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Omidi, M., Halvaei, I., Akyash, F., Ali Khalili, M., Agha-Rahimi, A., & Heydari, L. (2021). The exact synchronization timing between the cleavage embryo stage and duration of progesterone therapy-improved pregnancy rates in frozen embryo transfer cycles: A cross-sectional study. International Journal of Reproductive BioMedicine (IJRM), 19(3), 227–234. https://doi.org/10.18502/ijrm.v19i3.8570
https://doi.org/10.18502/ijrm.v19i3.8570
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authors
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Marjan Omidi
Marjan Omidi
Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Iman Halvaei
Iman Halvaei
Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Fatemeh Akyash
Fatemeh Akyash
Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Science, Yazd, Iran
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Mohammad Ali Khalili
Mohammad Ali Khalili
Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Azam Agha-Rahimi
Azam Agha-Rahimi
Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Leila Heydari
Leila Heydari
Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Published Date
- Mar 21, 2021
The exact synchronization timing between the cleavage embryo stage and duration of progesterone therapy-improved pregnancy rates in frozen embryo transfer cycles: A cross-sectional study
Abstract
Background: Synchronization between the embryonic stage and the uterine endometrial lining is important in the outcomes of the vitrified-warmed embryo transfer (ET) cycles.
Objective: The aim was to investigate the effect of the exact synchronization between the cleavage stage of embryos and the duration of progesterone administration on the improvement of clinical outcomes in frozen embryo transfer (FET) cycles.
Materials and Methods: 312 FET cycles were categorized into two groups: (A) day- 3 ET after three days of progesterone administration (n = 177) and (B) day-2 or -4 ET after three days of progesterone administration (n = 135). Group B was further divided into two subgroups: B1: day-2 ET cycles, that the stage of embryos were less than the administrated progesterone and B2: day-4 ET cycles, that the stage of embryos were more than the administrated progesterone. The clinical outcome measures were compared between the groups.
Results: The pregnancy outcomes between groups A and B showed a significant differences in the chemical (40.1% vs 27.4%; p = 0.010) and clinical pregnancies (32.8% vs 22.2%; p = 0.040), respectively. The rate of miscarriage tended to be higher and live birth rate tended to be lower in group B than in group A. Also, significantly higher rates were noted in chemical pregnancy, clinical pregnancy, and live birth in group A when compared with subgroup B2.
Conclusion: Higher rates of pregnancy and live birth were achieved in day-3 ET after three days of progesterone administration in FET cycles.
Key words: Endometrium, Embryo transfer, Pregnancy, Live birth, Progesterone.
References
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[2] Bellver J, Simón C. Implantation failure of endometrial origin: What is new? Curr Opin Obstet Gynecol 2018; 30: 229–236.
[3] Franasiak JM, Ruiz-Alonso M, Scott RT, Simón C. Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo. Fertil Steril 2016; 105: 861–866.
[4] Teh WT, McBain J, Rogers P. What is the contribution of embryo-endometrial asynchrony to implantation failure? J Assist Reprod Genet 2016; 33: 1419–1430.
[5] Sebastian-Leon P, Garrido N, Remohí J, Pellicer A, Diaz- Gimeno P. Asynchronous and pathological windows of implantation: Two causes of recurrent implantation failure. Hum Reprod 2018; 33: 626–635.
[6] Gomaa H, Casper RF, Esfandiari N, Bentov Y. Nonsynchronized endometrium and its correction in nonovulatory cryopreserved embryo transfer cycles. Reprod Biomed Online 2015; 30: 378–384.
[7] Mocanu EV, Cottell E, Waite K, Hennelly B, Collins C, Harrison RF. Frozen-thawed transfer cycles: Are they comparable with fresh? Ir Med J 2008; 101: 181–184.
[8] Balaban B, Urman B, Ata B, Isiklar A, Larman MG, Hamilton R, et al. A randomized controlled study of human day 3 embryo cryopreservation by slow freezing or vitrification: Vitrification is associated with higher survival, metabolism and blastocyst formation. Hum Reprod 2008; 23: 1976–1982.
[9] Debrock S, Peeraer K, Fernandez Gallardo E, De Neubourg D, Spiessens C, D’hooghe TM. Vitrification of cleavage stage day 3 embryos results in higher live birth rates than conventional slow freezing: A RCT. Hum Reprod 2015; 30: 1820–1830. [10] Paulson RJ. Hormonal induction of endometrial receptivity. Fertil Steril 2011; 96: 530–535.
[11] Kuleshova LL, Lopata A. Vitrification can be more favorable than slow cooling. Fertil Steril 2002; 78: 449–454.
[12] Groenewoud ER, Macklon NS, Cohlen BJ, ANTARCTICA trial study group. Cryo-thawed embryo transfer: Natural versus artificial cycle. A non-inferiority trial. BMC Womens Health 2012; 12: 27.
[13] Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update 2013; 19: 458–470.
[14] Kim HH, Matevossian K. It’s all about timing: Is the window of implantation different for day 5 and 6 blastocysts? Fertil Steril 2020; 114: 69–70.
