Lipidome profile of follicular fluid in patients with ovarian endometrioma and its role in predicting IVF outcomes
Vardanyan V.A., Smolnikova V.Yu., Chagovets V.V., Makarova N.P., Kalinina E.A.
Relevance: Lipidome profile of follicular fluid (FF) in patients with ovarian endometrioma (OMA) offers valuable information about oocyte competence, embryo viability, and IVF outcomes.
Objective: To create a model for predicting the probability of clinical pregnancy in patients with OMA undergoing IVF based on the lipidome profile of follicular fluid.
Materials and methods: Patients baseline characteristics were collected, lipidome profile of FF and IVF outcomes in patients with OMA were analyzed (n=41). The lipidome signature of follicular fluid was analyzed using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used to create a differential model.
Results: Comparative analysis of FF samples from women who achieved pregnancy versus those with negative result revealed differences in lipidome signature within each group that correlated with IVF outcomes. Based on these findings, a predictive OPLS model was developed. The model allows to differentiate pregnant and non-pregnant women based on the levels of lipids belonging to the following classes: cholesteryl esters, phosphatidylcholines, sphingomyelins and triglycerides.
Conclusion: Lipidome profiling of follicular fluid using HPLC-MS allows for fairly accurate differentiation between women who achieve pregnancy and those who do not. These results are consistent with international data and confirm the potential for using this method to predict IVF outcomes in patients with ovarian endometriomas.
Authors' contributions: Smolnikova V.Yu., Chagovets V.V., Vardanyan V.A. – study concept and design; Vardanyan V.A., Chagovets V.V. – data collection and processing, statistical analysis, manuscript writing; Smolnikova V.Yu. – overall supervision of the clinical study and methodology, coordination of authors; Makarova N.P., Kalinina E.A. – editing.
Conflicts of interest: The authors declare no conflicts of interest.
Funding: The study had no sponsorship.
Ethical Approval: The study was approved by the local Ethics Committee of the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, 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 on request from the corresponding author after approval from the principal investigator.
For citation: Vardanyan V.A., Smolnikova V.Yu., Chagovets V.V., Makarova N.P., Kalinina E.A. Lipidome profile of follicular fluid in patients with ovarian endometrioma and its role in predicting IVF outcomes.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (10): 98-106 (in Russian)
https://dx.doi.org/10.18565/aig.2025.209
Keywords
follicular fluid
lipidome profile
ovarian endometrioma
assisted reproductive technologies
References
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Эндометриоз. 2024. [Ministry of Health of the Russian Federation. Clinical guidelines. Endometriosis. 2024. (in Russian)].
- Leone U., Chiappa V., Ceccaroni M., Roviglione G., Savelli L., Ferrero S. et al. Epidemiology of infertility in women with endometriosis. Best Pract. Res. Clin. Obstet. Gynaecol. 2024; 92: 102454. https://dx.doi.org/10.1016/j.bpobgyn.2023.102454
- Casalechi M., Di Stefano G., Fornelli G., Somigliana E., Viganò P. Impact of endometriosis on the ovarian follicles. Best Pract. Res. Clin. Obstet. Gynaecol. 2024; 92: 102430. https://dx.doi.org/10.1016/j.bpobgyn.2023.102430
- Giacomini E., Sanchez A., Sarais V., Beitawi S., Candiani M., Viganò P. Characteristics of follicular fluid in ovaries with endometriomas. Eur. J. Obstet. Gynecol. Reprod. Biol. 2017; 209: 34-8. https://dx.doi.org/10.1016/j.ejogrb.2016.01.032
