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Anti-Müllerian hormone in guiding the selection of a freeze-all versus a fresh embryo transfer strategy: a cohort study

  • Assisted Reproduction Technologies
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Abstract

Purpose

To explore an interaction effect between serum anti-Müllerian hormone (AMH) levels and the relative treatment effect of a freeze-all versus a fresh embryo transfer strategy on live birth.

Methods

This was a retrospective cohort study investigating couples with infertility and eligible for both freeze-all and fresh embryo transfer between 2017 and 2019. Women with an absolute indication for a freeze-all strategy were excluded. Multivariable fractional polynomial interaction analysis within a logistic regression model was used to evaluate whether the treatment effect of a freeze-all versus a fresh transfer strategy varied at different AMH levels. Non-linear interactions were also considered. The primary outcome was the live birth after the first transfer.

Results

A total of 13,503 women underwent a fresh embryo transfer and 2247 women underwent a freeze-all strategy. Live birth rates were slightly higher in the freeze-all group compared to those in the fresh embryo transfer group (35% vs 33%). There was a non-linear interaction between baseline serum AMH levels and the relative treatment effect of a freeze-all strategy versus a fresh transfer strategy on live birth (P = 0.0161). The benefit on live birth from a freeze-all embryo transfer strategy was greatest in women with a high serum level (> 7 ng/ml). The interaction remained valid when different imputation methods were used.

Conclusion

As serum AMH level increased, there was a nonlinear increase in relative treatment effect of a freeze-only transfer versus a fresh transfer strategy on live birth, and such an effect reaches its maximum in women with high AMH levels.

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References

  1. Datta J, Palmer MJ, Tanton C, Gibson LJ, Jones KG, Macdowall W, et al. Prevalence of infertility and help seeking among 15 000 women and men. Hum Reprod. 2016;31(9):2108–18. https://doi.org/10.1093/humrep/dew123.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Dyer S, Chambers GM, de Mouzon J, Nygren KG, Zegers-Hochschild F, Mansour R, et al. International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010. Hum Reprod. 2016;31(7):1588–609. https://doi.org/10.1093/humrep/dew082.

    Article  PubMed  CAS  Google Scholar 

  3. Wyns C Bergh C Calhaz-Jorge C De Geyter C Kupka MS Motrenko T et al. ART in Europe 2016: results generated from European registries by ESHRE Human reproduction open. 2020;2020(3):hoaa032. https://doi.org/10.1093/hropen/hoaa032

  4. Mizrachi Y, Horowitz E, Farhi J, Raziel A, Weissman A. Ovarian stimulation for freeze-all IVF cycles: a systematic review. Human Reprod Update. 2020;26(1):118–35. https://doi.org/10.1093/humupd/dmz037.

    Article  CAS  Google Scholar 

  5. Griesinger G, Kolibianakis EM, Papanikolaou EG, Diedrich K, Van Steirteghem A, Devroey P, et al. Triggering of final oocyte maturation with gonadotropin-releasing hormone agonist or human chorionic gonadotropin Live birth after frozen-thawed embryo replacement cycles. Fertil Steril. 2007;88(3):616–21. https://doi.org/10.1016/j.fertnstert.2006.12.006.

    Article  PubMed  CAS  Google Scholar 

  6. Bosdou JK, Venetis CA, Tarlatzis BC, Grimbizis GF, Kolibianakis EM. Higher probability of live-birth in high, but not normal, responders after first frozen-embryo transfer in a freeze-only cycle strategy compared to fresh-embryo transfer: a meta-analysis. Hum Reprod. 2019;34(3):491–505. https://doi.org/10.1093/humrep/dey388.

    Article  PubMed  CAS  Google Scholar 

  7. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril. 2011;96(2):344–8. https://doi.org/10.1016/j.fertnstert.2011.05.050.

    Article  PubMed  Google Scholar 

  8. Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Eng J Med. 2019;375(6):523–33. https://doi.org/10.1056/NEJMoa1513873.

    Article  Google Scholar 

  9. Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ, et al. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019;393(10178):1310–8. https://doi.org/10.1016/s0140-6736(18)32843-5.

