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Progesterone and estrogen levels are associated with live birth rates following artificial cycle frozen embryo transfers

  • Assisted Reproduction Technologies
  • Published:
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Abstract

Purpose

Does an association exist between serum progesterone and estradiol levels and live birth rates in artificial cycle frozen embryo transfer (AC-FET)?

Methods

Retrospective cohort study was based on prospectively collected data at a university-affiliated fertility center. Included were all cycles using an artificial endometrial preparation with estradiol hemihydrate (Estrofem, 2 mg/8 h) and vaginal progesterone (Endometrin 100 mg/8 h), autologous oocytes, and cleavage stage embryo transfers. Serum progesterone and estradiol levels were measured 14 days after FET. A total of 921 cycles in 568 patients from to December 2010 to June 2019 were investigated. Live birth was the primary outcome measure.

Results

Significant association was found between live birth and progesterone as well as estradiol levels (progesterone 14.65 vs 11.62 ng/ml, p = 0.001; estradiol 355.12 vs 287.67 pg/ml, p = 0.001). A significant difference in live birth rate was found below and above the median progesterone level (10.9 ng/ml, p = 0.007). Lower estradiol level was significantly associated with lower live birth rate (< 188.2 pg/ml 8.3%, > 263.1 pg/ml 16%, p = 0.02).

Conclusions

Serum progesterone and estradiol levels impact live birth rate in AC-FET.

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References

  1. Turkgeldi E, Hanege BY, Yildiz S, Keles I, Ata B. Subcutaneous versus vaginal progesterone for vitrified–warmed blastocyst transfer in artificial cycles. Reprod Biomed Online. 2020;41:248–53. https://doi.org/10.1016/j.rbmo.2020.04.007.

    Article  CAS  PubMed  Google Scholar 

  2. Vuong LN, Dang VQ, Ho TM, Huynh BG, Ha DT, Pham TD, et al. IVF transfer of fresh or frozen embryos in women without polycystic ovaries. N Engl J Med. 2018;378:137–47. https://doi.org/10.1056/nejmoa1703768.

    Article  PubMed  Google Scholar 

  3. Simón C, Martín JC, Pellicer A. Paracrine regulators of implantation. Bailliere’s Best Pract Res Clin Obstet Gynaecol. 2000. https://doi.org/10.1053/beog.2000.0121.

    Article  Google Scholar 

  4. Glujovsky D, Pesce R, Sueldo C, QuinteiroRetamar AM, Hart RJ, Ciapponi A. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes. Cochrane Database Syst Rev. 2020;10:CD006359. https://doi.org/10.1002/14651858.CD006359.pub3.

    Article  PubMed  Google Scholar 

  5. Mackens S, Santos-Ribeiro S, van de Vijver A, Racca A, Van Landuyt L, Tournaye H, et al. Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum Reprod. 2017;32:2234–42. https://doi.org/10.1093/humrep/dex285.

    Article  CAS  PubMed  Google Scholar 

  6. Boynukalin FK, Gultomruk M, Cavkaytar S, Turgut E, Findikli N, Serdarogullari M, et al. Parameters impacting the live birth rate per transfer after frozen single euploid blastocyst transfer. PLoS ONE. 2020;15:1–15. https://doi.org/10.1371/journal.pone.0227619.

    Article  CAS  Google Scholar 

  7. Sier JH, Thumser AE, Plant NJ. Linking physiologically-based pharmacokinetic and genome-scale metabolic networks to understand estradiol biology. BMC Syst Biol. 2017;11:1–16. https://doi.org/10.1186/s12918-017-0520-3.

    Article  CAS  Google Scholar 

  8. Labarta E, Rodríguez C. Progesterone use in assisted reproductive technology. Best Pract Res Clin Obstet Gynaecol. 2020. https://doi.org/10.1016/j.bpobgyn.2020.05.005.

    Article  PubMed  Google Scholar 

  9. Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril. 1994;62:485–90. https://doi.org/10.1016/s0015-0282(16)56935-0.

    Article  CAS  PubMed  Google Scholar 

  10. Alsbjerg B, Labarta E, Humaidan P. Serum progesterone levels on day of embryo transfer in frozen embryo transfer cycles—the truth lies in the detail. J Assist Reprod Genet. 2020;37:2045–6. https://doi.org/10.1007/s10815-020-01851-1.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Balaban B, Brison D, Calderón G, Catt J, Conaghan J, Cowan L, et al. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26:1270–83. https://doi.org/10.1093/humrep/der037.

    Article  Google Scholar 

  12. Mesen TB, Young SL. Progesterone and the luteal phase: a requisite to reproduction. Obstet Gynecol Clin North Am. 2015. https://doi.org/10.1016/j.ogc.2014.10.003.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cédrin-Durnerin I, Isnard T, Mahdjoub S, Sonigo C, Seroka A, Comtet M, et al. Serum progesterone concentration and live birth rate in frozen–thawed embryo transfers with hormonally prepared endometrium. Reprod Biomed Online. 2019;38:472–80. https://doi.org/10.1016/j.rbmo.2018.11.026.

