The Challenge: Frequent Clinic Visits for Ovarian Sonograms

The need for serial vaginal sonographies to monitor ovarian stimulation for ART treatments remains a major logistic challenge for patients as well as for health-care providers. This hampers access to ART treatment for many couples or renders it strenuous and expensive from an organizational point of view (Figure 4.1).

Figure 4.1 The rationale for home monitoring in relation to relieving patient stress

Sonograms are currently made by various care providers: gynecologists, reproductive nurses, midwives, radiologists, sonographers. Traditionally, for monitoring of ovarian stimulation, women have to come to the care provider working at or collaborating with the center. This could include different personnel or the same during a single cycle. A Cochrane review states in plain language that following up the follicular phase of an IVF/ICSI attempt by ultrasound alone yields similar results to ultrasound combined with hormone determinations[1,2], putting sonography at the crux of cycle monitoring.

Recording images using a vaginal probe is in itself an easy procedure, entailing no risks or health hazard. Making a sonogram is technically such a simple and a no-risk gesture that it does not necessarily need to be performed by a health-care professional and certainly not by a highly specialized reproductive physician. The chapter author has explored in a step-wise manner whether self-operated endo-vaginal telemonitoring (SOET), simply called home sonography, could be a method for patients and/or their partners to make vaginal sonographies themselves anytime, anywhere[3–7], assuming this would alleviate the stress of the monitoring period.

A Practical Solution

Home sonography allows patients to make their sonograms themselves using a small, safe, and easy-to-use customized device, allowing registration of real-time images under direct visual control of the patient or her partner (Figure 4.2). The instrument consists of a tablet PC, to which a vaginal probe is connected using USB technology. Images are sent with proper identification and secured privacy over the Internet to the center where a care provider receives, stores, analyzes, and interprets the images. A structured report is sent, containing advice on the dose of gonadotropins to be self-injected during the following day(s)[8], the timing for the next sonogram, the precise timing of hCG injection, and of oocyte retrieval.

Figure 4.2 Schematic presentation of the solution provided by home sonography

Initially we questioned 25 consecutive couples regarding their attitude toward home sonography. Their willingness to use a SOET technology prompted further research[3].

Then we sought proof of concept. During 20 attempts, patients were monitored traditionally by one physician. After each sonogram, they repeated the sonogram themselves using normal hospital equipment. Images were sent over the hospital intranet as a proxy for the worldwide Internet, stored at the receiving end of a connected in-house PC, and replayed for measurement and analysis. Another physician, blinded to the treatment, later repeated all measurements in one single session. There was excellent congruence between both sets of measurements and a perfect overlap between all clinical decisions taken by both observers. All patients agreed on a very positive experience, as did the midwives involved in this early phase of the study[4].

Next, a two-year prospective randomized trial was conducted comparing clinical and laboratory outcomes between home sonography (using a prototype instrument, now not in use anymore) and traditional sonography, as well as patient-reported outcomes and a health-economic analysis[5]. Inclusion criteria were: <41 years of age, ICSI, no poor response, two ovaries. One-hundred-and-twenty-one randomized patients completed the study cycle with (n=59) or without (n=62) home sonography. Patient characteristics (age, partner age, BMI, smoking, treatment rank, AMH) in both groups were comparable. Similar conception rates were obtained, as well as a similar number of follicles >15 mm. The number of ova at ovum pickup, (log 2 of) the number of metaphase II oocytes, the number of transferable embryos available at ET, the number of morphologically excellent embryos, and the number of embryos frozen were all comparable. The home sonography group showed a significantly higher feeling of empowerment and more partner participation than the control group. Comparing home sonography patients with their own historical controls in previous attempts, which were monitored traditionally, showed an increased feeling of empowerment, partner participation, feeling of discretion, less stress, and a trend toward more contentedness. A health-economic analysis showed home sonography cycles to have significant financial advantage over traditional monitoring. In particular, the cost of transportation for the patient was lower[5].

