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Premature progesterone elevation during the early and mid-follicular phases in fresh in vitro fertilization (IVF) cycles is associated with lower live birth, clinical pregnancy, and implantation rates

  • Assisted Reproduction Technologies
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Abstract

Purpose

Evaluate follicular phase progesterone elevation (≥ 1.5 ng/mL) prior to trigger during IVF stimulation and its effects on live birth rate (LBR), clinical pregnancy rate (CPR), and implantation rate (IR) in fresh IVF cycles.

Methods

This was a retrospective cohort study within an academic clinic. A total of 6961 fresh IVF and IVF/ICSI cycles from October 1, 2015 to June 30, 2021 were included and grouped by progesterone (PR) prior to trigger: PR < 1.5 ng/mL (low PR group) and PR ≥ 1.5 ng/mL (high PR group). Main outcome measures included LBR, CPR, and IR.

Results

Among all cycle starts, 1568 (22.5%) were in the high PR group and 5393 (77.5%) were in the low PR group. Of the cycles which proceeded to an embryo transfer, 416 (11.1%) were in the high PR group and 3341 (88.9%) were in the low PR group. The high PR group had significantly lower IR (RR 0.75; 95% CI 0.64–0.88), CPR (aRR 0.74; 95% CI 0.64–0.87), and LBR (aRR 0.71; 95% CI 0.59–0.85) compared to the low PR group. When stratified by progesterone on the day of trigger (TPR), there was a clinically notable decrease in IR (16.8% vs 23.3%), CPR (28.1% vs 36.0%), and LBR (22.8% vs 28.9%) in the high PR group compared to the low PR group even when TPR < 1.5 ng/mL.

Conclusions

In fresh IVF cycles in which TPR < 1.5 ng/mL, progesterone elevation ≥ 1.5 ng/mL at any point in time prior to trigger negatively impacts IR, CPR, and LBR. This data supports testing of serum progesterone in the follicular phase prior to trigger, as these patients may benefit from a freeze-all approach.

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Data availability

Data were collected from a prospectively maintained departmental database at Brigham and Women’s Hospital.

Code availability

All statistical analyses were performed with SAS® version 9.4 (Cary, NC, USA).

References

  1. Wu Z, et al. Effect of HCG-day serum progesterone and estradiol concentrations on pregnancy outcomes in GnRH agonist cycles. Reprod Biomed Online. 2012;24:511–20. https://doi.org/10.1016/j.rbmo.2012.02.003.

    Article  CAS  PubMed  Google Scholar 

  2. Papanikolaou EG, Pados G, Grimbizis G, et al. GnRH-agonist versus GnRH-antagonist IVF cycles: is the reproductive outcome affected by the incidence of progesterone elevation on the day of HCG triggering? A randomized prospective study. Hum Reprod. 2012;27(6):1822–8.

    Article  CAS  PubMed  Google Scholar 

  3. 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(2):347–54.

    Article  PubMed  Google Scholar 

  4. Corti L, Papaleo E, Pagliardini L, Rabellotti E, Molgora M, La Marca A, et al. Fresh blastocyst transfer as a clinical approach to overcome the detrimental effect of progesterone elevation at hCG triggering: a strategy in the context of the Italian law. Eur J Obstet Gynecol Reprod Biol. 2013;171(1):73–7.

    Article  CAS  PubMed  Google Scholar 

  5. Huang CC, Lien YR, Chen HF, Chen MJ, Shieh CJ, Yao YL, et al. The duration of pre-ovulatory serum progesterone elevation before hCG administration affects the outcome of IVF/ICSI cycles. Hum Reprod. 2012;27(7):2036–45.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update. 2003;9(6):515–22.

    Article  PubMed  Google Scholar 

  8. Fanchin R, Ferreira AL, Righini C, De Ziegler D, Olivennes F, Frydman R. Consequences of premature progesterone elevation on the outcome of in vitro fertilization: insights into a controversy. Fertil Steril. 1997;68(5):799–805.

    Article  CAS  PubMed  Google Scholar 

  9. Huang B, Ren X, Wu L, Zhu L, Xu B, Li Y, et al. Elevated progesterone levels on the day of oocyte maturation may affect top quality embryo IVF cycles. PLoS One. 2016;11(1):e0145895.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Papanikolaou EG, Kolibianakis EM, Pozzobon C, Tank P, Tournaye H, Bourgain C, et al. Progesterone rise on the day of human chorionic gonadotropin administration impairs pregnancy outcome in day 3 single-embryo transfer, while has no effect on day 5 single blastocyst transfer. Fertil Steril. 2009;91(3):949–52.

