Infertility treatment outcomes in women over 40 years treated by assisted reproductive technologies using their own oocytes cultured in low lactate embryo culture medium
Khachatryan L.V., Smolnikova V.Yu., Makarova N.P., Sysoeva A.P., Kulakova E.V., Kalinina E.A.
Relevance: Advanced maternal age is one of the most significant non-modifiable factors affecting fertility and success of assisted reproductive technology (ART) programs. Currently, researchers are focusing on optimizing the embryonic stage to enhance embryo viability and implantation potential.
Objective: To study pregnancy outcomes in women over 40 years of age following infertility treatment using ART with oocytes cultured in low-lactate embryo culture medium.
Materials and methods: This study included 520 infertile couples with women of advanced reproductive age (>40 years). They were divided into two groups based on the embryo culture medium used: group 1 (n=264), which used low-lactate CSCM-NX medium, and group 2 (n=256), which used one-stage classical G-TL medium.
Results: Embryo culture in low-lactate medium (group 1) resulted in a statistically significant increase in the embryo blastulation rate (39.0% compared to 31.1% in group 2, p=0.05) and blastocyst rate (p=0.04). Additionally, embryo culture in low-lactate medium led to a statistically significant decrease in the number of cycles with canceled embryo transfers because of unsatisfactory quality (14.7% in group 1 compared to 24.2% in group 2; RR=0.61, 95% CI: 0.43–0.88, p=0.007), and an increase in the pregnancy rate (14.4% in group 1 compared to 8.2% in group 2; RR=1.8, 95% CI: 1.0–3.3, p=0.02). There was no statistically significant difference in birth rate.
Conclusion: For women of advanced reproductive age, the use of a low-lactate embryo culture medium is a promising approach to increase blastocyst rates, which may reduce the number of ovarian stimulations and improve the chances of obtaining euploid embryos and live births.
Authors' contributions: Khachatryan L.V. – data collection and analysis, review and analysis of relevant literature, drafting of the manuscript; Smolnikova V.Yu., Kalinina E.A., Kulakova E.V. – drafting of the manuscript, critical analysis; Makarova N.P., Sysoeva A.P. – conception and design of the study, editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: There was no funding for this study.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
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: Khachatryan L.V., Smolnikova V.Yu., Makarova N.P., Sysoeva A.P., Kulakova E.V., Kalinina E.A. Infertility treatment outcomes in women over 40 years treated by assisted reproductive technologies
using their own oocytes cultured in low lactate embryo culture medium.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (4): 71-78 (in Russian)
https://dx.doi.org/10.18565/aig.2025.46
Keywords
assisted reproductive technology (ART)
optimization of embryonic stage
advanced reproductive age
low lactate embryo culture medium
References
- Сухих Г.Т., Назаренко Т.А., ред. Бесплодие в позднем репродуктивном возрасте: реалии и перспективы. М.: Издательство «Медком-Про»; 2024. 560 с. [Sukhikh G.T., Nazarenko T.A., ed. Infertility in late reproductive age: realities and prospects. Moscow: Medkom-Pro Publishing House; 2024. 560 p. (in Russian)].
- Драпкина Ю.С., Макарова Н.П., Васильев Р.А., Амелин В.В., Калинина Е.А. Сравнение прогностических моделей, построенных с помощью разных методов машинного обучения, на примере прогнозирования результатов лечения бесплодия методом вспомогательных репродуктивных технологий. Акушерство и гинекология. 2024; 2: 97-105. [Drapkina Yu.S., Makarova N.P., Vasiliev R.A., Amelin V.V., Kalinina E.A. Comparison of predictive models built with different machine learning techniques using the example of predicting the outcome of assisted reproductive technologie. Obstetrics and Gynegology. 2024; (2): 97-105. (in Russian)]. https://dx.doi.org/10.18565/aig.2024.124.
- Datta A.K., Campbell S., Diaz-Fernandez R., Nargund G. Livebirth rates are influenced by an interaction between male and female partners' age: analysis of 59 951 fresh IVF/ICSI cycles with and without male infertility. Hum. Reprod. 2024; 39(11): 2491-500. https://dx.doi.org/10.1093/humrep/deae198.
- Mazzilli R., Cimadomo D., Innocenti F., Taggi M., Cermisoni G.C., Ginesi S. et al. A WHO 2021-based comprehensive scheme outlining sperm parameters' associations with IVF outcomes in PGT-A cycles. Andrology. 2024; Nov 28. https://dx.doi.org/10.1111/andr.13811.
- Seifer D.B., Feinberg E.C., Hsu A.L. Ovarian aging and fertility. JAMA. 2024; 332(20): 1750-51. https://dx.doi.org/10.1001/jama.2024.18207.
