Effect of Colony Stimulating Factor on Implantation and Pregnancy Rates Following IVF (in Vitro Fertilization): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Colony Stimulating Factor on Implantation and Pregnancy Rates Following IVF (in Vitro Fertilization) (NCT01202656), a randomized phase 1, phase 2 study. The primary outcome is Embryo Implantation and Clinical Pregnancy Rates.

2. Clinical Question

The trial asks a question about outcomes after embryo transfer, rather than IVF procedures in general. It compares G-CSF with saline in a randomized crossover design. The record's treatment-sequence labels indicate that participants were assigned to a G-CSF-then-saline sequence or a saline-then-G-CSF sequence. The detailed timing and conduct of each treatment period are not reported in the registry record.

The registry lists embryo implantation and clinical pregnancy rates as the primary outcome, but its description defines two related measures rather than one identical measure. Implantation is based on the number of gestational sacs relative to embryos transferred. Clinical pregnancy uses evidence of viability at a later threshold. The posted arm results give gestational-sac counts, not separate results for each defined measure, and do not report the number of embryos transferred. The primary question is therefore clinically framed, while the posted numerical results provide only a limited view of its components.

3. Trial Design

The registry describes NCT01202656 as a randomized, quadruple-masked, crossover trial with phases listed as PHASE1 and PHASE2. Its status is completed. The sponsor is the Center for Human Reproduction. The record gives a start date of 2010-09 and a primary completion date of 2012-12. Enrollment is listed as 129.

The two treatment sequences are labeled G-CSF then Saline and Saline then G-CSF. The interventions are listed as G-CSF and saline, and the arm results are presented under those treatment names. A crossover design differs from a parallel-group design because a participant may receive both treatments in sequence. That feature can make within-person comparisons relevant, but it also means that sequence, period, and possible carryover effects may matter to interpretation. The registry record does not report the sequence-generation details, treatment-period duration, washout interval, or how the analysis handled period or carryover effects.

The outcome timeframe is 26 to 30 days after embryo transfer for the gestational-sac-based implantation measure. The registry also defines clinical pregnancy as a gestational sac with evidence of a viable pregnancy at least 28 days after transfer. Live birth rates are listed as a secondary outcome, but the posted results described in the record do not include a live-birth estimate.

The primary outcome's planning text states an anticipated change from an implantation rate of 10% to 20%, with about 200 embryos transferred in each study arm for 80% power and alpha of 0.05. This is a planning statement expressed in embryos transferred; it is not an observed result or a statement of the number enrolled. Details of the trial's actual sample-size justification and statistical plan are not reported in the registry record.

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.

Before assignment: The principal reasons for refusal to participate were ''lack of interest'' and technical difficulties in presenting in timely fashion for the treatment to the center. Women with renal disease, sickle cell disease, or a history of malignancy were considered ineligible. No consenting patient was excluded from participation for medical reasons.

Cycle 1

CrossoverCycle

Analysis population for the primary outcome, as defined in the registry: Presuming an implantation rate of 10% and anticipating a 10% increase to 20% with treatment, about 200 embryos transferred in each study arm would be needed for 80% power and alpha of 0.05.

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 Embryo Implantation and Clinical Pregnancy Rates, measured over 26 to 30 days after embryo transfer.

The primary outcome is titled “Embryo Implantation and Clinical Pregnancy Rates.” The implantation definition counts gestational sacs in the endometrial cavity 26 to 30 days after embryo transfer and relates that count to the number of embryos transferred. The clinical-pregnancy definition requires a gestational sac with evidence of a viable pregnancy at least 28 days after transfer. These measures address different stages of the outcome: a gestational sac is evidence of implantation, while the clinical-pregnancy definition additionally requires evidence of viability.

These measures are used because embryo transfer alone does not establish whether an embryo implants or whether a pregnancy progresses to the stated clinical criterion. A gestational-sac-based endpoint can therefore describe an outcome closer to the biological process the intervention is intended to affect than a procedural measure such as the number of embryos transferred. The endpoint definitions also make clear that the denominator for an implantation rate is embryos, not necessarily participants.

