Personalized IVF preparation in women of advanced reproductive age: Cohort study results
DOI:
https://doi.org/10.37800/RM.2.2025.535Keywords:
infertility, advanced reproductive age, ART outcomes, preconception preparationAbstract
Relevance: Despite the widespread implementation of modern assisted reproductive technologies (ART), global infertility rates remain consistently high. One of the key factors limiting the success of ART is the increasing reproductive age of female patients. As a woman ages, the likelihood of conception naturally declines, significantly worsening ART outcomes. Therefore, patients of advanced reproductive age require more detailed and comprehensive preparation for ART and a well-defined medical care algorithm.
The study aimed to assess the effectiveness of a preparation algorithm for patients of advanced reproductive age undergoing in vitro fertilization (IVF) programs.
Materials and Methods: A prospective cohort study was conducted from January to December 2023. The study included two groups of patients: the main group, consisting of 30 women who underwent individualized preconception preparation, and the control group of 39 women who received the standard examination and preparation protocol before undergoing IVF and embryo transfer. A training algorithm adapted for the Kazakh population has been developed and tested.
Results: The patient groups were comparable in age and anamnesis. In both groups, the genetic markers of folate metabolism did not differ from the general population. The average numbers and quality of oocytes and blastocysts were comparable. The pregnancy rate was at 63.3% in the main group vs. 43.6% among the controls (p < 0.05); the live birth rate was 46.67% vs. 23.1% (p = 0.040). The pregnancy loss rate amounted to 47.1% among the controls, three times higher than in the main group (15.8%, p = 0.043).
Conclusion: Personalizing the preparation of women of advanced reproductive age for ART improves the efficiency of ART programs by increasing the likelihood of pregnancy and live births while reducing reproductive losses. The molecular genetic methods further increase the selection accuracy of embryos with high implantation potential.
References
Hanson B, Johnstone E, Dorais J, Silver B, Peterson CM, Hotaling J. Female infertility, infertility-associated diagnoses, and comorbidities: a review. J Assist Reprod Genet. 2017;34(2):167-177.
https://doi.org/10.1007/s10815-016-0836-8
Lokshin V, Valiev R, Rybina A, Zaichenko K. “Poor responders” – modern ideas, principles of management in ART programs. Review. The Bulletin. 2019;2(378).
https://doi.org/10.32014/2019.2518-1467.54
Lokshin V, Omar M, Karibaeva S. Assisted Reproductive Technologies in the Republic of Kazakhstan: A 6-Year Trend Analysis from Efficacy to Availability. J Reprod Infertil. 2022;23(1).
https://publish.kne-publishing.com/index.php/JRI/article/view/8454
La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: From theory to practice. Hum Reprod Update. 2014;20(1):124-140. https://doi.org/10.1093/humupd/dmt037
Gleicher N, Kushnir VA, Albertini DF, Barad DH. Improvements in IVF in women of advanced age. J Endocrinol. 2016;230(1):F1-6.
https://doi.org/10.1530/JOE-16-0105
Gruhn JR, Zielinska AP, Shukla V, Blanshard R, Capalbo A, Cimadomo D, Nikiforov D, Chan AC, Newnham LJ, Vogel I, Scarica C, Krapchev M, Taylor D, Kristensen SG, Cheng J, Ernst E, Bjørn AB, Colmorn LB, Blayney M, Elder K, Liss J, Hartshorne G, Grøndahl ML, Rienzi L, Ubaldi F, McCoy R, Lukaszuk K, Andersen CY, Schuh M, Hoffmann ER. Europe PMC Funders Group Chromosome errors in human eggs shape natural fertility over reproductive lifespan. 2020;365(6460):1466-1469.
https://doi.org/10.1126/science.aav7321
Tan TY, Lau SK, Loh SF, Tan HH. Female ageing and reproductive outcome in assisted reproduction cycles. Singapore Med J. 2014 Jun;55(6):305-309. http://dx.doi.org/10.11622/smedj.2014081
De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V; European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open [Internet]. 2020 Feb 24;2020(1):hoz038.
