The alteration of first trimester screening markers in fresh and frozen-thawed blastocyst transfers

Abstract

Objective: The aim of this study was to investigate whether first trimester combined screening for major fetal trisomies is influenced by assisted reproduction techniques (ART) from blastocyst transfer, with or without cryopreservation.

Methods: This study is a retrospective analysis involving 115 singleton pregnancies with euploid fetuses recruited between January 2017 and December 2017. Sixty-five women conceived with fresh blastocysts from in vitro fertilization (IVF) cycles (fresh-blasto), 50 with frozen-thawed blastocysts. All cases underwent ultrasound assessment at 11+0 - 13+6 weeks with measurements of crown rump length, nuchal translucency (NT) , free beta-human chorionic gonadotrophin (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) concentrations.

Results: Baseline characteristics and pregnancy outcomes did not differ substantially among the study groups. The NT was not significantly different in the frozen-thawed -blasto compared to the fresh-blasto group (p = 0.741). The free β-hCG levels was not significantly different in frozen-thawed-blasto group compared to fresh-blasto group (p = 0.495). The two groups showed no significant difference in the PAPP-A levels (p = 0.139). The median delta crown rump length was also not significantly different among the two groups (p = 0.758).

Conclusions: In ART pregnancies from blastocyst transfer, with or without cryopreservation, the NT measurement, free β-hCG concentration and PAPP-A levels did not show any significant difference. These features are apparently unrelated to the outcome of pregnancy and may be due to alterations or delays in embryogenesis or placentation with potential relevance for the screening test performance. 

Keywords

• Assisted reproductive technique,blastocyst,first trimester screening,frozen-thawed embryo transfer,fresh embryo transfer

References

1. [1] Anckaert E, Schiettecatte J, Sleurs E, Devroey P, Smitz J. First trimester screening for Down’s syndrome after assisted reproductive technology: non-male factor infertility is associated with elevated free beta-human chorionic gonadotropin levels at 10-14 weeks of gestation. Fertil Steril 2008;90:1206-10.
2. [2] Krantz DA, Hallahan TW, Orlandi F, Buchanan P, Larsen JW, Macri JN. First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency. Obstet Gynecol 2000;96:207-13.
3. [3] Spencer K, Nicolaides KH. Screening for trisomy 21 in twins using first trimester ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years experience. Br J Obstet Gynecol 2003;110:276-80.
4. [4] Spencer K, Souter V, Tul N, Snijders R, Nicolaides KH. A screening program for trisomy 21 at 10-14 weeks using fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 1999;13:231-7.
5. [5] Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience. Br J Obstet Gynecol 2003;110:281-6.
6. [6] Brambati B, Macintosh MC, Teisner B. Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) in the first trimester in association with abnormal fetal karyotype. Br J Obstet Gynaecol 1993;100:324-6.
7. [7] Brambati B, Tului L, Bonacchi I, Shrimanker K, Suzuki Y, Grudzinskas JG. Serum PAPP-A and free beta-hCG are firsttrimester screening markers for Down syndrome. Prenat Diagn 1994;14:1043-7.
8. [8] Wald NJ, George L, Smith D, Densem JW, Petterson K. Serum screening for Down’s syndrome between 8 and 14 weeks ofpregnancy. International prenatal screening research group. Br J Obstet Gynaecol 1996;103:407-12.

9. [9] Haddow JE, Palomaki GE, Knight GJ, Williams J, Miller WA, Johnson A. Screening of maternal serum for fetal Down’ssyndrome in the first trimester. N Engl J Med 1998;338:955-61.
10. [10] Spencer K. The influence of smoking on maternal serum PAPPA and free beta-hCG levels in the first trimester of pregnancy. Prenat Diagn 1999;19:1065-6.
11. [11] Bindra R, Heath V, Liao A, Spencer K, Nicolaides KH. One stop clinic for assessment of risk for trisomy 21 at 11-14 weeks: a prospective study of 15 030 pregnancies. Ultrasound Obstet Gynecol 2002;20:219-25.
12. [12] De Graaf IM, Cuckle HS, Pajkrt E, Leschot NJ, Bleker OP, van Lith JM. Co-variables in first trimester maternal serum screening. Prenat Diagn 2000;20:186-9.
13. [13] Niemimaa M, Heinonen S, Seppala M, Ryynanen M. The influence of smoking on the pregnancy-associated plasma protein A, free beta human chorionic gonadotrophin and nuchal translucency. BJOG 2003;110:664-7.
14. [14] Liao AW, Heath V, Kametas N, Spencer K, Nicolaides KH. First-trimester screening for trisomy 21 in singleton pregnancies achieved by assisted reproduction. Hum Reprod 2001;16:1501-4.
15. [15] Maymon R, Shulman A. Serial first- and second-trimester Down’s syndrome screening tests among IVF-versus naturally conceived singletons. Hum Reprod 2002;17:1081-5.
16. [16] Orlandi F, Rossi C, Allegra A. First trimester screening with free beta-hCG, PAPP-A and nuchal translucency in pregnancies conceived with assisted reproduction. Prenat Diagn 2002;22:718-21.
17. [17] Bersinger NA, Wunder D, Vanderlick F. Maternal serum levels of placental proteins after in vitro fertilisation and their implications for prenatal screening. Prenat Diagn 2004;24:471-7.
18. [18] Niemimaa M, Heinonen S, Seppala M, Hippelainen M, Martikainen H, Ryynanen M. First-trimester screening for Down’s syndrome in in-vitro fertilization pregnancies. Fertil Steril 2001;76:1282-83.
19. [19] Maymon R, Shulman A. Integrated first- and second-trimester Down syndrome screening test among unaffected IVF pregnancies. Prenat Diagn 2004;24:125-9.
20. [20] Ghisoni L, Ferrazzi E, Castagna C, Levi Setti PE, Masini AC, PigniA. Prenatal diagnosis after ART success: the role of early combined screening tests in counselling pregnant patients. Placenta 2003;24:99-103.
21. [21] Ong CY, Liao AW, Spencer K, Munim S, Nicolaides KH. First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. Br J Obstet Gynecol 2000;107:1265-70.
22. [22] Phil K, Larsen T, Krebs L, Christiansen M. First trimester maternal serum PAPP-A, β-hCG and ADAM12 in prediction of small-for-gestational-age fetuses. Prenat Diagn 2008;28:1131-5.
23. [23] Chen H, Egan JO, Ohlu JF. Regulation and activities of alpha-fetoprotein. Crit Rev Eukaryot Gene Expr 1997;7:11-41.
24. [24] Gardner DK, Balaban B. Choosing between day 3 and day 5 embryo transfers. Clin Obstet Gynecol 2006;49:85-92.
25. [25] 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.
26. [26] Ranta JK, Raatikainen K, Romppanen J, Pulkki K, Heinonen S. Increased time-to-pregnancy and first trimester Down's syndrome screening. Hum Reprod 2010;25:412-7.
27. [27] Bellver J, Casanova C, Garrido N, Lara C, Remohí J, Pellicer A, et al. Additive effect of factors related to assisted conception on the reduction of maternal serum PAPP-A concentrations and the increasedfalse-positive rates in first-trimester Down syndrome screening. Fertil Steril 2013;100:1314-20.
28. [28] Cavoretto P, Dallagiovanna C, Vigano P, Somigliana E, Persico N, Papaleo E, et al. First trimester combined screening test in pregnancies derived from blastocyst transfer. Eur J Obstet Gynecol Reprod Biol 2016;198:50-5.