Advantages of Home Telemonitoring

A comparison between the disadvantages of the present way of monitoring ovarian stimulation for ART and the advantages of SOET as we have experienced it until today is pictured in Figures 4.1–4.3. Patients do not need to go the center to have sonograms performed. This saves them time and money spent on gas, car usage, train, or bus. They avoid loss of income during working hours. Weekends and their important social and household functions are less interrupted by half- or full-day trips to the center. Patients living far from centers do not have to spend time or money for costly stays of a week or more at a hotel near the center. Centers performing IVF are less crowded by routine patients only needing a sonogram. Measurements based on home sonograms are more standardized and reproducible and can be performed at ease, allowing decreased interobserver variation.

Figure 4.3 Advantages of telemonitoring in ART

Communication with the patient is smoother, more complete and more personalized, and all information needed is documented in print. Questions accompanying the images are answered properly and not hurriedly by a stressed doctor, midwife, or nurse. More time is thus available for truly necessary interactions between doctors/nurses and patients that need to be performed in person with the staff at the center. This reduces excessively long waiting lists for consultations of new patients. Treatments are possible for patients who live far from the center. Home sonography makes follow-up of ovarian stimulation easier not only for the patient but also for the physician as well because images can be retrieved and analyzed at any time and in any place where Wi-Fi is available.

Billing can be simplified by using a fixed price for one monitoring ART ovarian stimulation attempt instead of per sonography, leaving the method used to monitor free to doctor and patient. A major hidden aspect resides at the employers’ side or by avoiding loss of direct income and transportation cost in those with independent jobs. There is more convenience and discretion for the patient and a stronger involvement of the partner, now often reduced to the role of driver. The sheer feeling of empowerment in women and their partners is clearly enhanced. Sonograms can also be made or assisted by the partner who, in 50% of cases, is at the origin of the subfertility and, in many cases, will be more than happy to be able to participate in an active way.

Home sonography is not intended to replace all standard sonograms made by professional care providers. These will remain needed in complicated cases, or when abnormal images (e.g., cysts, hydrosalpinges, unexpected tumors, endometriosis) are observed, or at the request from the anxious type of patient. It is meant to alleviate an abnormal amount of time-consuming, routine work, and to allow patients living far from the center to make fewer demanding sacrifices.

Present Clinical Experience Using Home Sonography

Following the 2014 RCT, we introduced home sonography as a routine possibility for telemonitoring follicular growth. At present the system is used by a small percentage of patients only.

In one hundred consecutive ICSI cycles in 78 different patients over a 14-month period, the Sonaura system (Sonaura LLC, Fort Collis, Colorado, United States) was used[7]. Patients were counseled regarding the possibility of poor response and hyperstimulation. According to the Cochrane review mentioned earlier, there were no systematic serum E2 measurements performed. Patients were shown the introductory movie available at www.mysonaura.com. Teaching is only mandatory in first-time users (n=78), not in repeat users (n=22) because the system is very intuitive, especially for the present generation of young adults raised among tablets and smartphones. For teaching, we use any high-end instrument, either after suppression with an oral contraceptive or early in a natural cycle. The Sonaura system is not presently devised for sonograms during the early follicular phase. A slightly filled bladder may be helpful for teaching, but is not advisable for later recordings. The pelvis should ideally be normal with a normal location of the ovaries. The black streaks of the pulsating iliac artery and the pulseless veins are identified, the adjoining slightly darker grayish ovaries visualized, and, if useful, an antral follicle count is performed. Dilated ovarian veins may be conspicuous. Usually the endometrium is visible, although not with the triple-line image at this time of the cycle. The uterus is outlined as a grayish pear-like organ, containing the endometrium, which will steadily show up as a banana-like figure with a triple-line image. It is also mentioned to the patient that images of the uterus are not very important, because gonadotrophin dosage does not depend on them. A short (15 seconds) registration of the uterus is mainly intended to distinguish left and right ovarian recordings from each other.

Probe movements (sideways, forward, backward, and rotating) are demonstrated when searching for the resting ovaries.

It is always pointed out that home sonography is not a goal in itself, but a facilitating tool. Should either the doctor or the patient desire so, a professional sonogram is possible in the center daily, the full year round. First sonograms are not required before day seven or eight of gonadotropin injection. The patient with the shortest follicular phase received hCG on day nine of stimulation. So-called random stimulation regimens where stimulation is started at any moment of the cycle, are compatible with using Sonaura, for they will more frequently show follicular structure in contrast to day 2–3 or pill-suppressed cycles.

