Oocyte Competence, Embryological Outcomes and miRNA Signature of Different Sized Follicles from Poor Responder Patients
Abstract
:1. Introduction
2. Results
2.1. Baseline Reproductive Characteristics
2.2. Follicles Larger than 11.5 mm Had Superior Embryology Outcomes
2.3. An Oocyte Maturation-Related miRNA Signature Was Maintained in the Follicular Fluid of Different-Sized Follicles
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Study Design
4.3. miRNA Isolation from Follicular Fluid and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR)
4.4. Assessment of Clinical Outcomes
4.5. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ubaldi, F.; Rienzi, L.; Ferrero, S.; Baroni, E.; Sapienza, F.; Cobellis, L.; Greco, E. Management of Poor Ovarian Responders in IVF. Reprod. Biomed. Online 2005, 10, 235–246. [Google Scholar] [CrossRef] [PubMed]
- Vaiarelli, A.; Cimadomo, D.; Ubaldi, N.; Rienzi, L.; Ubaldi, F.M. What Is New in the Management of Poor Ovarian Response in IVF? Curr. Opin. Obstet. Gynecol. 2018, 30, 155–162. [Google Scholar] [CrossRef] [PubMed]
- Oudendijk, J.F.; Yarde, F.; Eijkemans, M.J.C.; Broekmans, F.J.M.; Broer, S.L. The Poor Responder in IVF: Is the Prognosis Always Poor? A Systematic Review. Hum. Reprod. Update 2012, 18, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Patrizio, P.; Vaiarelli, A.; Levi Setti, P.E.; Tobler, K.J.; Shoham, G.; Leong, M.; Shoham, Z. How to Define, Diagnose and Treat Poor Responders? Responses from a Worldwide Survey of IVF Clinics. Reprod. Biomed. Online 2015, 30, 581–592. [Google Scholar] [CrossRef]
- Humaidan, P.; Alviggi, C.; Fischer, R.; Esteves, S.C. The Novel POSEIDON Stratification of ‘Low Prognosis Patients in Assisted Reproductive Technology’ and Its Proposed Marker of Successful Outcome. F1000Research 2016, 5, 2911. [Google Scholar] [CrossRef]
- Scott, R.T.; Hofmann, G.E.; Muasher, S.J.; Acosta, A.A.; Kreiner, D.K.; Rosenwaks, Z. Correlation of Follicular Diameter with Oocyte Recovery and Maturity at the Time of Transvaginal Follicular Aspiration. J. Vitr. Fertil. Embryo Transf. 1989, 6, 73–75. [Google Scholar] [CrossRef]
- Haines, C.J.; Emes, A.L. The Relationship between Follicle Diameter, Fertilization Rate, and Microscopic Embryo Quality. Fertil. Steril. 1991, 55, 205–207. [Google Scholar] [CrossRef]
- Shapiro, B.S.; Rasouli, M.A.; Verma, K.; Raman, A.; Garner, F.C.; Aguirre, M.; Kaye, L.; Bedient, C. The Effect of Ovarian Follicle Size on Oocyte and Embryology Outcomes. Fertil. Steril. 2022, 117, 1170–1176. [Google Scholar] [CrossRef]
- Abbara, A.; Vuong, L.N.; Ho, V.N.A.; Clarke, S.A.; Jeffers, L.; Comninos, A.N.; Salim, R.; Ho, T.M.; Kelsey, T.W.; Trew, G.H.; et al. Follicle Size on Day of Trigger Most Likely to Yield a Mature Oocyte. Front. Endocrinol. 2018, 9, 193. [Google Scholar] [CrossRef]