    Article  PubMed  Google Scholar 

  10. Wong KM, van Wely M, Verhoeve HR, Kaaijk EM, Mol F, van der Veen F, et al. Transfer of fresh or frozen embryos: a randomised controlled trial. Hum Reprod. 2021;36(4):998–1006. https://doi.org/10.1093/humrep/deaa305.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, et al. Transfer of fresh versus frozen embryos in ovulatory women. N Eng J M. 2018;378(2):126–36. https://doi.org/10.1056/NEJMoa1705334.

    Article  Google Scholar 

  12. 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 EngJ M. 2018;378(2):137–47. https://doi.org/10.1056/NEJMoa1703768.

    Article  Google Scholar 

  13. Stormlund S Sopa N Zedeler A Bogstad J Prætorius L Nielsen HS, et al. Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilisation in women with regular menstrual cycles: multicentre randomised controlled trial Bmj 2020;370:m2519 https://doi.org/10.1136/bmj.m2519; www.icmje.org/coi_disclosure.pdf and declare: support from the Reprounion collaborative study, cofinanced by the European Union, Interreg V ÖKS for the submitted work; PH has received grants and personal fees from Merck, Gedeon Richter, and IBSA, and grants from MSD and Ferring outside the submitted work; NPP reports grants and personal fees from MSD, Merck Serono, Ferring, Theramex, and BESINS International, and personal fees from IBSA and Gedeon Richter outside the submitted work; ANA reports personal fees from Merck and Ferring, and grants from Roche Diagnostics, outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work. All other authors declare no competing interests.

  14. Blockeel C, Campbell A, Coticchio G, Esler J, Garcia-Velasco JA, Santulli P, et al. Should we still perform fresh embryo transfers in ART? Hum Reprod. 2019;34(12):2319–29. https://doi.org/10.1093/humrep/dez233.

    Article  PubMed  CAS  Google Scholar 

  15. Ben Rafael Z. Should we still offer elective freezing of all embryos in all IVF cycles? Hum Reprod. 2020;35(10):2179–84. https://doi.org/10.1093/humrep/deaa204.

    Article  PubMed  Google Scholar 

  16. Hingorani AD, Windt DAvd, Riley RD, Abrams K, Moons KGM, Steyerberg EW, et al. Prognosis research strategy (PROGRESS) 4: stratified medicine research. BMJ. 2013

  17. Dewailly D, Andersen CY, Balen A, Broekmans F, Dilaver N, Fanchin R, et al. The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update. 2014;20(3):370–85. https://doi.org/10.1093/humupd/dmt062.

    Article  PubMed  Google Scholar 

  18. Fleming R, Seifer DB, Frattarelli JL, Ruman J. Assessing ovarian response: antral follicle count versus anti-Mullerian hormone. Reprod Biomed Online. 2015;31(4):486–96. https://doi.org/10.1016/j.rbmo.2015.06.015.

    Article  PubMed  CAS  Google Scholar 

  19. Xu H, Zeng L, Yang R, Feng Y, Li R, Qiao J. Retrospective cohort study: AMH is the best ovarian reserve markers in predicting ovarian response but has unfavorable value in predicting clinical pregnancy in GnRH antagonist protocol. Arch Gynecol Obstet. 2017;295(3):763–70. https://doi.org/10.1007/s00404-016-4274-8.

    Article  PubMed  CAS  Google Scholar 

  20. Acharya KS, Acharya CR, Bishop K, Harris B, Raburn D, Muasher SJ. Freezing of all embryos in in vitro fertilization is beneficial in high responders, but not intermediate and low responders: an analysis of 82,935 cycles from the Society for Assisted Reproductive Technology registry. Fertility and sterility. 2018;110(5):880–7. https://doi.org/10.1016/j.fertnstert.2018.05.024.

    Article  PubMed  Google Scholar 

  21. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018;33(9):1602–18. https://doi.org/10.1093/humrep/dey256.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zheng X, Chen Y, Yan J, Wu Y, Zhuang X, Lin S, et al. Effect of repeated cryopreservation on human embryo developmental potential. Reprod Biomed Online. 2017;35(6):627–32. https://doi.org/10.1016/j.rbmo.2017.08.016.