- Brinca A.T., Peiró A.M., Evangelio P.M., Eleno I., Oliani A.H., Silva V. et al. Follicular fluid and blood monitorization of infertility biomarkers in women with endometriosis. Int. J. Mol. Sci. 2024; 25(13): 7177. https://dx.doi.org/10.3390/ijms25137177
- Fiscus J., Fraison É., Renault L., Salle B., Panthu B., Labrune E. Metabolic signature of follicular fluid to understand infertility-related diseases: a narrative review. Reprod. Biomed. Online. 2024; 48(6): 103762. https://dx.doi.org/10.1016/j.rbmo.2023.103762
- Wallace M., Cottell E., Gibney M.J., McAuliffe F.M., Wingfield M., Brennan L. An investigation into the relationship between the metabolic profile of follicular fluid, oocyte developmental potential, and implantation outcome. Fertil. Steril. 2012; 97(5): 1078-84.e1-8. https://dx.doi.org/10.1016/j.fertnstert.2012.01.122
- Singh R., Sinclair K.D. Metabolomics: approaches to assessing oocyte and embryo quality. Theriogenology. 2007; 68 Suppl. 1: S56-62. https://dx.doi.org/10.1016/j.theriogenology.2007.04.007
- Dabaja M.Z., Santos A.A., Christofolini D.M., Barbosa C.P., de Oliveira D.N., de Oliveira A.N. et al. Comparative metabolomic profiling of women undergoing in vitro fertilization procedures reveals potential infertility-related biomarkers in follicular fluid. Sci. Rep. 2022; 12(1): 20531. https://dx.doi.org/10.1038/s41598-022-24775-5
- Zhang Y., He C., He Y., Zhu Z. Follicular fluid metabolomics: tool for predicting IVF outcomes of different infertility causes. Reprod. Sci. 2025; 32(4): 921-34. https://dx.doi.org/10.1007/s43032-024-01664-y
- Adamyan L., Pivazyan L., Zarova E., Avetisyan J., Laevskaya A., Sarkisova A. et al. Metabolomic biomarkers of endometriosis: a systematic review. Journal of Endometriosis and Uterine Disorders. 2024; 7: 100077. https://dx.doi.org/10.1016/j.jeud.2024.100077
- Kobayashi H., Imanaka S. Recent progress in metabolomics for analyzing common infertility conditions that affect ovarian function. Reprod. Med. Biol. 2024; 23(1): e12609. https://dx.doi.org/10.1002/rmb2.12609
- Folch J., Lees M., Sloane Stanley G.H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 1957; 226(1): 497-509.
- Trygg J., Wold S. Orthogonal projections to latent structures (O-PLS). J. Chemom. 2002; 16: 119-28. https://dx.doi.org/10.1002/cem.695
- Wold S., Sjöström M., Eriksson L. PLS-regression: a basic tool of chemometrics. Chemometrics and Intelligent Laboratory Systems. 2001; 58(2): 109-30. https://dx.doi.org/10.1016/S0169-7439(01)00155-1
- Guo H., Zhu Q., Gao H., Lyu Q., Chai W., Wu L. et al. Metabolomics analysis of follicular fluid in ovarian endometriosis women receiving progestin-primed ovary stimulation protocol for in vitro fertilization. Sci. Rep. 2023; 13(1): 5747. https://dx.doi.org/10.1038/s41598-023-32797-w
- Revelli A., Gennarelli G., Biasoni V., Chiadò A., Carosso A., Evangelista F. et al. The ovarian sensitivity index (OSI) significantly correlates with ovarian reserve biomarkers, is more predictive of clinical pregnancy than the total number of oocytes, and is consistent in consecutive IVF cycles. J. Clin. Med. 2020; 9(6): 1914. https://dx.doi.org/10.3390/jcm9061914
- Фортыгина Ю.А., Макарова Н.П., Драпкина Ю.С., Новоселова А.В., Чаговец В.В., Франкевич В.Е., Калинина Е.А. Сравнительный анализ липидного профиля крови и фолликулярной жидкости женщин, проходящих лечение бесплодия методами вспомогательных репродуктивных технологий. Акушерство и гинекология. 2024; 4: 93-102. [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. Obstetrics and Gynecology. 2024; (4): 93-102 (in Russian)]. https://dx.doi.org/10.18565/aig.2024.62
