Extended embryo culture in natural and modified cycles in assisted reproductive technology programs
DOI:
https://doi.org/10.37800/RM.3.2022.76-86Keywords:
assisted reproductive technologies (ART), natural cycle (NC), modified natural cycle (mNC), cleavage-stage, blastocyst-stage, extended cultivation, embryo transferAbstract
Relevance: About 20% of women undergoing assisted reproductive technology art (ART) programs encounter low responses following ovarian stimulation. One of the effective medical strategies for “poor” responders is to conduct IVF / ICSI programs in a natural or modified natural cycle. The application of extended embryo culture improved embryo selection, increased ART programs’ effectiveness, and reduced the number of embryos per transfer. But in the case of “poor” responders, the additional embryo selection by applying extended embryo culture may not be effective.
The study aimed to compare the effectiveness of ART programs with embryo transfer on the third or fifth day of development in natural and modified natural cycles.
Methods: This study included natural or modified natural IVF/ICSI cycles conducted in 2013-2019 at the Institute of Reproductive Medicine (Almaty, Kazakhstan). The patients who underwent natural or modified natural IVF/ICSI cycles were divided into two groups: group A (185 cycles), with embryo transfer on Day 3 of development, and group B (171 cycles), with extended embryo culture and embryo transfer on Day 5.
Results: The clinical pregnancy rate and implantation rate were significantly increased in group B (Day 5 embryo transfer) compared to group A (Day 3 embryo transfer): 25,7 and 22,1% vs. 15,14 and 12,72%, respectively (р<0,05). The ongoing pregnancy rate was significantly higher in group B: 21,9 vs. 8,1% (р<0,001). The miscarriage rate was higher in group A: 44,8 vs.14,3% (р<0,001). The live birth rate was significantly lower in group A: 8.11 vs. 21.9% (р<0,001).
Conclusion: Our study showed that blastocyst transfers are more effective in natural and modified natural cycles than cleavage-stage embryo transfers, even in the case of “poor” responders.
References
Xin Z.M., Xu B., Jin H.X., Song W.Y., Sun Y.P. Day 3 embryo transfer may have better pregnancy outcomes in younger than 35-year-old patients with poor ovarian response // J. Assist. Reprod. Genet. – 2012. – Vol. 29(10). – P. 1077-1081. https://doi.org/10.1007/s10815-012-9830-y
Montoya-Botero P., Polyzos N. The endometrium during and after ovarian hyperstimulation and the role of segmentation of infertility treatment // Best Pract. Res. Clin. End. Metab. – 2019. – Vol. 33(1). – P. 61-75. https://doi.org/10.1016/j.beem.2018.09.003
Di Guardo F., Blockeel C., De Vos M., Palumbo M., Christoforidis N., Tournaye H., Drakopoulos P. Poor ovarian response and the possible role of natural and modified natural cycles // Ther. Adv. Reprod. Health. – 2022. – Vol. 16. https://doi.org/10.1177/26334941211062026
Zegers-Hochschild F., Adamson G., Dyer S., Racowsky C., de Mouzon J., Sokol R., Rienzi L., Sunde A., Schmidt L., Cooke I., Simpson J., van der Poel S. The international glossary on infertility and fertility care, 2017 // Fertil. Steril. – 2017. – Vol. 108(3). – P. 393-406. https://doi.org/10.1016/j.fertnstert.2017.06.005
Youssef M., Wely van M., Al-Inany H., Madani T., Jahangiri N., Khodabakhshi S., Alhalabi M., Akhondi M., Ansaripour S., Tokhmechy R., Zarandi L., Rizk A., El-Mohamedy M., Shaeer E., Khattab M., Mochtar M., Veen van der F. A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial // Hum. Reprod. – 2017. – Vol. 32(1). – P. 112-118. https://doi.org/10.1093/humrep/dew282
Moffat R., Hansali C., Schoetzau A., Ahler A., Gobrecht U., Beutler S., Raggi A., Sartorius G., De Geyter C. Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders // Hum. Reprod. – 2021. – Vol. 36(4). – P. 987-997. https://doi.org/10.1093/humrep/deaa336
Maheshwari A., Hamilton M., Bhattacharya S. Should we be promoting embryo transfer at the blastocyst stage? // Repr. Biomed/ Online. – 2016. – Vol. 32(2). – P. 142-146. 1. https://doi.org/10.1016/j.rbmo.2015.09.016
Glujovsky D., Quinteiro R., Alvarez Sedo C., Ciapponi A., Cornelisse S., Blake D. Cleavage stage versus blastocyst-stage embryo transfer in assisted reproductive technology // Cochr. Data. of Syst. Rev. – 2022. – Vol. 19(5). – Art. ID: CD002118. https://doi.org/10.1002/14651858.CD002118.pub6
Neblett M., Kim T., Jones T., Baumgarten S., Coddington C., Zhao Y., Shenoy C. Is there still a role for a cleavage stage embryo transfer? // F. S. Rep. – 2021. – Vol. 29(3). – P. 269-274. https://doi.org/10.1016/j.xfre.2021.06.004.
