Comparative analysis of estrogen metabolites when using different forms of estrogen-containing medications in a cryo-protocol for preparation with gonadotropin-releasing hormone agonists
Objective: To compare the levels of urinary estradiol metabolites in women with COMT rs4680 gene polymorphisms and different types of estrogen support in a cryo-protocol using gonadotropin-releasing hormone (GnRH) agonists and hormone replacement therapy (HRT).Kvashnina E.V., Tutakov M.A., Tomina E.V., Shilova N.V.
Materials and methods: Thirty-nine ART cryo-cycles were analyzed; the level of estrone and estradiol metabolites was measured. The urinary levels of hydroxyestrone, methoxyestrone, and estradiol were estimated in women on the day of progesterone start. The indicators were comparatively analyzed according to the estrogen type used: 0.1% transdermal estradiol gel in Group 1 and estradiol valerate pills 2 mg in Group 2 after the preliminary use of GnRH agonists.
Results: The use of oral estrogens is associated with the higher urinary level (by 10 times or more) of hydroxylated forms of metabolites than that of the transdermal gel for any of the COMT gene polymorphism variants. The COMT AA and GA gene polymorphisms are related to the higher level of hydroxylated estrogen metabolic products regardless of the estrogen type used in the protocol. Thus, in women with AA polymorphism who used transdermal estradiol, the level of hydroxyl forms was 1.5 times higher than that in those with GG polymorphism (p=0.014). In women with GA polymorphism, the urinary level of these metabolites was 1.6 times higher than that in those with the GG genotype (p=0.010).
Conclusion: The cryo-protocol that uses GnRH agonists in combination with 0.1% transdermal estradiol gel is characterized by the higher level of methoxy forms of estrogen metabolites than hat of estradiol valerate pills. In patients with COMT AG and GG polymorphisms in the long protocol, it is advisable to apply transdermal estrogen as a drug that does not increase the accumulation of hydroxylated forms of estrogen metabolites.
Authors' contributions: Kvashnina E.V. – setting the task of the investigation, raw material collection, writing and editing the text of the article; Tutakov M.A. – control and collection of data from the embryological stage of the investigation; Tomina E.V. – data consolidation in an electronic worksheet; Shilova N.V. – work with literary sources, statistical processing of investigation results, writing the text of the article
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article has been prepared in line with the initiative topic.
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 on request from the corresponding author after approval from the principal investigator.
For citation: Kvashnina E.V., Tutakov M.A., Tomina E.V., Shilova N.V. Comparative analysis of estrogen metabolites when using different forms of estrogen-containing medications in a cryo-protocol for preparation with gonadotropin-releasing hormone agonists.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (2): 126-133 (in Russian)
https://dx.doi.org/10.18565/aig.2023.17
Keywords
0.1% transdermal estradiol gel
COMT polymorphism
cryo-protocol safety
hormone replacement therapy
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Received 26.01.2023
Accepted 01.02.2023
About the Authors
Elena V. Kvashnina, PhD, Leading Reproductive Specialist, Network of Reproductive Health Clinics "Center for IVF"; Chief Physician, clinic Center for IVF "Partus", Yekaterinburg, +7(343)288-53-39, doctor.kvashnina@gmail.com, 620026, Russia, Yekaterinburg, Mamin-Sibiryak str., 171A.Maksim A. Tutakov, Leading Embryologist, Center IVF Center Partus Clinic, Yekaterinburg, +7(343)288-53-39, tutakov@ivf-partus.ru.
620026, Russia, Yekaterinburg, Mamin-Sibiryak str., 171A.
Olesya S. Vakhlova, obstetrician-gynecologist, fertility specialist, Center IVF Center Partus Clinic, Yekaterinburg, +7(343)288-53-39, dr.vakhlova@mail.ru,
620026, Russia, Yekaterinburg, Mamin-Sibiryak str., 171A.
Evgenia V. Tomina, Deputy Director for Organizational and Methodological Work, Center IVF Center Partus Clinic, Yekaterinburg, +7(343)288-53-39,
tomina@ivf-partus.ru, 620026, Russia, Yekaterinburg, Mamin-Sibiryak str., 171A.
Natalya V. Shilova, PhD, Gen-lab Ltd., Moscow, +7(495)774-57-57, nvshilova@gmail.com, 107078, Russia, Moscow, Kalanchevskaya str., 31-4.
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