Advice

Clinical and technical evidence

Clinical and technical evidence

A literature search was carried out for this briefing in accordance with the interim process and methods statement for medtech innovation briefings. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.

Published evidence

There are 3 studies summarised in this briefing, including a total of 226 people. The evidence includes 2 prospective observational studies (1 of which was a pilot study) and 1 retrospective pilot study. The clinical evidence and its strengths and limitations are summarised in the overall assessment of the evidence.

Overall assessment of the evidence

The evidence base for Proov Confirm is limited and comes from pilot and observational studies. All 3 studies had no comparators and relatively small sample sizes. All studies tracked pregnanediol‑3a‑glucuronide (PdG) hormone for a short duration of approximately 1 cycle. None of the studies were done in the UK.

Overall, the results suggest that Proov Confirm has the potential to accurately confirm ovulation. One study associated positive PdG cycles with increased pregnancy rates and lower odds of a first-trimester pregnancy loss.

To improve the evidence base, further research with larger sample sizes across multiple sites, ideally in the UK, is needed. Also, studies comparing the technology to standard care in the NHS can help evaluate the impact on changes to clinical management.

Beckley et al. (2022)

Intervention and comparator

Proov Confirm with mobile application diagnostic device, no comparator.

Key outcomes

Of the total 185 people, 172 enrolled in the study had a complete cycle, and 54 (31.4%) of those with complete cycles reported pregnancies. Of these pregnancies, 35 (64.8%) resulted from a PdG-positive cycle, with a miscarriage rate of 14.3% (5 out of 35). Nineteen pregnancies (35.2%) resulted from PdG-negative cycles, with a miscarriage rate of 89.5% (17 out of 19). The association of a negative or positive cycle with pregnancy outcome was significant (2‑sided p=0.0001).

Strengths and limitations

A main limitation of the study is that 45% of people with a complete cycle were reported to be on 1 or more fertility medications for ovarian stimulation, ovarian induction, or luteal phase support. People were recruited on the basis that they were established users of the app and had also already completed 1 cycle using Proov Confirm. The study was funded and carried out by the company.

Leiva et al. (2019)

Intervention and comparator

Proov Confirm, no comparator.

Key outcomes

Of the 28 people recruited to the study, 22 contributed 1 cycle each for analysis. Ages ranged from 18 to 42 years with a recorded median luteal phase of 12 days. Peak fertility was determined either by using luteinising hormone (LH) test strips or by tracking cervical mucus production. The specificity of the PdG test for confirming ovulation was 100%. The sensitivity varied depending on whether a peak-fertility mucus day or a positive LH test was seen during the cycle. Sensitivity was 85% if a positive LH test was followed by 3 consecutive positive PdG tests. Sensitivity was 88% if a peak-fertility mucus day was followed by 3 consecutive positive PdG tests. Fifty percent of users found the test results easy to understand.

Strengths and limitations

The study measured serum progesterone levels as an additional approach to confirm ovulation and determine the specificity of the tests. It also provided an estimate of the number of ultrasound-monitored cycles that will be needed to expect a narrow confidence interval range between 95% and 100% in future studies. The main limitation of the study was the small sample size from a single centre, which limits its generalisability.

Bouchard et al. (2019)

Intervention and comparator

Proov Confirm, no comparator.

Key outcomes

People in the study had a mean age of 33.6 years and produced 34 menstrual cycles of data with the luteal phase ranging from 10 to 16 days. There were 17 menstrual cycles of data using PdG test sticks for each of the 7 microgram/ml and 5 microgram/ml thresholds. When the 7 microgram/ml test strips were used, 59% (10 out of 17) of menstrual cycles had a positive confirmation of ovulation. When the 5 microgram/ml test strips were used, 82.4% (14 out of 17) had a positive confirmation of ovulation. The positive PdG tests happened 2 to 10 days after the second peak reading of LH on the monitor, with the most frequent positive results on days 4 and 5 past the surge. But all 14 of the menstrual cycles that had a positive PdG with the 5 microgram/ml test strips had a narrower window, happening 2 to 5 days past the LH surge, with the positive test happening most frequently on days 4 and 5. The 95% confidence intervals were 0.64 to 1.00 for the 5 microgram/ml test and 0.36 to 0.82 for the 7 microgram/ml test.

Strengths and limitations

The main limitation of the study was the small sample size.

Sustainability

The company claims the technology reduces the environmental impact (for example, through less travel and better use of NHS resources) and minimises waste by reducing single-use plastic. There is no published evidence to support these claims.

Recent and ongoing studies