    Article  PubMed  Google Scholar 

  23. Chi H, Qiao J, Li H, Liu P, Ma C. Double measurements of serum HCG concentration and its ratio may predict IVF outcome. Reprod Biomed Online. 2010;20(4):504–9. https://doi.org/10.1016/j.rbmo.2010.01.005.

    Article  PubMed  CAS  Google Scholar 

  24. Hu KL, Liu FT, Xu H, Li R, Qiao J. Association of serum anti-Müllerian hormone and other factors with cumulative live birth rate following IVF. Reprod Biomed Online. 2020.https://doi.org/10.1016/j.rbmo.2020.01.024.

  25. Embryology ASiRMaESIGo. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270–83. https://doi.org/10.1093/humrep/der037.

    Article  Google Scholar 

  26. Hu KL, Zheng X, Hunt S, Li X, Li R, Mol BW. Blastocyst quality and perinatal outcomes in women undergoing single blastocyst transfer in frozen cycles. Hum Reprod Open. 2021;2021(4):hoab036. https://doi.org/10.1093/hropen/hoab036.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Correia KF, Dodge LE, Farland LV, Hacker MR, Ginsburg E, Whitcomb BW, et al. Confounding and effect measure modification in reproductive medicine research. Hum Reprod. 2020;35(5):1013–8. https://doi.org/10.1093/humrep/deaa051.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Royston P, Sauerbrei W. A new approach to modelling interactions between treatment and continuous covariates in clinical trials by using fractional polynomials. Stat Med. 2004;23(16):2509–25. https://doi.org/10.1002/sim.1815.

    Article  PubMed  Google Scholar 

  29. Royston P, Sauerbrei W. Two techniques for investigating interactions between treatment and continuous covariates in clinical trials. 2009;9(2):230-51. https://doi.org/10.1177/1536867x0900900204.

  30. Bartlett JW, Morris TP. Multiple imputation of covariates by substantive-model compatible fully conditional specification. Stata Journal. 2015;15(2):437–56.

  31. Psaty BM, Siscovick DS. Minimizing bias due to confounding by indication in comparative effectiveness research: the importance of restriction. Jama. 2010;304(8):897–8. https://doi.org/10.1001/jama.2010.1205.

    Article  PubMed  CAS  Google Scholar 

  32. Sik A, Oral S, Aba YA, Ozolcay O, Koc M, Sismanoglu A. Pregnancy results after fresh embryo transfer and selective frozen-thawed embryo transfer: Single-center experience. J Gynecol Obstet Hum Reprod. 2020;49(4):101707. https://doi.org/10.1016/j.jogoh.2020.101707.

    Article  PubMed  Google Scholar 

  33. Shah MS, Caballes M, Lathi RB, Baker VL, Westphal LM, Milki AA. In vitro fertilization outcomes after fresh and frozen blastocyst transfer in South Asian compared with Caucasian women. Fertil Steril. 2016;105(6):1484–7. https://doi.org/10.1016/j.fertnstert.2016.02.027.

    Article  PubMed  Google Scholar 

  34. Healy MW, Patounakis G, Connell MT, Devine K, DeCherney AH, Levy MJ, et al. Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles? Fertil Steril. 2016;105(1):93-9.e1. https://doi.org/10.1016/j.fertnstert.2015.09.015.

    Article  PubMed  CAS  Google Scholar 

  35. Xu B, He YQ, Wang Y, Lu Y, Hong Y, Wang Y, et al. Frozen embryo transfer or fresh embryo transfer: clinical outcomes depend on the number of oocytes retrieved. Euro J Obstet Gynecol Reprod Biol. 2017;215:50–4. https://doi.org/10.1016/j.ejogrb.2017.05.023.

    Article  Google Scholar 

  36. Wang A, Santistevan A, Hunter Cohn K, Copperman A, Nulsen J, Miller BT, et al. Freeze-only versus fresh embryo transfer in a multicenter matched cohort study: contribution of progesterone and maternal age to success rates. Fertil Steril. 2017;108(2):254-61.e4. https://doi.org/10.1016/j.fertnstert.2017.05.007.

    Article  PubMed  CAS  Google Scholar 

  37. Vuong LN, Pham TD, Dang VQ, Ho TM, Ho VNA, Norman RJ, et al. Live birth rates with a freeze-only strategy versus fresh embryo transfer: secondary analysis of a randomized clinical trial. Reprod Biomed Online. 2019;38(3):387–96. https://doi.org/10.1016/j.rbmo.2018.12.012.

