Skip to main content

Advertisement

SpringerLink
Log in

Metaphase-II oocyte competence is unlinked to the gonadotrophins used for ovarian stimulation: a matched case–control study in women of advanced maternal age

  • Assisted Reproduction Technologies
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

An impact of different gonadotrophins selection for ovarian stimulation (OS) on oocyte competence has yet to be defined. In this study, we asked whether an association exists between OS protocol and euploid blastocyst rate (EBR) per metaphase-II (MII) oocytes.

Methods

Cycles of first preimplantation genetic testing for aneuploidies conducted by women ≥ 35 years old with their own metaphase-II oocytes inseminated in the absence of severe male factor (years 2014–2018) were clustered based on whether recombinant FSH (rec-FSH) or human menopausal gonadotrophin (HMG) was used for OS, then matched for the number of fresh inseminated eggs. Four groups were outlined: rec-FSH (N = 57), rec-FSH plus rec-LH (N = 55), rec-FSH plus HMG (N = 112), and HMG-only (N = 127). Intracytoplasmic sperm injection, continuous blastocyst culture, comprehensive chromosome testing to assess full-chromosome non-mosaic aneuploidies and vitrified-warmed euploid single embryo transfers (SETs) were performed. The primary outcome was the EBR per cohort of MII oocytes. The secondary outcome was the live birth rate (LBR) per first SETs.

Results

Rec-FSH protocol was shorter and characterized by lower total gonadotrophin (Gn) dose. The linear regression model adjusted for maternal age showed no association between the Gn adopted for OS and EBR per cohort of MII oocytes. Similarly, no association was reported with the LBR per first SETs, even when adjusting for blastocyst quality and day of full blastulation.

Conclusion

In view of enhanced personalization in OS, clinicians shall focus on different endpoints or quantitative effects related to Gn action towards follicle recruitment, development, and atresia. Here, LH and/or hCG was administered exclusively to women with expected sub/poor response; therefore, we cannot exclude that specific Gn formulations may impact patient prognosis in other populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Law YJ, Zhang N, Venetis CA, Chambers GM, Harris K. The number of oocytes associated with maximum cumulative live birth rates per aspiration depends on female age: a population study of 221 221 treatment cycles. Hum Reprod. 2019;34(9):1778–87. https://doi.org/10.1093/humrep/dez100.

    Article  Google Scholar 

  2. Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016;31(2):370–6. https://doi.org/10.1093/humrep/dev316.

  3. Magnusson A, Kallen K, Thurin-Kjellberg A, Bergh C. The number of oocytes retrieved during IVF: a balance between efficacy and safety. Hum Reprod. 2017:1–7. https://doi.org/10.1093/humrep/dex334.

  4. Rienzi L, Cimadomo D, Vaiarelli A, Gennarelli G, Holte J, Livi C, et al. Measuring success in IVF is a complex multidisciplinary task: time for a consensus? Reprod Biomed Online. 2021;43(5):775–8. https://doi.org/10.1016/j.rbmo.2021.08.012.

  5. Maheshwari A, McLernon D, Bhattacharya S. Cumulative live birth rate: time for a consensus? Hum Reprod. 2015;30(12):2703–7. https://doi.org/10.1093/humrep/dev263.

    Article  Google Scholar 

  6. Maggiulli R, Cimadomo D, Fabozzi G, Papini L, Dovere L, Ubaldi FM, et al. The effect of ICSI-related procedural timings and operators on the outcome. Hum Reprod. 2020;35(1):32–43. https://doi.org/10.1093/humrep/dez234.

    Article  Google Scholar 

  7. Cimadomo D, Capalbo A, Dovere L, Tacconi L, Soscia D, Giancani A, et al. Leave the past behind: women’s reproductive history shows no association with blastocysts’ euploidy and limited association with live birth rates after euploid embryo transfers. Hum Reprod. 2021;36(4):929–40. https://doi.org/10.1093/humrep/deab014.

