Pregnancy outcome prediction after embryo transfer based on serum human chorionic gonadotrophin concentrations

Česká verze

Authors: Balasičová K. ^1,2; Kraus A. ³; Peterová L. ¹; Nykolaichuk R. ⁴; Toporcerová S. ^1,2
Authors place of work: Centrum pre asistovanú reprodukciu Gyncare, s. r. o., Košice, Slovenská republika ¹; Gynekologicko-pôrodnícka klinika LF UPJŠ v Košiciach, Slovenská republika ²; Ústav matematiky a statistiky, Přirodovědecká fakulta, MU Brno, Česká republika ³; Gynekologicko-porodnické oddělení, Karlovarská krajská nemocnice a. s., Česká republika ⁴
Published in the journal: Ceska Gynekol 2022; 87(1): 4-12
Category: Původní práce
doi: https://doi.org/10.48095/cccg20224

Summary

Objective: The aim of the study was to evaluate the predictive value of the human chorionic gonadotropin (hCG) concentration on the 14^th and 16^th post-ovulation day after embryo transfer/cryoembryo transfer as well as the dynamics of its increase with respect to the outcome of pregnancy. Materials and methods: In total, 130 embryo transfers and cryoembryo transfers in women aged 22 to 38 years who experienced a single embryo transfer or single cryoembryo transfer with confirmed pregnancy (hCG level over 15 IU/l on 14^th post-ovulation day – D14) were selected. The input parameters (hCG D14, hCG D16, hCG D16-D14, hCG D16/D14 and positivity of at least 2.5-fold increase in hCG D16 compared to hCG D14) were evaluated by regression analysis in relation to the outcome parameters (biochemical pregnancy, clinical pregnancy, clinical pregnancy terminated by abortion up to 12 weeks of gestation, clinical pregnancy terminated by childbirth). Results: Single concentrations of hCG D14 and D16, as well as the difference between these concentrations, were a statistically significant indicator of the prediction of biochemical pregnancy (P = 0.000215, P = 0.000227 and P = 0.000421). Contrary to expectations, the proportion of hCG D16 and D14 concentrations did not show statistical significance for either parameter, as well as the fulfilment of the condition of at least a 2.5fold increase in hCG D16 compared to D14. None of the studied input parameters was confirmed as a statistically significant marker for the prediction of miscarriage in the whole group of patients. However, in the group of confirmed clinical pregnancies, the serum concentration of hCG D16 (P = 0.0248) and the difference between concentrations D16 and D14 (P = 0.0185) were confirmed as a positive predictor of the progression of pregnancy until delivery. Conclusions: Single hCG concentrations are a good prognostic factor for predicting the outcome of pregnancy, but the determination of the cut-off limit is limited by inter-laboratory deviation as well as by timing of blood collection for hCG determination on the exact post-ovulatory day. The results of individual studies are therefore difficult to use in clinical practice. The dynamics of hCG concentrations appear to be a more reliable predictor of pregnancy outcome. In our cohort, we confirmed the statistical significance of the difference in hCG concentration between the 16^th and 14^th post-ovulation day not only for the prediction of biochemical pregnancy, but also as a predictor of the progression of clinical pregnancy into childbirth. To determine the optimal values of this difference, it is necessary to evaluate a larger group of patients. Conversely, the statistical significance of the proportion of hCG concentrations between the 16^th and 14^th post-ovulation day was not confirmed.

Keywords:

Embryo transfer – in vitro fertilisation – human chorionic gonadotrophin – cryoembryo transfer – biochemical pregnancy – hCG dynamics – ongoing pregnancy – childbirth after embryo transfer

Zdroje

1. Lin S, Li R, Wang Y et al. Increased maternal serum hCG concentrations in the presence of a female fetus as early as 2 weeks after IVF-ET. J Gynecol Onstet Hem Reprod 2021; 50 (7): 102053. doi: 10.1016/j.jogoh.2020.102053.

2. Kuspinar G, Kasapoglu I, Cakir C et al. What is the effect of embryo morfology on serum b-hCG levels? Eur Obstet Gynecol Reprod Biol 2019; 233 (2): 107–113. doi: 10.1016/j.ejogrb.2018. 12.001.

3. Sung N, Kwak-Kim J, Koo HS et al. Serum hCG-b levels of postovulatory day 12 and 14 with the sequential application of hCG-b fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle. J Assist Reprod Genet 2016; 33 (9): 1185–1194. doi: 10.1007/s10815-016-0744-y.

4. Ramu S, Acacio B, Adamowicz M et al. Human chorionic gonadotropin from day 2 spent embryo culture media and its relationship to embryo development. Fertil Steril 2011; 96 (3): 615–617. doi: 10.1016/j.fertnstert.2011.06.035.