    Article  PubMed  Google Scholar 

  38. Yu Y, Zhao S, Li Y, Niu Y, Wei D, Zhang S, et al. Live birth after a freeze-only strategy versus fresh embryo transfer in three randomized trials considering progesterone concentration. Reprod Biomed Online. 2020;41(3):395–401. https://doi.org/10.1016/j.rbmo.2020.04.021.

    Article  PubMed  CAS  Google Scholar 

  39. 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. Hum Reprod Update. 2013;19(5):433–57. https://doi.org/10.1093/humupd/dmt014.

    Article  PubMed  CAS  Google Scholar 

  40. Roque M, Haahr T, Geber S, Esteves SC, Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update. 2019;25(1):2–14. https://doi.org/10.1093/humupd/dmy033.

    Article  PubMed  Google Scholar 

  41. Santos-Ribeiro S, Mackens S, Popovic-Todorovic B, Racca A, Polyzos NP, Van Landuyt L, et al. The freeze-all strategy versus agonist triggering with low-dose hCG for luteal phase support in IVF/ICSI for high responders: a randomized controlled trial. Hum Reprod. 2020;35(12):2808–18. https://doi.org/10.1093/humrep/deaa226.

    Article  PubMed  Google Scholar 

  42. Wang S, Zhang Y, Mensah V, Huber WJ, 3rd, Huang YT, Alvero R. Discordant anti-müllerian hormone (AMH) and follicle stimulating hormone (FSH) among women undergoing in vitro fertilization (IVF): which one is the better predictor for live birth? J Ovarian Res. 2018;11(1):60. https://doi.org/10.1186/s13048-018-0430-z. research by The Care New England – Women & Infants Hospital IRB (IRBNet ID: 948046–1). CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

  43. Lukaszuk K, Liss J, Kunicki M, Jakiel G, Wasniewski T, Woclawek-Potocka I, et al. Anti-Müllerian hormone (AMH) is a strong predictor of live birth in women undergoing assisted reproductive technology. Reprod Biol. 2014;14(3):176–81. https://doi.org/10.1016/j.repbio.2014.03.004.

    Article  PubMed  Google Scholar 

  44. Lyttle Schumacher BM, Jukic AMZ, Steiner AZ. Antimüllerian hormone as a risk factor for miscarriage in naturally conceived pregnancies. Fertil Steril. 2018;109(6):1065-71.e1. https://doi.org/10.1016/j.fertnstert.2018.01.039.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

We thank Lixue Chen in Peking University Third Hospital for helping us to collect the data.

Funding

This study was supported by the National Science Fund for Distinguished Young Scholars (Rong Li, Grant No. 81925013) and National Key Research and Development Program of China (Rong Li, Grant No. 2018YFC1004100). RW is supported by an NHMRC Emerging Leadership Investigator Grant (2009767).

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Authors

Contributions

KL.H, RL, and RW conceived and design the study; KL.H and RW conducted the analysis and designed the figures and tables; KL.H reviewed the literature and wrote the first draft; KL.H, RW, and BWM revised the manuscript. All authors participated in the discussion of analysis and interpretation of data in this article.

Corresponding author

Correspondence to Rong Li.

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Ethics approval

Institutional Review Board (IRB) approval for this retrospective cohort study was obtained from the Ethics Committee of Peking University Third Hospital (reference: 2018S2-002).

Competing interests

BWM is supported by a NHMRC Investigator grant (GNT1176437), and BWM reports consultancy for ObsEva, Merck Merck KGaA, iGenomix, and Guerbet. The other authors have no conflict of interest to declare.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Kai-Lun Hu and Rui Yang are joint first authors.

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Hu, KL., Yang, R., Xu, H. et al. Anti-Müllerian hormone in guiding the selection of a freeze-all versus a fresh embryo transfer strategy: a cohort study. J Assist Reprod Genet 39, 2325–2333 (2022). https://doi.org/10.1007/s10815-022-02564-3

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  • DOI: https://doi.org/10.1007/s10815-022-02564-3

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