Comparative analysis of blood and follicular fluid lipid profiles in women undergoing infertility treatment with assisted reproductive technologies
Fortygina Yu.A., Makarova N.P., Drapkina Yu.S., Novoselova A.V., Gamisonia A.M., Chagovets V.V., Frankevich V.E., Kalinina E.A.
Background: Follicle fluid (FF) composition can significantly affect oocyte development, fertilization, and early embryo cleavage. Therefore, studying the molecular composition of FF can provide valuable insights into the mechanisms and factors that influence oogenesis. Investigating the lipid profile of FF as an additional marker for assessing oocyte quality has shown promising results. However, FF collection is an invasive procedure; therefore, it is important to explore indirect sources of information about FF composition.
Objective: To compare the lipid profiles of blood plasma and FF in women undergoing infertility treatment using assisted reproductive technology (ART).
Materials and methods: The study involved 40 married couples, aged 24–39 years, with a normal body mass index (up to 25 kg/m2), seeking infertility treatment with ART. Patients underwent ovarian stimulation following a protocol with gonadotropin-releasing hormone antagonists (GnRH antagonists). On the day of the puncture, FF and blood plasma were collected and cryopreserved. Liquid chromatography with mass spectrometry was used to determine the molecular compositions of the samples.
Results: The study determined the lipid composition of FF (175 lipids) and blood plasma (185 lipids). Among these molecules, 70 lipids were identical in both FF and blood plasma. Of these, 42 lipids showed a statistically significant correlation. Additionally, when analyzing the correlation between plasma lipid levels and FF from the left and right ovaries, 25 lipids were identified, with plasma levels significantly correlated with FF from the left ovary, and 40 lipids showed a significant correlation with FF from the right ovary. The levels of all 175 identified lipids showed a statistically significant correlation between the left and right ovarian FF.
Conclusion: These findings suggest that the similarities and differences found between blood plasma and FF lipidomes can be used to develop noninvasive methods for assessing oocyte status and predicting the effectiveness of ART. The study results suggest the potential for personalized infertility treatment and preparation for ART programs, as well as a deeper understanding of the mechanisms underlying impaired oocyte maturation and the causes of low fertilization rates.
Authors' contributions: Makarova N.P., Chagovets V.V., Frankevich V.E., Kalinina E.A. – conception and design of the study; Fortygina Yu.A., Novoselova A.V., Gamisonia A.M., Chagovets V.V. – material collection and processing, statistical analysis; Fortygina Yu.A., Drapkina Yu.S. – drafting of the manuscript; Kalinina E.A., Makarova N.P. – 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.
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: Fortygina Yu.A., Makarova N.P., Drapkina Yu.S., Novoselova A.V., Gamisonia A.M., Chagovets V.V., Frankevich V.E., Kalinina E.A. Comparative analysis of blood and follicular fluid lipid profiles in women undergoing infertility treatment with assisted reproductive technologies.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (4): 93-102 (in Russian)
https://dx.doi.org/10.18565/aig.2024.62
Keywords
ART
infertility
lipids
oocyte
follicular fluid
mass spectrometry
References
- Министерство здравоохранения Российской Федерации. Женское бесплодие (современные подходы к диагностике и лечению). Клинические рекомендации (протокол лечения). 2019: 33. [Ministry of Health of the Russian Federation. Female infertility (modern approaches to diagnosis and treatment). Clinical guidelines (treatment protocol). 2019: 33. (in Russian)].
- Назаренко Т.А. Вспомогательная репродукция в клинической практике. Разбор клинических случаев с использованием международных и отечественных рекомендаций. М.: МедКом-Про; 2020. 121с. [Nazarenko T.A. Assisted reproduction in clinical practice. Analysis of clinical cases using international and domestic recommendations. M.: MedCom-Pro; 2020. 121p. (in Russian)].