Goldman R., Racowsky C., Farland L., Munné S., Ribustello L., Fox J. Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients // Hum. Reprod. – 2017. – Vol. 32(4). – P. 853-859. https://doi.org/10.1093/humrep/dex008
Orvieto R., Jonish-Grossman A., Maydan S., Noach-Hirsh M., Dratviman-Storobinsky O., Aizer A. Cleavage-stage human embryo arrest, is it embryo genetic composition or others? // Repr. Biol. End. – 2022. – Vol. 20(1). – P. 1-5. https://doi.org/10.1186/s12958-022-00925-2
Niakan K., Han J., Pedersen R., Simon C., Pera R. Human pre-implantation embryo development // Development. – 2012. – Vol. 139(5). – P. 829-841. https://doi.org/10.1242/dev.060426
Polyzos N., Corona R., Van De Vijver A., Blockeel C., Drakopoulos P., Vloeberghs V., De Vos M., Camus M., Humaidan P., Tournaye H. Corifollitropin alfa followed by hpHMG in GnRH agonist protocols. Two prospective feasibility studies in poor ovarian responders // Gyn. End. – 2015. – Vol. 31(11). – P. 885-890. https://doi.org/10.3109/09513590.2015.1065481
Zhang Y., Zhang C., Shu J., Guo J., Chang HM., Leung P., Sheng J-Z., Huang H. Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis // Hum. Reprod. Up. – 2020. – Vol. 26(2). – P. 247-263. https://doi.org/10.1093/humupd/dmz046
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. – Vol. 26(6). – P. 1270-1283. https://doi.org/10.1093/humrep/der037
Fernández-Shaw S., Cercas R., Braña C., Villas C., Pons I. Ongoing and cumulative pregnancy rate after cleavage stage versus blastocyst-stage embryo transfer using vitrification for cryopreservation: impact of age on the results // J. Assist. Reprod. Gen. – 2015. – Vol. 32(2). – P. 177-184. https://doi.org/10.1007/s10815-014-0387-9
Glujovsky D., Farquhar C. Cleavage-stage or blastocyst transfer: what are the benefits and harms? // Fertil. Steril. – 2016. – Vol. 106. – P. 244-250. https://doi.org/10.1016/j.fertnstert.2016.06.029
Martins W., Nastri C., Rienzi L., Poel van der S., Gracia C., Racowsky C. Blastocyst vs cleavage stage embryo transfer: systematic review and meta-analysis of reproductive outcomes // Ultra. Obstet. Gyn. – 2017. – Vol. 49. – P. 583-591. https://doi.org/10.1002/uog.17327
Kaur P., Swarankar M., Maheshwari M., Acharya V. A comparative study between cleavage stage embryo transfer at day 3 and blastocyst stage transfer at day 5 in in-vitro fertilization/intra-cytoplasmic sperm injection on clinical pregnancy rates // J. Hum. Repr. Sci. – 2014. – Vol. 7. – P. 194-197. https://doi.org/10.4103/0974-1208.142481
Canovas S., Ross P., Kelsey G., Coy P. DNA methylation in embryo development: epigenetic impact of ART (assisted reproductive technologies) // BioEssays. – 2017. – Vol. 39(11). – Art. ID: 1700106. https://doi.org/10.1002/bies.201700106
Barker D. The origins of the developmental origins theory // J. Int. Med. – 2007. – Vol. 261(5). – P. 412-417. https://doi.org/10.1111/j.1365-2796.2007.01809.x
Aljahdali A., Airina R., Velazquez M., Sheth B., Wallen K., Osmond C., Watkins A., Eckert J, Smyth N., Fleming T. The duration of embryo culture after mouse IVF differentially affects cardiovascular and metabolic health in male offspring // Hum. Reprod. – 2020. – Vol. 35(11). – P. 2497-2514. https://doi.org/10.1093/humrep/deaa205
Papanikolaou E., Kolibianakis E., Tournaye H., Venetis C., Fatemi H., Tarlatzis B., Devroey P. Live birth rates after transfer of an equal number of blastocysts or cleavage-stage embryos in IVF. A systematic review and meta-analysis // Hum. Reprod. – 2008. – Vol. 23(1). – P. 91-99. https://doi.org/10.1093/humrep/dem339
Haas J., Meriano J., Laskin C., Bentov Y., Barzilay E., Casper R., Cadesky K. Clinical pregnancy rate following frozen embryo transfer is higher with blastocysts vitrified on day 5 than on day 6 // J. Assist. Rep. Gen. – 2016. – Vol. 33(12). – P. 1553-1557. https://doi.org/10.1007/s10815-016-0818-x
Tannus S., Cohen Y., Henderson S, Ma’mari Al N., Shavit T., Son W-Y., Dahan M. Fresh transfer of day 5 slow-growing embryos versus deferred transfer of vitrified, fully expanded day 6 blastocysts: which is the optimal approach? // Hum. Reprod. – 2019. – Vol. 34(1). – P. 44-51. https://doi.org/10.1093/humrep/dey351