- Jiang Y.C., Che Q., Lu X., Liu M., Ye Y., Cao X. et al. Follicular fluid and plasma lipidome profiling and associations towards embryonic development outcomes during ART treatment. Front. Endocrinol. (Lausanne). 2024; 15: 1464171. https://dx.doi.org/10.3389/fendo.2024.1464171
- Vouk K., Hevir N., Ribič-Pucelj M., Haarpaintner G., Scherb H., Osredkar J. et al. Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis. Hum. Reprod. 2012; 27(10): 2955-65. https://dx.doi.org/10.1093/humrep/des152
- Pocate-Cheriet K., Santulli P., Kateb F., Bourdon M., Maignien C., Batteux F. et al. The follicular fluid metabolome differs according to the endometriosis phenotype. Reprod. Biomed. Online. 2020; 41(6): 1023-37. https://dx.doi.org/10.1016/j.rbmo.2020.09.002
- Liu T., Qu J., Tian M., Yang R., Song X., Li R. et al. Lipid metabolic process involved in oocyte maturation during folliculogenesis. Front. Cell. Dev. Biol. 2022; 10: 806890. https://dx.doi.org/10.3389/fcell.2022.806890
- Zarezadeh R., Nouri M., Hamdi K., Shaaker M., Mehdizadeh A., Darabi M. Fatty acids of follicular fluid phospholipids and triglycerides display distinct association with IVF outcomes. Reprod. Biomed. Online. 2021; 42(2): 301-9. https://dx.doi.org/10.1016/j.rbmo.2020.09.024
- Sturmey R.G., Reis A., Leese H.J., McEvoy T.G. Role of fatty acids in energy provision during oocyte maturation and early embryo development. Reprod. Domest. Anim. 2009; 44 Suppl. 3: 50-8. https://dx.doi.org/10.1111/j.1439-0531.2009.01402.x
- Turkoglu O., Zeb A., Graham S., Szyperski T., Szender J.B., Odunsi K. et al. Metabolomics of biomarker discovery in ovarian cancer: a systematic review of the current literature. Metabolomics. 2016; 12(4): 60. https://dx.doi.org/10.1007/s11306-016-0990-0
- Zhang M., Wang Y., Di J., Zhang X., Liu Y., Zhang Y. et al. High coverage of targeted lipidomics revealed lipid changes in the follicular fluid of patients with insulin-resistant polycystic ovary syndrome and a positive correlation between plasmalogens and oocyte quality. Front. Endocrinol. (Lausanne). 2024; 15: 1414289. https://dx.doi.org/10.3389/fendo.2024.1414289
- Zhang Y., Liu X., Deng M., Xu C., Zhang Y., Wu D. et al. Ferroptosis induced by iron overload promotes fibrosis in ovarian endometriosis and is related to subpopulations of endometrial stromal cells. Front. Pharmacol. 2022; 13: 930614. https://dx.doi.org/10.3389/fphar.2022.930614
- Turathum B., Gao E.-M., Grataitong K., Liu Y.-B., Wang L., Dai X. et al. Dysregulated sphingolipid metabolism and autophagy in granulosa cells of women with endometriosis. Front. Endocrinol. (Lausanne). 2022; 13: 906570. https://dx.doi.org/10.3389/fendo.2022.906570
Received 06.08.2025
Accepted 13.10.2025
About the Authors
Victoria A. Vardanyan, PhD student, Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center for Obstertrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(903)299-60-77, vvictoria5@yandex.ru,https://orcid.org/0000-0001-9057-1736
Veronika Yu. Smolnikova, Dr. Med. Sci., Leading Researcher, 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,
https://orcid.org/0000-0002-8025-4849
Vitaly V. Chagovets, PhD (in Physics and Mathematics), 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. Oparin str., 4, vvchagovets@gmail.com,
https://orcid.org/0000-0002-5120-376X
Natalya P. Makarova, Dr. Med. Sci., Leading Researcher, 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., makarova@oparina4.ru,
https://orcid.org/0000-0003-1396-7272
Elena A. Kalinina, Dr. Med. Sci., Professor, Head of the IVF Department 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
