Abstract
Purpose: Our purpose was to examine implantation of singleton pregnancies achieved following various assisted reproductive technologies (ARTs) through the appearance and rising titers of serum human chorionic gonadotropin (hCG) levels.
Methods: A total of 114 singleton pregnancies resulting from in vitro fertilization and intrauterine insemination was analyzed. Patients were divided into five groups according to the type of ovarian stimulation protocol [gonadotropin stimulation with/without the use of gonadotropin-releasing hormone agonist (GnRHa), long protocol, or flare-up technique] and to the day of embryo transfer (day 2 or day 3 after oocyte retrieval). Serial serum hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mIU/ml (hCG 10 ), which was used as an estimate of detectable implantation. The slopes of the regression lines were used to estimate the rising speed of hCG.
Results: There were no significant differences in the days of hCG in maternal serum to reach 10 mIU/ml (implantation) or in the slopes of the regression lines for all five studied groups.
Conclusions: The appearance of hCG in maternal serum was used to assess the time of clinically detectable implantation. Furthermore, because hCG production is a marker of trophoblastic activity, its serum doubling time was used as an indicator of embryo quality. Results showed that in various ART protocols with and without GnRHa, there were no significant differences in implantation time or embryo quality. Embryo development in early pregnancy follows a preprogrammed-timing schedule and depends mainly on the embryonic age of the health, successfully implanted conceptus.
Similar content being viewed by others
REFERENCES
Confino E, Demir RH, Friberg J, Gleicher N: The predictive value of hCG β subunit levels in pregnancies achieved by in vitro fertilization and embryo transfer: an international collaborative study. Fertil Steril 1986;45: 526–531
Dor J, Rudak E, Rotmench S, Levran D, Blankstein J, Lusky A, Nebel L, Serr DM, Mashiach S: The role of early post-implantation beta-HCG levels in the outcome of pregnancies following in-vitro fertilization. Hum Reprod 1988;3(5):663–667
Smitz J, Devroey P, Camus M, Deschacht J, Khan I, Staessen C, Van Waesberghe L, Wisanto A, Van Steirteghem AC: The luteal phase and early pregnancy after combined GnRH-agonist/HMG treatment for superovulation in IVF or GIFT. Hum Reprod 1988;3(5):585–590
Tulchinsky D, Tulchinsky A, Paoletti-Falcone V, Nash H, Pazdziorko S, Brown K: Delayed embryo implantation following in vitro fertilization and embryo transfer (IVFET). J Assist Reprod Genet 1996;13(7):536–539
Tur-Kaspa I, Myers SA, Confino E, Friberg J, Dudkiewicz AB, Gleicher N: Ovarian stimulation protocol for in vitro fertilization with gonadotropin-releasing hormone agonist widens the implantation window. Fertil Steril 1990;53(5):859–864
Englert Y, Roger M, Belaish-Allart J, Jondet M, Frydman R, Testart J: Delayed appearance of plasmatic chorionic gonadotropin in pregnancies after in vitro fertilization and embryo transfer. Fertil Steril 1984;42:835–838
Meldrum DR, Gutlay AL, Wisot A, Kempton W, Hamilton F, Huynh D: Routine pituitary suppression with leuprolide before ovarian stimulation for oocyte retrieval. Fertil Steril 1989;51:455–459
Pados G, Taslatzis BC, Bontis J, Lagos S, Papadimas J Spanos E, Mantalenakis S: Evaluation of different ovarian stimulation protocols for in vitro fertilization. Gynecol Endocrinol 1995;9(2):103–112
Liu H-C, Lai Y-M, Davis O, Berkeley AS, Graf, M, Grifo J, Cohen J, Rosenwaks Z: Improved pregnancy outcome with gonadotropin releasing hormone agonist (GnRH-a) stimulation is due to the improvement in oocyte quantity rather than quality. J Assist Reprod Genet 1992;9(4):338–344
Pellicer A, Tarin JJ, Miró F, Sampaio M, De los Santos MJ, Remohi J. The use of gonadotropin releasing-hormone analogues (GnRHa), in in-vitro fertilization: Some clinical and experimental investigations of a direct effect on the human ovary. Hum Reprod 1992;7(Suppl 1):39–47
Minaretzis D, Jakubowski M, Mortola JF, Pavlou SN: Gonadotropin-releasing hormone receptor gene expression in human ovary and granulosa-lutein cells. J Clin Endocrinol Metab 1995;80(2):430–434
Testart J, Forman R, Belaish-Allart J, Volante M, Hazout A, Strubb N, Frydman R: Embryo quality and uterine receptivity in in-vitro fertilization cycles with or without agonists of gonadotropin-releasing hormone. Hum Reprod 1989;14(2):198–201