    Article  CAS  Google Scholar 

  8. Capalbo A, Hoffmann ER, Cimadomo D, Ubaldi FM, Rienzi L. Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging. Hum Reprod Update. 2017;23(6):706–22. https://doi.org/10.1093/humupd/dmx026.

    Article  CAS  Google Scholar 

  9. Mazzilli R, Cimadomo D, Vaiarelli A, Capalbo A, Dovere L, Alviggi E, et al. Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles. Fertil Steril. 2017. https://doi.org/10.1016/j.fertnstert.2017.08.033.

    Article  Google Scholar 

  10. Leao Rde B, Esteves SC. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech. Clinics (Sao Paulo). 2014;69(4):279–93. https://doi.org/10.6061/clinics/2014(04)10.

    Article  Google Scholar 

  11. Lunenfeld B, Bilger W, Longobardi S, Alam V, D'Hooghe T, Sunkara SK. The development of gonadotropins for clinical use in the treatment of infertility. Front Endocrinol (Lausanne). 2019;10:429. https://doi.org/10.3389/fendo.2019.00429.

  12. Hodges CA, Ilagan A, Jennings D, Keri R, Nilson J, Hunt PA. Experimental evidence that changes in oocyte growth influence meiotic chromosome segregation. Hum Reprod. 2002;17(5):1171–80. https://doi.org/10.1093/humrep/17.5.1171.

    Article  CAS  Google Scholar 

  13. Elbling L, Colot M. Abnormal development and transport and increased sister-chromatid exchange in preimplantation embryos following superovulation in mice. Mutat Res. 1985;147(4):189–95. https://doi.org/10.1016/0165-1161(85)90057-3.

    Article  CAS  Google Scholar 

  14. Spielmann H, Vogel R. Genotoxic and embryotoxic effects of gonadotropin hyperstimulated ovulation on murine oocytes, preimplantation embryos and term fetuses. Ann Ist Super Sanita. 1993;29(1):35–9.

    CAS  Google Scholar 

  15. Verberg MF, Macklon NS, Nargund G, Frydman R, Devroey P, Broekmans FJ, et al. Mild ovarian stimulation for IVF. Hum Reprod Update. 2009;15(1):13–29. https://doi.org/10.1093/humupd/dmn056.

    Article  CAS  Google Scholar 

  16. Testart J, Belaisch-Allart J, Frydman R. Relationships between embryo transfer results and ovarian response and in vitro fertilization rate: analysis of 186 human pregnancies. Fertil Steril. 1986;45(2):237–43. https://doi.org/10.1016/s0015-0282(16)49161-2.

    Article  CAS  Google Scholar 

  17. Pellicer A, Ruiz A, Castellvi RM, Calatayud C, Ruiz M, Tarin JJ, et al. Is the retrieval of high numbers of oocytes desirable in patients treated with gonadotrophin-releasing hormone analogues (GnRHa) and gonadotrophins? Hum Reprod. 1989;4(5):536–40. https://doi.org/10.1093/oxfordjournals.humrep.a136940.

    Article  CAS  Google Scholar 

  18. Sato A, Otsu E, Negishi H, Utsunomiya T, Arima T. Aberrant DNA methylation of imprinted loci in superovulated oocytes. Hum Reprod. 2007;22(1):26–35. https://doi.org/10.1093/humrep/del316.

  19. Baart EB, Martini E, Eijkemans MJ, Van Opstal D, Beckers NG, Verhoeff A, et al. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007;22(4):980–8. https://doi.org/10.1093/humrep/del484.

    Article  Google Scholar 

  20. Labarta E, Bosch E, Alama P, Rubio C, Rodrigo L, Pellicer A. Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles. J Clin Endocrinol Metab. 2012;97(10):E1987–94. https://doi.org/10.1210/jc.2012-1738.

    Article  CAS  Google Scholar 

  21. Labarta E, Bosch E, Mercader A, Alama P, Mateu E, Pellicer A. A higher ovarian response after stimulation for IVF is related to a higher number of euploid embryos. Biomed Res Int. 2017;2017:5637923. https://doi.org/10.1155/2017/5637923.