- Wang X., Tian P.Z., Zhao Y.J., Lu J., Dong C.Y., Zhang C.L. The association between female age and pregnancy outcomes in patients receiving first elective single embryo transfer cycle: a retrospective cohort study. Sci. Rep. 2024; 14((1): 19216. https://dx.doi.org/10.1038/s41598-024-70249-1.
- Sermondade N., Sonigo C., Pasquier M., Ahdad-Yata N., Fraison E., Grynberg M. Searching for the optimal number of oocytes to reach a live birth after in vitro fertilization: a systematic review with meta-analysis. F&S Reviews. 2023; 4(2): 101-15.
- Neves A.R., Montoya-Botero P., Sachs-Guedj N., Polyzos N.P. Association between the number of oocytes and cumulative live birth rate: A systematic review. Best Pract. Res. Clin. Obstet. Gynaecol. 2023; 87: 102307. https://dx.doi.org/10.1016/j.bpobgyn.2022.102307.
- Zagers M.S., Laverde M., Goddijn M., de Groot J.J., Schrauwen F.A.P., Vaz F.M., Mastenbroek S. The composition of commercially available human embryo culture media. Hum. Reprod. 2025; 40(1): 30-40. https://dx.doi.org/10.1093/humrep/deae248.
- Gardner D.K. Lactate production by the mammalian blastocyst: manipulating the microenvironment for uterine implantation and invasion? Bioessays. 2015; 37(4): 364-71. https://dx.doi.org/10.1002/bies.201400155.
- Morbeck D.E., Baumann N.A., Oglesbee D. Composition of single-step media used for human embryo culture. Fertil. Steril. 2017; 107(4): 1055-1060.e1. https://dx.doi.org/10.1016/j.fertnstert.2017.01.007.
- Gardner D.K., Schoolcraft W.B. In vitro culture of human blastocysts. In: Jansen R., Mortimer D. eds. Towards Reproductive Certainty: Infertility and Genetics Beyond 1999: The Plenary Proceedings of the 11th World Congress on In Vitro Fertilization and Human Reproductive Genetics. Parthenon Press, Pearl River; 1999: 378-88.
- Gurner K.H., Evans J., Hutchison J.C., Harvey A.J., Gardner D.K. A microenvironment of high lactate and low pH created by the blastocyst promotes endometrial receptivity and implantation. Reprod. Biomed. Online. 2022; 44(1): 14-26. https://dx.doi.org/10.1016/j.rbmo.2021.09.012.
- Rinaudo P. Understanding embryo metabolism to improve embryo selection. RBMO. 2023; 47(Suppl.): 103425.
- Gardner D.K. Lactate production by the mammalian blastocyst: manipulating the microenvironment for uterine implantation and invasion? Bioessays. 2015; 37(4): 364-71. https://dx.doi.org/10.1002/bies.201400155.
- Kobanawa M. Fertilization, embryo culture, and clinical results using low lactate embryo culture medium for pre-culture, insemination, and beyond. Reprod. Med. Biol. 2022; 21(1): e12458. https://dx.doi.org/10.1002/rmb2.12458.
- Hammond E.R., Morbeck D. Reducing the stress of culture? Low lactate embryo culture medium increases usable blastocyst rate for woman of advanced material age. Fertil. Steril. 2020; 114(3): e7. https://dx.doi.org/10.1016/j.fertnstert.2020.08.045.
Received 25.02.2025
Accepted 31.03.2025
About the Authors
Lia V. Khachatryan, PhD student at the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Faculty of Postgraduate Professional Training of Physicians, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8-2, +7(963)977-88-94, leahkhachatryan@gmail.com, https://orcid.org/0000-0003-4867-500XVeronika Yu. Smolnikova, Dr. Med. Sci., Leading Researcher at the Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, v_smolnikova@oparina4.ru
Natalya P. Makarova, Dr. Med. Sci., Leading Researcher at the Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, np_makarova@oparina4.ru,
https://orcid.org/0000-0003-1396-7272
Anastasia P. Sysoeva, PhD, Clinical Embryologist, Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, sysoeva.a.p@gmail.com, https://orcid.org/0000-0002-6502-4498
Elena V. Kulakova, Dr. Med. Sci., Senior Researcher at the Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center
for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, e_kulakova@oparina4.ru,
https://orcid.org/0000-0002-4433-4163
Elena A. Kalinina, Dr. Med. Sci., Professor, Head of the Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center
for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, e_kalinina@oparina4.ru,
https://orcid.org/0000-0002-8922-2878
Similar Articles
