The LOVE study was a randomized, double-blind, placebo-controlled trial conducted between February 1, 2017 and March 30, 2018 at an academic medical center. This study has been registered as a clinical trial (NCT02979990). The LOVE study has received institutional review board approval from the University of California, San Francisco (IRB 16-20821). All participants provided written consent to participate in the LOVE study.
All patients undergoing their first round of ovarian stimulation for planned oocyte cryopreservation (CO) or IVF at our medical center were recruited to participate in the study. To be included in the study, patients had to be over the age of 18 and have internet access. In our practice, all patients, regardless of study enrollment, were required to participate in a two-hour IVF medication course. This course was taught by one of our nurse practitioners who would review the preparation and administration of the most common IVF medications. Participants typically entered the course shortly after confirming an ovarian stimulation plan with their doctor. However, drug treatment may have been taken away from when they actually started ovarian stimulation weeks or months later. On rare occasions, a patient may have deferred the IVF drug class, in which case the patient would be excluded from enrollment in the LOVE study.
Patients were also excluded if their physician advised against participating in the study or if a patient had already completed an ovarian stimulation cycle prior to enrollment.
Development of the study intervention
The LOVE Study videos were developed by a multidisciplinary team of doctors and nurses. There were two types of LOVE Study videos: placebo control videos, which will be referred to as “control videos” and experimental videos. The review videos included a video previously developed by our clinic that served as an IVF orientation and was available to all patients regardless of enrollment status in the LOVE study. Participants in the control group also had access to a video on the physiology of ovarian stimulation developed by the LOVE study team. Experimental videos reviewed common medications participants might encounter during treatment. Each video included an explanation of the supplies needed for administering the medications and a demonstration of how to administer the medications. Experimental video topics included: needle information, space preparation for drug administration, follicle-stimulating hormone (FSH) agent, human menopausal gonadotropin (hMG) agent, human chorionic gonadotropin (hCG) “Trigger shot”, progesterone preparation, and progesterone injection. Study videos are available for public access at https://crh.ucsf.edu/medication-videos
Each participant received a unique username and password to access the study website (Fig. 2). Once logged in, their account would give them access to videos based on their treatment group. Participants in the control group only had access to the control videos, while participants in the experimental group had access to both the control videos and the experimental videos to guard against the possibility of an independent effect of the placebo videos.
In line with our inclusion criteria, all participants completed our in-person IVF medication education course. Patients who enrolled in the LOVE study were randomized in a 1:1 ratio to a control or experimental group. Randomization was achieved by assigning control or experimental access to videos on the study platform for each study account. Randomization of counts was computerized and counts were assigned by a research associate who was not involved in study recruitment or analysis. Participants were told that the study videos were educational, but the specific content of the videos was not described. Participants and investigators were not informed of the patient’s study assignment. Participants were not required to watch the study videos. However, participants in the control group who chose to log on to the study website were given access to “control” videos of the ovarian stimulation process and an orientation to IVF. The participants in the experimental group had access to all the videos: the “experimental” videos on IVF drugs and also the control videos. Unmasking of study assignments occurred after study closure at the time of initial data analysis. Study closure occurred after the enrollment goal was achieved, but the indication for ovarian stimulation for participants was not assessed.
Participants were asked to complete online surveys, administered by Redcap at the time of registration and at the end of ovarian stimulation13. The initial survey included questions about demographics and a 10-item PSS, completed before the start of their ovarian stimulation cycle and up to the second day of ovarian stimulation. The second survey was carried out at the time of the triggering of the final oocyte maturation up to 16 days after the triggering injection and before the determination of the pregnancy status. Patients who responded to the final survey after this time were excluded from the analysis.
It is important to note that participants were encouraged, but not required, to watch study videos. In addition, other educational videos that were not produced by the LOVE study were routinely made available to patients. Participants were neither encouraged nor discouraged from accessing additional educational content. This scenario best represented the educational environment that typical patients would encounter in our clinical setting.
The primary outcome of the LOVE study was the ISES score at the end of ovarian stimulation. Although the ISES was developed to more broadly describe infertile patients’ perceptions regarding diagnosis and treatment, given its potential to be associated with clinical differences, we used it in this study as a measure of burden. processing in which higher ISES scores may represent less processing load. The ISES score comes from a 16-item questionnaire rated from 1 to 9 on a Likert scale. Scores could range from 16 to 144. Higher scores were associated with stronger self-rated ability to cope with infertility diagnosis and treatment. In a prospective cohort study of 44 women, ISES scores were about 10% higher at the time of egg retrieval in women who conceived during that cycle. We considered a 10% difference in ISES scores to be clinically important, with the potential to have both psychological and treatment-related benefits.
There were several secondary results. We used the Ferti-QoL-T questionnaire which is used internationally to assess the general and treatment-related quality of life of people with infertility. The treatment portion of the instrument consists of 10 items that assess patients’ quality of life with respect to fertility treatment and is scored from 0 to 4. Higher scores are associated with better quality of life with a maximum score of 4014.
We also used the Perceived Stress Scale (PSS), which was first developed by Sheldon Cohen et al.,15.16. The PSS has been used in a wide variety of settings and the scores correlate well with other measures of stress10.17. The PSS score is based on a 10-point questionnaire to assess stress over the past month. Scores can vary between 0 and 40, with higher scores being associated with higher levels of stress16. Finally, participants were asked whether they felt confident about taking their assigned medications and whether they found the videos helpful, had made medication errors, needed medication assistance from from the staff or would recommend the videos to others. Participants were also asked whether or not they watched the videos.
We hypothesized that participants exposed to the experimental videos would have higher ISES scores than patients exposed to the control videos. For the primary outcome of ISES scores, 107 participants would be needed in each group to detect a 10% difference at a power of 0.8 with a standard deviation of 24.5. The target recruitment for this study was 250 participants seeking IVF assuming a 14% dropout rate, which was similar to other infertility-related randomized clinical trials18.19.
The demographics between the control group and the experimental group were assessed using you-tests or chi-square tests where applicable. Continuous outcomes (ISES, FertiQoL-T and PSS scores) were compared between experimental and control groups using a you-test in an intention-to-treat and per-protocol analysis that limited the analysis to patients who approved viewing study videos. Participants’ ratings of video quality – whether or not they found the videos beneficial (useful, confidence-enhancing, worthy of recommendation, etc.) were assessed using univariate logistic regressions.
The normality of the main result (ISES score) was confirmed by the Shapiro-Wilk test. Data are presented as point estimates and significance has been determined at p
Summary of reports
Further information on the research design can be found in the summary of nature research reports linked to this article.