Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-669899f699-tpknm Total loading time: 0 Render date: 2025-05-04T16:59:07.672Z Has data issue: false hasContentIssue false

Chapter 5 - Implantation

Published online by Cambridge University Press:  16 April 2025

By
Emma Lucas  and
Nick S. Macklon
Edited by
Roy G. Farquharson ,
Mary D. Stephenson  and
Mariëtte Goddijn
Roy G. Farquharson
Affiliation:
Liverpool Women’s Hospital
Mary D. Stephenson
Affiliation:
University of Illinois, Chicago
Mariëtte Goddijn
Affiliation:
Amsterdam University Medical Centers
Get access

Summary

The apparent inefficiency of human Implantation remains perplexing and is the cause of much distress when it occurs in the context of fertility treatments. Many of the prevailing paradigms that have shaped our understanding of implantation have been extrapolated from imperfect animal models, but in recent years in-vitro models have revealed novel insights into the role of the endometrium as an active, rather than passive participant in implantation. Evidence has emerged of the existence of a biosensor function ascribed to the decidualised endometrial stroma which allows for a maternal strategy of rejecting poorly viable embryos. In this chapter, this new understanding of the regulation of implantation and of the aetiology of recurrent miscarriage is addressed and implications for clinical management are considered.

Keywords

Implantationembryoearly pregnancydecidualizationimplantation failuremiscarriage
Type
Chapter
Information
Early Pregnancy , pp. 32 - 42
Publisher: Cambridge University Press
Print publication year: 2025

