Comparison of pregnancy outcomes between 4th day morula and 5th day blastocyst after embryo transfer: a retrospective cohort study.
Assisted reproduction
Blastocyst
Early follicular phase prolonged protocol
IVF/ICSI outcome
Morula
Journal
BMC pregnancy and childbirth
ISSN: 1471-2393
Titre abrégé: BMC Pregnancy Childbirth
Pays: England
ID NLM: 100967799
Informations de publication
Date de publication:
03 Jul 2024
03 Jul 2024
Historique:
received:
19
12
2023
accepted:
20
05
2024
medline:
4
7
2024
pubmed:
4
7
2024
entrez:
3
7
2024
Statut:
epublish
Résumé
This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05). When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.
Sections du résumé
BACKGROUND
BACKGROUND
This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5).
METHODS
METHODS
From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes.
RESULTS
RESULTS
In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05).
CONCLUSION
CONCLUSIONS
When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.
Identifiants
pubmed: 38961359
doi: 10.1186/s12884-024-06597-7
pii: 10.1186/s12884-024-06597-7
doi:
Types de publication
Journal Article
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
458Informations de copyright
© 2024. The Author(s).
Références
Gardner DK, Lane M. Culture and selection of viable blastocysts: a feasible proposition for human IVF? Hum Reprod Update. 1997;3(4):367–82.
pubmed: 9459282
doi: 10.1093/humupd/3.4.367
De Croo I, De Sutter P, Tilleman K. A stepwise approach to move from a cleavage-stage to a blastocyst-stage transfer policy for all patients in the IVF clinic. Hum Reprod Open. 2020;2020(3):hoaa034.
pubmed: 32995561
pmcid: 7508027
doi: 10.1093/hropen/hoaa034
Glujovsky D et al. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev, 2016(6): p. CD002118.
Long X, et al. Pregnancy outcomes of Single/Double blastocysts and cleavage embryo transfers: a Retrospective Cohort Study of 24,422 frozen-thawed cycles. Reprod Sci. 2020;27(12):2271–8.
pubmed: 32840740
doi: 10.1007/s43032-020-00247-x
Coticchio G, et al. The enigmatic morula: mechanisms of development, cell fate determination, self-correction and implications for ART. Hum Reprod Update. 2019;25(4):422–38.
pubmed: 30855681
doi: 10.1093/humupd/dmz008
Lagalla C, et al. Embryos with morphokinetic abnormalities may develop into euploid blastocysts. Reprod Biomed Online. 2017;34(2):137–46.
pubmed: 27938863
doi: 10.1016/j.rbmo.2016.11.008
Brison DR, Sturmey RG, Leese HJ. Metabolic heterogeneity during preimplantation development: the missing link? Hum Reprod Update. 2014;20(5):632–40.
pubmed: 24795173
doi: 10.1093/humupd/dmu018
Vassena R, et al. Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development. Development. 2011;138(17):3699–709.
pubmed: 21775417
pmcid: 4074286
doi: 10.1242/dev.064741
Sunderam, S., et al., Assisted Reproductive Technology Surveillance - United States, 2017. Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002), 2020. 69(9): p. 1–20.
doi: 10.15585/mmwr.ss6909a1
Duffy CR. Multifetal gestations and Associated Perinatal risks. NeoReviews. 2021;22(11):e734–46.
pubmed: 34725138
doi: 10.1542/neo.22-11-e734
Wang H, et al. Effects of changing culture medium on preimplantation embryo development in rabbit. Zygote. 2022;30(3):338–43.
pubmed: 34583788
doi: 10.1017/S0967199421000721
Swain JE. Controversies in ART: considerations and risks for uninterrupted embryo culture. Reprod Biomed Online. 2019;39(1):19–26.
pubmed: 31109893
doi: 10.1016/j.rbmo.2019.02.009
Zhao YY, Yu Y, Zhang XW. Overall blastocyst quality, Trophectoderm Grade, and inner cell Mass Grade predict pregnancy outcome in euploid blastocyst transfer cycles. Chin Med J (Engl). 2018;131(11):1261–7.
pubmed: 29786036
doi: 10.4103/0366-6999.232808
Wang L, et al. IVF embryo choices and pregnancy outcomes. Prenat Diagn. 2021;41(13):1709–17.
pubmed: 34480803
doi: 10.1002/pd.6042
Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod, 2011. 26(6):1270–83.