- McCulloh, D.H.; Kutchukhidze, N.; Charkviani, T.; Zhorzholadze, T.; Barbakadze, T.; Munné, S.; Chkonia, L. Follicle Size Indicates Oocyte Maturity and Blastocyst Formation but Not Blastocyst Euploidy Following Controlled Ovarian Hyperstimulation of Oocyte Donors. Hum. Reprod. 2020, 35, 545–556. [Google Scholar] [CrossRef]
- Wittmaack, F.M.; Kreger, D.O.; Blasco, L.; Tureck, R.W.; Mastroianni, L.; Lessey, B.A. Effect of Follicular Size on Oocyte Retrieval, Fertilization, Cleavage, and Embryo Quality in in Vitro Fertilization Cycles: A 6-Year Data Collection. Fertil. Steril. 1994, 62, 1205–1210. [Google Scholar] [CrossRef] [PubMed]
- Ectors, F.J.; Vanderzwalmen, P.; Van Hoeck, J.; Nijs, M.; Verhaegen, G.; Delvigne, A.; Schoysman, R.; Leroy, F. Relationship of Human Follicular Diameter with Oocyte Fertilization and Development after In-Vitro Fertilization or Intracytoplasmic Sperm Injection. Hum. Reprod. 1997, 12, 2002–2005. [Google Scholar] [CrossRef] [PubMed]
- Bergh, C.; Broden, H.; Lundin, K.; Hamberger, L. Comparison of Fertilization, Cleavage and Pregnancy Rates of Oocytes from Large and Small Follicles. Hum. Reprod. 1998, 13, 1912–1915. [Google Scholar] [CrossRef] [PubMed]
- Salha, O.; Nugent, D.; Dada, T.; Kaufmann, S.; Levett, S.; Jenner, L.; Lui, S.; Sharma, V. The Relationship between Follicular Fluid Aspirate Volume and Oocyte Maturity in In-Vitro Fertilization Cycles. Hum. Reprod. 1998, 13, 1901–1906. [Google Scholar] [CrossRef]
- Triwitayakorn, A.; Suwajanakorn, S.; Pruksananonda, K.; Sereepapong, W.; Ahnonkitpanit, V. Correlation between Human Follicular Diameter and Oocyte Outcomes in an ICSI Program. J. Assist. Reprod. Genet. 2003, 20, 143–147. [Google Scholar] [CrossRef]
- Nogueira, D.; Friedler, S.; Schachter, M.; Raziel, A.; Ron-El, R.; Smitz, J. Oocyte Maturity and Preimplantation Development in Relation to Follicle Diameter in Gonadotropin-Releasing Hormone Agonist or Antagonist Treatments. Fertil. Steril. 2006, 85, 578–583. [Google Scholar] [CrossRef]
- Rosen, M.P.; Shen, S.; Dobson, A.T.; Rinaudo, P.F.; McCulloch, C.E.; Cedars, M.I. A Quantitative Assessment of Follicle Size on Oocyte Developmental Competence. Fertil. Steril. 2008, 90, 684–690. [Google Scholar] [CrossRef]
- Kahraman, S.; Cetinkaya, C.P.; Cetinkaya, M.; Yelke, H.; Colakoglu, Y.K.; Aygun, M.; Montag, M. The Effect of Follicle Size and Homogeneity of Follicular Development on the Morphokinetics of Human Embryos. J. Assist. Reprod. Genet. 2017, 34, 895–903. [Google Scholar] [CrossRef]
- Mohr-Sasson, A.; Orvieto, R.; Blumenfeld, S.; Axelrod, M.; Mor-Hadar, D.; Grin, L.; Aizer, A.; Haas, J. The Association between Follicle Size and Oocyte Development as a Function of Final Follicular Maturation Triggering. Reprod. Biomed. Online 2020, 40, 887–893. [Google Scholar] [CrossRef]
- Reproduction, O.F. Relationship Between Maturation Follicular Sizes in Table. Culture 1985, 417, 413–417. [Google Scholar]
- Mehri, S.; Levi Setti, P.E.; Greco, K.; Sakkas, D.; Martinez, G.; Patrizio, P. Correlation between Follicular Diameters and Flushing versus No Flushing on Oocyte Maturity, Fertilization Rate and Embryo Quality. J. Assist. Reprod. Genet. 2014, 31, 73–77. [Google Scholar] [CrossRef] [PubMed]