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Manders, M., McLindon, L., Schulze, B., Beckmann, M. M., Kremer, J. A. M., Farquhar, C.. Timed intercourse for couples trying to conceive. Cochrane Database Syst Rev. 2015;17(3):CD011345.Google Scholar
Stanford, J. B., Willis, S. K., Hatch, E. E., Rothman, K. J., Wise, L. A.. Fecundability in relation to use of mobile computing apps to track the menstrual cycle. Hum Reprod. 2020;35(10):2245–52.CrossRefGoogle ScholarPubMed
Wilcox, A. J., Harmon, Q., Doody, K., Wolf, D. P., Adashi, E. Y.. Preimplantation loss of fertilized human ova: estimating the unobservable. Hum Reprod. 2020;35(4):743–50.CrossRefGoogle ScholarPubMed
Wilcox, A. J., Weinberg, C. R., O’Connor, J. F., Baird, D. D., Schlatterer, J. P., Canfield, R. E., et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319(4):189–94.CrossRefGoogle ScholarPubMed
Vanneste, E., Voet, T., Le Caignec, C., Ampe, M., Konings, P., Melotte, C., et al. Chromosome instability is common in human cleavage-stage embryos. Nat Med. 2009;15(5):577–83.CrossRefGoogle ScholarPubMed
McCoy, R. C.. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm. Trends Genet. 2017;33(7):448–63.CrossRefGoogle ScholarPubMed
Gleicher, N., Patrizio, P., Mochizuki, L., Barad, D. H.. Previously reported and here added cases demonstrate euploid pregnancies followed by PGT-A as “mosaic” as well as “aneuploid” designated embryos. Reprod Biol Endocrinol. 2023;21(1):25.CrossRefGoogle ScholarPubMed
Greco, E., Minasi, M. G., Fiorentino, F.. Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N Engl J Med. 2015;373(21):2089–90.CrossRefGoogle ScholarPubMed
Hardy, K., Hardy, P. J., Jacobs, P. A., Lewallen, K., Hassold, T. J.. Temporal changes in chromosome abnormalities in human spontaneous abortions: results of 40 years of analysis. Am J Med Genet. 2016;170(10):2671–80.CrossRefGoogle Scholar
Hardy, P. J., Hardy, K.. Chromosomal instability in first trimester miscarriage: a common cause of pregnancy loss? Transl Pediatr. 2018;7(3):211–18.CrossRefGoogle ScholarPubMed
Kolte, A. M., Westergaard, D., Lidegaard, Ø., Brunak, S., Nielsen, H. S.. Chance of live birth: a nationwide, registry-based cohort study. Hum Reprod. 2021;36(4):1065–73.CrossRefGoogle ScholarPubMed
Muter, J., Kong, C.-S., Brosens, J. J.. The role of decidual subpopulations in implantation, menstruation and miscarriage. Front Reprod Health. 2021;3:804921.CrossRefGoogle ScholarPubMed
Brosens, J. J., Salker, M. S., Teklenburg, G., Nautiyal, J., Salter, S., Lucas, E. S., et al. Uterine selection of human embryos at implantation. Sci Rep. 2014;4:3894.CrossRefGoogle ScholarPubMed
Ma, Y., Zhang, P., Wang, F., Yang, J., Yang, Z., Qin, H.. The relationship between early embryo development and tumourigenesis. J Cell Mol Med. 2010;14(12):2697–701.CrossRefGoogle ScholarPubMed
Muter, J., Lynch, V. J., McCoy, R. C., Brosens, J. J.. Human embryo implantation. Development. 2023;150(10):dev201507.CrossRefGoogle ScholarPubMed
Macklon, N., Brosens, J. J.. Decidualization and recurrent miscarriage. In Farquharson, R. G., Stephenson, M. D., eds., Early pregnancy. 2nd ed.: Cambridge University Press; 2017.Google Scholar
Gellersen, B., Brosens, I. A., Brosens, J. J.. Decidualization of the human endometrium: mechanisms, functions, and clinical perspectives. Semin Reprod Med. 2007;25(6):445–53.CrossRefGoogle ScholarPubMed
Salker, M. S., Nautiyal, J., Steel, J. H., Webster, Z., Šucurović, S., Nicou, M., et al. Disordered IL-33/ST2 activation in decidualizing stromal cells prolongs uterine receptivity in women with recurrent pregnancy loss. PloS One. 2012;7(12):e52252.CrossRefGoogle ScholarPubMed
Lucas, E. S., Vrljicak, P., Muter, J., Diniz-da-Costa, M. M., Brighton, P. J., Kong, C.-S., et al. Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Commun Biol. 2020;3(1):37.CrossRefGoogle ScholarPubMed
Lucas, E. S., Dyer, N. P., Murakami, K., Lee, Y. H., Chan, Y.-W., Grimaldi, G., et al. Loss of endometrial plasticity in recurrent pregnancy loss. Stem Cells. 2016;34(2):346–56.CrossRefGoogle ScholarPubMed
Brighton, P. J., Maruyama, Y., Fishwick, K., Vrljicak, P., Tewary, S., Fujihara, R., et al. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. eLife. 2017;6.CrossRefGoogle ScholarPubMed
