Effect of GnRH analogues for pituitary suppression on oocyte morphology in repeated ovarian stimulation cycles

Bianca Ferrarini Zanetti, Daniela Paes de Almeida Ferreira Braga, Amanda Souza Setti, Assumpto Iaconelli Jr, Edson Borges Jr, Bianca Ferrarini Zanetti, Daniela Paes de Almeida Ferreira Braga, Amanda Souza Setti, Assumpto Iaconelli Jr, Edson Borges Jr

Abstract

Objective: To compare the effect of pituitary suppression regimens on oocyte morphology in consecutive ICSI cycles of the same patients.

Methods: Data was obtained from 200 matched consecutive intracytoplasmic sperm injection (ICSI) cycles performed in 100 couples undergoing the first cycle with the GnRH agonist and the following cycle with the GnRH antagonist regimen, from January 2010 to August 2016, in a private university-affiliated IVF centre. The effects of the pituitary suppression type on oocyte morphology were assessed by multivariate General Linear Models.

Results: Mean interval between cycles was 185.32±192.85 days. Maternal age, body mass index, and total FSH dose administered were similar in both patients' cycles. Antagonist cycles presented lower incidence of dark cytoplasm (0.69±3.28% vs. 4.40±17.70%, p=0.047), Smooth endoplasmic reticulum (SER cluster (4.37±11.62% vs. 7.36±17.17%, p=0.046), and ZP defects (6.05±14.76% vs. 11.84±25.13%, p=0.049). Similar numbers of follicles retrieved oocytes, and mature oocytes were observed between the GnRH groups, as well as the fertilisation rate, number of obtained embryos, high-quality embryo rates, and the clinical outcomes.

Conclusion: GnRH antagonist's inhibitory effect on the ovaries in consecutive ICSI cycles results in improved oocyte maturity and morphology, despite similar laboratory and clinical outcomes, compared to the GnRH agonist treatment.

Keywords: GnRH; ICSI; oocyte dysmorphisms; oocyte morphology; pituitary suppression.

Conflict of interest statement

CONFLICT OF INTERESTS

There is no conflict of interest to declare.

