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Self-operated endovaginal telemonitoring: a prospective, clinical validation study

      Objective

      To study the comparability of self-operated endovaginal telemonitoring (SOET) with conventional two-dimensional transvaginal sonography (2D-TVS) monitoring during assisted reproductive technology (ART) cycles.

      Design

      Single center, observational, single-blinded cohort study.

      Setting

      University-affiliated in vitro fertilization center.

      Patient(s)

      A total of 60 women undergoing ART cycles.

      Intervention(s)

      Explanation, training, and use of SOET system, and measurements of follicular and endometrial diameter with SOET and 2D-TVS.

      Main Outcome Measure(s)

      Correlation of the total number of follicles >10 mm measured by SOET versus conventional 2D-TVS.

      Result(s)

      In 16 cases (26.7%) the images were judged unsuitable for analysis. In these excluded cases the body mass index (BMI) was statistically significantly higher (29.3 vs. 24.4 kg/m2). The total number of follicles >10 mm was highly similar comparing SOET with conventional 2D-TVS (r = 0.91). For the concordance of whether more than 19 follicles or more than 25 follicles >10 mm were present, we found agreement between the methods in 43 of 44 cases (κ = 0.88) and 43 of 44 cases (κ = 0.85), respectively. For concordance on predefined human chorionic gonadotropin administration criteria, agreement was found in 39 of 44 cases (κ = 0.734).

      Conclusion(s)

      The incidence of SOET videos not suitable for analysis seems to be associated with higher BMI. Otherwise, SOET showed good agreement with conventional 2D-TVS both for follicles and endometrium measurements. More importantly we also found good concordance regarding the cutoffs relevant for clinical decisions.

      Key Words

      Discuss: You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/pereirai-self-operated-endovaginal-telemonitoring/
      The endovaginal ultrasonographic monitoring of follicular growth during assisted reproductive technology (ART) cycles is essential for timing of sexual intercourse or intrauterine insemination (IUI) as well as for monitoring ovarian response to follicle-stimulating hormone stimulation in patients undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). For the latter, finding the optimal time-point for human chorionic gonadotropin (hCG) administration and detecting hyperresponding patients who are at risk for developing ovarian hyperstimulation syndrome (OHSS) are of great clinical importance. For monitoring the ovarian activity, patients typically need to undergo several scheduled examinations during the course of one treatment cycle, which is burdensome for the patient and uses precious resources of the treatment center.
      Performing transvaginal sonography (TVS) at home by the patient or partner in ovulation induction (OI) or COS cycles could eliminate some—if not all, in selected cases—monitoring visits at the treatment center. The self-operated endovaginal telemonitoring (SOET; SONAURA) system consists of a vaginal probe connected by universal serial bus (USB) to a small tablet that is suitable for home use by the patient (Fig. 1). A specific website application to which the recorded data are immediately uploaded allows the operator to perform follicular and endometrial two-dimensional (2D) measurements using the video recorded by the patient.
      Figure thumbnail gr1
      Figure 1The self-operated endovaginal telemonitoring (SOET) system used in this study (SONAURA).
      As yet, only one clinical study on SOET in COS on IVF patients has been performed (
      • Gerris J.
      • Delvigne A.
      • Dhont N.
      • Vandekerckhove F.
      • Madoc B.
      • Buyle M.
      • et al.
      Self-operated endovaginal telemonitoring versus traditional monitoring of ovarian stimulation in assisted reproduction: an RCT.
      ), in which SOET was not inferior in terms of number of metaphase 2 oocytes obtained as compared with conventional 2D TVS. However, the study was prematurely terminated and did not allow the assessment of infrequent events such as OHSS occurrence in the cases erroneously not canceled because of ovarian hyperresponse. Our study tested the comparability of SOET with 2D-TVS when performed in the same patient, on the same day, and we extended the tested population to patients undergoing ovulation induction (OI) or intrauterine insemination (IUI). We examined the correlation between SOET and 2D-TVS findings as well as the concordance between the systems in detecting predefined criteria usually employed for clinical decisions during monitoring, such as the follicular size to trigger final oocyte maturation and the total number of follicles to estimate the risk of OHSS.

      Material and methods

      Between May and June 2015, we performed a prospective, single center, observational, single-blinded cohort study comparing SOET with conventional 2D-TVS monitoring during ART cycles, including monitoring of natural cycles, OI cycles with clomiphene citrate or follicle-stimulating hormone, and COS cycles for IVF or ICSI. The study took place at a university-affiliated IVF center. Institutional review board approval was not necessary because no pharmaceutic drugs were tested, the ultrasound device is marked for conformity in the European Economic Area (CE labeled), and the SOET findings did not alter the clinical treatment. However, all relevant data protection regulations were followed.