- Dubey, A.K.; An Wang, H.; Duffy, P.; Penzias, A.S. The Correlation between Follicular Measurements, Oocyte Morphology, and Fertilization Rates in an in Vitro Fertilization Program. Fertil. Steril. 1995, 64, 787–790. [Google Scholar] [CrossRef] [PubMed]
- Tian, T.; Li, Y.; Lv, J.; Chen, L.; Wang, Y.; Yang, R.; Liu, P.; Li, R.; Qiao, J. The Potential Influence of Follicle Diameter on Natural Cycle in Vitro Fertilization among Women with Diminished Ovarian Reserve: A Retrospective Cohort Study. J. Ovarian Res. 2023, 16, 195. [Google Scholar] [CrossRef] [PubMed]
- Wirleitner, B.; Okhowat, J.; Vištejnová, L.; Králíčková, M.; Karlíková, M.; Vanderzwalmen, P.; Ectors, F.; Hradecký, L.; Schuff, M.; Murtinger, M. Relationship between Follicular Volume and Oocyte Competence, Blastocyst Development and Live-Birth Rate: Optimal Follicle Size for Oocyte Retrieval. Ultrasound Obstet. Gynecol. 2018, 51, 118–125. [Google Scholar] [CrossRef]
- Teramoto, S.; Osada, H.; Sato, Y.; Shozu, M. Nondominant Small Follicles Are a Promising Source of Mature Oocytes in Modified Natural Cycle in Vitro Fertilization and Embryo Transfer. Fertil. Steril. 2016, 106, 113–118. [Google Scholar] [CrossRef]
- Helmer, A.; Magaton, I.; Stalder, O.; Stute, P.; Surbek, D.; von Wolff, M. Optimal Timing of Ovulation Triggering to Achieve Highest Success Rates in Natural Cycles—An Analysis Based on Follicle Size and Oestradiol Concentration in Natural Cycle IVF. Front. Endocrinol. 2022, 13, 855131. [Google Scholar] [CrossRef]
- Andersen, C.Y. Characteristics of Human Follicular Fluid Associated with Successful Conception after in Vitro Fertilization. J. Clin. Endocrinol. Metab. 1993, 77, 1227–1234. [Google Scholar] [CrossRef]
- MILLER, K. Follicle Size and Implantation of Embryos from In Vitro Fertilization. Obstet. Gynecol. 1996, 88, 583–586. [Google Scholar] [CrossRef]
- Bhaskaran, M.; Mohan, M. MicroRNAs. Vet. Pathol. 2014, 51, 759–774. [Google Scholar] [CrossRef]
- Turchinovich, A.; Weiz, L.; Burwinkel, B. Extracellular MiRNAs: The Mystery of Their Origin and Function. Trends Biochem. Sci. 2012, 37, 460–465. [Google Scholar] [CrossRef]
- Moreno-Moya, J.M.; Vilella, F.; Simón, C. MicroRNA: Key Gene Expression Regulators. Fertil. Steril. 2014, 101, 1516–1523. [Google Scholar] [CrossRef]
- He, L.; Hannon, G.J. MicroRNAs: Small RNAs with a Big Role in Gene Regulation. Nat. Rev. Genet. 2004, 5, 522–531. [Google Scholar] [CrossRef]
- Sánchez, F.; Smitz, J. Molecular Control of Oogenesis. Biochim. Biophys. Acta Mol. Basis Dis. 2012, 1822, 1896–1912. [Google Scholar] [CrossRef] [PubMed]
- Ohlsson Teague, E.M.C.; Print, C.G.; Hull, M.L. The Role of MicroRNAs in Endometriosis and Associated Reproductive Conditions. Hum. Reprod. Update 2010, 16, 142–165. [Google Scholar] [CrossRef] [PubMed]
