P-603 Viability of home monitoring of estrone-3-glucuronide (E1-3G) urine levels in controlled ovarian stimulation: A pilot study
Authors: Vladimirov I K , Tacheva D , Gatev I , Rangelova M , Vladimirov M 
Published: June 2023

Study question

Can the regular determination of E1-3G levels in the patient's urine be used for successful monitoring of progestin-primed ovarian stimulation protocol (PPOS)?

Summary answer

Regular determination of E1-3G levels in urine can be successfully used in ovarian stimulation (OS), significantly reducing patient visits to the clinic.

What is known already

To reduce direct and indirect costs and to optimize the workload in IVF clinics, innovative approaches are being sought. It has only recently become possible to implement elements of telemedicine in OS monitoring. Patients have begun performing vaginal sonograms on their own.

Studies have further shown that there is a close correlation in the growth of E2 in serum and E1-3G in urine during the menstrual cycle and ovarian stimulation. Thus, theoretical models for the use of urinary E1-3G in ovarian stimulation were developed, which are subject to experimental verification and analysis.

Study design, size, duration

This is a pilot study carried out in a clinic, which aims to establish the growth rate of E1-3G and to determine its upper and lower limits of growth on each consecutive day at which stimulation is adequate and safe. Inclusion criteria were patients aged &lt; 40 years and AMH ≧ 1.1 ng/mL. From September to December 2022, in total 28 first ovarian stimulatiоn cycles from 28 infertility patients were included.

Participants/materials, setting, methods

A PPOS protocol with fixed doses of gonadotropins was used. From the second day of stimulation, the patients determined the E1-3G levels in their urine every day at home with a portable analyzer. In parallel, a standard ultrasound follow-up protocol was applied, accompanied by determination of E2, LH and P levels, in order to optimally control stimulation. Patients' convenience of this new approach was assessed using a questionnaire developed for the purpose.

Main results and the role of chance

The average female age was 32,1 years (±4.4), BMI 22,9 kg/m2 (±4,3), AMH 3,9 ng/ml (±2,7), stimulation days 10,1 (±1,2), collected oocytes 12,6 (±8,5), MII oocytes 10,8 (±7,9), fertilization rate 83,4% (±22,7), blastocyst formation 66,9% (±28,6), good quality blastocysts 31,1% (±16,6).

The log-linear mixed effect model (LLMM) estimation produced reasonable estimates of 49% average day-to-day growth rates (slope fixed effect), with one standard deviation (SD) range of 25% to 77% across patients (SD of the slope random effect).

Moreover, there was a comparatively high correlation of 0.76 between the individual growth rates of E1G estimated over days 3-6 (the slope random effects of the LLMM model) and the E1-3G levels at day 10. In this way, the estimated slope random effects appear to have a prognostic value and may potentially have therapeutic implications, for example, adjustment of the stimulation dose. Moreover, the Spearman correlation between Estradiol and E1-3G was 0.83

After analyzing interviews and questionnaires, patients evaluated the applied method as easy and convenient, with 97% of them preferring OS monitoring to be performed in this manner compared to the standard method, which includes regular ultrasound examinations and determination of serum hormone levels.

Limitations, reasons for caution

The small statistical sample size is a limitation of this study, which was carried out in a single clinic. The results have to be confirmed in other clinics and with more diverse populations.

Wider implications of the findings

This is the first study to analyze the dynamics of E1-3G in the PPOS protocol and the limits of its increase during the entire OS. The results confirm our theoretical model for the successful use of urinary E1-3G in OS. The method is easy to apply and well-accepted by patients.

Trial registration number

N/A