Impact of serum progesterone levels at embryo transfer on HRT-FET outcomes: A systematic review

Authors

  • D.B. Makhadiyeva Ecomed Clinic
  • I.D. Yergaliyev
  • S.B. Baikoshkarova
  • Zh.R. Azhetova
  • A.M. Irgebayeva

DOI:

https://doi.org/10.37800/RM.3.2025.560

Keywords:

progesterone, frozen embryo transfer (FET), pregnancy, in vitro fertilization (IVF), assisted reproductive technologies (ART)

Abstract

Relevance: The effectiveness of assisted reproductive technologies (ART) remains a primary goal of reproductive medicine. Despite significant breakthroughs in the field, a significant proportion of patients fail to achieve a successful outcome of in vitro fertilization (IVF) treatment. The impact of various factors, including serum progesterone (P4) level on embryo transfer day, on ART outcomes remains poorly understood and requires further research.

This study aimed to evaluate the relationship between serum progesterone levels at embryo transfer and outcomes of hormone replacement therapy in frozen embryo transfer cycles.

Materials and Methods: This literature review analyzes publications in English, Kazakh and Russian for 2015-2025, indexed in the PubMed, Scopus and Web of Science databases.

Results: P4 levels at embryo transfer play a pivotal role in determining the success of HRT-FET cycles, with robust evidence corroborating a lower threshold of approximately 8-10 ng/mL in women undergoing vaginal progesterone administration for luteal phase support (LPS). In patients with parenteral or combined progesterone regimens for LPS, the lower threshold is different and appears to be higher or even non-existent. A detrimental upper P4 level at embryo transfer remains unconvincing. Individual patient and treatment characteristics, along with hormone assay variability, underscore the need for personalized P4 monitoring and LPS.

Conclusion: This review emphasizes the need for large, methodologically rigorous prospective studies to elucidate the impact of P4 levels at embryo transfer in HRT-FET cycles. A deeper understanding of individualized progesterone thresholds and their interaction with patient and treatment variables could transform current strategies for LPS, shifting toward more personalized protocols that optimize implantation and live birth outcomes in ART.

References

1. Kupka MS, Chambers GM, Dyer S, Zegers-Hochschild F, de Mouzon J, Ishihara O, Banker M, Jwa SC, Fu B, Elgindy E, Baker V. International Committee for Monitoring Assisted Reproductive Technology world report: assisted reproductive technology, 2015 and 2016. Fertil Steril. 2024;122(5):875-893.

https://doi.org/10.1016/j.fertnstert.2024.07.009

2. Smeenk J, Wyns C, De Geyter C, Bergh C, Cuevas I, de Neubourg D, Kupka MS, Rezabek K, Baldani D, Tandler-Schneider A, Goossens V. O-121 Assisted Reproductive Technology (ART) in Europe 2021 and development of a strategy of vigilance: Preliminary results generated from European registers by the ESHRE EIM Consortium. Hum Reprod. 2024;39(Supplement_1):deae108-136.

https://doi.org/10.1093/humrep/deae108.136

3. Lokshin V, Suleimenova M, Akhmetova A, Aripova R, Baikoshkarova S, Chalova L, Diamantidi N, Dzhusubalieva T, Imtosimi D, Karabalin A, Kim V, Kryldakov A, Lapina E, Magarmanova S, Makisheva A, Mukhamedyarov D, Nigmatova N, Nigmetova K, Otarbayev M, Pokotilo L, Tararaka N, Tararaka S, Toleubayeva K, Yakhyarova M, Yermekov M, Yessenamanova S. Assisted Reproductive Technologies in Kazakhstan (National Registry Data, 2021). Reprod Med Cent Asia. 2025;1:10-19.

https://doi.org/10.37800/RM.1.2025.443

4. Dias Da Silva I, Wuidar V, Zielonka M, Pequeux C. Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview. Cells. 2024;13(15):1236.

https://doi.org/10.3390/cells13151236

5. de Ziegler D, Pirtea P, Ayoubi JM. Implantation Failures and Miscarriages in Frozen Embryo Transfers Timed in Hormone Replacement Cycles (HRT): A Narrative Review. Life. 2021;11(12):1357.

