HOME - ROMANIAN
Friday, September 24, 2021   00:42 EET
 

Project

 

Artificial Intelligence Algorithms in Male Infertility Diagnosis Based on New Molecular Approaches

Project Code: PN-III-P2-2.1-PED-2019-4402

Acronym: ARIAMIND

Programme: - PED

Financier: UEFISCDI

Project duration: 24 months (octombrie 2020 – septembrie 2022)

Coordinating Institution: Stefan S. Nicolau Institute of Virology (www.virology.ro)

Address: 285 Mihai Bravu Ave., sector 3, Bucharest, Romania; tel/fax: 021 3242590

Project leader: Dr. BOTEZATU ANCA, CSII

e-mail: gnanka30 @ yahoo.com

Research Team: Dr. Botezatu Anca CSII, Dr, Anton Gabriela CS I, Dr. Adriana Plesa CSII, Dr. Iancu Iulia Virginia CS III, Dr. Huica Irina CSIII, Drd Fudulu Alina CS, Drd Albulescu Adrian CS

Total Budget: 637500 lei

Total Buget IVN: 225000 lei

Abstract

Causes of male infertility were reported as mainly Y chromosome deletions. However only 10-15% of infertile patients shows such anomalies. Studies regarding infertility expanded from the genetic level to epigenetic factors.  The proposal aims to improve investigation protocols and diagnosis for male infertile patients. This scope will be achieved through developing a method for epigenetic profiler (panel) which will evaluate the level of methylation for selected genes involved in male infertility and to develop a decision support system (DSS) based on artificial intelligence (AI) that can predict the results a from a questionnaire, hormonal profile, infection status, methylation panel and semen analysis. The novelty of current proposal is to elaborate a new protocol and AI based algorithms to investigate infertile men, not only to diagnose, but to improve the selection for assisted reproduction techniques (ART). Such investigations, protocols are not introduced yet in the current practice worldwide, and are the subject of great interest for researchers and especially for clinicians who expect validating and transferring research results into the clinic as soon as possible. Despite the fact that the number of clinics performing assisted reproductive procedures is high, the success rate is low due to lack of opportunities for testing at the molecular level functionality sperm and oocytes.

 

Concrete objectives of the project

Despite the fact that the number of clinics performing assisted reproductive procedures is high, the success rate is low due to lack of opportunities for testing at the molecular level functionality of the sperm and oocytes. Evidence showed that epigenetic modifications of the sperm cells could affect the semen parameters, embryo development, the outcome of ART and long-term effects during the offspring lifetime. The main objectives of the project are:

· Selection of a group of infertile male patients according to specific inclusion/exclusion diagnostic criteria using clinical, biochemical, cytogenetic, microbiological data and sperm cytology determination.

· Improving the male infertility diagnosis protocol by testing the patients on a multiplex panel for targeted methylation sequencing on NGS.

 · Biostatistics and bioinformatic data analysis. Data classification and ranking. Data mining.

· Developing AI algorithms that intend to help the clinician in the formulation of the diagnosis, making of therapeutic decisions and the outcome prediction for infertile men.

References

1.         Lutz, W., O'Neill, B. C., & Scherbov, S. (2003). Europe's population at a turning point. Science, 299(5615), 1991-1992.

2. Skouby, S. O. (2004). Contraceptive use and behavior in the 21st century: a comprehensive study across five European countries.The European Journal of Contraception & Reproductive Health Care, 9(2), 57-68.

3. Skakkebæk, N. E., Jørgensen, N., Main, K. M., Meyts, E. R. D., Leffers, H., Andersson, A. M., ... &Toppari, J. (2006). Is human fecundity declining? International journal of andrology, 29(1), 2-11.

4. Winters, B. R., & Walsh, T. J. (2014). The epidemiology of male infertility. Urologic Clinics, 41(1),195-204.

5. Katz, D. J., Teloken, P., & Shoshany, O. (2017). Male infertility-the other side of the equation. Australian family physician, 46(9), 641.

