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Serum progesterone concentration on day of embryo transfer in donor oocyte cycles

  • Paula C. Brady
  • Daniel J. Kaser
  • Elizabeth S. Ginsburg
  • Rachel K. Ashby
  • Stacey A. Missmer
  • Katharine F. Correia
  • Catherine RacowskyEmail author
Assisted Reproduction Technologies

Abstract

Purpose

To evaluate the association between serum progesterone (P) levels on the day of embryo transfer (ET) and pregnancy rates in fresh donor IVF/ICSI cycles.

Methods

Fresh donor cycles with day 3 ET from 10/2007 to 8/2012 were included (n = 229). Most cycles (93 %) were programmed with a gonadotropin releasing hormone (GnRH) agonist; oral, vaginal or transdermal estradiol was used for endometrial priming, and intramuscular P was used for luteal support (50–100 mg/day). Recipient P levels were measured at ET, and P dose was increased by 50–100 % if <20 ng/mL per clinic practice. The main outcome measure was rate of live birth (> = 24 weeks gestational age). Generalized estimating equations were used to account for multiple cycles from the same recipient, adjusted a priori for recipient and donor age.

Results

Mean recipient serum P at ET was 25.5 ± 10.1 ng/mL. Recipients with P < 20 ng/mL at ET, despite P dose increases after ET, were less likely to achieve clinical pregnancy (RR = 0.75, 95 % CI = 0.60–0.94, p = 0.01) and live birth (RR = 0.77, 95 % CI = 0.60–0.98, p = 0.04), as compared to those with P ≥ 20 ng/mL. P dose increases were more often required in overweight and obese recipients.

Conclusions

Serum P levels on the day of ET in fresh donor IVF/ICSI cycles were positively correlated with clinical pregnancy and live birth rates. An increase in P dose after ET was insufficient to rescue pregnancy rates. Overweight and obese recipients may require higher initial doses of P supplementation. Future research is needed to define optimal serum P at ET and the interventions to achieve this target.

