Abstract
Purpose
The aim of the study was to compare the levels of angiogenic markers and markers of placentation between pregnancies conceived with fresh (ET) and vitrified-warmed blastocyst transfer (FET).
Methods
Women with singleton pregnancies resulting from fresh ET or FET during the period between 2013 and 2017 were included in this prospective observational study. Fresh ET was performed in a stimulated and FET in natural cycle. At 6–7 weeks of gestation, after ultrasound confirmation of a single gestational sac with a viable embryo, serum levels of free β-hCG, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PIGF) and fms-like tyrosine kinase (sFlt-1) were measured. Data on the patients’ characteristics, pregnancy complications and outcomes were collected from a questionnaire and National Perinatal Information System of Slovenia.
Results
Among 211 pregnancies, 126 were achieved with fresh ET and 85 with FET. There were no significant differences in perinatal outcome, pregnancy complication and PIGF level between the fresh ET and FET group. Women achieving pregnancy with FET had significant higher levels of free β-hCG (40.20 ± 30.62 IU/L vs. 28.74 ± 23.52, p = 0.002), PAPP-A (0.09 ± 0.06 vs. 0.06 ± 0.05 IU/L, p = 0.004) and sFlt-1 (596.19 ± 283.06 vs. 436.53 ± 248.23 pg/L, p < 0.0001) compared to women having conceived with fresh ET. There were no significant differences in the levels of evaluated biomarkers between patients with different pregnancy outcomes and complications.
Conclusion
Levels of angiogenic markers and markers of placentation differ between pregnancies achieved with fresh ET and FET which may reflect altered implantation and early placentation with some forms of assisted reproductive technologies.
Similar content being viewed by others
References
Herrero L, Martinez M, Garcia-Velasco JA. Current status of human oocyte and embryo cryopreservation. Curr Opin Obstet Gynecol. 2011;23:245–50.
Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Similar ongoing pregnancy rates after blastocyst transfer in fresh donor cycles and autologous cycles using cryopreserved bipronuclear oocytes suggest similar viability of transferred blastocysts. Fertil Steril. 2010;93:319–21.
Roque M, Lattes K, Serra S, Sola I, Geber S, Carreras R, et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril. 2013;99:156–62.
Sha T, Yin X, Cheng W, Massey IY. Pregnancy-related complications and perinatal outcomes resulting from transfer of cryopreserved versus fresh embryos in vitro fertilization: a meta-analysis. Fertil Steril. 2018 Feb;109(2):330–42.
Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2012;98:368–77.
Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril. 2011;96:344–8.
Kansal Kalra S, Ratcliffe SJ, Milman L, Gracia CR, Coutifaris C, Barnhart KT. Perinatal morbidity after in vitro fertilization is lower with frozen embryo transfer. Fertil Steril. 2011;95:548–53.
Imudia AN, Awonuga AO, Doyle JO, Kaimal AJ, Wright DL, Toth TL, et al. Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization. Fertil Steril. 2012;97:1374–9.
Barnhart KT. Introduction: are we ready to eliminate the transfer of fresh embryos in in vitro fertilization? Fertil Steril. 2014;102:1–2.
Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril. 2014;102:10–8.
Amor DJ, Xu JX, Halliday JL, Francis I, Healy DL, Breheny S, et al. Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome. Hum Reprod. 2009;24:1330–8.
Hui PW, Lam YH, Tang MH, NG EH, Yeung WS, Ho PC. Maternal serum pregnancy-associated plasma protein-A and free beta-human chorionic gonadotrophin in pregnancies conceived with fresh and frozen-thawed embryos from in vitro fertilization and intracytoplasmic sperm injection. Prenat Diagn. 2005;25(5):390–3.
Lee MS, Cantonwine D, Little SE, et al. Angiogenic markers in pregnancies conceived through in vitro fertilization. Am J Obstet Gynecol. 2015;213(2):212.e211–8.
Woo I, Chan Y, Sriprasert I, Louie K, Ingles S, Stanczyk F, et al. The role of angiogenic markers in adverse perinatal outcomes: fresh versus frozen embryo transfers. J Assist Reprod Genet. 2017;34(12):1639–43.
Vlaisavljević V, Kovačič B, Gavrić-Lovrec V, Reljič M. Simplification of the clinical phase of IVF and ICSI treatment in programmed cycles. Int J Gynaecol Obstet. 2000;69:35–42.
Kovačič B, Vlaisavljević V. Importance of blastocyst morphology in selection for transfer. In: Wu B, editor. Advances in embryo transfer. Rijeka: Intech; 2012. p. 161–77.
