Clinical use of expanded genetic testing in the management of couples with unexplained infertility

DOI

https://dx.doi.org/10.18565/aig.2024.274

Martirosyan Ya.O., Kadaeva A.I., Bolshakova A.S., Nazarenko T.A., Biryukova A.M., Askeralieva A.N.
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia

Objective: To clarify the proportion of unexplained infertility within the overall structure of infertility and analyze the clinical, embryologic, and genetic characteristics of patients with unexplained infertility (UI).
Materials and methods: Patients were selected from couples referred for IVF/ICSI programs. In the retrospective phase of the study, clinical and medical history data were analyzed from 1,500 married couples who underwent 2,156 stimulated cycles from 2020 to 2022 at V.I. Kulakov NMRC for OG&P. The observation group consisted of 156 married couples diagnosed with unexplained infertility, who were referred for IVF.
Results: Of the total number of patients included in the study, 10.4% were diagnosed with unexplained infertility. The cause of infertility was established in 89.6% of the couples. Patients with UI had a longer duration of infertility (on average 4.3 (1.2) years) compared to patients with an established cause of infertility (3.2 (2.4) years), with a statistically significant difference (p<0.001, Student's t-test). Patients with UI also exhibited lower AMH levels and lower antral follicle counts compared to the control group: mean levels were 2.6 (0.46) and 13.3 (2.9), respectively, versus 3.61 (2.04) and 14.2 (4.0) (p<0.001 and p=0.004, Mann–Whitney U-test). The number of oocytes retrieved by transvaginal ovarian puncture was similar in both the groups. Comparison of the parameters of subsequent embryological stages showed that all patients with UI had significantly reduced parameters compared to those in the group with an established cause of infertility: mature oocytes were 33.3% lower, correctly fertilized oocytes were 45.5% lower, and the number of embryos (blastocysts) available for transfer was 82.2% lower. Patients with UI who did not have blastocysts retrieved on day 5 of culture underwent genetic testing, which revealed genetic variants potentially linked to IVF failure.
Conclusion: Identifying the specific genetic determinants of female infertility enables a definitive diagnosis for couples, allowing them to consider alternative ART options. It also provides an opportunity to identify molecular factors and biological pathways involved in the acquisition of oocyte competence.

Authors' contributions: Martirosyan Ya.O., Kadayeva A.I., Bolshakova A.S., Nazarenko T.A., Biryukova A.M., Askeralieva A.N. – conception and design of the study, obtaining data for analysis, review of relevant publications, obtained data analysis, drafting of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: Source of funding: R&D 121040600410-7 Nazarenko T.A. “Solving the problem of infertility in modern conditions by developing a clinical and diagnostic model of infertile marriage and using innovative technologies in assisted reproduction programs.”
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Martirosyan Ya.O., Kadaeva A.I., Bolshakova A.S., Nazarenko T.A., Biryukova A.M., Askeralieva A.N. Clinical use of expanded genetic testing in the management of couples with unexplained infertility.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (12): 50-58 (in Russian)
https://dx.doi.org/10.18565/aig.2024.274

unexplained infertility

genetics

genetic testing

Full text (in Russian)

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Received 31.10.2024

Accepted 26.11.2024

Yana O. Martirosyan, Researcher at the F. Paulsen Research and Educational Center for ART, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
117997, Russia, Moscow, Ac. Oparin str., 4, marti-yana@yandex.ru, https://orcid.org/0000-0002-9304-4410
Albina I. Kadaeva, PhD student, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, albina.karimovai@mail.ru
Anna S. Bolshakova, Geneticist, Department of Clinical Genetics of the Institute of Reproductive Genetics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(495)438-24-11, a_bolshakova@oparina4.ru, https://orcid.org/0000-0002-7508-0899
Tatiana A. Nazarenko, Dr. Med. Sci., Head of the Institute of Reproductive Medicine, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
117997, Russia, Moscow, Ac. Oparin str., 4, +7(495)438-13-41, t.nazarenko@mail.ru, https://orcid.org/0000-0002-5823-1667
Almina M. Biryukova, PhD, Obstetrician-Gynecologist at the F. Paulsen Research and Educational Center for ART, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, 7(495)531-44-44, a_birukova@oparina4.ru
Ayuma N. Askeralieva, Clinical Resident, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(913)175-31-44.

Clinical use of expanded genetic testing in the management of couples with unexplained infertility

Martirosyan Ya.O., Kadaeva A.I., Bolshakova A.S., Nazarenko T.A., Biryukova A.M., Askeralieva A.N.

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