- Макарова Н.П., Лобанова Н.Н., Кулакова Е.В., Непша О.С., Екимов А.Н., Калинина Е.А. Влияние преимплантационного генетического тестирования на результаты программ вспомогательных репродуктивных технологий у супружеских пар с мужским фактором бесплодия. Акушерство и гинекология. 2021; 11: 154-64. [Makarova N.P., Lobanova N.N., Kulakova E.V., Nepsha O.S., Ekimov A.N., Kalinina E.A. Impact of preimplantation genetic testing on assisted reproductive technology outcomes in couples with male factor infertility. Obstetrics and Gynecology. 2021; (11): 154-64 (in Russian)]. https://dx.doi.org/10.18565/aig.2021.11.154-164.
- Чараева А.В., Макарова Н.П., Драпкина Ю.С., Калинина Е.А. Новые достижения в понимании молекулярных механизмов имплантации эмбриона человека в программах экcтракорпорального оплодотворения. Акушерство и гинекология. 2023; 3: 21-8. [Charaeva A.V., Makarova N.P., Drapkina Yu.S., Kalinina E.A. New advances in understanding the molecular mechanisms of human embryo implantation in in vitro fertilization programs. Obstetrics and Gynecology. 2023; (3): 21-8 (in Russian)]. https://dx.doi.org/10.18565/aig.2022.281.
- Cordeiro F.B., Montani D.A., Pilau E.J., Gozzo F.C., Fraietta R., Turco E.G.L. Ovarian environment aging: follicular fluid lipidomic and related metabolic pathways. J. Assist. Reprod. Genet. 2018; 35(8): 1385-93. https://dx.doi.org/10.1007/s10815-018-1259-5.
- Shehadeh A., Bruck-Haimson R., Saidemberg D., Zacharia A., Herzberg S., Ben-Meir A. et al. A shift in follicular fluid from triacylglycerols to membrane lipids is associated with positive pregnancy outcome. FASEB J. 2019; 33(9): 10291-9. https://dx.doi.org/10.1096/fj.201900318RR.
- Nagy R.A., van Montfoort A.P.A., Groen H., Homminga I., Andrei D., Mistry R.H. et al. Anti-oxidative function of follicular fluid HDL and outcomes of modified natural cycle-IVF. Sci. Rep. 2019; 9(1): 12817. https://dx.doi.org/10.1038/s41598-019-49091-3.
- Николенко И.Г., Смольникова В.Ю., Чаговец В.В. Возможности прогнозирования исходов программ вспомогательных репродуктивных технологий у пациенток с эндометриоидными кистами яичников на основании метаболомного профиля фолликулярной жидкости. Акушерство и гинекология. 2020; 11: 44-8. [ Nikolenko I.G., Smolnikova V.Yu., Chagovets V.V. Possibilities of predicting the outcomes of assisted reproductive technology programs in patients with ovarian endometrioid cysts on the basis of the metabolic profile of follicular fluid. Obstetrics and Gynecology. 2020; (11): 44-8 (in Russian)]. https://dx.doi.org/10.18565/aig.2020.11.44-48.
- Wen X., Kuang Y., Zhou L., Yu B., Chen Q., Fu Y. et al. Lipidomic components alterations of human follicular fluid reveal the relevance of improving clinical outcomes in women using progestin-primed ovarian stimulation compared to short-term protocol. Med. Sci. Monit. 2018; 24: 3357-65. https://dx.doi.org/10.12659/MSM.906602.
- Matorras R., Martinez-Arranz I., Arretxe E., Iruarrizaga-Lejarreta M., Corral B., Ibañez-Perez J. et al. The lipidome of endometrial fluid differs between implantative and non-implantative IVF cycles. J. Assist. Reprod. Genet. 2020; 37(2): 385-94. https://dx.doi.org/10.1007/s10815-019-01670-z.
- Bouet P.E., Chao de la Barca J.M., El Hachem H., Descamps P., Legendre G., Reynier P. et al. Metabolomics shows no impairment of the microenvironment of the cumulus-oocyte complex in women with isolated endometriosis. Reprod. Biomed. Online. 2019; 39(6): 885-92. https://dx.doi.org/10.1016/j.rbmo.2019.08.001.
- Ban Y., Ran H., Chen Y., Ma L. Lipidomics analysis of human follicular fluid form normal-weight patients with polycystic ovary syndrome: a pilot study. J. Ovarian Res. 2021; 14(1): 135. https://dx.doi.org/10.1186/s13048-021-00885-y.