https://doi.org/10.1093/hropen/hoaa038
Локшин В., Омар М., Карибаева Ш, Джусубалиева Т., Байкошкарова С., Ахметова А.., Покотило Л, Дюсембинов К., Тарарака С., Магзумов Г. Вспомогательные репродуктивные технологии в Казахстане в 2018 году: Краткий отчет по эффективности и доступности. Репродуктивная медицина. 2021;2 (47):6-10.
Lokshin V, Omar M, Karibaeva Sh, Dzhusubalieva T, Baykoshkarova S, Akhmetova A, Pokotilo L, Dyusembinov K, Tararaka S, Magzumov G. Assisted reproductive technologies in Kazakhstan in 2018: Brief report on effectiveness and availability. Reproductive Medicine. 2021;2 (47):6-10.
https://doi.org/10.37800/RM2021-2-8
Grisendi V, Mastellari E, La Marca A. Ovarian Reserve Markers to Identify Poor Responders in the Context of Poseidon Classification. Front Endocrinol (Lausanne). 2019;10:281.
https://doi.org/10.3389/fendo.2019.00281
Lensen SF, Wilkinson J, Leijdekkers JA, La Marca A, Mol BWJ, Marjoribanks J, Torrance H, Broekmans FJ. Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI). Cochrane Database Syst Rev [Internet]. 2018;2018(2):12693. https://doi.org/10.1002/14651858.CD012693.pub2
Ilgaz NS, Aydos OS, Karadag A, Taspinar M, Eryilmaz OG, Sunguroglu A. Impact of follicle-stimulating hormone receptor variants in female infertility. J Assist Reprod Genet. 2015;32(11):1659-1668.
https://doi.org/10.1007/s10815-015-0572-5
Hanson B, Johnstone E, Dorais J, Silver B, Peterson CM, Hotaling J. Female infertility, infertility-associated diagnoses, and comorbidities: a review. J Assist Reprod Genet. 2017;34(2):167-177.
https://doi.org/10.1007/s10815-016-0836-8
Travis J O’Brien, Mariah M Kalmin, Arthur F Harralson, Adam M Clark, Ian Gindoff, Samuel J Simmens, David Frankfurter & Paul Gindoff. Association between the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) rs4073366 polymorphism and ovarian hyperstimulation syndrome during controlled ovarian hyperstimulation. Reprod Biol Endocrinol. 2013;11(1):1.
https://doi.org/10.1186/1477-7827-11-71
Yan Y, Gong Z, Zhang L, Li Y, Li X, Zhu L, Sun L. Association of follicle-stimulating hormone receptor polymorphisms with ovarian response in Chinese women: a prospective clinical study. PLoS One. 2013;8(10):e78138.
https://doi.org/10.1371/journal.pone.0078138
Ganesh V, Venkatesan V, Koshy T, Reddy SN, Muthumuthiah S, Paul SFD. Association of estrogen, progesterone and follicle stimulating hormone receptor polymorphisms with in vitro fertilization outcomes. Syst Biol Reprod Med. 2018;64(4):260-265.
https://doi.org/10.1080/19396368.2018.1482030
Lindgren I, Nenonen H, Henic E, Bungum L, Prahl A, Bungum M, Leijonhufvud I, Huhtaniemi I, Yding Andersen C, Lundberg Giwercman Y. Gonadotropin receptor variants are linked to cumulative live birth rate after in vitro fertilization. J Assist Reprod Genet. 2019;36(1):29-38.
https://doi.org/10.1007/s10815-018-1318-y
Biswas L, Tyc K, El Yakoubi W, Morgan K, Xing J, Schindler K. Meiosis interrupted: the genetics of female infertility via meiotic failure. Reproduction. 2021;161(2):R13-35.
