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Cited by 41Assisted Reproductive Technology and Twin PregnancyReproductive Health and TechnologiesPregnancy and preeclampsia studies

The impact of endometrial preparation for frozen embryo transfer on maternal and neonatal outcomes: a review

Open access
Lee, Jacqueline C., Badell, Martina L., Kawwass, Jennifer F.·2022·Reproductive Biology and Endocrinology
DOI 10.1186/s12958-021-00869-zPMC PMC8883648
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Abstract

The use of frozen embryo transfer in assisted reproductive technology (ART) has steadily increased since development in the early 1980’s. While there are many benefits to delayed frozen embryo transfer, certain adverse perinatal outcomes are noted to be more common in these transfers when compared to fresh transfers, specifically hypertensive disorders of pregnancy. Frozen embryo transfers require coordination between the embryo’s developmental stage and the endometrial environment and can occur in either ovulatory or programmed cycles. Though there is no consensus on the ideal method of endometrial preparation prior to frozen embryo transfer, emerging data suggests differences in maternal and neonatal outcomes, specifically increased rates of hypertensive disorders of pregnancy in programmed cycles. Other reported differences include an increased risk of cesarean delivery, placenta accreta, postpartum hemorrhage, low birthweight, preterm birth, post term delivery, macrosomia, large for gestational age, and premature rupture of membranes in programmed cycles. The mechanism by which these differences exist could reflect inherent differences in groups selected for each type of endometrial preparation, the role of super physiologic hormone environments in programmed cycles, or the unique contributions of the corpus luteum in ovulatory cycles that are not present in programmed cycles. Given that existing studies are largely retrospective and have several key limitations, further investigation is needed. Confirmation of these findings has implications for current practice patterns and could enhance understanding of the mechanisms behind important adverse perinatal outcomes in those pursuing assisted reproduction.

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  • The overall quality of evidence in the latest systematic review and meta-analysis was very low to moderate (moderate for key maternal outcomes such as hypertensive disorders in pregnancy and postpartum haemorrhage).

    “The overall quality of evidence used in the latest systematic review and meta-analysis was very low to moderate (moderate for key maternal outcomes such as hypertensive disorders in pregnancy and postpartum haemorrhage), which prevents us from making strong conclusions.”

    From Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial. (2024) · cites this paper as [25]

    The Strengths and limitations section (page unavailable) cautions that the mostly retrospective, non-randomized studies are subject to confounding and that their findings should be interpreted with caution. It does not report a systematic-review or meta-analysis evidence grade of “very low to moderate,” or grade hypertensive disorders and postpartum haemorrhage as moderate. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • A 2023 systematic review and meta-analysis found significantly higher risks for several adverse obstetric and neonatal outcomes in artificial versus natural FET cycles.

    “Existing data include a 2023 systematic review and meta-analysis, 7,25 which found significantly higher risks for several adverse obstetric and neonatal outcomes in artificial versus natural FET cycles.”

    From Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial. (2024) · cites this paper as [25]