References

    1. Baerwald A, Anderson P, Yuzpe A, Case A, Fluker M. Synchronization of ovarian stimulation with follicle wave emergence in patients undergoing in vitro fertilization with a prior suboptimal response: a randomized, controlled trial. Fertil Steril. (e1-2) 2012;98:881–887. doi: 10.1016/j.fertnstert.2012.06.051.
    1. Balaban B, Urman B. Effect of oocyte morphology on embryo development and implantation. Reprod Biomed Online. 2006;12:608–615. doi: 10.1016/S1472-6483(10)61187-X.
    1. Balaban B, Ata B, Isiklar A, Yakin K, Urman B. Severe cytoplasmic abnormalities of the oocyte decrease cryosurvival and subsequent embryonic development of cryopreserved embryos. Hum Reprod. 2008;23:1778–1785. doi: 10.1093/humrep/den127.
    1. Castillo J, Amaral A, Oliva R. Sperm nuclear proteome and its epigenetic potential. Andrology. 2014;2:326–338. doi: 10.1111/j.2047-2927.2013.00170.x.
    1. Cavagna M, Paes de Almeida Ferreira Braga D, Biaggioni Lopes F, de Cássia Savio Figueira R, Iaconelli Jr A, Borges Jr E. The effect of GnRH analogues for pituitary suppression on ovarian response in repeated ovarian stimulation cycles. Arch Med Sci. 2011;7:470–475. doi: 10.5114/aoms.2011.23414.
    1. Cota AM, Oliveira JB, Petersen CG, Mauri AL, Massaro FC, Silva LF, Nicoletti A, Cavagna M, Baruffi RL, Franco Jr JG. GnRH agonist versus GnRH antagonist in assisted -reproduction cycles: oocyte morphology. Reprod Biol Endocrinol. 2012;10:33–33. doi: 10.1186/1477-7827-10-33.
    1. Dahm R. Friedrich Miescher and the discovery of DNA. Dev Biol. 2005;278:274–288. doi: 10.1016/j.ydbio.2004.11.028.
    1. Dal Canto M, Guglielmo MC, Mignini Renzini M, Fadini R, Moutier C, Merola M, De Ponti E, Coticchio G. Dysmorphic patterns are associated with cytoskeletal alterations in human oocytes. Hum Reprod. 2017;32:750–757. doi: 10.1093/humrep/dex041.
    1. de Cássia S Figueira R, de Almeida Ferreira Braga DP, Semião-Francisco L, Madaschi C, Iaconelli Jr A, Borges Jr E. Metaphase II human oocyte morphology: contributing factors and effects on fertilization potential and embryo developmental ability in ICSI cycles. Fertil Steril. 2010;94:1115–1117. doi: 10.1016/j.fertnstert.2009.11.039.
    1. Detti L, Ambler DR, Yelian FD, Kruger ML, Diamond MP, Puscheck EE. Timing and duration of use of GnRH antagonist down-regulation for IVF/ICSI cycles have no impact on oocyte quality or pregnancy outcomes. J Assist Reprod Genet. 2008;25:177–181. doi: 10.1007/s10815-008-9217-2.
    1. Dominguez F, Pellicer A, Simon C. The chemokine connection: hormonal and embryonic regulation at the human maternal-embryonic interface--a review. Placenta. 2003;24:S48–S55. doi: 10.1016/S0143-4004(03)00134-6.
    1. Ebner T, Moser M, Tews G. Is oocyte morphology prognostic of embryo developmental potential after ICSI? Reprod Biomed Online. 2006;12:507–512. doi: 10.1016/S1472-6483(10)62006-8.
    1. Ebner T, Balaban B, Moser M, Shebl O, Urman B, Ata B, Tews G. Automatic user-independent zona pellucida imaging at the oocyte stage allows for the prediction of preimplantation development. Fertil Steril. 2010;94:913–920. doi: 10.1016/j.fertnstert.2009.03.106.
    1. Esfandiari N, Burjaq H, Gotlieb L, Casper RF. Brown oocytes: implications for assisted reproductive technology. Fertil Steril. 2006;86:1522–1525. doi: 10.1016/j.fertnstert.2006.03.056.
    1. Harton GL, Magli MC, Lundin K, Montag M, Lemmen J, Harper JC. European Society for Human Reproduction and Embryology (ESHRE) PGDConsortium/Embryology Special Interest Group. ESHRE PGD Consortium/Embryology Special Interest Group--best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS) Hum Reprod. 2011;26:41–46. doi: 10.1093/humrep/deq265.
    1. Hernandez ER. Embryo implantation and GnRH antagonists: embryo implantation: the Rubicon for GnRH antagonists. Hum Reprod. 2000;15:1211–1216. doi: 10.1093/humrep/15.6.1211.
    1. Jungheim ES, Meyer MF, Broughton DE. Best practices for controlled ovarian stimulation in in vitro fertilization. Semin Reprod Med. 2015;33:77–82. doi: 10.1055/s-0035-1546424.