The device used (Figure 4.2) features a patient part and a care provider part. The patient part consists of a dedicated tablet, connectable to an FDA-approved and cost-effectiveness compatible vaginal probe (Interson, Pleasanton, California, United States), delivered in a suitcase with gel, condoms, and written instructions. In between cycles, the probe is sanitized using a specific sporicidal and disinfectant foam (Tristel Duo, Tristel Solutions Limited, UK) based on chlorine dioxide[9,10]. Cleansing within a cycle needs dry cloth or absorptive paper. Images from an ongoing cycle stay on the tablet until it is returned at the time of oocyte retrieval. They are wiped as soon as the cycle is ended by the care provider, which makes the tablet available for another cycle.

Patients perform sonograms at home, but can do so wherever they happen to be if they have access to Wi-Fi. Recordings can be received, analyzed, and responded to by the care provider on different locations as well, all over the world. The idea is to make these interactions fit within the time frame of a regular ART clinic.

Recordings are sent as one uninterrupted recording in a fixed sequence setting: 30 seconds for the right ovary, 15 seconds for the uterus, 30 seconds for the left ovary. Settings are adaptable if wished by the care provider. Recording is started after a search during which the patient sweeps the probe in several directions creating a mental picture of the sequence she intends to record. This takes between 5 and 20 minutes. Women usually scan and record themselves, requiring help from their partners or third parties only if needed. After recording, the patient has access to a communication box where she can write down a message or ask questions.

The care provider part consists of specific software, which can be accessed anytime from any personal computer through a user-specific password. Encrypted and password-protected access to the recordings can be customized per doctor or per center and contains a home page, a list of all patients, a list of patients presently in treatment, and a list of currently active cycles. When creating a new cycle, a cycle-specific password and entry code are generated and automatically sent by email to the patient, who enters them at each recording. The recording is sent to the storage server using an encrypted communication protocol. When a new recording comes in, the care provider is notified by email on his or her mobile phone. For measurement, recordings can be stopped and replayed by the doctor or sonographer as often as needed. All follicles are measured in their two largest perpendicular diameters. After measuring all visible follicles, a reply is entered in the patient communication box comprising a brief description of the stimulation status, dosage instructions, the time when the next sonogram is expected, and, if needed, suggestions to improve image quality or some supportive words. It is then sent to the patient, who is equally notified by email that the response has come in on the tablet. All videos are stored in the cloud from where they can be retrieved again anytime and anywhere; e.g., to compare an ongoing cycle with previous attempts in the same patient. Blockchain technologies may be adapted in the future to add further security to individual patient data.

Patients are instructed to visualize the majority, if not all, of the largest follicles in such a way that the largest diameter and the diameter perpendicular to it come into view at the start of the recording. Recording starts with the probe pointed toward the largest follicle in its largest diameter. This allows the care provider to see immediately if the recording was successful. Almost all patients succeed in making very clear recordings, especially once follicles are>15 mm and nearing the end of stimulation.

Of a total of these 78 different patients, 62 patients went through 1 ICSI attempt using Sonaura, 11 patients went through 2 attempts, 4 patients went through 3 attempts, and 1 patient through 4 attempts. A total of 471 home sonograms were performed and analyzed (mean=4.71±1.48/attempt; range: 2–9). Ninety cycles were conducted without any in situ sonographic control between the start of the treatment and the moment of oocyte retrieval. In ten cycles at least one in situ sonogram was performed. There was only one true method failure; all other cases either confirmed poor or absent follicular growth or were performed for circumstantial reasons.

The total, clinical and OPRs per started cycle were 41%, 36%, and 30%. In 18% of cycles, there was no ET. On a per transfer basis these figures are 48.8%, 42.7%, and 35.4%. There were 30 ongoing pregnancies in 78 different women, equaling 38% of patients who obtained an ongoing pregnancy as of the time of writing. These figures are perfectly comparable to the general figures of the center.

The mean two-way distance per sonogram from home to the center in this series was 376±114 km. With 4.7 sonograms per attempt, this means an average of 1732±698 km of avoided transportation. At €0.3461/km, this is an average saving of €600 per attempt.

There were no complications. The large majority of patients and their partners were very positive about the use of the Sonaura system.