       Study Protocol

      Patients first underwent conventional 2D-TVS monitoring to measure endometrial thickness and the diameter of all follicles by calculating a mean value from two perpendicular axes. An experienced physician used a Voluson S6 2D (GE Healthcare). Patients then were asked to participate in the study when the following criteria has been met: willingness to use SOET, presence of two ovaries, and a body mass index (BMI) ≤40 kg/m2. Patients with ovaries that could not be visualized by conventional 2D-TVS were excluded.
      After the routine 2D-TVS examination, an explanation of the SOET system and patient training in SOET use were provided in a separate room. The patient was placed on a gynaecologic chair and learned the basic use of the tablet, including how to recognize the uterus and both ovaries. The training continued until the patient felt confident with the SOET procedure. The patient was then transferred to an outpatient room with a bed, where she self-recorded first her right ovary, then the uterus with the endometrium, and finally the left ovary while lying or sitting on a bed. After recording the images, which lasted by the default setting 30 seconds for each ovary and 15 seconds for the uterus, the patient was able to check the recorded images before transmitting the file by wireless LAN. If the patient did not consider the images to be useable, another recording could be made. The videos were then transmitted to imaging software where a different operator, who was not aware of the measurements yielded by the 2D-TVS, performed the 2D measurements of the follicles and endometrium. The video images could be stopped or played forward or backward, and two calipers were used to measure the endometrial diameter and each follicle at its two largest diameters. Video images were considered unsuitable for analysis if the endometrium or if at least one of the ovaries could not be visualized.

       Outcome Measures

      The primary outcome was defined as the correlation of the total number of follicles >10 mm measured by SOET versus conventional 2D-TVS. Furthermore, the number of follicles was assessed in four size categories: 11–14 mm, 15–17 mm, 18–20 mm, and ≥ 20 mm. Follicles ≤10 mm were not included in the analysis. The secondary outcomes were incidence of videos not suitable for analysis as judged by the operator; correlations in different follicle size categories (11–14 mm, 15–17 mm, 18–20 mm, >20 mm); correlation of endometrial thickness (mm) measured in a sagittal view; concordance if hCG criteria was reached, defined as one follicle ≥18 mm for IUI or timed intercourse cycles, and 3 or more follicles ≥18 mm for IVF or ICSI; or concordance if more than 19 follicles >10 mm or more than 25 follicles >10 mm were present. Each patient could enter the study only once and could thus contribute with only one paired observation to the total data set.

       Statistics

      All values are expressed as mean (±standard deviation) or proportion, as appropriate. Unpaired Student's t test and chi-square test were used for data assessment. A two-sided 95% confidence interval for the mean difference in the number of follicles present in each category with conventional 2D-TVS versus SOET was calculated. Agreement between the two methods was assessed with Pearson correlation coefficient and Cohen's kappa coefficient using SPSS version 23 (IBM). P<.05 was considered statistically significant.