- Zhu, X.; Han, T.; Sargent, I.L.; Yin, G.; Yao, Y. Differential Expression Profile of MicroRNAs in Human Placentas from Preeclamptic Pregnancies vs Normal Pregnancies. Am. J. Obstet. Gynecol. 2009, 200, 661.e1–661.e7. [Google Scholar] [CrossRef] [PubMed]
- Pineles, B.L.; Romero, R.; Montenegro, D.; Tarca, A.L.; Han, Y.M.; Kim, Y.M.; Draghici, S.; Espinoza, J.; Kusanovic, J.P.; Mittal, P.; et al. Distinct Subsets of MicroRNAs Are Expressed Differentially in the Human Placentas of Patients with Preeclampsia. Am. J. Obstet. Gynecol. 2007, 196, 261.e1–261.e6. [Google Scholar] [CrossRef] [PubMed]
- Moreno-Moya, J.M.; Franchi, N.A.; Martínez-Escribano, S.; Martínez-Conejero, J.A.; Bocca, S.; Oehninger, S.; Horcajadas, J.A. Transcriptome of Early Embryonic Invasion at Implantation Sites in a Murine Model. Reprod. Fertil. Dev. 2016, 28, 1487. [Google Scholar] [CrossRef]
- Hawkins, S.M.; Matzuk, M.M. Oocyte-Somatic Cell Communication and MicroRNA Function in the Ovary. Ann. Endocrinol. 2010, 71, 144–148. [Google Scholar] [CrossRef]
- Hossain, M.M.; Sohel, M.M.H.; Schellander, K.; Tesfaye, D. Characterization and Importance of MicroRNAs in Mammalian Gonadal Functions. Cell Tissue Res. 2012, 349, 679–690. [Google Scholar] [CrossRef]
- Otsuka, M.; Zheng, M.; Hayashi, M.; Lee, J.-D.; Yoshino, O.; Lin, S.; Han, J. Impaired MicroRNA Processing Causes Corpus Luteum Insufficiency and Infertility in Mice. J. Clin. Investig. 2008, 118, 1944–1954. [Google Scholar] [CrossRef]
- Moreno, J.M.; Núñez, M.J.; Quiñonero, A.; Martínez, S.; De La Orden, M.; Simón, C.; Pellicer, A.; Díaz-García, C.; Domínguez, F. Follicular Fluid and Mural Granulosa Cells MicroRNA Profiles Vary in in Vitro Fertilization Patients Depending on Their Age and Oocyte Maturation Stage. Fertil. Steril. 2015, 104, 1037–1046.e1. [Google Scholar] [CrossRef] [PubMed]
- Teramoto, S.; Kato, O. Minimal Ovarian Stimulation with Clomiphene Citrate: A Large-Scale Retrospective Study. Reprod. Biomed. Online 2007, 15, 134–148. [Google Scholar] [CrossRef] [PubMed]
- Sanchez, F.; Le, A.H.; Ho, V.N.A.; Romero, S.; Van Ranst, H.; De Vos, M.; Gilchrist, R.B.; Ho, T.M.; Vuong, L.N.; Smitz, J. Biphasic in Vitro Maturation (CAPA-IVM) Specifically Improves the Developmental Capacity of Oocytes from Small Antral Follicles. J. Assist. Reprod. Genet. 2019, 36, 2135–2144. [Google Scholar] [CrossRef] [PubMed]
- Cadenas, J.; la Cour Poulsen, L.; Mamsen, L.S.; Andersen, C.Y. Future Potential of in Vitro Maturation Including Fertility Preservation. Fertil. Steril. 2023, 119, 550–559. [Google Scholar] [CrossRef]
- Durinzi, K.L.; Saniga, E.M.; Lanzendorf, S.E. The Relationship between Size and Maturation in Vitro in the Unstimulated Human Oocyte. Fertil. Steril. 1995, 63, 404–406. [Google Scholar] [CrossRef]
- Conti, M.; Franciosi, F. Acquisition of Oocyte Competence to Develop as an Embryo: Integrated Nuclear and Cytoplasmic Events. Hum. Reprod. Update 2018, 24, 245–266. [Google Scholar] [CrossRef]
