Comparative analysis of estrogen metabolites when using different forms of estrogen-containing medications in a cryo-protocol for preparation with gonadotropin-releasing hormone agonists
- Authors: Kvashnina E.V.1, Tutakov M.A.1, Tomina E.V.1, Shilova N.V.2
-
Affiliations:
- Partus Center for Rehabilitation of Reproductive Function Disorders
- Gen-Lab Ltd.
- Issue: No 2 (2023)
- Pages: 126-133
- Section: Exchange of Experience
- URL: https://journals.eco-vector.com/0300-9092/article/view/340783
- DOI: https://doi.org/10.18565/aig.2023.17
- ID: 340783
Cite item
Open Access
Access granted
Abstract
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).
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.
Full Text
About the authors
Elena V. Kvashnina
Partus Center for Rehabilitation of Reproductive Function Disorders
Author for correspondence.
Email: doctor.kvashnina@gmail.com
PhD, Leading Reproductive Specialist; Chief Physician
Russian Federation, YekaterinburgMaksim A. Tutakov
Partus Center for Rehabilitation of Reproductive Function Disorders
Email: tutakov@ivf-partus.ru
Leading Embryologist
Russian Federation, YekaterinburgEvgenia V. Tomina
Partus Center for Rehabilitation of Reproductive Function Disorders
Email: tomina@ivf-partus.ru
Deputy Director for Organizational and Methodological Work
Russian Federation, YekaterinburgNatalya V. Shilova
Gen-Lab Ltd.
Email: nvshilova@gmail.com
PhD
Russian Federation, MoscowReferences
- Roque M., Haahr T., Geber S., Esteves S.C., Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum. Reprod. Update. 2019; 25(1): 2-14. https://dx.doi.org/10.1093/humupd/dmy033.
- Naimi Z.M.S., Kalinina E.A., Donnikov A.E., Alieva K.U., Dubarova A.H., Tukhvatullina Ya.A. Efficiency of assisted reproductive technology programs in stimulated-cycle embryo transfer versus cryopreserved-thawed embryo transfer. Obstetrics and Gynegology. 2016; (6): 11-7. (in Russian). https://dx.doi.org/10.18565/ aig.2016.6.11-17.
- Krasnopolskaya K.V., Nazarenko T.A., Sesina N.I., Aleksandrova V.R. IVF programs using embryos obtained from vitrified and native donor oocytes. Obstetrics and Gynegology. 2017; (3): 75-80. (in Russian). https://dx.doi.org/10.18565/aig.2017.3.75-80.
- Hosseini-Najarkolaei A., Moini A., Kashani L., Farid Mojtahedi M., Hosseini-Najarkolaee E., Salehi E. The effect of letrozole versus artificial hormonal endometrial preparation on pregnancy outcome after frozen-thawed embryos transfer cycles: a randomized clinical trial. Reprod. Biol. Endocrinol. 2020; 18(1): 115. https://dx.doi.org/10.1186/ s12958-020-00675-z.
- Guan Y., Fan H., Styer A.K., Xiao Z., Li Z., Zhang J. et al. A modified natural cycle results in higher live birth rate in vitrified-thawed embryo transfer for women with regular menstruation. Syst. Biol. Reprod. Med. 2016; 62(5): 335-42. https://dx.doi.org/10.1080/19396368.2016.1199064.
- Farhud D.D., Zokaei S., Keykhaei M., Hedayati M., Zarif Yeganeh M. In-Vitro fertilization impact on the risk of breast cancer: a review article. Iran. J. Public Health. 2021; 50(3): 438-47. https://dx.doi.org/10.18502/ ijph.v50i3.5583.
- Katalinic A., Shulman Lee P., Strauss J. F., Garcia-Velasco J. A., van den Anker J.N. A critical appraisal of safety data of dydrogesterone for the support of early pregnancy: a scoping review and meta-analysis. Reprod. Biomed. Online. 2022; 45(2): 365-73. https://dx.doi.org/10.1016/ j.rbmo.2022.03.032.
- Chagay N.V., Mkrtumyan A.M. Estrogen metabolism, lifetime methylation disorders, and breast cancer. Problems of Endocrinology. 2019; 65(3): 161-73. (in Russian).
- Sak K. The Val158Met polymorphism in COMT gene and cancer risk: role of endogenous and exogenous catechols. Drug Metab. Rev. 2017; 49(1): 56-83. https://dx.doi.org/10.1080/03602532.2016.1258075.
- Kvashnina E.V., Tutakov M.A., Vachlova O.S., Tomina E.V., Shilova N.V. Effect of hormone replacement therapy with estradiol in frozen embryo transfer on estrogen metabolism in women with various polymorphisms of catechol-O-methyltransferase gene. Obstetrics and Gynegology. 2021; (11): 213-20. (in Russian). https;/dx.doi.org/10.18565/ aig.2021.11.213-220.
- Kvashnina E.V., Tutakov M.A., Tomina E.V., Berestetskaya O.S., Nemstsveridze E.Ya., Shilova N.V. Segmentation of the cycle of assisted reproductive technologies as a tool to improve the efficiency of overcoming infertility. Ural Medical Journal. 2019; (5): 116-23. (in Russian).
- Lang T.A., Sesik M. How to describe statistics in medicine: an annotated cuide for authors, editors, and reviewers. Moscow: Practical Medicine; 2010. 485p. (in Russian).
- Klyukina L.A., Sosnova E.A., Ishchenko A.A. Assisted reproductive technology and uterine cancer risk. A systematic review and meta-analysis. Journal of Obstetrics and Women's Diseases. 2022. 71(3): 77–86. (in Russia). https;/dx.doi.org/10.17816/JOWD106237.
- Babaeva N.A., Ashrafyan L.A., Antonova I.B., Motskobili T.A., Lyustik A.V. The role of estrogen metabolites in the pathogenesis of breast, endometrial and ovarian cancer. Journal of Radiology and Nuclear Medicine. 2013; (13-1). Available at: http://vestnik.rncrr.ru/vestnik /v13/ papers/babaeva_v13.htm (in Russian).
- Zhai J., Jiang L., Wen A., Jia J., Zhu L., Fan B. Analysis of the relationship between COMT polymorphisms and endometriosis susceptibility. Medicine (Baltimore). 2019; 98(1): e13933. https://dx.doi.org/10.1097/ MD.0000000000013933.
- Qin X., Peng Q., Qin A., Chen Z., Lin L., Deng Y. et al. Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis. Diagn. Pathol. 2012; 7: 136. https;/dx.doi.org/10.1186/ 1746-1596-7-136.
- Musina E.V., Kogan I.Yu. Menopausal hormone therapy: oncological risk. Gynecology. 2020; 22(3): 29-32. (in Russian). https;/dx.doi.org/10.26442/ 20795696.2020.3.200154.
- Rosenberg E., Fredriksson A., Einbeigi Z., Bergh C., Strandell A. No increased risk of relapse of breast cancer for women who give birth after assisted conception. Hum. Reprod. Open. 2019; 2019(4): hoz039. https;/dx.doi.org/10.1093/hropen/hoz039.
Supplementary files