WHO. WHO manual of diagnostic ultrasound, vol. 2. 2nd ed. Geneva: Switzerland World Health Organization: World Health Organization & World Federation for Ultrasound in Medicine and Biology; 2013.
Keane KN, Mustafa KB, Hinchliffe P, Conceicao J, Yovich JL. Higher β-HCG concentrations and higher birthweights ensue from single vitrified embryo transfers. Reprod BioMed Online. 2016;33(2):149–60.
Reljič M, Knez J, Vlaisavljević V. Human chorionic gonadotropin levels are equally predictive for pregnancy outcome after fresh and vitrified-warmed blastocyst transfer. J Assist Reprod Genet. 2013;30(11):1459–63.
Kolibianakis EM, Venetis CA, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: which one is better? Curr Opin Obstet Gynecol. 2009;21:270–4.
Dumoulin JC, Land JA, Van Montfoort AP, Nelissen EC, Coonen E, Derhaag JG, et al. Effect of in vitro culture of human embryos on birthweight of newborns. Hum Reprod. 2010;25:605–12.
Kathiresan ASQ, Cruz-Almeida Y, Barrionuevo MJ, et al. Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization. Fertil Steril. 2011;96:1362–6.
Grin L, Indurski A, Leytes S, Rabinovich M, Friedler S. Trends in primeval β-hCG level increment after fresh and frozen-thawed IVF embryo transfer cycles. Gynecol Endocrinol. 2018 Oct;9:1–6.
Evans MI, Krantz DA, Hallahan TW, Galen RS. Meta-analysis of first trimester Down syndrome screening studies: free beta-human chorionic gonadotropin significantly outperforms intact human chorionic gonadotropin in a multimarker protocol. Am J Obstet Gynecol. 2007;196(3):198–205.
Fernando MR, Donato D, Felice P. Predictive value of hormone measurements in maternal and fetal complications of pregnancy. Endocrine. 2006;23(2):230–57.
Bellver J, Casanova C, Garrido N, Lara C, Remohi J, Pellicer A, et al. Additive effect of factors related to assisted conception on the reduction of maternal serum pregnancy-associated plasma protein A concentrations and the increased false-positive rates in first trimester Down syndrome screening. Fertil Steril. 2013;100(5):1314–20.
Tul N, Novak-Antolic Z. Serum PAPP-A levels at 10-14 weeks of gestation are altered in women after assisted conception. Prenat Diagn. 2006;26(13):1206–11.
Gjerris AC, Loft A, Pinborg A, Christiansen M, Tabor A. First trimester screening markers are altered in pregnancies conceived after IVF/ICSI. Ultrasound Obstet Gynecol. 2009;33(1):8–17.
Engels MA, Kooij M, Schats R, Twisk JW, Blankenstein MA, van Vugt JM. First-trimester serum marker distribution in singleton pregnancies conceived with assisted reproduction. Prenat Diagn. 2010;30(4):372–7.
Sahraravand M, Laitinen P, Järvelä I, Ryynänen M. First-trimester maternal serum ADAM12-s and PAPP-A levels are altered in pregnancies conceived after assisted reproduction techniques (ART). Prenat Diagn. 2016;36(2):163–9.
Hunt LP, McInerney-Leo AM, Sinnott S, Sutton B, Cincotta R, Duncombe G, et al. Low first-trimester PAPP-A in IVF (fresh and frozen-thawed) pregnancies, likely due to a biological cause. J Assist Reprod Genet. 2017;34(10):1367–75.
Giorgetti C, Vanden Meerschaut F, De Roo C, Saunier O, Quarello E, Hairion D, et al. Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies. Hum Reprod. 2013;28(10):2636–42.
Tomás C, Alsbjerg B, Martikainen H, Humaidan P. Pregnancy loss after frozen-embryotransfer—a comparison of three protocols. Fertil Steril. 2012;98(5):1165–9.
Morozov V, Ruman J, Kenigsberg D, Moodie G, Brenner S. Natural cycle cryo-thaw transfer may improve pregnancy outcome. J Assist Reprod Genet. 2007;24:119–23.
Kane SC, Costa FS, Brennecke S. First trimester biomarkers in the prediction of later pregnancy complications. Biomed Res Int. 2014;2014:807196.
Acknowledgements
The study was a part of the research programme P3–0327 funded by the Slovenian Research Agency.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Reljič, M., Porović, A. Maternal serum levels of angiogenic markers and markers of placentation in pregnancies conceived with fresh and vitrified-warmed blastocyst transfer. J Assist Reprod Genet 36, 1489–1495 (2019). https://doi.org/10.1007/s10815-019-01484-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-019-01484-z