Journal of Assisted Reproduction and Genetics

, Volume 32, Issue 10, pp 1491–1495 | Cite as

Early maternal serum ß-human chorionic gonadotropin (ß-hCG) levels and sex-related growth difference of IVF embryos

  • Efrat Esh-Broder
  • Galia Oron
  • Weon-Young Son
  • Hananel Holzer
  • Togas Tulandi
Reproductive Physiology and Disease



Maternal serum ß-human chorionic gonadotropin (ß-hCG) represents the trophoblastic cell mass and is an indirect measurement of embryo development at early implantation stage. Studies in animals and human embryos detected sex-related growth differences (SRGD) in favour of male embryos during the pre-implantation period. The purpose of our study was to correlate SRGD and maternal serum ß-hCG at 16 days after embryo transfer.


We retrospectively analysed all (fresh and frozen) non-donor, single embryo transfers (SET), elective and not elective, that were performed between December 2008 and December 2013. We included ß-hCG values from day 16 after oocyte collection of pregnancies resulting in live birth. Neonatal gender was retrieved from patient files. Male and female embryos were further grouped to cleavage and blastocyst stage transfers. Regression analysis for confounding variables included maternal age, maternal body mass index (BMI), use of micromanipulation (ICSI), embryo quality (grade), assisted hatching, day of transfer and fresh or frozen embryo transfer.


Seven hundred eighty-six non-donor SETs resulted in live birth. After including only day 16 serum ß-hCG results, 525 SETs were analysed. Neonatal gender was available for 522 cases. Mean maternal serum ß-hCG levels were similar, 347 ± 191 IU/L in the male newborn group and 371 ± 200 IU/L in the female group. The difference between ß-hCG levels remained insignificant after adjusting for confounding variables.


Early maternal ß-hCG levels after embryo transfers did not represent SRGD in our study.


ß-hCG IVF Embryo Sex related Sex-related growth difference 



The authors express their appreciation to Xiangming Tan PhD for his expert assistance in statistical analysis.