- Urrutia, A.G.; Cuevas, M.M.; Giner, A.M.; Carmona, J.M.; Insua, M.F.; Pellicer, A.; Herraiz, S.; Escriba Perez, M.J. Nicotinamide Mononucleotide (NMN) in Vitro Supplementation Improves Deficiencies in Nuclear and Cytoplasmic Competence of Germinal Vesicle Oocytes. Fertil. Steril. 2022, 118, e145–e146. [Google Scholar] [CrossRef]
- Vuong, L.N.; Le, A.H.; Ho, V.N.A.; Pham, T.D.; Sanchez, F.; Romero, S.; De Vos, M.; Ho, T.M.; Gilchrist, R.B.; Smitz, J. Live Births after Oocyte in Vitro Maturation with a Prematuration Step in Women with Polycystic Ovary Syndrome. J. Assist. Reprod. Genet. 2020, 37, 347–357. [Google Scholar] [CrossRef]
- Sánchez, F.; Lolicato, F.; Romero, S.; De Vos, M.; Van Ranst, H.; Verheyen, G.; Anckaert, E.; Smitz, J.E.J. An Improved IVM Method for Cumulus-Oocyte Complexes from Small Follicles in Polycystic Ovary Syndrome Patients Enhances Oocyte Competence and Embryo Yield. Hum. Reprod. 2017, 32, 2056–2068. [Google Scholar] [CrossRef]
- Fanton, M.; Cho, J.H.; Baker, V.L.; Loewke, K. A Higher Number of Oocytes Retrieved Is Associated with an Increase in 2PNs, Blastocysts, and Cumulative Live Birth Rates. Fertil. Steril. 2023, 119, 762–769. [Google Scholar] [CrossRef]
- Vermey, B.G.; Chua, S.J.; Zafarmand, M.H.; Wang, R.; Longobardi, S.; Cottell, E.; Beckers, F.; Mol, B.W.; Venetis, C.A.; D’Hooghe, T. Is There an Association between Oocyte Number and Embryo Quality? A Systematic Review and Meta-Analysis. Reprod. Biomed. Online 2019, 39, 751–763. [Google Scholar] [CrossRef] [PubMed]
- van der Gaast, M.H.; Eijkemans, M.J.C.; van der Net, J.B.; de Boer, E.J.; Burger, C.W.; van Leeuwen, F.E.; Fauser, B.C.J.M.; Macklon, N.S. Optimum Number of Oocytes for a Successful First IVF Treatment Cycle. Reprod. Biomed. Online 2006, 13, 476–480. [Google Scholar] [CrossRef] [PubMed]
- Vaughan, D.A.; Leung, A.; Resetkova, N.; Ruthazer, R.; Penzias, A.S.; Sakkas, D.; Alper, M.M. How Many Oocytes Are Optimal to Achieve Multiple Live Births with One Stimulation Cycle? The One-and-Done Approach. Fertil. Steril. 2017, 107, 397–404.e3. [Google Scholar] [CrossRef] [PubMed]
- Practice Committee of the American Society for Reproductive Medicine. Comparison of Pregnancy Rates for Poor Responders Using IVF with Mild Ovarian Stimulation versus Conventional IVF: A Guideline. Fertil. Steril. 2018, 109, 993–999. [Google Scholar] [CrossRef] [PubMed]
- Drakopoulos, P.; Bardhi, E.; Boudry, L.; Vaiarelli, A.; Makrigiannakis, A.; Esteves, S.C.; Tournaye, H.; Blockeel, C. Update on the Management of Poor Ovarian Response in IVF: The Shift from Bologna Criteria to the Poseidon Concept. Ther. Adv. Reprod. Heal. 2020, 14, 263349412094148. [Google Scholar] [CrossRef]
- Cuevas Saiz, I.; Carme Pons Gatell, M.; Vargas, M.C.; Delgado Mendive, A.; Rives Enedáguila, N.; Moragas Solanes, M.; Carrasco Canal, B.; Teruel López, J.; Busquets Bonet, A.; Hurtado de Mendoza Acosta, M.V. The Embryology Interest Group: Updating ASEBIR’s Morphological Scoring System for Early Embryos, Morulae and Blastocysts. Med. Reprod. Embriol. Clínica 2018, 5, 42–54. [Google Scholar] [CrossRef]