    The review’s ‘Maternal and neonatal outcomes by method of endometrial preparation’ section reports higher risks of several adverse obstetric and neonatal outcomes in programmed versus natural FET cycles. But this source is a 2022 review, not the 2023 systematic review and meta-analysis described in the citing sentence; our copy does not report a pooled meta-analysis of those outcomes. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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  1. [1]Niederberger C Pellicer A Cohen J Gardner DK Palermo GD O'Neill CL Forty years of IVF Fertil Steril 2018 110 2 185 324 e5 30053940
  2. [2]Zeilmaker GH Alberda AT van Gent I Rijkmans CM Drogendijk AC Two pregnancies following transfer of intact frozen-thawed embryos Fertil Steril 1984 42 2 293 296 6745463
  3. [3]Trounson A Mohr L Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo Nature. 1983 305 5936 707 709 6633637
  4. [4]Banker M Dyer S Chambers GM Ishihara O Kupka M de Mouzon J International Committee for Monitoring Assisted Reproductive Technologies (ICMART): world report on assisted reproductive technologies, 2013 Fertil Steril 2021 116 3 741 756 33926722
  5. [5]Practice Committee of the American Society for Reproductive Medicine Electronic address Aao, Practice Committee of the American Society for reproductive M. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline Fertil Steril 2016 106 7 1634 1647 27678032
  6. [6]Practice Committee of the American Society for Reproductive M, the Practice Committee for the Society for Assisted Reproductive Technologies Electronic address Aao. Guidance on the limits to the number of embryos to transfer: a committee opinion Fertil Steril 2021 116 3 651 654 34330423
  7. [7]Wong KM Mastenbroek S Repping S Cryopreservation of human embryos and its contribution to in vitro fertilization success rates Fertil Steril 2014 102 1 19 26 24890275
  8. [8]Donnez J Dolmans MM Fertility preservation in men and women: where are we in 2021? Are we rising to the challenge? Fertil Steril 2021 115 5 1089 1090 33823991
  9. [9]American College of O, Gynecologists’ Committee on Obstetric P, Committee on G, Food US, Drug A Committee opinion no 671: perinatal risks associated with assisted reproductive technology Obstet Gynecol 2016 128 3 e61 e68 27548556
  10. [10]Kawwass JF Badell ML Maternal and fetal risk associated with assisted reproductive technology Obstet Gynecol 2018 132 3 763 772 30095760
  11. [11]Practice Committee of American Society for Reproductive M Multiple gestation associated with infertility therapy: an American Society for Reproductive Medicine Practice committee opinion Fertil Steril 2012 97 4 825 834 22192352
  12. [13]Thomopoulos C Tsioufis C Michalopoulou H Makris T Papademetriou V Stefanadis C Assisted reproductive technology and pregnancy-related hypertensive complications: a systematic review J Hum Hypertens 2013 27 3 148 157 22495105
  13. [14]Shi Y Sun Y Hao C Zhang H Wei D Zhang Y Transfer of fresh versus frozen embryos in ovulatory women N Engl J Med 2018 378 2 126 136 29320646
  14. [15]Zaat T Zagers M Mol F Goddijn M van Wely M Mastenbroek S Fresh versus frozen embryo transfers in assisted reproduction Cochrane Database Syst Rev 2021 2 CD011184 33539543 PMC8095009
  15. [16]Wang A Santistevan A Hunter Cohn K Copperman A Nulsen J Miller BT 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 28579411
  16. [17]Sha T Yin X Cheng W Massey IY Pregnancy-related complications and perinatal outcomes resulting from transfer of cryopreserved versus fresh embryos in vitro fertilization: a meta-analysis Fertil Steril 2018 109 2 330 42 e9 29331236
  17. [18]Opdahl S Henningsen AA Tiitinen A Bergh C Pinborg A Romundstad PR Risk of hypertensive disorders in pregnancies following assisted reproductive technology: a cohort study from the CoNARTaS group Hum Reprod 2015 30 7 1724 1731 25924655