  1. 1.
    Karn MN, Penrose LS. Birth weight and gestation time in relation to maternal age, parity and infant survival. Ann Eugen. 1951;16(2):147–64.CrossRefPubMedGoogle Scholar
  2. 2.
    O’Neill KE, Tuuli M, Odibo AO, Odem RR, Cooper A. Sex-related growth differences are present but not enhanced in in vitro fertilization pregnancies. Fertil Steril. 2014;101(2):407–12. doi: 10.1016/j.fertnstert.2013.10.011.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Pedersen JF. Ultrasound evidence of sexual difference in fetal size in first trimester. Br Med J. 1980;281(6250):1253.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Valdivia RP, Kunieda T, Azuma S, Toyoda Y. PCR sexing and developmental rate differences in preimplantation mouse embryos fertilized and cultured in vitro. Mol Reprod Dev. 1993;35(2):121–6. doi: 10.1002/mrd.1080350204.CrossRefPubMedGoogle Scholar
  5. 5.
    Avery B, Madison V, Greve T. Sex and development in bovine in-vitro fertilized embryos. Theriogenology. 1991;35(5):953–63.CrossRefPubMedGoogle Scholar
  6. 6.
    Xu KP, Yadav BR, King WA, Betteridge KJ. Sex-related differences in developmental rates of bovine embryos produced and cultured in vitro. Mol Reprod Dev. 1992;31(4):249–52. doi: 10.1002/mrd.1080310404.CrossRefPubMedGoogle Scholar
  7. 7.
    Pergament E, Fiddler M, Cho N, Johnson D, Holmgren WJ. Sexual differentiation and preimplantation cell growth. Hum Reprod. 1994;9(9):1730–2.PubMedGoogle Scholar
  8. 8.
    Ray PF, Conaghan J, Winston RM, Handyside AH. Increased number of cells and metabolic activity in male human preimplantation embryos following in vitro fertilization. J Reprod Fertil. 1995;104(1):165–71.CrossRefPubMedGoogle Scholar
  9. 9.
    Dumoulin JC, Derhaag JG, Bras M, Van Montfoort AP, Kester AD, Evers JL, et al. Growth rate of human preimplantation embryos is sex dependent after ICSI but not after IVF. Hum Reprod. 2005;20(2):484–91. doi: 10.1093/humrep/deh614.CrossRefPubMedGoogle Scholar
  10. 10.
    Boklage CE. The epigenetic environment: secondary sex ratio depends on differential survival in embryogenesis. Hum Reprod. 2005;20(3):583–7. doi: 10.1093/humrep/deh662.CrossRefPubMedGoogle Scholar
  11. 11.
    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.CrossRefPubMedGoogle Scholar
  12. 12.
    Braunstein GD, Rasor JL, Engvall E, Wade ME. Interrelationships of human chorionic gonadotropin, human placental lactogen, and pregnancy-specific beta 1-glycoprotein throughout normal human gestation. Am J Obstet Gynecol. 1980;138(8):1205–13.PubMedGoogle Scholar
  13. 13.
    McCoy TW, Nakajima ST, Bohler Jr HC. Age and a single day-14 beta-HCG can predict ongoing pregnancy following IVF. Reprod Biomed Online. 2009;19(1):114–20.CrossRefPubMedGoogle Scholar
  14. 14.
    Porat S, Savchev S, Bdolah Y, Hurwitz A, Haimov-Kochman R. Early serum beta-human chorionic gonadotropin in pregnancies after in vitro fertilization: contribution of treatment variables and prediction of long-term pregnancy outcome. Fertil Steril. 2007;88(1):82–9. doi: 10.1016/j.fertnstert.2006.11.116.CrossRefPubMedGoogle Scholar
  15. 15.
    Shamonki MI, Frattarelli JL, Bergh PA, Scott RT. Logarithmic curves depicting initial level and rise of serum beta human chorionic gonadotropin and live delivery outcomes with in vitro fertilization: an analysis of 6021 pregnancies. Fertil Steril. 2009;91(5):1760–4. doi: 10.1016/j.fertnstert.2008.02.171.CrossRefPubMedGoogle Scholar
  16. 16.
    Steier JA, Myking OL, Bergsjo PB. Correlation between fetal sex and human chorionic gonadotropin in peripheral maternal blood and amniotic fluid in second and third trimester normal pregnancies. Acta Obstet Gynecol Scand. 1999;78(5):367–71.CrossRefPubMedGoogle Scholar
  17. 17.
    Gol M, Altunyurt S, Cimrin D, Guclu S, Bagci M, Demir N. Different maternal serum hCG levels in pregnant women with female and male fetuses: does fetal hypophyseal--adrenal--gonadal axis play a role? J Perinat Med. 2004;32(4):342–5. doi: 10.1515/jpm.2004.064.CrossRefPubMedGoogle Scholar
  18. 18.
    Gol M, Tuna B, Dogan E, Gulekli B, Bagci M, Altunyurt S, et al. Does fetal gender affect cytotrophoblast cell activity in the human term placenta? Correlation with maternal hCG levels. Acta Obstet Gynecol Scand. 2004;83(8):711–5. doi: 10.1111/j.0001-6349.2004.00491.x.CrossRefPubMedGoogle Scholar
  19. 19.
    Cowans NJ, Stamatopoulou A, Maiz N, Spencer K, Nicolaides KH. The impact of fetal gender on first trimester nuchal translucency and maternal serum free beta-hCG and PAPP-A MoM in normal and trisomy 21 pregnancies. Prenat Diagn. 2009;29(6):578–81. doi: 10.1002/pd.2246.CrossRefPubMedGoogle Scholar
  20. 20.
    Yaron Y, Lehavi O, Orr-Urtreger A, Gull I, Lessing JB, Amit A, et al. Maternal serum HCG is higher in the presence of a female fetus as early as week 3 post-fertilization. Hum Reprod. 2002;17(2):485–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Oron G, Son WY, Buckett W, Tulandi T, Holzer H. The association between embryo quality and perinatal outcome of singletons born after single embryo transfers: a pilot study. Hum Reprod. 2014;29(7):1444–51. doi: 10.1093/humrep/deu079.CrossRefPubMedGoogle Scholar
  22. 22.
    Reinblatt SL, Ishai L, Shehata F, Son WY, Tulandi T, Almog B. Effects of ovarian endometrioma on embryo quality. Fertil Steril. 2011;95(8):2700–2. doi: 10.1016/j.fertnstert.2011.03.002.CrossRefPubMedGoogle Scholar
  23. 23.
    Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Kathiresan AS, Cruz-Almeida Y, Barrionuevo MJ, Maxson WS, Hoffman DI, Weitzman VN, et al. Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization. Fertil Steril. 2011;96(6):1362–6. doi: 10.1016/j.fertnstert.2011.09.042.CrossRefPubMedGoogle Scholar
  25. 25.
    Kumbak B, Oral E, Karlikaya G, Lacin S, Kahraman S. Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome. Reprod Biomed Online. 2006;13(4):459–64.CrossRefPubMedGoogle Scholar
  26. 26.
    Papageorgiou TC, Leondires MP, Miller BT, Chang AS, Armstrong AB, Scott LA, et al. Human chorionic gonadotropin levels after blastocyst transfer are highly predictive of pregnancy outcome. Fertil Steril. 2001;76(5):981–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Zhang X, Barnes R, Confino E, Milad M, Puscheck E, Kazer RR. Delay of embryo transfer to day 5 results in decreased initial serum beta-human chorionic gonadotropin levels. Fertil Steril. 2003;80(6):1359–63.CrossRefPubMedGoogle Scholar
  28. 28.
    Pinborg A, Lidegaard O, la Cour FN, Andersen AN. Consequences of vanishing twins in IVF/ICSI pregnancies. Hum Reprod. 2005;20(10):2821–9. doi: 10.1093/humrep/dei142.CrossRefPubMedGoogle Scholar
  29. 29.
    Kaminski MA, Ford SP, Youngs CR, Conley AJ. Lack of effect of sex on pig embryonic development in vivo. J Reprod Fertil. 1996;106(1):107–10.CrossRefPubMedGoogle Scholar
  30. 30.
    Peippo J, Bredbacka P. Sex-related growth rate differences in mouse preimplantation embryos in vivo and in vitro. Mol Reprod Dev. 1995;40(1):56–61. doi: 10.1002/mrd.1080400108.CrossRefPubMedGoogle Scholar
  31. 31.
    Kausche A, Jones GM, Trounson AO, Figueiredo F, MacLachlan V, Lolatgis N. Sex ratio and birth weights of infants born as a result of blastocyst transfers compared with early cleavage stage embryo transfers. Fertil Steril. 2001;76(4):688–93.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyMcGill UniversityMontrealCanada

Personalised recommendations