https://doi.org/10.1530/REP-20-0422
Zeng S, Wang X, Wang Y, Xu Z, Zhang J, Liu W, Qian L, Chen X, Wei J, Yang X, Gong Z, Yan Y. MTHFR C677T polymorphism is associated with follicle-stimulating hormone levels and controlled ovarian hyperstimulation response: a retrospective study from the clinical database. Fertil Steril. 2019;111(5):982-990.e2. https://doi.org/10.1016/j.fertnstert.2019.01.016
Wang X, Sun X, Tang B, Liu L, Feng X. Effect of polymorphisms of MTHFR in controlled ovarian stimulation: a systematic review and meta-analysis. J Assist Reprod Genet. 2021;38(9):2237-2249.
https://doi.org/10.1007/s10815-021-02236-8
Ishitani H, Ikeda S, Egashira K, Sugimoto M, Kume S, Minami N, Ohta T. Embryonic MTHFR contributes to blastocyst development. J Assist Reprod Genet. 2020;37(8):1807-1814.
https://doi.org/10.1007/s10815-020-01898-0
Chalova L, Lokshin V, Orazov M, Rybina A, Kim T, Kinzhibayev A. Modern methods of diagnosis and treatment of chronic endometritis, in preparing patients for assisted reproductive treatment technologies (literature review). Reports of the National Academy of Sciences of the Republic of Kazakhstan. 2020;2(330):21-28.
https://doi.org/10.32014/10.32014/2020.2518-1483.27
Chen Y-Q, Fang R-L, Luo Y, Luo C-Q. Analysis of the diagnostic value of CD138 for chronic endometritis, the risk factors for the pathogenesis of chronic endometritis and the effect of chronic endometritis on pregnancy: a cohort study. BMC Womens Health. 2016;16(1):60.
https://doi.org/10.1186/s12905-016-0341-3
Park HJ, Kim YS, Yoon TK, Lee WS. Chronic endometritis and infertility. Clin Exp Reprod Med. 2016;43(4):185-192.
https://doi.org/10.5653/cerm.2016.43.4.185
Рыбина А.Н. Алгоритм ведения пациенток старшего репродуктивного возраста. Авторское свидетельство KZ58844. Казахстан; 2025 май 28.
Святова Г.С., Махмутова Ж.С. Популяционно-генетический анализ полиморфизма гена метилентетрагидрофолатредуктазы при дефектах невральной в казахской популяции : монография. Алматы, 2008. 156 с.
Svyatova G.S., Makhmutova Zh.S. Population genetic analysis of methylenetetrahydrofolate reductase gene polymorphism in neural defects in the Kazakh population: monograph. Almaty, 2008. 156 p. Russian. ISBN 978-601-7048-06-8.
Kalimagambetov AM, Mukhamediyarova SK, Bekimbek AT, Rakisheva ZB, Belousov VY, Solomadin MV, Sadueva KA. Association of folate cycle polymorphic genes with pregnancy complications in women of the Kazakh ethnic group. Exp Biol. 2020;82(1):110-119.
https://www.researchgate.net/publication/343260803
Vitagliano A, Saccardi C, Noventa M, Di Spiezio Sardo A, Saccone G, Cicinelli E, Pizzi S, Andrisani A, Litta PS. Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis. Fertil Steril. 2018;110(1):103-112.e1.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 А.Н. Рыбина, А.Т. Абшекенова, Е. Аскар, Ш.К. Карибаева, Р.К. Валиев
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The articles published in this Journal are licensed under the CC BY-NC-ND 4.0 (Creative Commons Attribution – Non-Commercial – No Derivatives 4.0 International) license, which provides for their non-commercial use only. Under this license, users have the right to copy and distribute the material in copyright but are not permitted to modify or use it for commercial purposes. Full details on the licensing are available at https://creativecommons.org/licenses/by-nc-nd/4.0/.