  18. [19]Sites CK Wilson D Barsky M Bernson D Bernstein IM Boulet S Embryo cryopreservation and preeclampsia risk Fertil Steril 2017 108 5 784 790 28974308 PMC10999961
  19. [20]Luke B Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies Am J Obstet Gynecol 2017 217 3 270 281 28322775 PMC9761478
  20. [21]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 30388233
  21. [22]Maheshwari A Pandey S Amalraj Raja E Shetty A Hamilton M Bhattacharya S Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update 2018 24 1 35 58 29155965
  22. [23]Casper RF Yanushpolsky EH Optimal endometrial preparation for frozen embryo transfer cycles: window of implantation and progesterone support Fertil Steril 2016 105 4 867 872 26820769
  23. [24]Ghobara T Gelbaya TA Ayeleke RO Cycle regimens for frozen-thawed embryo transfer Cochrane Database Syst Rev 2017 7 CD003414 28675921 PMC6483463
  24. [25]Greco E Litwicka K Arrivi C Varricchio MT Caragia A Greco A The endometrial preparation for frozen-thawed euploid blastocyst transfer: a prospective randomized trial comparing clinical results from natural modified cycle and exogenous hormone stimulation with GnRH agonist J Assist Reprod Genet 2016 33 7 873 884 27221477 PMC4930788
  25. [26]Mounce G McVeigh E Turner K Child TJ Randomized, controlled pilot trial of natural versus hormone replacement therapy cycles in frozen embryo replacement in vitro fertilization Fertil Steril 2015 104 4 915 20 e1 26255087
  26. [27]Groenewoud ER Cohlen BJ Al-Oraiby A Brinkhuis EA Broekmans FJ de Bruin JP A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer Hum Reprod 2016 31 7 1483 1492 27179265 PMC5853593
  27. [28]von Versen-Hoynck F Schaub AM Chi YY Chiu KH Liu J Lingis M Increased preeclampsia risk and reduced aortic compliance with in vitro fertilization cycles in the absence of a corpus luteum Hypertension. 2019 73 3 640 649 30636552 PMC6434532
  28. [29]Jing S Li XF Zhang S Gong F Lu G Lin G Increased pregnancy complications following frozen-thawed embryo transfer during an artificial cycle J Assist Reprod Genet 2019 36 5 925 933 30924053 PMC6541721
  29. [30]Saito K Kuwahara A Ishikawa T Morisaki N Miyado M Miyado K Endometrial preparation methods for frozen-thawed embryo transfer are associated with altered risks of hypertensive disorders of pregnancy, placenta accreta, and gestational diabetes mellitus Hum Reprod 2019 34 8 1567 1575 31299081
  30. [31]Ginstrom Ernstad E Wennerholm UB Khatibi A Petzold M Bergh C Neonatal and maternal outcome after frozen embryo transfer: increased risks in programmed cycles Am J Obstet Gynecol 2019 221 2 126 e1 126e18 30910545
  31. [32]Wang B Zhang J Zhu Q Yang X Wang Y Effects of different cycle regimens for frozen embryo transfer on perinatal outcomes of singletons Hum Reprod 2020 35 7 1612 1622 32681726
  32. [33]Zong L Liu P Zhou L Wei D Ding L Qin Y Increased risk of maternal and neonatal complications in hormone replacement therapy cycles in frozen embryo transfer Reprod Biol Endocrinol 2020 18 1 36 32366332 PMC7199365
  33. [34]Makhijani R Bartels C Godiwala P Bartolucci A Nulsen J Grow D Maternal and perinatal outcomes in programmed versus natural vitrified-warmed blastocyst transfer cycles Reprod BioMed Online 2020 41 2 300 308 32505542
  34. [35]Hu KL Zhang D Li R Endometrium preparation and perinatal outcomes in women undergoing single-blastocyst transfer in frozen cycles Fertil Steril 2021 115 6 1487 1494 33487443
  35. [36]Thygesen LC Ersboll AK When the entire population is the sample: strengths and limitations in register-based epidemiology Eur J Epidemiol 2014 29 8 551 558 24407880
  36. [38]Kumar S Gordon GH Abbott DH Mishra JS Androgens in maternal vascular and placental function: implications for preeclampsia pathogenesis Reproduction. 2018 156 5 R155 RR67 30325182 PMC6198264