6. Gianotten, J., Lombardi, M. P., Zwinderman, A. H., Lilford, R. J., & Van Der Veen, F. (2004).

Idiopathic impaired spermatogenesis: genetic epidemiology is unlikely to provide a short-cut to better understanding. Human reproduction update, 10(6), 533-539.

7. Filipponi, D., & Feil, R. (2009). Perturbation of genomic imprinting in oligozoospermia. Epigenetics, 4(1), 27-30.

8. Ramesh, A. N., Kambhampati, C., Monson, J. R., & Drew, P. J. (2004). Artificial intelligence in medicine. Annals of The Royal College of Surgeons of England, 86(5), 334.

9. Healthcare remains the hottest AI category for deals. https://www.cbinsights.com/research/artificialintelligence-healthcare-startups-investors/ accessed 9 Oct 2019).

10. Hammoud, S. S., Nix, D. A., Zhang, H., Purwar, J., Carrell, D. T., & Cairns, B. R. (2009). Distinctive chromatin in human sperm packages genes for embryo development. Nature, 460(7254), 473.

11. Stuppia, L., Franzago, M., Ballerini, P., Gatta, V., & Antonucci, I. (2015). Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health. Clinical epigenetics, 7(1), 120.

12. Paun, D., Draganescu, D. D., Paun, S., Joja, O., Vladoiu, S., & Draganescu, H. (2015). INFERTILITY IN MEN--BIOETHICAL AND GENETIC CONSIDERATIONS. Revista Romana de Bioetica, 13(2).

13. Vladoiu, S., Draganescu, D. D., Botezatu, A., Anton, G., Oros, S., Paun, D. L., ... & Badiu, C. (2016). Correlations between Polymorphisms of Estrogen 1, Vitamin D Receptors and Hormonal Profile in Infertile Men. Acta Endocrinologica (Bucharest), 12(2), 137.

14. Vladoiu, S., Draganescu, D. D., Botezatu, A., Anton, G., Oros, S., Paun, D. L., ... & Badiu, C. (2016). Correlations between Polymorphisms of Estrogen 1, Vitamin D Receptors and Hormonal Profile in Infertile Men. Acta Endocrinologica (Bucharest), 12(2), 137.

15. Ianas, O., Manda, D., Draganescu, D. D., Calarasu, R., Busu, C., & Vladoiu, S. (2006). Circadian changes of melatonin secretion in male idiopathic infertility. ACTA ENDOCRINOLOGICABUCHAREST-, 2(2), 129.

16. Mares, M., Socolov, D., Doroftei, B., Botezatu, A., & Goia, C. D. (2009). The prevalence of some bacterial markers in female patients undergoing an initial infertility evaluation in north-east Romania. Roum Arch Microbiol Immunol, 68(3), 171-4.

17. Botezatu, A., Socolov, R., Socolov, D., Iancu, I. V., & Anton, G. (2014). Methylation pattern of methylene tetrahydrofolate reductase and small nuclear ribonucleoprotein polypeptide N promoters in oligoasthenospermia: a case-control study. Reproductive biomedicine online, 28(2), 225-231.

18. Kobayashi, H., Sato, A., Otsu, E., Hiura, H., Tomatsu, C., Utsunomiya, T., ... & Arima, T. (2007). Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Human molecular genetics, 16(21), 2542-2551.

19. Houshdaran, S., Cortessis, V. K., Siegmund, K., Yang, A., Laird, P. W., & Sokol, R. Z. (2007).

Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal

human sperm. PloS one, 2(12), e1289.

20. Botezatu, A., Puiu, M., Cucu, N., Diaconu, C. C., Badiu, C., Arsene, C., ... & Anton, G. (2016).

Comparative molecular approaches in Prader–Willi syndrome diagnosis. Gene, 575(2), 353-358.

RO EN