Tao J, et al. The neglected morula/compact stage embryo transfer. Hum Reprod. 2002;17(6):1513–8.
pubmed: 12042270
doi: 10.1093/humrep/17.6.1513
Fabozzi G, et al. Morphological assessment on day 4 and its prognostic power in selecting viable embryos for transfer. Zygote. 2016;24(4):477–84.
pubmed: 26350430
doi: 10.1017/S0967199415000404
Gardner DK, Schoolcraft WB. In vitro culture of human blastocyst. Towards reproductive certainty infertility & genetics beyond. 1999.
Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11(3):307–11.
pubmed: 10369209
doi: 10.1097/00001703-199906000-00013
Zhang HN, et al. Comparison of pregnancy outcomes between single-Morula embryo transfer and single-blastocyst transfer in fresh IVF/ICSI cycles. Med Sci Monit. 2021;27:e928737.
pubmed: 33566796
pmcid: 7884499
Simopoulou M, et al. Should the flexibility enabled by performing a day-4 embryo transfer remain as a valid option in the IVF laboratory? A systematic review and network meta-analysis. J Assist Reprod Genet. 2019;36(6):1049–61.
pubmed: 31111304
pmcid: 6603118
doi: 10.1007/s10815-019-01475-0
Strelchenko N, et al. Morula-derived human embryonic stem cells. Reprod Biomed Online. 2004;9(6):623–9.
pubmed: 15670408
doi: 10.1016/S1472-6483(10)61772-5
Hirate Y, et al. Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos. Curr Biology: CB. 2013;23(13):1181–94.
doi: 10.1016/j.cub.2013.05.014
Sang L, et al. Atlas of receptor genes expressed by the bovine morula and corresponding ligand-related genes expressed by uterine endometrium. Mol Reprod Dev. 2021;88(10):694–704.
pubmed: 34596291
pmcid: 8558826
doi: 10.1002/mrd.23534
Lesny P, et al. Uterine junctional zone contractions during assisted reproduction cycles. Hum Reprod Update. 1998;4(4):440–5.
pubmed: 9825859
doi: 10.1093/humupd/4.4.440
Maitre JL. Mechanics of blastocyst morphogenesis. Biol Cell. 2017;109(9):323–38.
pubmed: 28681376
doi: 10.1111/boc.201700029
Morbeck DE. Air quality in the assisted reproduction laboratory: a mini-review. J Assist Reprod Genet. 2015;32(7):1019–24.
pubmed: 26238385
pmcid: 4531860
doi: 10.1007/s10815-015-0535-x
Braga DP, et al. The importance of the cleavage stage morphology evaluation for blastocyst transfer in patients with good prognosis. J Assist Reprod Genet. 2014;31(8):1105–10.
pubmed: 24893729
pmcid: 4130936
doi: 10.1007/s10815-014-0266-4
SJ Phillips, NL Dean, WM Buckett, SL Tan. Consecutive transfer of day 3 embryos and of day 5–6 blastocysts increases overall pregnancy rates associated with blastocyst culture. Assisted Reproduction and Genetics. 2003;20:461-4.
doi: 10.1023/B:JARG.0000006708.26464.23
Luong TM, Le NQK. Artificial intelligence in time-lapse system: advances, applications, and future perspectives in reproductive medicine. J Assist Reprod Genet. 2024;41(2):239–52.