    1. Kol S. Embryo implantation and GnRH antagonists: GnRH antagonists in ART: lower embryo implantation? Hum Reprod. 2000;15:1881–1882. doi: 10.1093/humrep/15.9.1881.
    1. Kumar P, Sharma A. Gonadotropin-releasing hormone analogs: Understanding advantages and limitations. J Hum Reprod Sci. 2014;7:170–174. doi: 10.4103/0974-1208.142476.
    1. Lai Q, Zhang H, Zhu G, Li Y, Jin L, He L, Zhang Z, Yang P, Yu Q, Zhang S, Xu JF, Wang CY. Comparison of the GnRH agonist and antagonist protocol on the same patients in assisted reproduction during controlled ovarian stimulation cycles. Int J Clin Exp Pathol. 2013;6:1903–1910.
    1. Lazzaroni-Tealdi E, Barad DH, Albertini DF, Yu Y, Kushnir VA, Russell H, Wu YG, Gleicher N. Oocyte Scoring Enhances Embryo-Scoring in Predicting Pregnancy Chances with IVF Where It Counts Most. PLoS One. 2015;10:e0143632. doi: 10.1371/journal.pone.0143632.
    1. Machtinger R, Laurent LC, Baccarelli AA. Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum Reprod Update. 2016;22:182–193. doi: 10.1093/humupd/dmv055.
    1. Meriano JS, Alexis J, Visram-Zaver S, Cruz M, Casper RF. Tracking of oocyte dysmorphisms for ICSI patients may prove relevant to the outcome in subsequent patient cycles. Hum Reprod. 2001;16:2118–2123. doi: 10.1093/humrep/16.10.2118.
    1. Murber A, Fancsovits P, Ledó N, Gilan ZT, Rigó Jr J, Urbancsek J. Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study. Reprod Biol Endocrinol. 2009;7:103–103. doi: 10.1186/1477-7827-7-103.
    1. Otsuki J, Okada A, Morimoto K, Nagai Y, Kubo H. The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes. Hum Reprod. 2004;19:1591–1597. doi: 10.1093/humrep/deh258.
    1. Rienzi L, Balaban B, Ebner T, Mandelbaum J. The oocyte. Hum Reprod. 2012;27:i2–21. doi: 10.1093/humrep/des200.
    1. Setti AS, Figueira RC, Braga DP, Colturato SS, Iaconelli Jr A, Borges Jr E. Relationship between oocyte abnormal morphology and intracytoplasmic sperm injection outcomes: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2011;159:364–370. doi: 10.1016/j.ejogrb.2011.07.031.
    1. Setti AS, Figueira RC, de Almeida Ferreira Braga DP, Azevedo MC, Iaconelli Jr A, Borges Jr E. Oocytes with smooth endoplasmic reticulum clusters originate blastocysts with impaired implantation potential. Fertil Steril. 2016;106:1718–1724. doi: 10.1016/j.fertnstert.2016.09.006.
    1. Shi SL, Yao GD, Jin HX, Song WY, Zhang FL, Yang HY, Sun YP. Correlation between morphological abnormalities in the human oocyte zona pellucida, fertilization failure and embryonic development. Int J Clin Exp Med. 2016;9:260–267.
    1. Shrestha D, La X, Feng HL. Comparison of different stimulation protocols used in in vitro fertilization: a review. Ann Transl Med. 2015;3:137–137. doi: 10.3978/j.issn.2305-5839.2015.04.09.
    1. Siklenka K, Erkek S, Godmann M, Lambrot R, McGraw S, Lafleur C, Cohen T, Xia J, Suderman M, Hallett M, Trasler J, Peters AH, Kimmins S. Disruption of histone methylation in developing sperm impairs offspring health transgenerationally. Science. 2015;350(aab2006) doi: 10.1126/science.aab2006.
    1. Takekida S, Matsuo H, Maruo T. GnRH agonist action on granulosa cells at varying follicular stages. Mol Cell Endocrinol. 2003;202:155–164. doi: 10.1016/S0303-7207(03)00077-7.
    1. Ten J, Mendiola J, Vioque J, de Juan J, Bernabeu R. Donor oocyte dysmorphisms and their influence on fertilization and embryo quality. Reprod Biomed Online. 2007;14:40–48. doi: 10.1016/S1472-6483(10)60762-6.
    1. Van Blerkom J. Occurrence and developmental consequences of aberrant cellular organization in meiotically mature human oocytes after exogenous ovarian hyperstimulation. J Electron Microsc Tech. 1990;16:324–346. doi: 10.1002/jemt.1060160405.
    1. Veeck LL. Oocyte assessment and biological performance. Ann N Y Acad Sci. 1988;541:259–274. doi: 10.1111/j.1749-6632.1988.tb22263.x.
    1. Xavier P, Gamboa C, Calejo L, Silva J, Stevenson D, Nunes A, Martinez-de-Oliveira J. A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy. Eur J Obstet Gynecol Reprod Biol. 2005;120:185–189. doi: 10.1016/j.ejogrb.2004.11.005.

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