Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 32, Issue 9, pp 1395–1399 | Cite as

Serum progesterone levels greater than 20 ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates

  • Jason D. KofinasEmail author
  • Jennifer Blakemore
  • David H. McCulloh
  • Jamie Grifo
Assisted Reproduction Technologies

Abstract

Background

Progesterone (P4) is essential for support of the endometrium and implantation of an embryo in the normal menstrual cycle. In programed frozen embryo transfer cycles using exogenous P4 is necessary, as the endogenous production of P4 requires a functioning corpus luteum that is not present in programed cycles. To date, there is continuing debate about ideal serum estradiol and P4 values in frozen embryo transfer cycles.

Methods

Patients underwent single euploid embryo frozen transfer cycles from 2010 to 2013 at a single large academic center. Patients using donor oocytes and patients with changes in progesterone dose during the cycles in question were excluded. All cycles were programed and intramuscular P4 was used exclusively. Only patients administering the same daily dose of P4 throughout the cycle were included (N = 213 patients). Main outcomes were ongoing pregnancy/live birth rates (OPR/LBR), clinical pregnancy rates (CPR), and spontaneous abortions/biochemical pregnancies. CPR was defined by the presence of a sac on 1st trimester ultrasound. Missed abortions were calculated per pregnancy with a sac. Receiver operator characteristic curves (ROC curves) and chi-squared tests were performed for statistical analysis.

Results

Two groups based on day 19 P4 levels were compared (group A, P4 < 20 ng/ml; group B, P4 > 20 ng/ml). OPR/LBRs were 65 vs. 49 %, group A vs. B, p value = 0.02, RR = 1.33 (1.1–1.7). Missed abortion and biochemical rates were higher in group B as opposed to group A, 27 vs. 12 %, p = 0.01, RR = 0.45(0.24–0.86). When P4 was stratified into five groups based on nanogram per milliliter of progesterone on day 19 (10–15, 15–20, 20–30, 30–40, and >40), there was a trend downward in OPR/LBR (70, 62, 52, 50, and 33 %, respectively). There was also an increase in missed abortion/biochemical rates (7, 15, 27, 32, and 20 %, respectively). Multiple logistic regression showed an increase in OPR/LBR when accounting for age, day 2 FSH, weight, number of embryos biopsied, and number of euploid embryos.

Conclusion

P4 levels >20 ng/ml on the day of transfer (during frozen single euploid embryo transfer cycles) were associated with decreased OPR/LBR.

Keywords

Luteal support In vitro fertilization Pregestational screening Progesterone Frozen embryo transfer 