    Article  CAS  Google Scholar 

  22. Barash OO, Hinckley MD, Rosenbluth EM, Ivani KA, Weckstein LN. High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer. Hum Reprod. 2017;32(11):2209–17. https://doi.org/10.1093/humrep/dex299.

    Article  CAS  Google Scholar 

  23. Wu Q, Li H, Zhu Y, Jiang W, Lu J, Wei D, et al. Dosage of exogenous gonadotropins is not associated with blastocyst aneuploidy or live-birth rates in PGS cycles in Chinese women. Hum Reprod. 2018;33(10):1875–82. https://doi.org/10.1093/humrep/dey270.

    Article  CAS  Google Scholar 

  24. Irani M, Canon C, Robles A, Maddy B, Gunnala V, Qin X, et al. No effect of ovarian stimulation and oocyte yield on euploidy and live birth rates: an analysis of 12 298 trophectoderm biopsies. Hum Reprod. 2020;35(5):1082–9. https://doi.org/10.1093/humrep/deaa028.

    Article  CAS  Google Scholar 

  25. Morin SJ, Patounakis G, Juneau CR, Neal SA, Scott RT, Seli E. Diminished ovarian reserve and poor response to stimulation in patients <38 years old: a quantitative but not qualitative reduction in performance. Hum Reprod. 2018;33(8):1489–98. https://doi.org/10.1093/humrep/dey238.

    Article  CAS  Google Scholar 

  26. Alviggi C, Conforti A. Mild/moderate versus full stimulation. Fertil Steril. 2022;117(4):664–8. https://doi.org/10.1016/j.fertnstert.2022.02.022.

    Article  Google Scholar 

  27. Ubaldi FM, Capalbo A, Vaiarelli A, Cimadomo D, Colamaria S, Alviggi C, et al. Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation. Fertil Steril. 2016;105(6):1488–95 e1. https://doi.org/10.1016/j.fertnstert.2016.03.002.

  28. Vaiarelli A, Cimadomo D, Conforti A, Schimberni M, Giuliani M, D’Alessandro P, et al. Luteal phase after conventional stimulation in the same ovarian cycle might improve the management of poor responder patients fulfilling the Bologna criteria: a case series. Fertil Steril. 2020;113(1):121–30. https://doi.org/10.1016/j.fertnstert.2019.09.012.

    Article  CAS  Google Scholar 

  29. Cimadomo D, Scarica C, Maggiulli R, Orlando G, Soscia D, Albricci L, et al. Continuous embryo culture elicits higher blastulation but similar cumulative delivery rates than sequential: a large prospective study. J Assist Reprod Genet. 2018. https://doi.org/10.1007/s10815-018-1195-4.

    Article  Google Scholar 

  30. 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):124–40. https://doi.org/10.1093/humupd/dmt037.

    Article  CAS  Google Scholar 

  31. Casarini L, Riccetti L, Paradiso E, Benevelli R, Lazzaretti C, Sperduti S, et al. Two human menopausal gonadotrophin (hMG) preparations display different early signaling in vitro. Mol Hum Reprod. 2020;26(12):894–905. https://doi.org/10.1093/molehr/gaaa070.

    Article  CAS  Google Scholar 

  32. Maggiulli R, Giancani A, Cimadomo D, Ubaldi FM, Rienzi L. Human blastocyst biopsy and vitrification. J Vis Exp. 2019;(149). https://doi.org/10.3791/59625.

  33. Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, et al. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod. 2014;29(6):1173–81. https://doi.org/10.1093/humrep/deu033.

    Article  Google Scholar 

  34. Treff NR, Tao X, Ferry KM, Su J, Taylor D, Scott RT Jr. Development and validation of an accurate quantitative real-time polymerase chain reaction-based assay for human blastocyst comprehensive chromosomal aneuploidy screening. Fertil Steril. 2012;97(4):819–24. https://doi.org/10.1016/j.fertnstert.2012.01.115.

    Article  CAS  Google Scholar 

  35. Capalbo A, Poli M, Rienzi L, Girardi L, Patassini C, Fabiani M, et al. Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial. Am J Hum Genet. 2021;108(12):2238–47. https://doi.org/10.1016/j.ajhg.2021.11.002.