5. Butler SA, Luttoo J, Freire MO et al. Human chorionic gonadotropin (hCG) in the secretome of cultured embryos: hyperglycosylated hCG and hCG-free beta submit are potential markers for infertility management and treatment. Reprod Sci 2013; 20 (9): 1038–1045. doi: 10.1177/ 1933719112472739.

6. Han X, Yin B, Lin S et al. Increased maternal hCG concentration in early in vitro pregnancy with elevated basal FSH. PLoS One 2018; 13 (9): e0203610. doi: 10.1371/journal.pone.0203 610.

7. Wu Y, Liu H. Possibility of live birth in patients with low serum b-hCG 14 days after blastocyst transfer. J Ovarian Res 2020; 13 (1): 132. doi: 10.1186/s13048-020-00732-6.

8. Kahyoğlu İ, Demir B, Aksakal SE et al. Value of post-transfer day-12 beta human chorionic gonadotropin levels of pregnancy outcome predicition of intracytoplasmic sperm injection cycles. Balkan Med J 2017; 34 (5): 450–457. doi: 10.4274/balkanmedj.2016.1769.

9. Yuan L, Yu L, Sun Z et al. Association between 7-day serum b-hCG levels after frozen-thawed embryo transfer and pregnancy outcomes: a single centre retrospective study from China. BMJ Open 2020; 10 (10): e035332. doi: 10.1136/bmjopen-2019-035332.

10. Hammarberg K, Astbury J, Baker H. Women‘s experience of IVF: a follow-up study. Hum Reprod 2001; 16 (2): 374–383. doi: 10.1093/ humrep/16.2.374.

11. Ryniec J, Esfandiari N. Early serum hCG in IVF: are we trending in the right direction? Reprod Sci 2021; 28 (7): 1827–1838. doi: 10.1007/s43032-020-00347-8.

12. Kim YJ, Shin JH, Hur JY et al. Predicitive value of serum progesterone level on b-hCG check day in women with previous repeated miscarriages after in vitro fertilization. PloS One 2017; 12 (7): e0181229. doi: 10.1371/journal.pone.0181229.

13. McCoy TW, Nakajima ST, Bohler HC jr. Age and single day-14 beta-HCG can predict onogoing pregnancy following IVF. Reprod Biomed Online 2009; 19 (1): 114–120. doi: 10.1016/ s1472-6483 (10) 60054-5.

14. Tanbo TG, Zucknick M, Eskild A. Maternal concentrations of human chorionic gonadotrophin in very early IVF pregnancies and duration of pregnancy: a follow-up study. Reprod Biomed Online 2018; 37 (2): 208–215. doi: 10.1016/j.rbmo.2018.04.048.

15. Hobeika E, Singh S, Malik S et al. Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort. J Assist Reprod Genet 2017; 34 (10): 1333–1340. doi: 10.1007/s10815-017-0987-2.

16. Naredi N, Singh SK, Sharma R. Does first serum beta-human chorionic gonadotropin value prognosticate the early pregnyncy outcome in an in-vitro fertilisation cycle? J Hum Reprod Sci 2017; 10 (2): 108–113. doi: 10.4103/jhrs.JHRS_50_16.

17. Zbořilová B, Březinová J, Tkadlec E et al. HCG level after embryo transfer as a prognostic indicator of pregnancy finished with delivery. Ceska Gynekol 2018; 83 (5): 329–336.

18. Grin L, Indurski A, Leytes S et al. Trends in primeval b-hCG level increment after fresh and frozen- thawed IVF embryo transfer cycles. Gynecol Endocrinol 2019; 35 (3): 261–266. doi: 10.1080/09513590.2018.1519789.

19. Zhao WE, Li YJ, Ou JP et al. Predicitive value of initial serum human chorionic gonadotropin levels for pregnancies after single fresh and frozen blastocyst transfer. J Huazhong Univ Sci Technolog Med Sci 2017; 37 (3): 395–400. doi: 10.1007/s11596-017-1746-4.

20. Xiong F, Sun Q, Li GG et al. Initial serum HCG levels are higher in pregnant women with a male fetus after fresh or frozen single blastocyst transfer: a retrospective cohort study. Taiwan J Obstet Gynecol 2019; 58 (6): 833–839. doi: 10.1016/j.tjog.2019.09.019.

21. Al Mamari N, Al Zawawi N, Khayat S et al. Revisiting serum b HCG cut-off levels and pregnancy outcomes using single embryo transfer. J Assist Reprod Genet 2019; 36 (11): 2307–2313. doi: 10.1007/s10815-019-01 583-x.

22. Wang ZM, Gao Y, Zhang D et al. Predictive value of serum b-human chorionic gonadotropin for early pregnancy outcomes. Arch Gynecol Obstet 2020; 301 (1): 295–302. doi: 10.1007/s00404-019-05388-2.