      Results

      All the women who, after explanation of SOET, agreed to enter the study completed the ultrasound. Sixty patients were enrolled in the study. In 16 cases (26.7%) the images were judged unsuitable for analysis. The reason for considering the video unusable was the nonvisualization of: the left ovary in six cases (37.5%), both ovaries and endometrium in five cases (31.3 %), both ovaries in four cases (25%), and the left ovary and the endometrium in one case (6.3%). In these excluded cases the mean BMI was 29.3 ± 8.2 kg/m2; 56.2% had a BMI over 25 kg/m2, and 37.5% had a BMI over 30 kg/m2. We found no significant differences in other variables between patients with and without usable videos (Table 1).
      Table 1Demographics of the study population.
      DemographicsTotal (n = 60)Patients with usable SOET video (n = 44)Patients without usable SOET video (n = 16)P value
      Patients with versus without SOET results.
      Age (y)
      Values are mean ± standard deviation.
      34.1 ± 4.933.9 ± 4.634.3 ± 5.7.85
      BMI (kg/m2)
      Values are mean ± standard deviation.
      25.7 ± 6.024.4 ± 4.529.3 ± 8.2.005
      No. OI cycles13/60 (21.7%)9/44 (20.5%)4/16 (25%).731
      No. of IUI cycles18/60 (30%)14/44 (31.8%)4/16 (25%).755
      No. of IVF-ICSI cycles29/60 (48.3%)21/44 (47.7%)8/16 (50%)1.000
      No. of monofollicular growth cycles28/60 (46.7%)19/44 (43.2%)9/16 (56.3%).397
      No. of follicles >10 mm on 2D-TVS
      Values are mean ± standard deviation.
      13.3 ± 6.713.1 ± 6.813.6 ± 6.6.848
      Note: 2D-TVS = two-dimensional transvaginal sonography; IUI = intrauterine insemination; IVF-ICSI = intracytoplasmic sperm injection in in vitro fertilization; OI = ovulation induction; SOET = self-operated endovaginal telemonitoring.
      a Patients with versus without SOET results.
      b Values are mean ± standard deviation.
      In the remaining 44 cases, in which the images were judged suitable for analysis, the mean age of the participants was 33.9 ± 4.6 years and the mean BMI was 24.4 ± 4.5 kg/m2. In this group 31.8% had a BMI over 25 kg/m2 and 9.1% over 30 kg/m2.
      The total number of follicles >10 mm was highly similar when comparing SOET and conventional 2D-TVS (r = 0.91, P<.0001) (Fig. 2). Furthermore, statistically significant correlations were found for all categories of follicular size and the endometrial diameter: endometrial diameter (r = 0.77, P<.0001); follicle size categories 11–14 mm: r = 0.72, P<.0001; 15–17 mm: r = 0.68, P<.0001; 18–20 mm: r = 0.54, P<.0001 and >20 mm: r = 0.49, P=.001. The number of follicles present in each category with the two systems is presented in Table 2.
      Figure thumbnail gr2
      Figure 2Scatter plot of two-dimensional transvaginal sonography (2D-TVS) versus self-operated endovaginal telemonitoring (SOET) measurements.
      Table 2Mean follicles numbers derived from 2D-TVS versus SOET.
      FolliclesConventional 2D-TVSSOETMean difference95% CI
      Size (mm)
       11–142.11 ± 3.381.43 ± 1.74−0.68−0.46 to 1.82
       15–171.02 ± 1.641.2 ± 1.62+0.18−0.87 to 0.51
       18–200.59 ± 0.690.66 ± 1.6+0.07−0.59 to 0.45
       >200.16 ± 0.370.2 ± 0.46+0.04−0.22 to 0.13
      Total no.13.1 ± 6.812.1 ± 6.8−1−1.74 to 3.87
      Note: Values are mean ± standard deviation. CI = confidence interval; 2D-TVS = two-dimensional transvaginal sonography; SOET = self-operated endovaginal telemonitoring.
      For the concordance between SOET and conventional 2D-TVS of whether more than 19 follicles >10 mm were present, we found agreement in 43 of 44 cases (κ = 0.88, P<.0001). The single discordant case was an ICSI cycle in which conventional 2D-TVS follicle count was 20 and SOET follicle count 13. When analyzing whether more than 25 follicles >10 mm were present, we found agreement between the two methods in 43 of 44 cases (κ = 0.85, P<.0001). The discordant case was an ICSI cycle in which there was a difference of nine follicles between conventional 2D-TVS and SOET (total follicle count of 30 with conventional 2D-TVS and 21 with SOET). For concordance on hCG criteria reached, we found agreement in 39 of 44 cases (κ = 0.734, P<.0001). The five discordant cases are detailed in Supplemental Table 1.

