Sildenafil Vaginal Gel Co-treatment With Clomiphene Citrate in Infertile Women With Thin Endometrium: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sildenafil Vaginal Gel Co-treatment With Clomiphene Citrate in Infertile Women With Thin Endometrium (NCT02710981), a non-randomized na study. The primary outcome is Endometrial Thickness.

2. Clinical Question

3. Trial Design

This was a prospective self-controlled clinical trial with non-randomized allocation, no masking, and a sequential model. Women first underwent a clomiphene citrate-only cycle, identified as the 6th ovulation-induction cycle. Those who did not conceive then continued clomiphene citrate and received sildenafil vaginal gel in a later cycle, identified as the 7th. The trial therefore compared measurements from different cycles in the same intended study population rather than assigning participants at random to concurrent arms.

The eligibility description concerns women with prior clomiphene citrate failure and thin endometrium: five prior ovulatory cycles of clomiphene citrate induction without conception, with endometrial thickness <8mm in at least three cycles. The record states enrollment of 42. Its brief summary says 36 women received the combination in the 7th cycle, while the arm description says 41 women who did not conceive on the clomiphene-only cycle received the combination. Adverse-event risk counts also differ by event category and group. The registry record does not reconcile these counts, so the number assessed for each outcome should not be assumed to be identical.

For the clomiphene-only cycle, the record describes clomiphene citrate 100 mg/day for 5 days. In the later cycle, the same clomiphene regimen was supplemented with sildenafil vaginal gel, described as 5 gm twice daily from cycle day 8 until HCG injection; the brief summary says the gel contained 50 mg sildenafil. Endometrial thickness and uterine artery Doppler were measured on the day of HCG administration.

The record lists a study start of 2015-06, primary completion of 2016-01, and status of completed. It does not report a randomized allocation procedure, masking, or a concurrent control group. A self-controlled sequence can reduce differences between participants, but cycle order and other changes over time remain possible explanations for differences between measurements.

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: As this is a self controlled clinical trial, participants in the clomiphene citrate only arm (6th ovulation induction cycle) are the same participant in the clomiphene citrate plus sildenafil vaginal gel arm (7th ovulation induction cycle).

6th Ovulation Induction Cycle (5 Days)

7th Ovulation Induction Cycle (5 Days)

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 Endometrial Thickness, measured over Day of HCG administration.

The primary endpoint is endometrial thickness, recorded as a continuous measure in millimeters. The registry describes a transvaginal sonographic measurement of the maximal distance spanning the endometrial-myometrial interface on each endometrial stripe in a sagittal plane in the uterine fundus. Measurement was scheduled for the day of HCG administration in each cycle.

As a general statistical matter, a continuous measurement preserves more information about the size of an observed value than a classification that reduces it to categories. Reporting a mean and standard deviation can describe the center of the measured values and their spread. The registry identifies the planned summary as a mean with standard deviation. It does not report the mean, standard deviation, number measured, or comparison estimate for endometrial thickness in either cycle. Those results are therefore not reported in the registry record.

Endometrial thickness was selected as the primary outcome in this record, while uterine blood flow and clinical pregnancy rate are listed as secondary outcomes. The endpoint measures an anatomical feature at a specified time; by itself it does not establish a pregnancy outcome or explain why measurements might differ between cycles. Interpreting the measurement requires attention to the sequential design, the number of participants with data, and the uncertainty around any comparison. Those analysis details and results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a mean with standard deviation. As general statistical explanation, a mean is a summary of the central level of a continuous measurement, while a standard deviation describes how spread out individual measurements are around that mean. These summaries can help readers understand the distribution of endometrial thickness, but they do not by themselves quantify the uncertainty in a comparison between cycles. The registry record does not report the endpoint means or standard deviations.

What does a self-controlled comparison estimate?

In a self-controlled design, measurements from the same participant under different conditions may be compared. In general, this can reduce the influence of participant characteristics that do not change across the measurement occasions. For this trial, the clomiphene-only cycle came first and the combination cycle came later. The comparison is therefore also linked to cycle order. Differences in measurements could be associated with the added gel, but the sequential design does not by itself rule out changes over time or cycle-specific influences.

A suitable analysis of repeated measurements often needs to account for the fact that observations from the same participant are related rather than independent. That is a general consideration, not a description of an analysis used in this trial. The registry record reports 0 analyses and does not state whether a paired method, a model for repeated measures, or another approach was used. It also does not report whether all participants had measurements in both cycles.

How should uncertainty be read?

In general, a confidence interval describes a range of effect estimates compatible with the data and the assumptions of the statistical method. Its width reflects precision: a wider interval generally indicates less precision than a narrower one. A p-value, when reported, measures how unusual data would be under a specified null hypothesis and model; it does not quantify the size or clinical importance of an effect. Neither a confidence interval nor a p-value for endometrial thickness is reported in the registry record. No inference about the strength of statistical evidence can be made from an endpoint name or a planned summary statistic alone.

