Home Monitoring of Estrone-3-Glucuronide (E1-3G) Levels in Two Different Ovarian Stimulation Protocols: A Pilot Study

Background: Studies have shown a strong correlation between the growth of E2 in serum and estrone-3-glucuronide (E1-3G) in urine during ovarian stimulation. Thus, we developed theoretical models for using urinary E1-3G in ovarian stimulation and focused on their experimental verification and analysis. Methods: A prospective, observational pilot study was conducted involving 54 patients who underwent 54 cycles of ovarian stimulation. The goal was to establish the growth rate of urinary E1-3G during the course of stimulation and to determine the daily upper and lower limits of growth rates at which stimulation is appropriate and safe. Controlled ovarian stimulation was performed using two different stimulation protocols—an antagonist protocol in 25 cases and a progestin-primed ovarian stimulation protocol (PPOS) in 29 cases, with fixed doses of gonadotropins. From the second day of stimulation, patients self-measured their daily urine E1-3G levels at home using a portable analyzer. In parallel, a standard ultrasound follow-up protocol accompanied by a determination of E2, LH, and P levels was applied to optimally control stimulation. Results: The average daily growth rates in both groups were about 50%. The daily increase in E1-3G for the antagonist protocol ranged from 14% to 79%, while they were 28% to 79% for the PPOS protocol. Conclusion: This is the first study to analyze the dynamics of E1-3G in two different protocols and to estimate the limits of its increase during the entire course of the stimulation. The results confirm our theoretical model for the viability of using urinary E1-3G for monitoring ovarian stimulation.

Evaluation of Serum Anti-Müllerian Hormone (AMH) Values for 28,016 Bulgarian Women: Prognostic Statistical Model of Age Specific AMH Declining

The present study aims to establish a relationship between serum AMH levels and age in a large group of women living in Bulgaria, as well as to establish reference age-specific AMH levels in women that would serve as an initial estimate of ovarian age. A total of 28,016 women on the territory of the Republic of Bulgaria were tested for serum AMH levels with a median age of 37.0 years (interquartile range 32.0 to 41.0). For women aged 20 - 29 years, the Bulgarian population has relatively high median levels of AMH, similar to women of Asian origin. For women aged 30 - 34 years, our results are comparable to those of women living in Western Europe. For women aged 35 - 39 years, our results are comparable to those of women living in the territory of India and Kenya. For women aged 40 - 44 years, our results were lower than those for women from the Western European and Chinese populations, close to the Indian and higher than Korean and Kenya populations, respectively. Our results for women of Bulgarian origin are also comparable to US Latina women at age 30, 35 and 40 ages. On the base on constructed a statistical model to predicting the decline in AMH levels at different ages, we found non-linear structure of AMH decline for the low AMH 3.5) the dependence of the decline of AMH on age was confirmed as linear. In conclusion, we evaluated the serum level of AMH in Bulgarian women and established age-specific AMH percentile reference values based on a large representative sample. We have developed a prognostic statistical model that can facilitate the application of AMH in clinical practice and the prediction of reproductive capacity and population health.

Semen Quality in the General Population of Bulgaria

Background: With the accumulating evidence of semen difference between distinct populations we decided to conduct a population-based prospective study to assess the reproductive capabilities of the Bulgarian males. Objective: To evaluate the semen parameters in men from the general population of Bulgaria. To analyze the effects of BMI (Body mass index) and tobacco smoking on semen characteristics. Methods: 482 males without history of reproductive problems were included for the purpose of this study. The duration of our study was from April to May in 2016 and April in 2017. The volunteers were subdivided based on their smoking status and on their BMI. After semen collection, a conventional semen analysis was carried out manually by trained embryologists in an andrology laboratory according to WHO recommendations. The results were statistically analyzed and presented with their mean values. Result(s): After semen analysis we report a mean of 3.29 ml for semen volume, 40.68 × 106/ml for spermatozoa concentration, 128.38 × 106 for total sperm count, 52.54% of total motile spermatozoa in the ejaculate and a mean percentage of morphologically normal sperm standing at 9.6%. We did not find a negative effect of tobacco smoking on semen quality;however higher BMI is associated with lower sperm concentration per ml. Discussion and Conclusion(s): This is the first contemporary study, assessing semen quality in Bulgarians. The results obtained here show the lower quality of semen in Bulgaria, compared to other countries. No statistical differences were found between the semen quality of nonsmokers and smokers. Higher BMI was found to be associated with lower sperm concentration per milliliter.

A New Protocol for Controlled Ovarian Stimulation Monitoring by Self-Determination of Estrone-3-Glucuronide and Single Ultrasound (COSSESU)

Background: Answering the question of what is the optimal protocol for monitoring controlled ovarian stimulation (COS) still remains a challenge. The rapid introduction of new diagnostic methods and various components of telemedicine makes it possible to reduce the number of patient visits during ovarian stimulation, which will reduce the loss of time, costs, and risk for the patient from COVID-like situations. Methods: The different COS monitoring protocols are examined, thus proposing a new approach consisting of two successive phases. Results: In the first phase, E3G in urine samples is being examined, which is performed by the patient themselves with a small portable analyzer. Based on the results, the specialist prescribes the doses for stimulation. The second phase involves one single determination of the size and number of follicles at the end of stimulation, using TVUS, as well as the dynamics of serum levels of P4 and E2. This proves to be in many cases sufficient. Conclusions: It is of our opinion that on the basis of new diagnostic tests such as E3G in urine and telemedicine, patients are able to independently and actively participate in the treatment process. This new approach to COS monitoring can be successfully implemented in different protocols for ovarian stimulation.