  36. Vaiarelli A, Cimadomo D, Patrizio P, Venturella R, Orlando G, Soscia D, et al. Biochemical pregnancy loss after frozen embryo transfer seems independent of embryo developmental stage and chromosomal status. Reprod Biomed Online. 2018;37(3):349–57. https://doi.org/10.1016/j.rbmo.2018.05.019.

    Article  CAS  Google Scholar 

  37. Gardner DK, Schoolcraft B. In vitro culture of human blastocysts, toward reproductive certainty: fertility and genetics beyond. London: Parthenon Publishing; 1999. p. 378–88.

    Google Scholar 

  38. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril. 2017;108(3):393–406. https://doi.org/10.1016/j.fertnstert.2017.06.005.

    Article  Google Scholar 

  39. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod. 2017;32(9):1786–801. https://doi.org/10.1093/humrep/dex234.

    Article  Google Scholar 

  40. Cimadomo D, Soscia D, Vaiarelli A, Maggiulli R, Capalbo A, Ubaldi FM, et al. Looking past the appearance: a comprehensive description of the clinical contribution of poor-quality blastocysts to increase live birth rates during cycles with aneuploidy testing. Hum Reprod. 2019;34:1206–14.

    Article  Google Scholar 

  41. Palmerola KL, Vitez SF, Amrane S, Fischer CP, Forman EJ. Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A). J Assist Reprod Genet. 2019;36(1):153–7. https://doi.org/10.1007/s10815-018-1347-6.

  42. Deng J, Kuyoro O, Zhao Q, Behr B, Lathi RB. Comparison of aneuploidy rates between conventional in vitro fertilization and intracytoplasmic sperm injection in in vitro fertilization-intracytoplasmic sperm injection split insemination cycles. F S Rep. 2020;1(3):277–81. https://doi.org/10.1016/j.xfre.2020.07.006.

  43. De Munck N, El Khatib I, Abdala A, El-Damen A, Bayram A, Arnanz A, et al. Intracytoplasmic sperm injection is not superior to conventional IVF in couples with non-male factor infertility and preimplantation genetic testing for aneuploidies (PGT-A). Hum Reprod. 2020;35(2):317–27. https://doi.org/10.1093/humrep/deaa002.

    Article  CAS  Google Scholar 

  44. Goldman KN, Kramer Y, Hodes-Wertz B, Noyes N, McCaffrey C, Grifo JA. Long-term cryopreservation of human oocytes does not increase embryonic aneuploidy. Fertil Steril. 2015;103(3):662–8. https://doi.org/10.1016/j.fertnstert.2014.11.025.

    Article  Google Scholar 

  45. Forman EJ, Li X, Ferry KM, Scott K, Treff NR, Scott RT Jr. Oocyte vitrification does not increase the risk of embryonic aneuploidy or diminish the implantation potential of blastocysts created after intracytoplasmic sperm injection: a novel, paired randomized controlled trial using DNA fingerprinting. Fertil Steril. 2012;98(3):644–9. https://doi.org/10.1016/j.fertnstert.2012.04.028.

    Article  CAS  Google Scholar 

  46. Werner MD, Hong KH, Franasiak JM, Forman EJ, Reda CV, Molinaro TA, et al. Sequential versus Monophasic Media Impact Trial (SuMMIT): a paired randomized controlled trial comparing a sequential media system to a monophasic medium. Fertil Steril. 2016;105(5):1215–21. https://doi.org/10.1016/j.fertnstert.2016.01.005.

    Article  CAS  Google Scholar 

  47. Ata B, Kaplan B, Danzer H, Glassner M, Opsahl M, Tan SL, et al. Array CGH analysis shows that aneuploidy is not related to the number of embryos generated. Reprod Biomed Online. 2012;24(6):614–20. https://doi.org/10.1016/j.rbmo.2012.02.009.