[15] Sahmay S, Oral E, Saridogan E, Senturk L, Atasu T. Endometrial biopsy findings in infertility: Analysis of 12,949 cases. Int J Fertil Menopausal Stud 1995; 40: 316–321.
[16] Coutifaris C, Myers ER, Guzick DS, Diamond MP, Carson SA, Legro RS, et al. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 2004; 82: 1264–1272.
[17] Eftekhar M, Bagheri Baradaran R, Neghab N, Hosseinisadat R. Evaluation of pretreatment with Cetrotide in an antagonist protocol for patients with PCOS undergoing IVF/ICSI cycles: A randomized clinical trial. JBRA Assist Reprod 2018; 22: 238–243.
[18] Hill GA, Freeman M, Bastias MC, Rogers BJ, Herbert CM, Osteen KG, et al. The influence of oocyte maturity and embryo quality on pregnancy rate in a program for in vitro fertilization-embryo transfer. Fertil Steril 1989; 52: 801– 806.
[19] Chang EM, Han JE, Kim YS, Lyu SW, Lee WS, Yoon TK. Use of the natural cycle and vitrification thawed blastocyst transfer results in better in-vitro fertilization outcomes: Cycle regimens of vitrification thawed blastocyst transfer. J Assist Reprod Genet 2011; 28: 369–374.
[20] Morozov V, Ruman J, Kenigsberg D, Moodie G, Brenner S. Natural cycle cryo-thaw transfer may improve pregnancy outcome. J Assist Reprod Genet 2007; 24: 119–123.
[21] Wright KP, Guibert J, Weitzen S, Davy C, Fauque P, Olivennes F. Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer. Reprod Biomed Online 2006; 13: 321–325.
[22] Dong Z, Sun L, Zhang H, Chen Z, Jian Y. The frozenthawed embryo transfer timing determined by serum progesterone level: A retrospective follow-up study. Eur J Obstet Gynecol Reprod Biol 2014; 181: 210–213.
[23] Gardner DK, Weissman A, Howles CM, Shoham Z. Textbook of assisted reproductive techniques: Laboratory and clinical perspectives. United State: CRC Press; 2019.
[24] Revel A, Safran A, Laufer N, Lewin A, Reubinov BE, Simon A. Twin delivery following 12 years of human embryo cryopreservation: Case report. Hum Reprod 2004; 19: 328–329.
[25] Givens CR, Markun LC, Ryan IP, Chenette PE, Herbert CM, Schriock ED. Outcomes of natural cycles versus programmed cycles for 1677 frozen-thawed embryo transfers. Reprod Biomed Online 2009; 19: 380–384.
[26] Van De Vijver A, Polyzos NP, Van Landuyt L, Mackens S, Stoop D, Camus M, et al. What is the optimal duration of progesterone administration before transferring a vitrifiedwarmed cleavage stage embryo? A randomized controlled trial. Hum Reprod 2016; 31: 1097–1104.
[27] Sharma S, Majumdar A. Determining the optimal duration of progesterone supplementation prior to transfer of cryopreserved embryos and its impact on implantation and pregnancy rates: A pilot study. Int J Reprod Med 2016; 2016: 1–7.
[28] Ding J, Rana N, Dmowski WP. Length of progesterone treatment before transfer and implantation rates of frozenthawed blastocysts. Fertil Steril 2007; 88 (Suppl.): S330– S331.
[29] 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: 720–723.
[30] Chimote BN, Chimote NM. Tracking the implantation window: Synchronizing endometrial preparedness for implantation with stage of blastocyst to be transferred in antagonist IVF cycles involving single blastocyst transfers. Fertil Sci Res 2018; 5: 27–32.
[31] Agha-Rahimi A, Omidi M, Akyash F, Faramarzi A, Farshchi FA. Does overnight culture of cleaved embryos improve pregnancy rate in vitrified-warmed embryo transfer programme? Malays J Med Sci 2019; 26: 52–58.
[2] Bellver J, Simón C. Implantation failure of endometrial origin: What is new? Curr Opin Obstet Gynecol 2018; 30: 229–236.
[3] Franasiak JM, Ruiz-Alonso M, Scott RT, Simón C. Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo. Fertil Steril 2016; 105: 861–866.
[4] Teh WT, McBain J, Rogers P. What is the contribution of embryo-endometrial asynchrony to implantation failure? J Assist Reprod Genet 2016; 33: 1419–1430.
[5] Sebastian-Leon P, Garrido N, Remohí J, Pellicer A, Diaz- Gimeno P. Asynchronous and pathological windows of implantation: Two causes of recurrent implantation failure. Hum Reprod 2018; 33: 626–635.
[6] Gomaa H, Casper RF, Esfandiari N, Bentov Y. Nonsynchronized endometrium and its correction in nonovulatory cryopreserved embryo transfer cycles. Reprod Biomed Online 2015; 30: 378–384.
[7] Mocanu EV, Cottell E, Waite K, Hennelly B, Collins C, Harrison RF. Frozen-thawed transfer cycles: Are they comparable with fresh? Ir Med J 2008; 101: 181–184.
