and 8 in the embryo freezing group. These small counts limit the precision that can be expected from a comparison, and the registry does not report a confidence interval or inferential result. It specifically indicates that values for a two-arm binary comparison are missing or not estimable.

The record gives little information about participant flow. It does not state how many assigned participants reached embryo transfer, whether every participant had an ultrasound assessment, or how participants without a transfer or assessment were classified. The analysis population and missing-data handling are not reported in the registry record.

Other design and analysis details are also absent. The registry does not describe the randomization sequence or allocation concealment, identify a statistical method, or give a prespecified analysis plan. It does not report a trial-specific sample-size justification, interim analyses, or multiplicity procedures. These omissions restrict assessment of the conduct and analysis beyond the stated randomized, unmasked, parallel design.

The outcome information is narrow: one primary endpoint is listed, and no secondary outcomes are posted. The registry does not provide other reproductive outcomes or a detailed safety-surveillance account. Adverse-event entries show no reported serious or other events in the listed groups, but event definitions and follow-up details are not reported. The findings should therefore be interpreted as limited to the specific posted outcome and safety entries, rather than as a full account of clinical outcomes or harms.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: IVF Hyper-responders: Oocyte Vitrification Compared With Embryo Freezing — NCT02026193.
• Registry record last updated 2015-06-08; status last verified 2015-05.
• Results first posted 2015-06-08.
• 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

NCT02026193 is a completed, randomized, unmasked, parallel-group trial sponsored by Rambam Health Care Campus. The registry records a study start of 2014-01, primary completion of 2014-11, and enrollment of 11. The study compares oocyte vitrification with embryo freezing in IVF hyper-responders.

The primary endpoint is fetal heart activity detected by vaginal ultrasound one month after embryo transfer. The registry reports 0 participants with the outcome among 3 in the oocyte vitrification arm and 4 among 8 in the embryo freezing arm. It does not report a statistical estimate or uncertainty interval for the two-arm comparison and marks that comparison as not estimable. No secondary outcomes or analysis entries are posted.

The adverse-event entries report 0 serious and 0 other events in each listed group; deaths are not reported. Participant flow, missing-data handling, analysis population, and a trial-specific sample-size justification are not reported in the registry record.