Keywords

Donor oocyte Embryo transfer Implantation IVF/ICSI Progesterone Pregnancy rate 

Notes

Financial support

None

Financial disclosures

P.C. Brady: none

D.J. Kaser: none

E.S. Ginsburg: royalties from UpToDate

R.K. Ashby: none

S.A. Missmer: Associate Editor of Human Reproduction

K.F. Correia: none

C. Racowsky: Board member of ASRM; royalties from UpToDate

References

  1. 1.
    Strauss JF, Williams CJ. The ovarian life cycle. In: Strauss JF, Barbieri RL, editors. Reproductive endocrinology, 6th edn. Philadelphia; 2009. p. 155–90.Google Scholar
  2. 2.
    Sallam HN, Sallam A, Ezzeldin F, Agamia AF, Abou-Ali A. Reference values for the midluteal plasma progesterone concentration: evidence from human menopausal gonadotropin-stimulated pregnancy cycles. Fertil Steril. 1999;71:711–4.PubMedCrossRefGoogle Scholar
  3. 3.
    van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2011;5, CD009154.Google Scholar
  4. 4.
    Glujovsky D, Pesce R, Fiszbajn G, Sueldo C, Hart RJ, Ciapponi A. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD006359.Google Scholar
  5. 5.
    Fanchin R, Righini C, Olivennes F, Taylor S, de Ziegler D, Frydman R. Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum Reprod. 1998;13:1968–74.PubMedCrossRefGoogle Scholar
  6. 6.
    Check JH, Wilson C, Choe JK, Amui J, Brasile D. Evidence that high serum progesterone (P) levels on day of human chorionic gonadotropin (hCG) injection have no adverse effect on the embryo itself as determined by pregnancy outcome following embryo transfer using donated eggs. Clin Exp Obstet Gynecol. 2010;37:179–80.PubMedGoogle Scholar
  7. 7.
    Ochsenkühn R, Arzberger A, von Schönfeldt V, Gallwas J, Rogenhofer N, Crispin A, et al. Subtle progesterone rise on the day of human chorionic gonadotropin administration is associated with lower live birth rates in women undergoing assisted reproductive technology: a retrospective study with 2,555 fresh embryo transfers. Fertil Steril. 2012;98:347–54.PubMedCrossRefGoogle Scholar
  8. 8.
    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;98:664–70.PubMedCrossRefGoogle 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;97:1321–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Prapas Y, Prapas N, Jones EE, Duleba AJ, Olive DL, Chatziparasidou A, et al. The window for embryo transfer in oocyte donation cycles depends on the duration of progesterone therapy. Hum Reprod. 1998;13:720–3.PubMedCrossRefGoogle Scholar
  11. 11.
    Kaser DJ, Ginsburg ES, Missmer SA, Correia K, Racowsky C. Intramuscular progesterone versus 8 % Crinone vaginal gel for luteal phase support for day 3 cryopreserved embryo transfer. Fertil Steril. 2012;98:1464–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Tummon IS, Daniel SA, Kaplan BR, Nisker JA, Yuzpe AA. Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization. Fertil Steril. 1992;58:563–8.PubMedGoogle Scholar
  13. 13.
    Cheung LP, Lam PM, Lok IH, Chiu TT, Yeung SY, Tjer CC, et al. GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial. Hum Reprod. 2005;20:616–21.PubMedCrossRefGoogle Scholar
  14. 14.
    Reichman DE, Jackson KV, Racowsky C. Incidence and development of zygotes exhibiting abnormal pronuclear disposition after identification of two pronuclei at the fertilization check. Fertil Steril. 2010;94:965–70.PubMedCrossRefGoogle Scholar
  15. 15.
    Racowsky C, Combelles CMH, Nureddin A, Pan Y, Finn A, Miles L, et al. Day 3 and day 5 morphological predictors of embryo viability. Reprod BioMed Online. 2003;6:323–31.PubMedCrossRefGoogle Scholar
  16. 16.
    Greenland S. Modeling and variable selection in epidemiologic analysis. Am J Public Health. 1989;79:340–9.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Noyes N, Hampton BS, Berkeley A, Licciardi F, Grifo J, Krey L. Factors useful in predicting the success of oocyte donation: a 3-year retrospective analysis. Fertil Steril. 2001;76:92–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Remohí J, Ardiles G, García-Velasco JA, Gaitán P, Simón C, Pellicer A. Endometrial thickness and serum oestradiol concentrations as predictors of outcome in oocyte donation. Hum Reprod. 1997;12:2271–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Halasz M, Szekeres-Bartho J. The role of progesterone in implantation and trophoblast invasion. J Reprod Immunol. 2013;97(1):43–50.PubMedCrossRefGoogle Scholar
  20. 20.
    Kurihara I, Lee DK, Petit FG, Jeong J, Lee K, Lydon JP, et al. COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity. PLoS Genet. 2007;3:e102.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Yao MW, Lim H, Schust DJ, Choe SE, Farago A, Ding Y, et al. Gene expression profiling reveals progesterone-mediated cell cycle and immunoregulatory roles of Hoxa-10 in the preimplantation uterus. Mol Endocrinol. 2003;17:610–27.PubMedCrossRefGoogle Scholar
  22. 22.
    Jungheim ES, Schon SB, Schulte MB, DeUgarte DA, Fowler SA, Tuuli MG. IVF outcomes in obese donor oocyte recipients: a systematic review and meta-analysis. Hum Reprod. Hum Reprod. 2013;28:2720–7.Google Scholar
  23. 23.
    Bulletti C, de Ziegler D, Flamigni C, Giacomucci E, Polli V, Bolelli G, et al. Targeted drug delivery in gynaecology: the first uterine pass effect. Hum Reprod. 1997;12:1073–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Paula C. Brady
    • 1
  • Daniel J. Kaser
    • 1
  • Elizabeth S. Ginsburg
    • 1
  • Rachel K. Ashby
    • 1
  • Stacey A. Missmer
    • 1
    • 2
    • 3
  • Katharine F. Correia
    • 1
  • Catherine Racowsky
    • 1
    Email author
  1. 1.Department of Obstetrics, Gynecology and Reproductive Biology, Division of Reproductive MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Department of Medicine, Channing LaboratoryBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of EpidemiologyHarvard School of Public HealthBostonUSA

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