Demographic Characteristics | |
Age (years), median [IQR] | 37 [35–38] |
Weight (kg), mean (SD) | 59.02 (8.81) |
Height (m), mean (SD) | 1.637 (0.072) |
BMI (kg/m2), mean (SD) | 22.04 (3.13) |
Reproductive Characteristics | |
Stimulation time (days), mean (SD) | 11.28 (2.87) |
Total gonadotropin dose (IU), mean (SD) | 2042 (957.1) |
Serum E2 on trigger day (pg/mL), mean (SD) | 952.3 (392.3) |
Serum P4 on trigger day (ng/mL), mean (SD) | 0.583 (0.378) |
Serum AMH (ng/mL), median [IQR] | 0.47 [0.27–0.83] |
Follicular Diameter (mm) | Punctured Follicles (n) | Oocytes | Mature Oocytes (MII) | Fertilized Oocytes (2PN) | Blastocysts | Good-Quality Blastocysts | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n | PPF | n | PPF | Per Oocyte | n | PPF | Per MII Oocyte | n | PPF | Per 2PN Oocyte | n | PPF | Per 2PN Oocyte | ||
<9.5 | 43 | 12 | 27.91% | 6 | 13.95% | 50.00% | 2 | 4.65% | 33.33% | 1 | 2.33% | 50.00% | 0 | 0.00% | 0.00% |
9.5–<11.5 | 21 | 11 | 52.38% | 6 | 28.57% | 54.55% | 1 | 4.76% | 16.67% | 0 | 0.00% | 0.00% | 0 | 0.00% | 0.00% |
11.5–<13.5 | 21 | 14 | 66.67% | 13 | 61.90% | 92.86% | 11 | 52.38% | 84.62% | 3 | 14.29% | 27.27% | 0 | 0.00% | 0.00% |
13.5–<15.5 | 16 | 10 | 62.50% | 9 | 56.25% | 90.00% | 4 | 25.00% | 44.44% | 2 | 12.50% | 50.00% | 1 | 6.25% | 25.00% |
15.5–<17.5 | 15 | 13 | 86.67% | 11 | 73.33% | 84.62% | 7 | 46.67% | 63.64% | 5 | 33.33% | 71.43% | 3 | 20.00% | 42.86% |
17.5–19.5 | 23 | 17 | 73.91% | 13 | 56.52% | 76.47% | 11 | 47.83% | 84.62% | 6 | 26.09% | 54.55% | 4 | 17.39% | 36.36% |
≥19.5 | 39 | 27 | 69.23% | 22 | 56.41% | 81.48% | 14 | 35.90% | 63.64% | 7 | 17.95% | 50.00% | 4 | 10.26% | 28.57% |
Overall | 178 | 104 | 58.43% | 80 | 44.94% | 76.92% | 50 | 28.09% | 62.50% | 24 | 13.48% | 48.00% | 12 | 6.74% | 24.00% |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Yagüe-Serrano, R.; Palomar, A.; Quiñonero, A.; Gómez, V.H.; de los Santos, M.J.; Vidal, C.; Dominguez, F. Oocyte Competence, Embryological Outcomes and miRNA Signature of Different Sized Follicles from Poor Responder Patients. Int. J. Mol. Sci. 2024, 25, 10237. https://doi.org/10.3390/ijms251910237
Yagüe-Serrano R, Palomar A, Quiñonero A, Gómez VH, de los Santos MJ, Vidal C, Dominguez F. Oocyte Competence, Embryological Outcomes and miRNA Signature of Different Sized Follicles from Poor Responder Patients. International Journal of Molecular Sciences. 2024; 25(19):10237. https://doi.org/10.3390/ijms251910237
Chicago/Turabian StyleYagüe-Serrano, Roberto, Andrea Palomar, Alicia Quiñonero, Víctor Hugo Gómez, Maria José de los Santos, Carmen Vidal, and Francisco Dominguez. 2024. "Oocyte Competence, Embryological Outcomes and miRNA Signature of Different Sized Follicles from Poor Responder Patients" International Journal of Molecular Sciences 25, no. 19: 10237. https://doi.org/10.3390/ijms251910237