https://doi.org/10.3390/life11121357

6. Mumusoglu S, Polat M, Ozbek IY, Bozdag G, Papanikolaou EG, Esteves SC, Yarali H. Preparation of the endometrium for frozen embryo transfer: a systematic review. Front Endocrinol. 2021;12:688237.

https://doi.org/10.3389/fendo.2021.688237

7. Bila J, Makhadiyeva D, Dotlic J, Andjic M, Aimagambetova G, Terzic S, Bapayeva G, Laganà AS, Sarria-Santamera A, Terzic M. Predictive Role of Progesterone Levels for IVF Outcome in Different Phases of Controlled Ovarian Stimulation for Patients With and Without Endometriosis: Expert View. Reprod Sci. 2024;31(7):1819-1827.

https://doi.org/10.1007/s43032-024-01490-2

8. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, … Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

https://doi.org/10.1136/bmj.n71

9. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet]. www.ohri.ca. 2021. Available from:

https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

10. Labarta E, Mariani G, Holtmann N, Celada P, Remohí J, Bosch E. Low serum progesterone on embryo transfer day is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod. 2017;32(12):2437-2442.

https://doi.org/10.1093/humrep/dex316

11. 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 embryo transfer day on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone. Hum Reprod. 2021;36(3):683-692.

https://doi.org/10.1093/humrep/deaa322

12. Maignien C, Bourdon M, Marcellin L, Laguillier-Morizot C, Borderie D, A. Chargui, C. Patrat, G. Plu-Bureau, C. Chapron, P. Santulli. Low serum progesterone affects live birth rate in cryopreserved blastocyst transfer cycles using hormone replacement therapy. Reprod Biomed Online. 2022;44(3):469-477.

https://doi.org/10.1016/j.rbmo.2021.11.007

13. Melo P, Wood S, Petsas G, Chung Y, Easter C, Price M, Fishel S, Khairy M, Kingsland C, Lowe P, Rajkhowa M, Sephton V, Pandey S, Kazem R, Walker D, Gorodeckaja J, Wilcox M, Gallos I, Tozer A, Coomarasamy A. The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET). Hum Reprod Open. 2022;2022(4):hoac054.

https://doi.org/10.1093/hropen/hoac054

14. Kofinas J, Blakemore J, McCulloh D, 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;32:1395-1399.

https://doi.org/10.1007/s10815-015-0546-7

15. Boynukalin FK, Gultomruk M, Turgut E, Demir B, Fındıklı N, Serdarogullari M, Coban O, Yarkıner Z, Bahçeci M. 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 RBE. 2019;17(1):102.

https://doi.org/10.1186/s12958-019-0549-9

16. Tohma YA, Demir B, Dundar B, Boynukalin FK, Fındıklı N, Bahçeci M, Bozdag G. High serum progesterone levels on embryo transfer day in patients undergoing artificial frozenthawed blastocyst transfer: Is there a ceiling effect? Turk J Obstet Gynecol. 2024;21:153-157.

https://doi.org/10.4274/tjod.galenos.2024.38364

17. Alyasin A, Agha-Hosseini M, Kabirinasab M, Saeidi H, Nashtaei MS. Serum progesterone levels greater than 32.5 ng/mL on embryo transfer day are associated with lower live birth rate after artificial endometrial preparation: a prospective study. Reprod Biol Endocrinol. 2021;19(1):24.

https://doi.org/10.1186/s12958-021-00703-6

18. Mehrafza M, Raoufi A, Yousefi TZ, Samadnia S, Tamimi A, Hosseini A. Serum Progesterone Concentration and Ongoing Pregnancy Rate in Frozen-Thawed Embryo Transfers with Intramuscular Plus Vaginal Progesterone Administration for Endometrial Preparation. J Kerman Univ Med Sci. 2022;29(6):593-597.

https://doi.org/10.34172/jkmu.2022.74

19. Zhu Q, Huang J, Lin Y, Jiang L, Huang X, Zhu J. Association between serum progesterone levels on the day of frozen-thawed embryo transfer and pregnancy outcomes after artificial endometrial preparation. BMC Pregn Childbirth. 2023;23(1):401.