Liu H-C, Noyes N, Cohen J, Rosenwaks Z, Alikani M: Assisted hatching facilitates earlier implantation. Fertil Steril 1993;60:871–875
Scott RT, Oehninger S, Toner JP, Robinson S, Muasher SJ, Rosenwaks Z: Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome. Fertil Steril 1989;51:651–654
Simon T, Jones D, Oehninger S, Muasher S, Toner J: High doses of gonadotropins have no detrimental effect on in vitro fertilization outcome in normal responders. Fertil Steril 1995;63:1333–1336
Winslow KL, Oehninger S, Toner JP, Acosta AA, Brzyski RG, Muasher SJ: The gonadotropin-releasing hormone agonist stimulation test—a sensitive predictor of performance in the flare-up in vitro fertilization cycle. Fertil Steril 1991;56:711–717
Daya S: Human chorionic gonadotropin increase in normal early pregnancy. Am J Obstet Gynecol 1987;156:286–290
Kadar N, Bohrer M, Kemman E, Shelden R: A prospective, randomized study of the chorionic gonadotropin-time relationship in early gestation: Clinical implications. Fertil Steril 1993;60(3):409–412
Liu H-C, Jones GS, Kreiner D, Jones HW, Muasher SJ, Rosenwaks Z: β-Human chorionic gonadotropin as a monitor of pregnancy outcome in in vitro fertilization-embryo transfer patients. Fertil Steril 1988;50:89–94
Lenton EA, Neal LM, Sulaiman R: Plasma concentrations of human chorionic gonadotropin from the time of implantation until the second week of pregnancy. Fertil Steril 1982;37:773–778
Braunstein GD, Grodin JM, Vaitukaitis J, Ross GT: Secretory rates of human chorionic gonadotropin by normal trophoblast. Am J Obstet Gynecol 1973;115:447–450
Liu H-C, Jones GS, Jones HW, Rosenwaks Z: Mechanism and factor of early pregnancy wastage in in vitro fertilization-embryo transfer patients. Fertil Steril 1988;50:95–101
Edwards RG: Physiological and molecular aspects of human implantation. Hum Reprod 1995;10(Suppl 2):1–13
Hay DL, Lopata A: Chorionic gonadotropin secretion by human embryo in vitro. Clin Endocrinol Metab 1988;67(6):1322–1324
Woodward BJ, Lenton EA, Turner K: Human chorionic gonadotropin: Embryonic secretion is a time-dependent phenomenon. Hum Reprod 1993;8(9):1463–1468
Dokras A, Sargent IL, Ross C, Gardner RI, Barlow DH: The human blastocyst: Morphology and human chorionic gonadotropin secretion in vitro. Hum Reprod 1991;6(8)8:1143–1151
Woodward BJ, Lenton EA, Tuner K, Grace WF: Embryonic human chorionic gonadotropin secretion and hatching: Poor correlation with cleavage rate and morphological assessment during preimplantation development in vitro. Hum Reprod 1994;9(10):1909–1914
Glasser SR, Julian J, Munir MI, Soares MJ: Biological makers during early trophoblastic signals of the peri-implantation period. Environ Health Perspect 1987;74:129–147
Popkin R, Bramley TA, Currie A, Shaw RW, Baird DT, Eraser HM: Specific binding of luteinizing hormone releasing hormone to human luteal tissue. Biochem Biophys Res Commun 1983;114:50–754
Seshagiri PB, Terasawa E, Hearn JP: The secretion of gonadotropin-releasing hormone by peri-implantation embryos of the rhesus monkey: Comparison with the secretion of chorionic gonadotropin. Hum Reprod 1994;9(7):1300–1307
Khodr GS, Siler Khodr TM: Extrahypothalamic luteinizing hormone releasing factor (LRF): Release of immunoreactive LRF in vitro. Fertil Steril 1979;39:294–299
Belisle S, Guevin JF, Bellabarba D, Lehoux JG: Luteinizing hormone-releasing hormone binds to enriched human placental membranes and stimulates in vitro the synthesis of bioactive human chorionic gonadotropin. J Clin Endocrinol Metab 1984;59:119–124
Barnea ER, Kaplan M, Naor Z: Comparative stimulatory effect of gonadotropin releasing hormone (GnRH) and GnRH agonist upon pulsatile human chorionic gonadotropin secretion in superfused placental explants: Reversible inhibition by a GnRH antagonist. Hum Reprod 1991;6(8):1063–1069
Bergh PA, Navot D: The impact of embryonic development and endometrial maturity on the timing of implantation. Fertil Steril 1992;58:537–542
Pellicer A, Calatayud C, Miró F, Castellvi RM, Ruiz A, Ruiz M, Pérez M, Bonilla-Musoles F: Comparison of implantation and early development of human embryos fertilized in vitro versus in vivo using transvaginal ultrasound. J Ultrasound Med 1991;10:31–35
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hsu, MI., Kolm, P., Leete, J. et al. Analysis of Implantation in Assisted Reproduction Through the Use of Serial Human Chorionic Gonadotropin Measurements. J Assist Reprod Genet 15, 496–503 (1998). https://doi.org/10.1023/A:1022534521019
Issue Date:
DOI: https://doi.org/10.1023/A:1022534521019