    Article  CAS  PubMed  Google Scholar 

  14. Gaggiotti-Marre S, Martinez F, Coll L, Garcia S, Álvarez M, Parriego M, et al. Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates. Gynecol Endocrinol. 2019;35:439–42. https://doi.org/10.1080/09513590.2018.1534952.

    Article  CAS  PubMed  Google Scholar 

  15. Alsbjerg B, Thomsen L, Elbaek HO, Laursen R, Povlsen BB, Haahr T, et al. Progesterone levels on pregnancy test day after hormone replacement therapy-cryopreserved embryo transfer cycles and related reproductive outcomes. Reprod Biomed Online. 2018;37:641–7. https://doi.org/10.1016/j.rbmo.2018.08.022.

    Article  CAS  PubMed  Google Scholar 

  16. Commissaire M, Epelboin S, Vigan M, Tubiana S, Llabador MA, Gauché-Cazalis C, et al. Serum progesterone level and ongoing pregnancy rate following frozen-thawed embryo transfer after artificial endometrial preparation: a monocentric retrospective study. J Gynecol Obstet Hum Reprod. 2020. https://doi.org/10.1016/j.jogoh.2020.101828.

    Article  PubMed  Google Scholar 

  17. Basnayake SK, Volovsky M, Rombauts L, Osianlis T, Vollenhoven B, Healey M. Progesterone concentrations and dosage with frozen embryo transfers – what’s best? Aust New Zeal J Obstet Gynaecol. 2018;58:533–8. https://doi.org/10.1111/ajo.12757.

    Article  Google Scholar 

  18. Labarta E, Mariani G, Holtmann N, Celada P, Remohí J, Bosch E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod. 2017;32:2437–42. https://doi.org/10.1093/humrep/dex316.

    Article  CAS  PubMed  Google Scholar 

  19. Labarta E, Mariani G, Paolelli S, Rodriguez-Varela C, Vidal C, Giles J, et al. Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone. Hum Reprod. 2021;36:683–92. https://doi.org/10.1093/humrep/deaa322.

    Article  CAS  PubMed  Google Scholar 

  20. González-Foruria I, Gaggiotti-Marre S, Álvarez M, Martínez F, García S, Rodríguez I, et al. Factors associated with serum progesterone concentrations the day before cryopreserved embryo transfer in artificial cycles. Reprod Biomed Online. 2020;40:797–804. https://doi.org/10.1016/j.rbmo.2020.03.001.

    Article  CAS  PubMed  Google Scholar 

  21. Labarta E, Mariani G, Paolelli S, Rodriguez-Varela C, Vidal C, Giles J, Bellver J, Cruz F, Marzal A, Celada P, Olmo I, Alamá P, Remohi J, Bosch E. Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone. Hum Reprod. 2021;36(3):683–92. https://doi.org/10.1093/humrep/deaa322.

  22. Volovsky M, Pakes C, Rozen G, Polyakov A. Do serum progesterone levels on day of embryo transfer influence pregnancy outcomes in artificial frozen-thaw cycles? J Assist Reprod Genet. 2020;37:1129–35. https://doi.org/10.1007/s10815-020-01713-w.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Yovich JL, Conceicao JL, Stanger JD, Hinchliffe PM, Keane KN. Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement. Reprod Biomed Online. 2015;31:180–91. https://doi.org/10.1016/j.rbmo.2015.05.005.

    Article  CAS  PubMed  Google Scholar 

  24. Brady PC, Kaser DJ, Ginsburg ES, Ashby RK, Missmer SA, Correia KF, et al. Serum progesterone concentration on day of embryo transfer in donor oocyte cycles. J Assist Reprod Genet. 2014;31:569–75. https://doi.org/10.1007/s10815-014-0199-y.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Boynukalin FK, Gultomruk M, Turgut E, Demir B, Findikli N, Serdarogullari M, et al. Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers. Reprod Biol Endocrinol. 2019;17:1–8. https://doi.org/10.1186/s12958-019-0549-9.

    Article  CAS  Google Scholar 

  26. Liu YF, Wang F, Huang GY, Mao XG. The relationship between the hormone levels before transplantation and the outcomes of hormone replacement therapy frozen embryo transfer. Minerva Endocrinol. 2018. https://doi.org/10.23736/S0391-1977.17.02660-8.

    Article  PubMed  Google Scholar 

  27. Kofinas JD, Blakemore J, McCulloh DH, Grifo J. Serum progesterone levels greater than 20 ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. J Assist Reprod Genet. 2015;32:1395–9. https://doi.org/10.1007/s10815-015-0546-7.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Levy T, Gurevitch S, Hava B, Ashkenazi J, Magazanik A, Homburg R, et al. Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet. Hum Reprod. 1999;14:606–10. https://doi.org/10.1093/humrep/14.3.606.