[8] Balaban B, Urman B, Ata B, Isiklar A, Larman MG, Hamilton R, et al. A randomized controlled study of human day 3 embryo cryopreservation by slow freezing or vitrification: Vitrification is associated with higher survival, metabolism and blastocyst formation. Hum Reprod 2008; 23: 1976–1982.
[9] Debrock S, Peeraer K, Fernandez Gallardo E, De Neubourg D, Spiessens C, D’hooghe TM. Vitrification of cleavage stage day 3 embryos results in higher live birth rates than conventional slow freezing: A RCT. Hum Reprod 2015; 30: 1820–1830. [10] Paulson RJ. Hormonal induction of endometrial receptivity. Fertil Steril 2011; 96: 530–535.
[11] Kuleshova LL, Lopata A. Vitrification can be more favorable than slow cooling. Fertil Steril 2002; 78: 449–454.
[12] Groenewoud ER, Macklon NS, Cohlen BJ, ANTARCTICA trial study group. Cryo-thawed embryo transfer: Natural versus artificial cycle. A non-inferiority trial. BMC Womens Health 2012; 12: 27.
[13] Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update 2013; 19: 458–470.
[14] Kim HH, Matevossian K. It’s all about timing: Is the window of implantation different for day 5 and 6 blastocysts? Fertil Steril 2020; 114: 69–70.
[15] Sahmay S, Oral E, Saridogan E, Senturk L, Atasu T. Endometrial biopsy findings in infertility: Analysis of 12,949 cases. Int J Fertil Menopausal Stud 1995; 40: 316–321.
[16] Coutifaris C, Myers ER, Guzick DS, Diamond MP, Carson SA, Legro RS, et al. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 2004; 82: 1264–1272.
[17] Eftekhar M, Bagheri Baradaran R, Neghab N, Hosseinisadat R. Evaluation of pretreatment with Cetrotide in an antagonist protocol for patients with PCOS undergoing IVF/ICSI cycles: A randomized clinical trial. JBRA Assist Reprod 2018; 22: 238–243.
[18] Hill GA, Freeman M, Bastias MC, Rogers BJ, Herbert CM, Osteen KG, et al. The influence of oocyte maturity and embryo quality on pregnancy rate in a program for in vitro fertilization-embryo transfer. Fertil Steril 1989; 52: 801– 806.
[19] Chang EM, Han JE, Kim YS, Lyu SW, Lee WS, Yoon TK. Use of the natural cycle and vitrification thawed blastocyst transfer results in better in-vitro fertilization outcomes: Cycle regimens of vitrification thawed blastocyst transfer. J Assist Reprod Genet 2011; 28: 369–374.
[20] Morozov V, Ruman J, Kenigsberg D, Moodie G, Brenner S. Natural cycle cryo-thaw transfer may improve pregnancy outcome. J Assist Reprod Genet 2007; 24: 119–123.
[21] Wright KP, Guibert J, Weitzen S, Davy C, Fauque P, Olivennes F. Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer. Reprod Biomed Online 2006; 13: 321–325.
[22] Dong Z, Sun L, Zhang H, Chen Z, Jian Y. The frozenthawed embryo transfer timing determined by serum progesterone level: A retrospective follow-up study. Eur J Obstet Gynecol Reprod Biol 2014; 181: 210–213.
[23] Gardner DK, Weissman A, Howles CM, Shoham Z. Textbook of assisted reproductive techniques: Laboratory and clinical perspectives. United State: CRC Press; 2019.
[24] Revel A, Safran A, Laufer N, Lewin A, Reubinov BE, Simon A. Twin delivery following 12 years of human embryo cryopreservation: Case report. Hum Reprod 2004; 19: 328–329.
[25] Givens CR, Markun LC, Ryan IP, Chenette PE, Herbert CM, Schriock ED. Outcomes of natural cycles versus programmed cycles for 1677 frozen-thawed embryo transfers. Reprod Biomed Online 2009; 19: 380–384.
[26] Van De Vijver A, Polyzos NP, Van Landuyt L, Mackens S, Stoop D, Camus M, et al. What is the optimal duration of progesterone administration before transferring a vitrifiedwarmed cleavage stage embryo? A randomized controlled trial. Hum Reprod 2016; 31: 1097–1104.
[27] Sharma S, Majumdar A. Determining the optimal duration of progesterone supplementation prior to transfer of cryopreserved embryos and its impact on implantation and pregnancy rates: A pilot study. Int J Reprod Med 2016; 2016: 1–7.
[28] Ding J, Rana N, Dmowski WP. Length of progesterone treatment before transfer and implantation rates of frozenthawed blastocysts. Fertil Steril 2007; 88 (Suppl.): S330– S331.
[29] 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: 720–723.
[30] Chimote BN, Chimote NM. Tracking the implantation window: Synchronizing endometrial preparedness for implantation with stage of blastocyst to be transferred in antagonist IVF cycles involving single blastocyst transfers. Fertil Sci Res 2018; 5: 27–32.
[31] Agha-Rahimi A, Omidi M, Akyash F, Faramarzi A, Farshchi FA. Does overnight culture of cleaved embryos improve pregnancy rate in vitrified-warmed embryo transfer programme? Malays J Med Sci 2019; 26: 52–58.