The posted results report 32 for the G-CSF arm and 33 for the saline arm, with arm counts of 81 and 80, respectively. The record does not identify these arm counts as the number of embryos transferred, and it does not report the embryo-transfer denominators needed to reproduce the stated implantation-rate calculation. Nor does it give separate posted results for clinical pregnancy. Consequently, the listed numbers should be read as reported counts, not treated as rates or as complete reporting of both parts of the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry names a Cochran-Mantel-Haenszel analysis and reports p = 0.72. It does not give the test statistic, an effect estimate, a confidence interval, or details of the strata used. The method can be understood in general terms, but the record does not provide enough information to reconstruct exactly how it was applied in this trial.

What does a Cochran-Mantel-Haenszel test do?

In general, the Cochran-Mantel-Haenszel approach tests for an association between treatment group and outcome while accounting for one or more strata. Stratification can be useful when data are organized into categories that should be considered in the comparison. The method combines information across strata rather than treating every observation as if it came from one undifferentiated group. Which strata, if any, were used for this trial is not reported in the registry record.

A test p-value addresses compatibility between the observed data and a null hypothesis under the test's assumptions. It is not the probability that the null hypothesis is true, and it does not give the probability that a treatment will help or harm. A p-value also does not measure effect size. Without an estimated contrast and its uncertainty, a reader cannot tell from the p-value alone how large or small the underlying difference may be.

Why is the crossover design relevant?

In general, crossover trials assign treatment sequences so that participants can receive more than one intervention during different periods. Because outcomes from a participant may be related across periods, an analysis may need to account for that within-person structure. The order of treatments and any lingering effect from an earlier period can also matter. The registry identifies a crossover model and two treatment sequences, but does not report its analysis population, the period-specific outcome data, or how it handled within-person correlation, period effects, sequence effects, or carryover. The named test should not be assumed to have addressed these considerations without further documentation.

There is another endpoint-specific issue. The registry defines implantation as gestational sacs divided by embryos transferred, while the posted arm result is a count. A count can be informative, but a rate requires the relevant denominator. The number of embryos transferred by arm is not reported in the registry record. The arm counts labeled for the results cannot safely be substituted for embryo denominators because the record does not state that they represent embryos transferred.

What do the posted counts and p-value establish?

The results list 32 for G-CSF and 33 for saline, and the reported test gives p = 0.72. These are descriptive counts and a test result, not a complete estimate of the difference in implantation rates. No confidence interval is reported. A confidence interval is a general statistical device for expressing uncertainty around an estimated effect: it indicates a range of effect values compatible with the data and the method used. Without an estimate and interval, precision cannot be assessed from the registry result.

The p-value does not show whether the study was adequately powered to detect an effect of a particular size. The primary outcome description includes a planning illustration based on an implantation rate of 10% and an anticipated increase to 20%, with about 200 embryos transferred in each study arm for 80% power and alpha of 0.05. That statement concerns a planning scenario and the number of embryos transferred, not observed power. It does not establish that the trial enrolled the planned number of embryos or that the realized design had the stated power. The actual sample-size rationale and any revisions are not reported in the registry record.

How should statistical significance be distinguished from importance?

In general, statistical significance concerns how unusual the data would be under a specified null model and test assumptions. Clinical importance concerns whether an effect is meaningful for the outcome and context. Neither can be fully assessed from a p-value alone. A clinically important effect can be estimated imprecisely, while a statistically detectable effect need not be important. Here, because the registry does not report the rate denominator, an effect estimate, or a confidence interval, neither the magnitude nor the precision of the primary contrast can be judged from the posted result.

The registry lists one analysis and gives the p-value for that comparison. The record does not describe whether the analysis was prespecified, whether it was adjusted for any covariates or strata beyond what the method name implies, or whether the endpoint's two components were tested separately. General interpretation of any single p-value depends on the planned analysis and the number of questions examined. Those details are not reported in the registry record. The result is best read as the reported test for the stated comparison, without inferring unreported analytical choices.

10. Analyses Reported by the Sponsor

The sponsor's reported analysis is a Cochran-Mantel-Haenszel comparison with p = 0.72. The registry does not give an effect estimate or confidence interval for that analysis. It also does not report an independently recalculated estimate from the posted summary values. Therefore, there is no recalculated effect estimate to compare with the sponsor's result.