    Article  CAS  PubMed  Google Scholar 

  11. Kong N, Liu J, Jiang Y, Zhu Y, Zhang C, Yan G, Huang C. Adverse impact of elevated progesterone levels on human chorionic gonadotropin trigger day on blastocyst transfer outcomes in gonadotropin-releasing hormone agonist cycles. Europ J Obstet Gynecol Reprod Biol. 2022;276:107–12.

    Article  CAS  Google Scholar 

  12. Cheung LP, Lam PM, Lok IH, Chiu TTY, 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(3):616–21.

    Article  CAS  PubMed  Google Scholar 

  13. Dragisic KG, Davis OK, Fasouliotis SJ, Rosenwaks Z. Use of a luteal estradiol patch and a gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation for in vitro fertilization in poor responders. FertilSteril. 2005;84(4):1023–6.

    CAS  Google Scholar 

  14. 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(3):323–31.

    Article  PubMed  Google Scholar 

  15. Bakkensen JB, Brady P, Carusi D, Romanski P, Thomas AM, Racowsky C. Association between blastocyst morphology and pregnancy and perinatal outcomes following fresh and cryopreserved embryo transfer. J Assist Reprod Genet. 2019;36(11):2315–24.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mass General Brigham: Patient Estimates. https://patientgateway.massgeneralbrigham.org/MyChart-PRD/GuestEstimates/GetEstimateDetails?svcArea=WP-24e9uXCVWSzEYXIZBsDAXOsA-3D-3D-24kqE853cHDtZ-2BVmykh5-2BSDDgiEoWyT6eEOm3Ph7WnjIQ-3D&isMultiSA=True&token=CQjm7AI6eBiwytyBR1w0VPsC39krv2X5zJ6drr5baKA%3d&template=WP-24z9mHUnA3Ox-2Bo-2Btoi9zCuCg-3D-3D-24dUAenPTYUEh8alkBfUMubjZM94bRgGdyRNfHM3YJQOo-3D&needsRTETrue&location=. Accessed 1 Mar 2023

  17. Serum progesterone blood test costs. https://www.findlabtest.com/lab-test/hormone-testing/progesterone-blood-test-cost-quest-745. Accessed 1 Mar 2023

  18. Ozçakir HT, Levi R, Tavmergen E, Göker EN. Premature luteinization defined as progesterone estradiol ratio >1 on hCG administration day seems to adversely affect clinical outcome in long gonadotropin-releasing hormone agonist cycles. J ObstetGynaecol Res. 2004;30(2):100–4.

    Google Scholar 

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Acknowledgements

We would like to thank the clinical providers and embryology staff at the Center for Infertility and Reproductive Surgery at Brigham and Women’s Hospital for their contribution to this study.

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Authors and Affiliations

  1. Center for Infertility and Reproductive Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Jenny S. George, Kimberly W. Keefe, Andrea Lanes & Elena Yanushpolsky

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  1. Jenny S. George
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  2. Kimberly W. Keefe
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  3. Andrea Lanes
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  4. Elena Yanushpolsky
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Contributions

The authors confirm contribution to the paper as follows: study conception and design: KWK and EY; data collection: KWK and AL; analysis and interpretation of results: AL and JSG; drafting and manuscript preparation: JSG. All authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Jenny S. George.

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Ethics approval

This study was approved by the Mass General Brigham Human Research Committee at the Brigham and Women’s Hospital (Protocol # 2016P001715).

Consent to participate

The need for informed consent was waived by the Mass General Brigham Human Research Committee as all data was retrieved from routine clinical care medical records.

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The authors declare no competing interests.

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George, J.S., Keefe, K.W., Lanes, A. et al. Premature progesterone elevation during the early and mid-follicular phases in fresh in vitro fertilization (IVF) cycles is associated with lower live birth, clinical pregnancy, and implantation rates. J Assist Reprod Genet 40, 1029–1035 (2023). https://doi.org/10.1007/s10815-023-02786-z

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  • DOI: https://doi.org/10.1007/s10815-023-02786-z

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