What does the planning illustration mean?

The record describes a sample-size planning illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that non-time-to-event illustrations refer to participants per arm, while time-to-event illustrations refer to total events. These are planning assumptions, not a description of the trial’s actual design or a sample-size justification. No resulting participant counts for the illustration are reported in the registry record. A planning calculation based on an observed effect must not be interpreted as observed power or as evidence that the trial was adequately sized.

General sample-size calculations depend on assumptions about the effect to be detected, variability, significance threshold, power target, and analysis structure. In a repeated-measure design, the association between measurements from the same participant can matter. The registry record does not report a prospective sample-size rationale or the assumptions used to plan enrollment. The illustration’s equal-allocation assumption also does not describe the sequential self-controlled structure reported for this study.

Why does the design affect statistical interpretation?

Random allocation is generally used to balance, on average, both measured and unmeasured participant characteristics between treatment groups. This study is explicitly non-randomized and sequential, so that protection is not part of its design. Within-person comparison may control stable individual differences, but it cannot automatically control factors that change from one cycle to another. No adjustment strategy or model specification is reported in the registry record.

Finally, counts must be interpreted in relation to the particular outcome. The record’s brief summary says 36 women received the later-cycle combination, while the arm description says 41; adverse-event summaries use their own at-risk counts. Without a participant flow account or outcome-specific analysis populations, readers cannot establish which denominator applies to the primary endpoint. These omissions concern the interpretation of the posted data, not the general definition of the statistical methods.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Clomiphene Citrate Only Group (6th Ovulation Induc", "Clomiphene Citrate Plus Sildenafil Vaginal Gel (7t")
n   <- c(41, 36)
m   <- c(6.6, 9.3)
sp  <- c(1.4, 3.1)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Clomiphene Citrate Only Group (6th Ovulation Induc  41  6.600  1.400  6.158  7.042
CARM  Clomiphene Citrate Plus Sildenafil Vaginal Gel (7t  36  9.300  3.100  8.251  10.349

11. Multiplicity, Missing Data and Analysis Populations

The record lists endometrial thickness as the primary outcome and uterine blood flow and clinical pregnancy rate as secondary outcomes. It also reports 3 outcome measures and 0 analyses. No multiplicity strategy is reported in the registry record. As a general statistical matter, evaluating several outcomes can increase the chance of at least one apparently unusual result if each is tested separately. Whether and how to address this depends on the prespecified analysis plan, which is not reported in the registry record. No outcome-specific estimates or tests are reported, so the potential influence of multiplicity on findings cannot be assessed.

The registry record does not describe missing-data rules, imputation, exclusions, or sensitivity analyses. The brief summary reports 42 recruited and 36 women in the later cycle, while the arm description gives 41 women for that cycle. The adverse-event section also reports different numbers at risk by event category. The record does not explain the distinctions among these counts, identify reasons for nonparticipation or missing measurements, or state the analysis population for each outcome. It is therefore not possible to determine how many participants contributed paired primary-outcome measurements or whether missing outcomes could have affected the comparison.

The analysis population is also not defined beyond the descriptions of participants in each cycle. The registry record does not state whether analyses included all recruited participants, only those measured in both cycles, or another subset. These details matter because the population represented by an estimate depends on who contributes data and how missing observations are handled. The record’s absence of analysis entries leaves these points unresolved.

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.

Most frequent non-serious adverse event terms

The adverse-event record separates serious events from other events and gives at-risk counts for each category. In the clomiphene-only group, 0 serious events were reported among 42 at risk, and 0 other events among 41 at risk. In the combination group, 0 serious events were reported among 41 at risk, and 1 other event among 36 at risk. The death counts are not reported in the registry record.

These are descriptive counts, not a comparison adjusted for differences between groups or cycles. The group labels refer to sequential cycles, and the risk denominators are not the same for every event category. The registry record does not explain the differing denominators or provide further detail about the one other event, its timing, or its relationship to treatment. The counts should therefore be read as the adverse-event information recorded, not as a complete characterization of safety or as evidence that an event was caused by a particular treatment.

Zero recorded serious events does not establish that serious events cannot occur; it indicates that none were reported in these registry counts. The record does not provide an analysis of comparative risk, uncertainty intervals, or a fuller account of how events were collected. Safety conclusions beyond the reported counts are not supported by the registry record.

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

The record describes a prospective sequence in which women with prior clomiphene citrate failure and thin endometrium were assessed during a clomiphene-only cycle and, if they did not conceive, during a later cycle with sildenafil vaginal gel added. The stated primary question concerns endometrial thickness on the day of HCG administration. This design makes a within-person comparison possible for participants measured in both cycles, but the treatment sequence is not randomized and the later cycle has no concurrent control group.