    Article  CAS  PubMed  Google Scholar 

  29. Nahoul K, Dehennin L, Jondet M, Roger M. Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone. Maturitas. 1993;16:185–202. https://doi.org/10.1016/0378-5122(93)90064-O.

    Article  CAS  PubMed  Google Scholar 

  30. 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;99:4241–9. https://doi.org/10.1210/jc.2013-3937.

    Article  CAS  PubMed  Google Scholar 

  31. Archer DF, Fahy GE, Viniegra-Sibal A, Anderson FD, Snipes W, Foldesy RG. Initial and steady-state pharmacokinetics of a vaginally administered formulation of progesterone. Am J Obstet Gynecol. 1995;173:471–8. https://doi.org/10.1016/0002-9378(95)90268-6.

    Article  CAS  PubMed  Google Scholar 

  32. Wu G, Chen J, Hu X, Zhou H, Liu J, Lv D, et al. Pharmacokinetic properties of three forms of vaginal progesterone administered in either single or multiple dose regimen in healthy post-menopausal Chinese women. Front Pharmacol. 2017;8:1–9. https://doi.org/10.3389/fphar.2017.00212.

    Article  CAS  Google Scholar 

  33. Mackens S, Santos-Ribeiro S, Orinx E, De Munck N, Racca A, Roelens C, et al. Impact of serum estradiol levels prior to progesterone administration in artificially prepared frozen embryo transfer cycles. Front Endocrinol (Lausanne). 2020;11:1–8. https://doi.org/10.3389/fendo.2020.00255.

    Article  Google Scholar 

  34. Remohi J, Ardiles G, Garcia-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. https://doi.org/10.1093/humrep/12.10.2271.

    Article  CAS  PubMed  Google Scholar 

  35. Bocca S, Real EB, Lynch S, Stadtmauer L, Beydoun H, Mayer J, et al. Impact of serum estradiol levels on the implantation rate of cleavage stage cryopreserved-thawed embryos transferred in programmed cycles with exogenous hormonal replacement. J Assist Reprod Genet. 2015;32:395–400. https://doi.org/10.1007/s10815-014-0402-1.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Fritz R, Jindal S, Feil H, Buyuk E. Elevated serum estradiol levels in artificial autologous frozen embryo transfer cycles negatively impact ongoing pregnancy and live birth rates. J Assist Reprod Genet. 2017;34:1633–8. https://doi.org/10.1007/s10815-017-1016-1.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Levy T, Yairi Y, Bar-Hava I, Shalev J, Orvieto R, Ben-Rafael Z. Pharmacokinetics of the progesterone-containing vaginal tablet and its use in assisted reproduction. Steroids. 2000;65:645–9. https://doi.org/10.1016/S0039-128X(00)00121-5.

    Article  CAS  PubMed  Google Scholar 

  38. Neumann K, Depenbusch M, Schultze-Mosgau A, Griesinger G. Characterization of early pregnancy placental progesterone production by use of dydrogesterone in programmed frozen–thawed embryo transfer cycles. Reprod Biomed Online. 2020;40:743–51. https://doi.org/10.1016/j.rbmo.2020.01.019.

    Article  CAS  PubMed  Google Scholar 

  39. Neuhausser WM, Neuhausser WM, Neuhausser WM, Neuhausser WM, Neuhausser WM, Vaughan DA, et al. Non-inferiority of cleavage-stage versus blastocyst-stage embryo transfer in poor prognosis IVF patients (PRECiSE trial): study protocol for a randomized controlled trial. Reprod Health. 2020;17:1–10. https://doi.org/10.1186/s12978-020-0870-y.

    Article  Google Scholar 

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Authors and Affiliations

  1. Fertility Unit, Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel

    Ronit Beck-Fruchter, Simon Nothman, Shira Baram, Yoel Geslevich & Amir Weiss

  2. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Ronit Beck-Fruchter, Simon Nothman & Amir Weiss

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  1. Ronit Beck-Fruchter
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  2. Simon Nothman
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  3. Shira Baram
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  4. Yoel Geslevich
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  5. Amir Weiss
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Contributions

Ronit Beck Fruchter and Amir Weiss contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ronit Beck Fruchter, Simon Nothman, Shira Baram, Yoel Geslevich and Amir Weiss. The first draft of the manuscript was written by Ronit Beck Fruchter and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ronit Beck-Fruchter.

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This research study was conducted retrospectively from data obtained for clinical purposes. Approval was obtained from the ethics committee of HaEmek medical center.

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Beck-Fruchter, R., Nothman, S., Baram, S. et al. Progesterone and estrogen levels are associated with live birth rates following artificial cycle frozen embryo transfers. J Assist Reprod Genet 38, 2925–2931 (2021). https://doi.org/10.1007/s10815-021-02307-w

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  • DOI: https://doi.org/10.1007/s10815-021-02307-w

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