https://doi.org/10.1186/s12884-023-05596-4

20. Metello J, Tomás C, Bravo I, Branquinho M, Santos-Ribeiro S. Impact of Plasmatic Progesterone on the Day of Frozen Embryo Transfer in Hormone-induced Cycles. RBGO Gynecol Obstet. 2021;43:608-615.

https://doi.org/10.1055/s-0041-1735229

21. González-Foruria I, García S, Álvarez M, Racca A, Hernández M, Polyzos N, Coroleu B. Elevated serum progesterone levels before frozen embryo transfer do not negatively impact reproductive outcomes: a large retrospective cohort study. Fertil Steril. 2023;120(3 Pt 2):597-604.

https://doi.org/10.1016/j.fertnstert.2023.04.038

22. Dashti S, Tabibnejad N, Shamsi F, Gandom B. Predictive Value of Serum Progesterone Levels on The Day of Frozen-Thawed Embryo Transfer in Determining Pregnancy Outcomes in Infertile Women: A Cohort Prospective Study. Int J Fertil Steril. 2025;19:219-225.

https://doi.org/10.22074/ijfs.2024.2032890.1720

23. Chen W, Xu Y, Liu X, Pan J, Cai B, Zhou C, Xu Y, Gu F. Serum Progesterone Level on embryo transfer day Is Not a Reliable Predictor for Frozen–Thawed Embryo Transfer Outcomes With Euploid Blastocyst Transfer: A Retrospective Cohort Study. BJOG Int J Obstet Gynaecol. 2025;132 Suppl 2:53-61.

https://doi.org/10.1111/1471-0528.18045

24. Bulletti C, Bulletti FM, Sciorio R, Guido M. Progesterone: The Key Factor of the Beginning of Life. Int J Mol Sci. 2022;23(22):14138.

https://doi.org/10.3390/ijms232214138

25. Devine K, Richter KS, Jahandideh S, Widra EA, McKeeby JL. Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: a randomized clinical trial. Fertil Steril. 2021;116(3):633-643.

https://doi.org/10.1016/j.fertnstert.2021.04.013

26. Ghaedi B, Cheng W, Ameri S, Abdulkarim K, Costain N, Zia A, Thiruganasambandamoorthy V. Performance of single serum progesterone in the evaluation of symptomatic first-trimester pregnant patients: a systematic review and meta-analysis. Can J Emerg Med. 2022;24(6):611-621.

https://doi.org/10.1007/s43678-022-00332-x

27. du Boulet B, Ranisavljevic N, Mollevi C, Bringer-Deutsch S, Brouillet S, Anahory T. Individualized luteal phase support based on serum progesterone levels in frozen-thawed embryo transfer cycles maximizes reproductive outcomes in a cohort undergoing preimplantation genetic testing. Front Endocrinol. 2022;13:1051857.

https://doi.org/10.3389/fendo.2022.1051857

28. Boynukalin FK, Tohma YA, Yarkıner Z, Gultomruk M, Bozdag G, Ozkavukcu S, Bahçeci M, Demir B. Individualized luteal phase support in frozen-thawed embryo transfer after intramuscular progesterone administration might rectify live birth rate. Front Endocrinol. 2024;15:1412185.

https://doi.org/10.3389/fendo.2024.1412185

29. Xie J, Li N, Bai H, Shi J, Cai H. Overweight and obesity affect the efficacy of vaginal vs. intramuscular progesterone for luteal-phase support in vitrified-warmed blastocyst transfer. Fertil Steril. 2023;119(4):606-615.

https://doi.org/10.1016/j.fertnstert.2022.12.034

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Published

30.09.2025

How to Cite

Makhadiyeva, D., Yergaliyev, I., Baikoshkarova, S., Azhetova, Z., & Irgebayeva, A. (2025). Impact of serum progesterone levels at embryo transfer on HRT-FET outcomes: A systematic review. Reproductive Medicine (Central Asia), (3), 29–36. https://doi.org/10.37800/RM.3.2025.560

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