    Article  CAS  Google Scholar 

  48. Cimadomo D, Vaiarelli A, Petriglia C, Fabozzi G, Ferrero S, Schimberni M, et al. Oocyte competence is independent of the ovulation trigger adopted: a large observational study in a setting that entails vitrified-warmed single euploid blastocyst transfer. J Assist Reprod Genet. 2021;38(6):1419–27. https://doi.org/10.1007/s10815-021-02124-1.

    Article  Google Scholar 

  49. Thorne J, Loza A, Kaye L, Nulsen J, Benadiva C, Grow D, et al. Euploidy rates between cycles triggered with gonadotropin-releasing hormone agonist and human chorionic gonadotropin. Fertil Steril. 2019;112(2):258–65. https://doi.org/10.1016/j.fertnstert.2019.03.040.

    Article  CAS  Google Scholar 

  50. Lee CI, Chen HH, Huang CC, Chen CH, Cheng EH, Huang JY, et al. Effect of interval between human chorionic gonadotropin priming and ovum pick-up on the euploid probabilities of blastocyst. J Clin Med. 2020;9(6). https://doi.org/10.3390/jcm9061685.

  51. La Marca A, Capuzzo M, Sacchi S, Imbrogno MG, Spinella F, Varricchio MT, et al. Comparison of euploidy rates of blastocysts in women treated with progestins or GnRH antagonist to prevent the luteinizing hormone surge during ovarian stimulation. Hum Reprod. 2020;35(6):1325–31. https://doi.org/10.1093/humrep/deaa068.

    Article  CAS  Google Scholar 

  52. Ata B, Capuzzo M, Turkgeldi E, Yildiz S, La Marca A. Progestins for pituitary suppression during ovarian stimulation for ART: a comprehensive and systematic review including meta-analyses. Hum Reprod Update. 2021;27(1):48–66. https://doi.org/10.1093/humupd/dmaa040.

    Article  CAS  Google Scholar 

  53. Cimadomo D, Vaiarelli A, Colamaria S, Trabucco E, Alviggi C, Venturella R, et al. Luteal phase anovulatory follicles result in the production of competent oocytes: intra-patient paired case-control study comparing follicular versus luteal phase stimulations in the same ovarian cycle. Hum Reprod. 2018. https://doi.org/10.1093/humrep/dey217.

    Article  Google Scholar 

  54. Lockwood G, Cometti B, Bogstad J, Erb K, De Geyter C, Urbancsek J, et al. A randomized controlled trial comparing the efficacy and safety of two HMG preparations gaining their LH bioactivity from different HCG sources. Reprod Biomed Online. 2017;35(1):17–27. https://doi.org/10.1016/j.rbmo.2017.03.021.

  55. Conforti A, Esteves SC, Humaidan P, Longobardi S, D'Hooghe T, Orvieto R, et al. Recombinant human luteinizing hormone co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2021;19(1):91. https://doi.org/10.1186/s12958-021-00759-4.

  56. Bosch E, Alviggi C, Lispi M, Conforti A, Hanyaloglu AC, Chuderland D, et al. Reduced FSH and LH action: implications for medically assisted reproduction. Hum Reprod. 2021;36(6):1469–80. https://doi.org/10.1093/humrep/deab065.

    Article  CAS  Google Scholar 

  57. Santi D, Casarini L, Alviggi C, Simoni M. Efficacy of follicle-stimulating hormone (FSH) alone, FSH + luteinizing hormone, human menopausal gonadotropin or FSH + human chorionic gonadotropin on assisted reproductive technology outcomes in the “personalized” medicine era: a meta-analysis. Front Endocrinol (Lausanne). 2017;8:114. https://doi.org/10.3389/fendo.2017.00114.

    Article  Google Scholar 

  58. Capalbo A, Ubaldi FM, Rienzi L, Scott R, Treff N. Detecting mosaicism in trophectoderm biopsies: current challenges and future possibilities. Hum Reprod. 2017;32(3):492–8. https://doi.org/10.1093/humrep/dew250.