When a sponsor analysis and a simple recalculation from posted summary statistics differ, the sponsor's own analysis takes precedence, because it may use data or analytical details not available in a summary record. That distinction does not arise as a numerical comparison in this record: the posted information includes the test name and p-value, but not the outcome denominators or enough detail to independently reproduce the test. The arm counts alone cannot be used to reconstruct implantation rates, since the registry defines the rate using embryos transferred and does not report those denominators.

The sponsor's p-value should consequently be reported as the registry reports it, rather than replaced by a calculation that cannot be reproduced from the available information. It indicates no statistically clear difference under the reported test, but without an effect estimate and interval it does not show the magnitude or precision of the comparison. Further details of the sponsor's analysis, including any stratification and handling of crossover structure, are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry describes the primary outcome as embryo implantation and clinical pregnancy rates, and it lists live birth rates as a secondary outcome. These are related but distinct outcome concepts. The record does not report separate numerical results for implantation and clinical pregnancy, nor does it provide a live-birth result. It also does not state how the analyses of these outcomes were prioritized or whether any multiplicity adjustment was planned or used.

In general, testing several outcomes or several versions of an outcome can increase the chance that at least one result appears noteworthy by chance. A prespecified testing hierarchy or adjustment can address that issue, but no such strategy is reported in the registry record. The listed single analysis and its p-value do not establish whether other analyses were conducted or how their results were handled. No inference about multiplicity control should be made from the absence of additional posted tests alone.

The registry provides arm counts for the primary results, but does not report the number of embryos transferred by arm, which is the denominator in its implantation-rate definition. It also does not report how missing outcome observations, unavailable transfers, or participants without evaluable follow-up were handled. Missing-data methods, imputation procedures, and sensitivity analyses are not reported in the registry record.

The analysis population is also not specified in the posted results. The record does not say whether all randomized participants were analyzed according to assigned sequence, whether results were restricted to participants who completed both periods, or whether another population was used. This is particularly relevant in a crossover trial, where incomplete participation across periods can affect which observations contribute to a comparison. The numbers shown by arm should not be taken as evidence of a particular analysis population.

These reporting gaps limit assessment of both the primary outcome and the broader set of registered outcomes. They do not establish that missing data or multiplicity problems occurred; rather, the registry record does not report enough detail to determine how those issues were addressed.

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 reports zero serious adverse events among 81 at risk in the G-CSF group and zero among 80 at risk in the saline group. It also reports zero other adverse events among 81 at risk in the G-CSF group and zero among 80 at risk in the saline group. No serious adverse-event terms are listed. Death counts are not reported in the registry record.

These figures describe what was recorded in the registry, not proof that no adverse effects occurred. A zero count means that no events were entered for the stated category in the posted results; it does not rule out events that were not observed, not collected, or not reported. The registry record does not provide definitions of the adverse-event categories, the surveillance period, or details about how events were solicited and verified.

The counts also do not establish a precise comparison of safety between the treatments. No uncertainty interval or comparative safety analysis is reported. In a crossover study, timing in relation to treatment periods may be relevant to attribution, but period-specific adverse-event details are not reported. The figures should therefore be read as a limited summary of recorded events, not as a comprehensive assessment of safety.

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

The registry records a randomized, quadruple-masked crossover comparison of G-CSF and saline in the setting of IVF and embryo transfer. Its posted primary results include gestational-sac counts of 32 for G-CSF and 33 for saline, and a Cochran-Mantel-Haenszel p-value of 0.72. This describes the information that is available in the record; it does not by itself establish an effect on implantation or pregnancy.

The primary outcome definition depends on embryo-transfer denominators, but those denominators are not reported. The registry also does not provide separate numerical results for the clinical-pregnancy component, an effect estimate, or a confidence interval. As a result, the magnitude and precision of any contrast cannot be determined from the posted results. The p-value does not demonstrate equivalence and does not rule out effects that the available report cannot estimate precisely.

The endpoint definitions also should not be conflated. Implantation is defined using gestational sacs in relation to embryos transferred, while clinical pregnancy requires a gestational sac with evidence of viability at least 28 days after transfer. A gestational-sac count is not itself a reported clinical-pregnancy rate or a live-birth outcome. Although live birth rates are listed as secondary, their results are not reported in the registry record.