- Luan C.X., Xie W.D., Liu D., Li W., Yuan Z.W. Candidate circulating biomarkers of spontaneous miscarriage after IVF-ET identified via coupling machine learning and serum lipidomics profiling. Reprod. Sci. 2022; 29(3): 750-60. https://dx.doi.org/10.1007/s43032-021-00830-w.
- Núñez Calonge R., Guijarro J.A., Andrés C., Cortés S., Saladino M., Caballero P., Kireev R. Relationships between lipids levels in blood plasma, follicular fluid and seminal plasma with ovarian response and sperm concentration regardless of age and body mass index. Rev. Int. Androl. 2022; 20(3): 178-88. https://dx.doi.org/10.1016/j.androl.2021.02.004.
- Khan R., Jiang X., Hameed U., Shi Q. Role of lipid metabolism and signaling in mammalian oocyte maturation, quality, and acquisition of competence. Front. Cell. Dev. Biol. 2021; (9): 639704. https://dx.doi.org/10.3389/fcell.2021.639704.
- Фортыгина Ю.А., Макарова Н.П., Непша О.С., Лобанова Н.Н., Калинина Е.А. Роль липидомных исследований в репродукции человека и исходах программ лечения бесплодия методами вспомогательных репродуктивных технологий. Акушерство и гинекология. 2022; 10: 14-20. [Fortygina Yu.A., Makarova N.P., Nepsha O.S., Lobanova N.N., Kalinina E.A. The role of lipidomic studies in human reproduction and in the outcomes of infertility treatment programs using assisted reproductive technologies. Obstetrics and Gynecology. 2022; (10): 14-20 (in Russian)]. https://dx.doi.org/10.18565/aig.2022.10.14-20.
- Szczuko M., Kikut J., Komorniak N., Bilicki J., Celewicz Z., Ziętek M. The role of arachidonic and linoleic acid derivatives in pathological pregnancies and the human reproduction process. Int. J. Mol. Sci. 2020; 21(24): 9628. https://dx.doi.org/10.3390/ijms21249628.
- Wang J., Zheng W., Zhang S., Yan K., Jin M., Hu H. et al. An increase of phosphatidylcholines in follicular fluid implies attenuation of embryo quality on day 3 post-fertilization. BMC Biol. 2021; 19: 200. https://dx.doi.org/10.1186/s12915-021-01118-w.
- Liu L., Yin T.L., Chen Y., Li Y., Yin L., Ding J. et al. Follicular dynamics of glycerophospholipid and sphingolipid metabolisms in polycystic ovary syndrome patients. J. Steroid Biochem. Mol. Biol. 2019; 185: 142-9. https://dx.doi.org/10.1016/j.jsbmb.2018.08.008.
- Zhang Y., Zhang X., Lu M., Zou X. Ceramide-1-phosphate and its transfer proteins in eukaryotes. Chem. Phys. Lipids. 2021; 240: 105135. https://dx.doi.org/10.1016/j.chemphyslip.2021.105135.
- Timur B., Aldemir O., İnan N., Kaplanoğlu İ., Dilbaz S. Clinical significance of serum and follicular fluid ceramide levels in women with low ovarian reserve. Turk. J. Obstet. Gynecol. 2022; 19(3): 207-14. https://dx.doi.org/10.4274/tjod.galenos.2022.05760.
- Eliyahu E., Shtraizent N., Martinuzzi K., Barritt J., He X., Wei H. et al. Acid ceramidase improves the quality of oocytes and embryos and the outcome of in vitro fertilization. FASEB J. 2010; 24(4): 1229-38. https://dx.doi.org/10.1096/fj.09-145508.
- Meng X., Zhang J., Wan Q., Huang J., Han T., Qu T. et al. Influence of vitamin D supplementation on reproductive outcomes of infertile patients: a systematic review and meta-analysis. Reprod. Biol. Endocrinol. 2023; 21(1): 17. https://dx.doi.org/10.1186/s12958-023-01068-8.
- Fernando M., Ellery S.J., Marquina C., Lim S., Naderpoor N., Mousa A. Vitamin D-Binding protein in pregnancy and reproductive health. Nutrients. 2020; 12(5): 1489. https://dx.doi.org/10.3390/nu12051489.
