Abstract
Purpose
The purpose of this study was to determine which morphokinetic variables are related to embryo gender in a cohort of consecutive live births obtained through single blastocyst transfer following mild ovarian stimulation.
Methods
Eighty-one live births (49 % of them females) from successfully treated, consecutive infertile patients (maternal age 36.9 ± 3.8 years, range 28–46) who underwent minimal ovarian stimulation, prolonged embryo culture in a time-lapse monitoring (TLM) incubator and elective single blastocyst transfers during 2012–2014. Early (PNf, t2–t9, cc2a, b, s2, s3) and late (tM, tSB, tfullB, texpB1, and texpB2) morphokinetic variables were scored according to published consensus criteria and were normalized to the time of pronuclear fading. For each variable, the ranges with the highest proportion of female embryos (optimal range) were determined by detailed examination of histograms.
Results
Female embryo gender was associated both with late cleavage (t8), morula (tM), and blastocyst stage morphokinetic variables. The strongest associations (adjusted ORs, 7.0–7.8) were found for late, expanded stage blastocyst parameters; tfullB, texpB1, and texpB2. The proportion of female embryos was 69–71 and 25–26 % inside and outside of the optimal ranges, respectively. This allowed to predict 74–78 % of them, increasing their proportion by 57 % compared to the average.
Conclusions
Although the sample size of our cohort was limited, our findings suggest that several expanded blastocyst stage morphokinetic parameters are associated with female embryo gender. If confirmed on a larger sample these could be potentially used to increase the proportion of female embryos among non-invasively selected blastocysts following single embryo transfer.
Similar content being viewed by others
References
Kaser DJ, Racowsky C. Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review. Hum Reprod Update. 2014;20(5):617–31. doi:10.1093/humupd/dmu023.
Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Hickman CF. Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics. Reprod Biomed Online. 2013;26(5):477–85. doi:10.1016/j.rbmo.2013.02.006.
Meseguer M, Herrero J, Tejera A, Hilligsoe KM, Ramsing NB, Remohi J. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod. 2011;26(10):2658–71. doi:10.1093/humrep/der256.
Dal Canto M, Coticchio G, Mignini Renzini M, De Ponti E, Novara PV, Brambillasca F, et al. Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation. Reprod Biomed Online. 2012;25(5):474–80. doi:10.1016/j.rbmo.2012.07.016.
Rubio I, Galan A, Larreategui Z, Ayerdi F, Bellver J, Herrero J, et al. Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope. Fertil Steril. 2014;102(5):1287–94 e5. doi:10.1016/j.fertnstert.2014.07.738.
VerMilyea MD, Tan L, Anthony JT, Conaghan J, Ivani K, Gvakharia M, et al. Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: a blinded, multi-centre study. Reprod Biomed Online. 2014;29(6):729–36. doi:10.1016/j.rbmo.2014.09.005.
Ciray HN, Aksoy T, Goktas C, Ozturk B, Bahceci M. Time-lapse evaluation of human embryo development in single versus sequential culture media--a sibling oocyte study. J Assist Reprod Genet. 2012;29(9):891–900. doi:10.1007/s10815-012-9818-7.
Cruz M, Garrido N, Gadea B, Munoz M, Perez-Cano I, Meseguer M. Oocyte insemination techniques are related to alterations of embryo developmental timing in an oocyte donation model. Reprod Biomed Online. 2013;27(4):367–75. doi:10.1016/j.rbmo.2013.06.017.
Munoz M, Cruz M, Humaidan P, Garrido N, Perez-Cano I, Meseguer M. Dose of recombinant FSH and oestradiol concentration on day of HCG affect embryo development kinetics. Reprod Biomed Online. 2012;25(4):382–9. doi:10.1016/j.rbmo.2012.06.016.
Munoz M, Cruz M, Humaidan P, Garrido N, Perez-Cano I, Meseguer M. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study. Eur J Obstet Gynecol Reprod Biol. 2013;168(2):167–72. doi:10.1016/j.ejogrb.2012.12.038.
Wissing ML, Bjerge MR, Olesen AI, Hoest T, Mikkelsen AL. Impact of PCOS on early embryo cleavage kinetics. Reprod Biomed Online. 2014;28(4):508–14. doi:10.1016/j.rbmo.2013.11.017.
Kirkegaard K, Hindkjaer JJ, Ingerslev HJ. Effect of oxygen concentration on human embryo development evaluated by time-lapse monitoring. Fertil Steril. 2013;99(3):738–44 e4. doi:10.1016/j.fertnstert.2012.11.028.
Freour T, Dessolle L, Lammers J, Lattes S, Barriere P. Comparison of embryo morphokinetics after in vitro fertilization-intracytoplasmic sperm injection in smoking and nonsmoking women. Fertil Steril. 2013;99(7):1944–50. doi:10.1016/j.fertnstert.2013.01.136.
Serdarogullari M, Findikli N, Goktas C, Sahin O, Ulug U, Yagmur E, et al. Comparison of gender-specific human embryo development characteristics by time-lapse technology. Reprod Biomed Online. 2014;29(2):193–9. doi:10.1016/j.rbmo.2014.03.026.
Bronet F, Nogales MC, Martinez E, Ariza M, Rubio C, Garcia-Velasco JA, et al. Is there a relationship between time-lapse parameters and embryo sex? Fertil Steril. 2015;103(2):396–401 e2. doi:10.1016/j.fertnstert.2014.10.050.