  37. [39]Seely EW Solomon CG Insulin resistance and its potential role in pregnancy-induced hypertension J Clin Endocrinol Metab 2003 88 6 2393 2398 12788833
  38. [40]Taylor HS Pal L Seli E Fritz MA Speroff’s clinical gynecologic endocrinology and infertility 2020 9 Philadelphia Wolters Kluwer xiii, 1318
  39. [41]Chen JZ Sheehan PM Brennecke SP Keogh RJ Vessel remodelling, pregnancy hormones and extravillous trophoblast function Mol Cell Endocrinol 2012 349 2 138 144 22051447
  40. [42]Pereira MM Mainigi M Strauss JF Secretory products of the corpus luteum and preeclampsia Hum Reprod Update 2021 27 4 651 672 33748839 PMC8222764
  41. [43]Conrad KP Baker VL Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies Am J Phys Regul Integr Comp Phys 2013 304 2 R69 R72 PMC3543656 23100030
  42. [44]Conrad KP Rabaglino MB Post Uiterweer ED Emerging role for dysregulated decidualization in the genesis of preeclampsia Placenta. 2017 60 119 129 28693893 PMC5718949
  43. [45]von Versen-Hoynck F Strauch NK Liu J Chi YY Keller-Woods M Conrad KP Effect of mode of conception on maternal serum relaxin, creatinine, and sodium concentrations in an infertile population Reprod Sci 2019 26 3 412 419 29862889 PMC6728556
  44. [46]von Versen-Hoynck F Narasimhan P Selamet Tierney ES Martinez N Conrad KP Baker VL Absent or excessive corpus luteum number is associated with altered maternal vascular health in early pregnancy Hypertension. 2019 73 3 680 690 30636549 PMC6378337
  45. [47]Sacha CR Harris AL James K Basnet K Freret TS Yeh J Placental pathology in live births conceived with in vitro fertilization after fresh and frozen embryo transfer Am J Obstet Gynecol 2020 222 4 360 e1 360e16 31589863
  46. [49]Rolnik DL, Nicolaides KH, Poon LC. Prevention of preeclampsia with aspirin. Am J Obstet Gynecol. 2020. 32835720
  47. [50]Atallah A Lecarpentier E Goffinet F Doret-Dion M Gaucherand P Tsatsaris V Aspirin for prevention of preeclampsia Drugs. 2017 77 17 1819 1831 29039130 PMC5681618
  48. [51]Liu S Liston RM Joseph KS Heaman M Sauve R Kramer MS Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term CMAJ. 2007 176 4 455 460 17296957 PMC1800583
  49. [52]American College of O, Gynecologists, Society for Maternal-Fetal M Caughey AB Cahill AG Guise JM Safe prevention of the primary cesarean delivery Am J Obstet Gynecol 2014 210 3 179 193 24565430
  50. [53]Conrad KP Petersen JW Chi YY Zhai X Li M Chiu KH Maternal cardiovascular dysregulation during early pregnancy after in vitro fertilization cycles in the absence of a corpus luteum Hypertension. 2019 74 3 705 715 31352818 PMC6687559

Cited by

Sorted by citations

Authors
Lee, J. C., Badell, M. L., & Kawwass, J. F.
Affiliations
Emory University (US)
Corresponding author
Lee, Jacqueline C.
ORCID
Venue
Reproductive Biology and Endocrinology
Publisher
Springer Science and Business Media LLC
Published
2022-02-28
Volume
20
Issue
1
Pages
40-40
ISSN
1477-7827 (ISSN-L)
DOI
10.1186/s12958-021-00869-z
PMC
PMC8883648
OpenAlex
W4214647673
Cited by
41
References
3
Citations by year
2026: 6 · 2025: 12 · 2024: 10 · 2023: 7 · 2022: 6
FWCI
2.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Reproductive Biology and Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Assisted Reproductive Technology and Twin Pregnancy
  • Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
frozen embryo transfer, endometrial preparation, hypertensive disorders of pregnancy, perinatal outcomes, cesarean section, placenta accreta, postpartum hemorrhage, low birth weight, preterm birth, macrosomia, large for gestational age, premature rupture of membranes, assisted reproduction
MeSH terms
Embryo Transfer, Endometrium, Female, Humans, Infant, Newborn, Infertility, Pregnancy, Pregnancy Outcome, Reproductive Techniques, Assisted

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