- Ciepiela P., Dulęba A.J., Kowaleczko E., Chełstowski K., Kurzawa R. Vitamin D as a follicular marker of human oocyte quality and a serum marker of in vitro fertilization outcome. J. Assist. Reprod. Genet. 2018; 35(7): 1265-76. https://dx.doi.org/10.1007/s10815-018-1179-4.
- Antunes R.A., Mancebo A.C.A., Reginatto M.W., Deriquehem V.A.S., Areas P., Bloise E. et al. Lower follicular fluid vitamin D concentration is related to a higher number of large ovarian follicles. Reprod. Biomed. Online. 2018; 36(3): 277-84. https://dx.doi.org/10.1016/j.rbmo.2017.12.010.
- Kermack A.J., Wellstead S.J., Fisk H.L., Cheong Y., Houghton F.D., Macklon N.S. et al. The fatty acid composition of human follicular fluid is altered by a 6-week dietary intervention that includes marine omega-3 fatty acids. Lipids. 2021; 56(2): 201-9. https://dx.doi.org/10.1002/lipd.12288.
- Драпкина Ю.С., Калинина Е.А., Макарова Н.П., Мильчаков К.С., Франкевич В.Е. Искусственный интеллект в репродуктивной медицине: этические и клинические аспекты. Акушерство и гинекология. 2022; 11: 37-44. [Drapkina Yu.S., Kalinina E.A., Makarova N.P., Milchakov K.S., Frankevich V.E. Artificial intelligence in reproductive medicine: ethical and clinical aspects. Obstetrics and Gynecology. 2022; (11): 37-44 (in Russian)]. https://dx.doi.org/10.18565/aig.2022.11.37-44.
- Драпкина Ю.С., Макарова Н.П., Татаурова П.Д., Калинина Е.A. Поддержка врачебных решений с помощью глубокого машинного обучения при лечении бесплодия методами вспомогательных репродуктивных технологий. Медицинский Совет. 2023;(15):27-37. [Drapkina J.S., Makarova N.Р., Tataurova P.D., Kalinina E.A. Deep machine learning applied to support clinical decision-making in the treatment of infertility using assisted reproductive technologies. Medical Council. 2023; (15): 27-37. (in Russian)]. https://doi.org/10.21518/ms2023-368.
Received 20.03.2024
Accepted 02.04.2024
About the Authors
Yulia A. Fortygina, graduate student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, yu_fortygina@oparina4.ru, https://orcid.org/0000-0002-1251-0505Natalya P. Makarova, Dr. Bio. Sci., Leading Researcher, Department of IVF named after Professor 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. Oparina str., 4, np_makarova@oparina4.ru,
https://orcid.org/0000-0003-8922-2878
Yulia S. Drapkina, PhD, Researcher, Department of IVF named after Professor 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. Oparina str., 4, yu_drapkina@oparina4.ru, https://orcid.org/0000-0002-0545-1607
Anastasia V. Novoselova, Researcher, Laboratory of Metabolomics and Bioinformatics, Academician V.I. Kulakov National Medical Research Center for Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, a_novoselova@oparina4.ru
Alina M. Gamisonia, Researcher, Laboratory of Metabolomics and Bioinformatics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, a_gamisoniya@oparina4.ru, https://orcid.org/0000-0001-8532-4714
Vitaly V. Chagovets, PhD, Head of the Laboratory of Metabolomics and Bioinformatics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, vvchagovets@gmail.com, https://orcid.org/0000-0002-5120-376X
Vladimir E. Frankevich, Dr. Sci. in physics and mathematics, Head of the Department of Systems Biology in Human Reproduction, Deputy Director of the Institute of Translational Medicine, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4; Siberian State Medical University, Ministry of Health of Russia, v_frankevich@oparina4.ru, https://orcid.org/0000-0002-9780-4579
Elena A. Kalinina, Dr. Med. Sci., Professor, Head of the IVF Department named after Professor 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. Oparina str., 4, e_kalinina@oparina4.ru,
https://orcid.org/0000-0002-8922-2878
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