    Article  CAS  Google Scholar 

  59. Popovic M, Dhaenens L, Boel A, Menten B, Heindryckx B. Chromosomal mosaicism in human blastocysts: the ultimate diagnostic dilemma. Hum Reprod Update. 2020;26(3):313–34. https://doi.org/10.1093/humupd/dmz050.

    Article  CAS  Google Scholar 

  60. Paulson RJ, Treff N. Isn’t it time to stop calling preimplantation embryos “mosaic”? F&S Reports. 2020;1(3):164–5. https://doi.org/10.1016/j.xfre.2020.10.009.

    Article  Google Scholar 

  61. Wu L, Jin L, Chen W, Liu JM, Hu J, Yu Q, et al. The true incidence of chromosomal mosaicism after preimplantation genetic testing is much lower than that indicated by trophectoderm biopsy. Hum Reprod. 2021;36(6):1691–701. https://doi.org/10.1093/humrep/deab064.

    Article  CAS  Google Scholar 

  62. Kim J, Tao X, Cheng M, Steward A, Guo V, Zhan Y, et al. The concordance rates of an initial trophectoderm biopsy with the rest of the embryo using PGTseq, a targeted next-generation sequencing platform for preimplantation genetic testing-aneuploidy. Fertil Steril. 2022;117(2):315–23. https://doi.org/10.1016/j.fertnstert.2021.10.011.

  63. Capalbo A, Rienzi L. Mosaicism between trophectoderm and inner cell mass. Fertil Steril. 2017;107(5):1098–106. https://doi.org/10.1016/j.fertnstert.2017.03.023.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinica Valle Giulia, GeneraLife IVF, Via G. de Notaris 2B, 00197, Rome, Italy

    Alberto Vaiarelli, Danilo Cimadomo, Carlotta Scarafia, Federica Innocenti, Maria Giulia Amendola, Gemma Fabozzi, Laura Rienzi & Filippo Maria Ubaldi

  2. Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

    Livio Casarini

  3. Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy

    Livio Casarini

  4. Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, Naples, Italy

    Alessandro Conforti & Carlo Alviggi

  5. Obstetrics and Gynecology 1U, Physiology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant’Anna Hospital, University of Turin, Turin, Italy

    Gianluca Gennarelli & Chiara Benedetto

  6. Livet, GeneraLife IVF, Turin, Italy

    Gianluca Gennarelli

  7. Department of Clinical Medicine, Public Health, Life Sciences and Environment (MeSVA), University of L’Aquila, L’Aquila, Italy

    Maurizio Guido

  8. 9.Baby, GeneraLife IVF, Bologna, Italy

    Andrea Borini

  9. Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Urbino, Italy

    Laura Rienzi

Authors
  1. Alberto Vaiarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Danilo Cimadomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlotta Scarafia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Federica Innocenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Giulia Amendola
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gemma Fabozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Livio Casarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alessandro Conforti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carlo Alviggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gianluca Gennarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Chiara Benedetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Maurizio Guido
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Andrea Borini
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Laura Rienzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Filippo Maria Ubaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AV, DC, LR and FMU designed the study. DC, FI and MGA conducted the statistical analyses. AV, CS, DC and FI drafted the manuscript. All authors contributed to the collection, analysis and discussion of the data and revised and approved the manuscript.

Corresponding author

Correspondence to Alberto Vaiarelli.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

10815_2022_2684_MOESM1_ESM.pdf

Supplementary file1 Supplementary Fig. 1 Study flowchart. PGT-A, preimplantation genetic testing for aneuploidies; MII, metaphase II; TLI, time-lapse incubator; rec-FSH, recombinant FSH; HMG, human menopausal gonadotropin; rec-LH, recombinant LH; LBR, live birth rate; SET, single embryo transfer. (PDF 60 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vaiarelli, A., Cimadomo, D., Scarafia, C. et al. Metaphase-II oocyte competence is unlinked to the gonadotrophins used for ovarian stimulation: a matched case–control study in women of advanced maternal age. J Assist Reprod Genet 40, 169–177 (2023). https://doi.org/10.1007/s10815-022-02684-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-022-02684-w

Keywords

Search

Navigation