      Discussion

      We have demonstrated that the correlation between conventional 2D-TVS and SOET findings is high, but also that in a statistically significant number of cases no usable video could be obtained. Although this study was not designed to specifically identify the variables that cause nonsuitable videos, the higher BMI in the excluded cases suggests that SOET may not be adequate for overweight women. Other variables that might be important are dexterity of the patient and size/number of follicles to be visualized. Further studies are needed to establish which factors are associated with the difficulty in obtaining appropriate videos, thus allowing a better selection of the patients who could take advantage of SOET. It is also important to consider that in real use a single patient will develop expertise as the monitoring proceeds, which could then result in a lower incidence of unusable images.
      Measurements with SOET shows a tendency to obtain lower average number of follicles in the smallest category (11–14 mm), whereas the average number of follicles in the larger size categories was higher than those obtained with conventional 2D-TVS. As the mean difference on follicle count was lower than one follicle in all size categories, it is very unlikely that this small difference would affect treatment outcomes; we herein demonstrate that, on average, conventional 2D-TVS and SOET resulted in a similar number of follicles. The scatterplot also shows that good concordance between the two systems is also maintained in the outliers.
      The small differences observed on follicle counts and follicle size measurements between 2D-TVS and SOET is unlikely to substantially influence clinical decisions, as a strong correlation in hCG criteria and estimation of OHSS risk criteria between the two methods was found. Because in this study only five patients had more than 19 follicles >10 mm, a larger sample size would corroborate the confidence into the reliable prediction of OHSS risk. For the optimal time-point of hCG administration in routine patients, some leeway has been demonstrated in recent clinical studies (
      • Tremellen K.P.
      • Lane M.
      Avoidance of weekend oocyte retrievals during GnRH antagonist treatment by simple advancement or delay of hCG administration does not adversely affect IVF live birth outcomes.
      ,
      • Leader A.
      • Devroey P.
      • Witjes H.
      • Gordon K.
      Corifollitropin alfa or rFSH treatment flexibility options for controlled ovarian stimulation: a post hoc analysis of the Engage trial.
      ); for instance, postponement or earlier administration of hCG administration by 24 hours is unlikely to affect the clinical results of an IVF cycle.
      It is noteworthy, that any two measurement methods for follicular size and number are unlikely to yield identical results for all individuals. For example, Forman et al. showed that manual measurement of follicles with 2D ultrasound is often inaccurate and subject to significant intraobserver and interobserver variability (
      • Forman R.G.
      • Robinson J.
      • Yudkin P.
      • Egan D.
      • Reynolds K.
      • Barlow D.H.
      What is the true follicular diameter: an assessment of the reproducibility of transvaginal ultrasound monitoring in stimulated cycles.
      ,
      • Ata B.
      • Seyhan A.
      • Reinblatt S.L.
      • Shalom-Paz E.
      • Krishnamurthy S.
      • Tan S.L.
      Comparison of automated and manual follicle monitoring in an unrestricted population of 100 women undergoing controlled ovarian stimulation for IVF.
      ). The relevant issues when comparing a new method to an established standard are the magnitude of the difference between the two methods, the direction of the mean effect, and the incidence with which extreme outliers may occur. For all these aspects, the present data are reassuring in all cases were an appropriate video file could be obtained.
      During the period of follicle monitoring, SOET saves time both for the patient and for the sonographer. Previous studies showed that in addition to saving time, SOET has other important advantages. When using SOET, patients were more satisfied, felt more empowered, and experienced a higher sense of discretion. The active participation of the partner was higher, and, overall, the couple experienced less stress. Also, SOET could diminish the total cost of an ART cycle by decreasing the travel costs for the patient, the productivity losses experienced by the employer, and thus improve society overall (
      • Gerris J.
      • Delvigne A.
      • Dhont N.
      • Vandekerckhove F.
      • Madoc B.
      • Buyle M.
      • et al.
      Self-operated endovaginal telemonitoring versus traditional monitoring of ovarian stimulation in assisted reproduction: an RCT.
      ). However, it is noteworthy that as yet little is known about the distribution of individual patient preferences when they have the option to choose between 2D-TVS and SOET, or how this varies across settings and populations. This topic would require further studies.
      In our study patients were not blinded to the results of the conventional 2D-TVS, and this could be considered a limitation of the study. Further studies are needed to allow the use of self-monitoring as a single monitoring method. It also would be interesting to analyze interobserver and intraobserver variations of SOET measurements.
      For the implementation of SOET into a clinical IVF program, distinct medicolegal aspects are likely to play a role in different settings, and thus potential liability issues resulting from adverse events occurring in SOET cycles need to be dealt with by, for example, exemptions from liability wherever the legal frame works allows such agreements between care providers and patients. In conclusion, SOET appears to be a worthy addendum to routine patient care in selected cases.

      Appendix

      Supplemental Table 12D-TVS versus SOET hCG criterion discordant cases.
      CaseType of ART cycleConventional 2D-TVSSOET
      1OI1 follicle: > 20 mm

      1 follicle: 18–20 mm
      2 follicles: 15–17 mm
      2OI1 follicle: 18–20 mm1 follicle: 10–14 mm
      3IUI1 follicle: 18–20 mm1 follicle: 15–17 mm
      4IUI1 follicle: 15–17 mm1 follicle: 18–20 mm
      5OI1 follicle: 18–20 mm1 follicle: 15–17 mm
      Note: ART = assisted reproduction technology; 2D-TVS = two-dimensional transvaginal sonography; hCG = human chorionic gonadotropin; IUI = intrauterine insemination; OI = ovulation induction; SOET = self-operated endovaginal telemonitoring.

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