pubmed: 37880512
doi: 10.1007/s10815-023-02973-y
Tartia AP, et al. Time-lapse KIDScoreD5 for prediction of embryo pregnancy potential in fresh and vitrified-warmed single-embryo transfers. Reprod Biomed Online. 2022;45(1):46–53.
pubmed: 35523712
doi: 10.1016/j.rbmo.2022.03.019
Kang SM, et al. Clinical outcomes of elective single morula embryo transfer versus elective single blastocyst embryo transfer in IVF-ET. J Assist Reprod Genet. 2012;29(5):423–8.
pubmed: 22382643
pmcid: 3348276
doi: 10.1007/s10815-012-9736-8
Li RS, et al. Day 4 good morula embryo transfer provided compatible live birth rate with day 5 blastocyst embryo in fresh IVF/ET cycles. Taiwan J Obstet Gynecol. 2018;57(1):52–7.
pubmed: 29458903
doi: 10.1016/j.tjog.2017.12.008
Doron-Lalehzari A, et al. Are morphokinetic parameters of embryo development associated with adverse perinatal outcomes following fresh blastocyst transfer? Reprod Biomed Online. 2021;42(1):207–16.
pubmed: 33168490
doi: 10.1016/j.rbmo.2020.09.030
Souza R, et al. The influence of nutrients intake during pregnancy on baby’s birth weight: a systematic review. J Trop Pediatr. 2021;67(2):fmab034.
pubmed: 34059907
doi: 10.1093/tropej/fmab034
Hui D, et al. Morula transfer achieves better clinical outcomes than post-thawed cleavage embryos after overnight culture in frozen embryo transfer (FET) cycles. J Assist Reprod Genet. 2020;37(4):945–52.
pubmed: 32072380
pmcid: 7183030
doi: 10.1007/s10815-020-01708-7
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):270–81.
pubmed: 28322775
pmcid: 9761478
doi: 10.1016/j.ajog.2017.03.012
Blumenfeld Z. The ovarian hyperstimulation syndrome. Vitam Horm. 2018;107:423–51.
pubmed: 29544639
doi: 10.1016/bs.vh.2018.01.018
Xin ZM, et al. Pregnancy outcomes of day 5 embryo transfer in patients at high risk of developing ovarian hyperstimulation syndrome and analysis of factors affecting blastocyst formation. J Int Med Res. 2013;41(4):1127–34.
pubmed: 23847293
doi: 10.1177/0300060513485910
Vitagliano A, Paffoni A, Viganò P. Does maternal age affect assisted reproduction technology success rates after euploid embryo transfer? A systematic review and meta-analysis. Fertil Steril. 2023;120(2):251–65.
pubmed: 36878347
doi: 10.1016/j.fertnstert.2023.02.036
Sermondade N, et al. Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(4):439–51.
pubmed: 30941397
doi: 10.1093/humupd/dmz011
Liao Z, et al. The Effect of Endometrial thickness on pregnancy, maternal, and perinatal outcomes of women in fresh cycles after IVF/ICSI: a systematic review and Meta-analysis. Front Endocrinol (Lausanne). 2021;12:814648.
pubmed: 35222264
doi: 10.3389/fendo.2021.814648
Bedenk J, Vrtačnik-Bokal E, Virant-Klun I. The role of anti-Müllerian hormone (AMH) in ovarian disease and infertility. J Assist Reprod Genet. 2020;37(1):89–100.
pubmed: 31755000
doi: 10.1007/s10815-019-01622-7
Labarta E, et al. Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone. Hum Reprod. 2021;36(3):683–92.
pubmed: 33340402
doi: 10.1093/humrep/deaa322
Alyasin A, et al. Serum progesterone levels greater than 32.5 ng/ml on the day of embryo transfer are associated with lower live birth rate after artificial endometrial preparation: a prospective study. Reprod Biol Endocrinol. 2021;19(1):24.
pubmed: 33602270
pmcid: 7890906
doi: 10.1186/s12958-021-00703-6