The trial's crossover structure adds questions about periods and within-participant comparisons, but analytical handling of those features is not reported. Likewise, the record does not describe missing-data methods or the analysis population. These limitations do not show that the trial was improperly conducted; they restrict what can be concluded from the registry report.

In short, the posted information documents the trial design, reported counts, and sponsor-reported test result. It does not supply the denominators and uncertainty information needed for a rate-based assessment of the primary outcome, or enough detail to assess all relevant design and analysis choices. The result should be interpreted as incomplete evidence about the specified treatment comparison, not as proof for or against a treatment effect.

14. Why This Trial Matters Statistically

This trial illustrates why outcome definitions and reported results need to be read together. The registry defines implantation as a rate based on embryos transferred, but the results provide counts without the embryo denominators. A count and a rate answer different questions. Without the denominator specified by the outcome definition, the posted values cannot be interpreted as the stated rate or independently checked against it.

It also shows why a p-value is not a complete account of a treatment comparison. The reported p-value of 0.72 gives the result of a named test, but the record does not include an effect estimate or confidence interval. Readers therefore cannot evaluate the size of the contrast or its precision. A result that is not statistically clear is not automatically evidence of equivalence, and a p-value cannot replace an estimate of effect.

The crossover design raises another general statistical issue: results can depend on how repeated observations within participants and differences between treatment periods are modeled. The registry identifies the design and treatment sequences, but does not report how those features were handled in analysis. This makes it difficult to judge how closely the posted comparison reflects the structure of the trial.

Finally, the trial record distinguishes planning assumptions from observed outcomes. Its planning illustration uses embryos transferred per arm and a specified assumed change in implantation rate. That information should not be mistaken for an observed rate, the number enrolled, or observed power. Keeping design assumptions, outcome definitions, and posted results separate is essential to interpreting a clinical trial record accurately.

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 main trial-specific limitation in the registry report is that it does not give the number of embryos transferred by arm, even though embryos transferred are the denominator in the stated implantation-rate definition. The posted values are counts, and the record does not say that the arm counts correspond to embryos. A rate-based comparison therefore cannot be reconstructed from the information reported.

The primary outcome title includes both implantation and clinical pregnancy, but the registry provides no separate numerical results for the two definitions. It reports neither an effect estimate nor a confidence interval, and does not provide a live-birth result despite listing live birth rates as a secondary outcome. This limits evaluation of both the magnitude of the primary comparison and the later outcome named in the record.

Because the study is labeled crossover, period-specific results and the handling of within-participant dependence, treatment sequence, and possible carryover would be relevant to interpretation. Those analytical details are not reported. The registry also does not describe eligibility criteria in detail, participant characteristics, treatment-period timing, or any washout interval.

Information about missing outcomes, the analysis population, and multiplicity procedures is not reported in the registry record. The safety summary lists zero serious and other adverse events in each group, but does not describe event definitions, collection methods, or surveillance timing; death counts are not reported. These gaps prevent a full assessment of outcome completeness, statistical precision, and safety reporting. They are limitations of the available registry account and should not be treated as evidence that unreported procedures or events did or did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Colony Stimulating Factor on Implantation and Pregnancy Rates Following IVF (in Vitro Fertilization) — NCT01202656.
• Registry record last updated 2014-12-02; status last verified 2014-11.
• Results first posted 2014-12-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01202656 is a completed randomized, quadruple-masked crossover trial sponsored by the Center for Human Reproduction. It lists PHASE1 and PHASE2, enrollment of 129, and a start date of 2010-09 with primary completion in 2012-12. The trial compared G-CSF and saline in treatment sequences labeled G-CSF then Saline and Saline then G-CSF.

The primary outcome concerns embryo implantation and clinical pregnancy after IVF and embryo transfer. The registry reports gestational-sac counts of 32 for G-CSF and 33 for saline, with arm counts of 81 and 80, and a Cochran-Mantel-Haenszel p-value of 0.72. It does not report embryo-transfer denominators, an effect estimate, a confidence interval, separate clinical-pregnancy results, or results for the listed secondary outcome of live birth.

The registry reports zero serious and zero other adverse events in each group. Details about missing data, analysis populations, and crossover analysis are not reported. The available results therefore provide a limited statistical account of the comparison and do not permit a precise rate-based interpretation of the primary outcome.