Polumiskova A., Shishimorova M., Tevkin S., Jussubaliyeva T., The best of the worst: analyze of outcome in artificial reproductive technologies (ART) fresh cycles with transfers of slow-growing embryos and expanded poor-quality blastocysts // Hum. Reprod. – 2022. – Vol. 37 (Suppl.1). – Art. ID: deac107.128. https://doi.org/10.1093/humrep/deac107.128
Chamayou S., Patrizio P., Storaci G., Tomaselli V., Alecci C., Ragolia C., Crescenzo C., Guglielmino A. The use of morphokinetic parameters to select all embryos with full capacity to implant // J. Assist. Reprod. Genet. – 2013. – Vol. 30(5). – P. 703-710. https://doi.org/10.1007/s10815-013-9992-2
Petersen B.M., Boel M., Montag M., Gardner D.K. Development of a generally applicable morphokinetic algorithm capable of predicting the implantation potential of embryos transferred on Day 3 // Hum. Reprod. – 2016. – Vol. 31(10). – P. 2231-2244. https://doi.org/10.1093/humrep/dew188
Bartolacci, A., Dal Canto M., Guglielmo M., Mura L., Brigante C., Mignini Renzini M., Buratini J. Early embryo morphokinetic is a better predictor of post-ICSI live birth than embryo morphology: Speed is more important than beauty at the cleavage stage // Zygote. – 2021. – Vol. 29(6). – P. 495-502. https://doi.org/10.1017/S0967199421000253
Nguyen D.P., Pham Q.T., Tran T.L, Vuong L.N., Ho T.M. Blastocyst Prediction of Day-3 Cleavage-Stage Embryos Using Machine Learning // Fertil. Reprod. – 2021. – Vol. 4. – P. 150-155. https://doi.org/10.1142/s266131822150016x
Kato K., Ueno S., Berntsen J., Kragh M.F., Okimura T., Kuroda T. Does embryo categorization by existing artificial intelligence, morphokinetic or morphological embryo selection models correlate with blastocyst euploidy rates? // Reprod. BioMed. Online. – 2022. – In press. https://doi.org/10.1016/j.rbmo.2022.09.010
Bori L., Meseguer F., Valera M.A., Galan A., Remohi J., Meseguer M. The higher the score, the better the clinical outcome: a retrospective evaluation of automatic embryo grading as a support tool for embryo selection in IVF laboratories // Hum. Reprod. – 2022. – Vol. 37(6). – P. 1148–1160. https://doi.org/10.1093/humrep/deac066
Mantzouratou A., Delhanty J. Aneuploidy in the human cleavage-stage embryo // Cytogen. Gen. Res. – 2011. – Vol. 133 (2-4). – P. 141-148. https://doi.org/10.1159/000323794
Maurer M., Ebner T., Puchner M., Mayer R.B., Shebl O., Oppelt P., Duba H.C. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest // Int J Fertil Steril. – 2015. – Vol. 9(3). – P. 346-353. https://doi.org/10.22074/ijfs.2015.4550
Munné S., Chen S., Colls P., Garrisi J., Zheng X., Cekleniak N., Lenzi M., Hughes P., Fischer J., Garrisi M., Tomkin G, Cohen J. Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos // Rep. Bio. Online. – 2007. – Vol. 14(5). – P. 628-634. https://doi.org/10.1016/s1472-6483(10)61057-7
Gu C., Li K., Li R., Li L., Li X., Dai X., He Y. Chromosomal Aneuploidy Associated with clinical characteristics of pregnancy loss // Front Genet. – 2021. – Vol. 12. – P. 667-697. https://doi.org/10.3389/fgene.2021.667697
Ouyang Y., Tan Y., Yi Y., Gong F., Lin G., Li X., Lu G. Correlation between a chromosomal distribution and embryonic findings on ultrasound in early pregnancy loss after IVF-embryo transfer // Hum. Reprod. – 2016. – Vol. 31(10). – P. 2212-2218. https://doi.org/10.1093/humrep/dew201
Downloads
Published
How to Cite
Issue
Section
License
The articles published in this Journal are licensed under the CC BY-NC-ND 4.0 (Creative Commons Attribution – Non-Commercial – No Derivatives 4.0 International) license, which provides for their non-commercial use only. Under this license, users have the right to copy and distribute the material in copyright but are not permitted to modify or use it for commercial purposes. Full details on the licensing are available at https://creativecommons.org/licenses/by-nc-nd/4.0/.