The registry record does not report the primary outcome values, the comparison estimate, or its uncertainty. It also does not report results for uterine blood flow or clinical pregnancy rate. Accordingly, the posted record does not show whether endometrial thickness was higher, lower, or similar in the later cycle, nor how precisely any difference was estimated. It cannot support a conclusion about the size or statistical significance of a treatment-associated change.

The design also limits causal interpretation. Measurements in the later cycle could differ for reasons related to adding sildenafil gel, but they could also reflect changes between cycles. A self-controlled design can account for stable participant features in a paired analysis, but does not remove time-related or cycle-related influences. The analysis method and whether paired measurements were available are not reported.

The registry record contains differing counts for women in the later cycle: the brief summary states 36, while the arm description states 41. It does not reconcile these numbers or establish outcome-specific analysis populations. This uncertainty makes it difficult to understand who contributed to each result, especially when no outcome results are posted.

The record’s adverse-event counts describe no serious events reported in either group and one other event in the combination group, with the category-specific denominators stated in the safety description. Those counts do not establish comparative safety or causation. Overall, the registry record documents a clinical question and study sequence, but does not provide the results or analysis detail needed to judge the observed outcome contrast, its precision, or its clinical importance.

14. Why This Trial Matters Statistically

This trial is statistically notable because its comparison is sequential and self-controlled rather than randomized. The same participants could contribute measurements during clomiphene citrate alone and during a later cycle with sildenafil vaginal gel added. That structure highlights a useful general distinction: controlling for stable differences between individuals is not the same as controlling for changes that occur over time. Since the combination cycle followed the clomiphene-only cycle, cycle order is inseparable from the treatment sequence in the design described.

The registry record also illustrates why participant counts and analysis populations matter. It gives 42 as the enrollment, states 36 women in the later cycle in the brief summary, and describes 41 women receiving the combination in the arm description. The adverse-event denominators differ by category. Without a reconciliation or outcome-specific counts, the reader cannot know from the record which participants contributed to each comparison.

A further statistical lesson is the distinction between identifying an endpoint and reporting its evidence. Endometrial thickness is clearly named as the primary outcome, with a measurement definition, unit, and timing. But the registry record does not report the mean, standard deviation, comparison estimate, interval estimate, or analysis. Naming the outcome and its summary format is not enough to evaluate the result.

The record refers to a sample-size planning illustration based on an observed effect, while offering no stated numerical result for that illustration and no trial-specific design justification. Such a planning exercise is not observed power. The case underscores the need to distinguish a retrospective planning calculation from prospective design decisions, and to interpret any proposed sample size in light of the study’s actual allocation and repeated-measure structure.

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 limitation for statistical interpretation is the absence of reported outcome results. The registry identifies endometrial thickness as primary but does not provide the observed means, standard deviations, comparison estimate, confidence interval, or p-value. Secondary outcomes are named without results. The record therefore does not permit assessment of the direction, magnitude, or precision of the outcomes.

The non-randomized, sequential self-controlled design leaves treatment condition tied to cycle order. Although within-person measurements can reduce the influence of stable participant characteristics in a suitable analysis, the registry record does not report the analysis method or whether measurements were paired. Changes between cycles remain possible explanations for any contrast, and no concurrent control group is described.

Participant counts are not consistent across the record’s descriptions of the later cycle. The brief summary states 36 women received combination treatment, while the arm description states 41. The primary endpoint’s population is not reported, and the registry does not explain missing measurements, exclusions, or the analysis population. These gaps prevent a clear account of data completeness.

The statistical plan is not reported. The record does not describe a sample-size justification, multiplicity handling, missing-data methods, covariate adjustment, or interim analyses. It reports 0 analyses. The sample-size planning assumptions are described as an illustration based on an observed effect, not as the trial’s own design. Finally, adverse-event counts are limited to the reported categories and denominators; the record does not provide details for the other event or death counts. These limitations constrain interpretation without establishing that any unreported procedure was or was not conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sildenafil Vaginal Gel Co-treatment With Clomiphene Citrate in Infertile Women With Thin Endometrium — NCT02710981.
• Registry record last updated 2020-05-05; status last verified 2020-04.
• Results first posted 2020-05-05.
• 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

NCT02710981 is a completed prospective self-controlled clinical trial sponsored by Assiut University. The registry record gives a study start of 2015-06 and primary completion of 2016-01. It describes a non-randomized, unmasked, sequential comparison in women with prior clomiphene citrate failure and thin endometrium.

The primary outcome was endometrial thickness in millimeters, measured by transvaginal sonography on the day of HCG administration. The clomiphene-only cycle was followed by a cycle using clomiphene citrate with sildenafil vaginal gel. Uterine blood flow and clinical pregnancy rate were listed as secondary outcomes.

The registry record reports 42 enrolled but gives unreconciled counts for the later cycle. It lists 3 outcome measures and 0 analyses. Primary and secondary outcome results, the statistical analysis, and the handling of missing data are not reported in the registry record. The safety record lists no serious events in either group and 1 other event in the combination group, using the category-specific risk counts.