References

  1. 1.
    Daya S. Luteal support: progestogens for pregnancy protection. Maturitas. 2009;65(s1):S29–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Veleva Z, Orava M, Nuojua-Huttunen S, Tapanainen JS, Martikainen H. Factors affecting the outcome of frozen-thawed embryo transfer. Hum Reprod. 2013;28(9):2425–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Bjuresten K, Landgren B, Hovatta O, Stavreus-Evers A. Luteal phase progesterone increases live birth rate after frozen embryo transfer. Fertil Steril. 2011;95(2):534–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Kim C, Lee Y, Lee K, Kwon S, Kim S, Chae H, et al. The effect of luteal phase progesterone supplementation on natural frozen-thawed embryo transfer cycles. Obstet Gynecol Sci. 2014;57(4):291–6.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Penzias AS. Luteal phase support. Fertil Steril. 2002;77(2):318–23.PubMedCrossRefGoogle Scholar
  6. 6.
    Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus IM injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014;29(8):1706–11.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Datab Syst Rev 2011;(10):CD009154. doi: 10.1002/14651858.CD009154.pub2.
  8. 8.
    Silverberg KM, Burns WN, Olive DL, Riehl RM, Schenken RS. Serum progesterone levels predict success of in vitro fertilization/embryo transfer in patients stimulated with leuprolide acetate and human menopausal gonadotropins. J Clin Endocrinol Metabol. 1991;73(4):797–803.CrossRefGoogle Scholar
  9. 9.
    Xu B, Li Z, Zhang H, Jin L, Li Y, Ai J, et al. Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles. Fertil Steril. 2012;97(6):1321–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Niemann H, Sacher B, Elsaesser F. Pregnancy rates relative to recipient plasma progesterone levels on the day of nonsurgical transfer of frozen/thawed bovine embryos. Theriognology. 1985;23(4):631–9.CrossRefGoogle Scholar
  11. 11.
    Zhe D, Sun L, Zhang H, Chen Z, Jian Y. The frozen-thawed embryo transfer timing determined by serum progesterone level: a retrospective follow-up study. Eur J Obstet Gynecol Reprod Biol. 2014;181:210–3.CrossRefGoogle Scholar
  12. 12.
    Gardner DK, Lane M. Culture and selection of viable blastocysts: a feasible proposition for human IVF? Hum Reprod Update. 1997;3:367–82.PubMedCrossRefGoogle Scholar
  13. 13.
    Gutierrez-Mateo C, Colls P, Sanchez-Garcia J, Escudero T, Prates R, Ketterson K, et al. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011;95:953–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Colls P, Escudero T, Fischer J, Cekleniak NA, Ben-Ozer S, Meyer B, et al. Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos. Reprod BioMed Online. 2012;24(6):621–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Kramer YG, Kofinas JD, Melzer K, Noyes N, McCaffrey C, Buldo-Licciardi J, et al. Assessing Morphokinetic Parameters via Time Lapse Microscopy (TLM) to predict euploidy: are aneuploidy risk classification models universal? J Assist Reprod Genet. 2014;31(9):1231–42.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Paulson RJ, Collins MG, Yankov VI. Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab. 2014;99(11):4241–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Santos-Ribeiro S, Polyzos NP, Haentjens P, Smitz J, Camus M, Tournaye H, et al. Live birth rates after IVF are reduced by both low and high progesterone levels on the day of human chorionic gonadotrophin administration. Hum Reprod. 2014;29(8):1698–705.PubMedCrossRefGoogle Scholar
  18. 18.
    Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60,000 cycles. Reprod Biomed Online. 2012;97:1321–7.Google Scholar
  19. 19.
    Huang R, Fang C, Xu S, Yi Y, Liang X. Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles. Fertil Steril. 2012;98:644–70.CrossRefGoogle Scholar
  20. 20.
    Burns WN, Witz CA, Klein NA, Silverberg KM, Schenken RS. Serum progesterone concentrations on the day after human chorionic gonadotrophin administration and progesterone/oocyte ratios predict In vitro fertilization/embryo transfer outcome. J Assist Reprod Genet. 1994;11:17–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Huang CC, Lien YR, Chen HF, Chen MJ, SHieh CJ, et al. The duration of pre-ovulatory serum progesterone elevation before hcg administration affects the outcome of IVF/ICSI cycles. Hum Reprod. 2012;27:2036–45.PubMedCrossRefGoogle Scholar
  22. 22.
    Check JH, AMui J, Choe JK, Brasile D. Relationship of serum progesterone level the day after human chorionic gonadotropin injection on outcome following in vitro fertilization embryo transfer. Clin Exp Obstet Gynecol. 2009;36:214–5.PubMedGoogle Scholar
  23. 23.
    Brady PC, Kaser DJ, Ginsburg ES, Ashby RK, Missmer SA, Correia KF. Racowsky. Serum progesterone concentration on day of embryo transfer in donor oocyte cycles. J Assist Reprod Genet. 2014;31(5):569–75.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jason D. Kofinas
    • 1
    Email author
  • Jennifer Blakemore
    • 1
  • David H. McCulloh
    • 1
  • Jamie Grifo
    • 1
  1. 1.NYU Fertility Center, NYU Langone School of MedicineNew YorkUSA

Personalised recommendations