Weston G, Osianlis T, Catt J, Vollenhoven B. Blastocyst transfer does not cause a sex-ratio imbalance. Fertil Steril. 2009;92(4):1302–5. doi:10.1016/j.fertnstert.2008.07.1784.
Alfarawati S, Fragouli E, Colls P, Stevens J, Gutierrez-Mateo C, Schoolcraft WB, et al. The relationship between blastocyst morphology, chromosomal abnormality, and embryo gender. Fertil Steril. 2011;95(2):520–4. doi:10.1016/j.fertnstert.2010.04.003.
Richter KS, Anderson M, Osborn BH. Selection for faster development does not bias sex ratios resulting from blastocyst embryo transfer. Reprod Biomed Online. 2006;12(4):460–5.
Hentemann MA, Briskemyr S, Bertheussen K. Blastocyst transfer and gender: IVF versus ICSI. J Assist Reprod Genet. 2009;26(8):433–6. doi:10.1007/s10815-009-9337-3.
Kato K, Takehara Y, Segawa T, Kawachiya S, Okuno T, Kobayashi T, et al. Minimal ovarian stimulation combined with elective single embryo transfer policy: age-specific results of a large, single-centre, Japanese cohort. Reprod Biol Endocrinol. 2012;10:35. doi:10.1186/1477-7827-10-35.
Bodri D, Kawachiya S, Kondo M, Kato R, Matsumoto T. Oocyte retrieval timing based on spontaneous luteinizing hormone surge during natural cycle in vitro fertilization treatment. Fertil Steril. 2014;101(4):1001–7 e2. doi:10.1016/j.fertnstert.2014.01.016.
Alpha Scientists in Reproductive M, Embryology ESIGo. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270–83. doi:10.1093/humrep/der037.
Kato K, Ueno S, Yabuuchi A, Uchiyama K, Okuno T, Kobayashi T, et al. Women’s age and embryo developmental speed accurately predict clinical pregnancy after single vitrified-warmed blastocyst transfer. Reprod Biomed Online. 2014;29(4):411–6. doi:10.1016/j.rbmo.2014.06.007.
Kuwayama M. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. Theriogenology. 2007;67(1):73–80. doi:10.1016/j.theriogenology.2006.09.014.
Kirkegaard K, Kesmodel US, Hindkjaer JJ, Ingerslev HJ. Time-lapse parameters as predictors of blastocyst development and pregnancy outcome in embryos from good prognosis patients: a prospective cohort study. Hum Reprod. 2013;28(10):2643–51. doi:10.1093/humrep/det300.
Gardner DK, Surrey E, Minjarez D, Leitz A, Stevens J, Schoolcraft WB. Single blastocyst transfer: a prospective randomized trial. Fertil Steril. 2004;81(3):551–5. doi:10.1016/j.fertnstert.2003.07.023.
Zhang J, Chang L, Sone Y, Silber S. Minimal ovarian stimulation (mini-IVF) for IVF utilizing vitrification and cryopreserved embryo transfer. Reprod Biomed Online. 2010;21(4):485–95. doi:10.1016/j.rbmo.2010.06.033.
Ciray HN, Campbell A, Agerholm IE, Aguilar J, Chamayou S, Esbert M, et al. Proposed guidelines on the nomenclature and annotation of dynamic human embryo monitoring by a time-lapse user group. Hum Reprod. 2014;29(12):2650–60. doi:10.1093/humrep/deu278.
Bodri D, Sugimoto T, Serna JY, Kondo M, Kato R, Kawachiya S, et al. Influence of different oocyte insemination techniques on early and late morphokinetic parameters: retrospective analysis of 500 time-lapse monitored blastocysts. Fertil Steril. 2015;104(5):1175–81 e2. doi:10.1016/j.fertnstert.2015.07.1164.
Liu Y, Chapple V, Feenan K, Roberts P, Matson P. Time-lapse videography of human embryos: using pronuclear fading rather than insemination in IVF and ICSI cycles removes inconsistencies in time to reach early cleavage milestones. Reprod Biol. 2015;15(2):122–5. doi:10.1016/j.repbio.2015.03.002.
Chang HJ, Lee JR, Jee BC, Suh CS, Kim SH. Impact of blastocyst transfer on offspring sex ratio and the monozygotic twinning rate: a systematic review and meta-analysis. Fertil Steril. 2009;91(6):2381–90. doi:10.1016/j.fertnstert.2008.03.066.
Kirkegaard K, Campbell A, Agerholm I, Bentin-Ley U, Gabrielsen A, Kirk J, et al. Limitations of a time-lapse blastocyst prediction model: a large multicentre outcome analysis. Reprod Biomed Online. 2014;29(2):156–8. doi:10.1016/j.rbmo.2014.04.011.
Freour T, Le Fleuter N, Lammers J, Splingart C, Reignier A, Barriere P. External validation of a time-lapse prediction model. Fertil Steril. 2015;103(4):917–22. doi:10.1016/j.fertnstert.2014.12.111.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Financial support
None.
Additional information
Capsule
Blastocyst stage morphokinetic variables are predictive of female embryo gender following single blastocyst transfer
Rights and permissions
About this article
Cite this article
Bodri, D., Kawachiya, S., Sugimoto, T. et al. Time-lapse variables and embryo gender: a retrospective analysis of 81 live births obtained following minimal stimulation and single embryo transfer. J Assist Reprod Genet 33, 589–596 (2016). https://doi.org/10.1007/s10815-016-0678-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-016-0678-4