Hertig, A. T., Rock, J., Adams, E. C.. A description of 34 human ova within the first 17 days of development. Am J Anat. 1956;98(3):435–93.CrossRefGoogle ScholarPubMed
Siriwardena, D., Boroviak, T. E.. Evolutionary divergence of embryo implantation in primates. Philos Trans R Soc Lond B Biol Sci. 2022;377(1865):20210256.CrossRefGoogle ScholarPubMed
Mika, K., Lynch, V. J.. Transposable elements continuously remodel the regulatory landscape, transcriptome, and function of decidual stromal cells. Genome Biol Evol. 2022;14(12):evac164.CrossRefGoogle ScholarPubMed
Carter, A. M., Enders, A. C., Pijnenborg, R.. The role of invasive trophoblast in implantation and placentation of primates. Philos Trans R Soc Lond B Biol Sci. 2015;370(1663):20140070.CrossRefGoogle ScholarPubMed
Lee, K. Y., DeMayo, F. J.. Animal models of implantation. Reproduction. 2004;128(6):679–95.CrossRefGoogle ScholarPubMed
Raja, E. A., Bhattacharya, S., Maheshwari, A., McLernon, D. J.. A comparison of perinatal outcomes following fresh blastocyst or cleavage stage embryo transfer in singletons and twins and between singleton siblings. Hum Reprod Open. 2023;2023(2):hoad003.CrossRefGoogle ScholarPubMed
Aplin, J. D., Ruane, P. T.. Embryo-epithelium interactions during implantation at a glance. J Cell Sci. 2017;130(1):15–22.CrossRefGoogle ScholarPubMed
Schlafke, S., Enders, A. C.. Cellular basis of interaction between trophoblast and uterus at implantation. Biol Reprod. 1975;12(1):41–65.CrossRefGoogle ScholarPubMed
Enders, A. C., Schlafke, S.. Cytological aspects of trophoblast-uterine interaction in early implantation. Am J Anat. 1969;125(1):1–29.CrossRefGoogle ScholarPubMed
Ruan, Y. C., Chen, H., Chan, H. C.. Ion channels in the endometrium: regulation of endometrial receptivity and embryo implantation. Human Reprod Update. 2014;20(4):517–29.CrossRefGoogle ScholarPubMed
Myers, K. M., Elad, D.. Biomechanics of the human uterus. Wiley Interdiscip Rev Syst Biol Med. 2017;9(5).CrossRefGoogle ScholarPubMed
Ezzati, M., Djahanbakhch, O., Arian, S., Carr, B. R.. Tubal transport of gametes and embryos: a review of physiology and pathophysiology. J Assist Reprod Genet. 2014;31(10):1337–47.CrossRefGoogle ScholarPubMed
Lang, F., Rajaxavier, J., Singh, Y., Brucker, S. Y., Salker, M. S.. The enigmatic role of serum & glucocorticoid inducible kinase 1 in the endometrium. Front Cell Dev Biol. 2020;8:556543.CrossRefGoogle ScholarPubMed
Salker, M. S., Christian, M., Steel, J. H., Nautiyal, J., Lavery, S., Trew, G., et al. Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure. Nat Med. 2011;17(11):1509–13.CrossRefGoogle ScholarPubMed
Levi, N., Papismadov, N., Solomonov, I., Sagi, I., Krizhanovsky, V.. The ECM path of senescence in aging: components and modifiers. FEBS J. 2020;287(13):2636–46.CrossRefGoogle ScholarPubMed
Rawlings, T. M., Makwana, K., Taylor, D. M., Molè, M. A., Fishwick, K. J., Tryfonos, M., et al. Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids. eLife. 2021;10:e69603.CrossRefGoogle Scholar
Ruane, P. T., Garner, T., Parsons, L., Babbington, P. A., Wangsaputra, I., Kimber, S. J., et al. Trophectoderm differentiation to invasive syncytiotrophoblast is promoted by endometrial epithelial cells during human embryo implantation. Hum Reprod. 2022;37(4):777–92.CrossRefGoogle ScholarPubMed
Weimar, C. H., Kavelaars, A., Brosens, J. J., Gellersen, B., de Vreeden-Elbertse, J. M. T., Heijnen, C. J., et al. Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos. PloS One. 2012;7(7):e41424.CrossRefGoogle ScholarPubMed
Teklenburg, G., Salker, M., Molokhia, M., Lavery, S., Trew, G., Aojanepong, T., et al. Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. PloS One. 2010;5(4):e10258.CrossRefGoogle ScholarPubMed
Kong, C.-S., Ordonez, A. A., Turner, S., Tremaine, T., Muter, J., Lucas, E. S., et al. Embryo biosensing by uterine natural killer cells determines endometrial fate decisions at implantation. FASEB J. 2021;35(4):e21336.CrossRefGoogle ScholarPubMed
Berkhout, R. P., Keijser, R., Repping, S., Lambalk, C. B., Afink, G. B., Mastenbroek, S., et al. High-quality human preimplantation embryos stimulate endometrial stromal cell migration via secretion of microRNA hsa-miR-320a. Hum Reprod. 2020;35(8):1797–807.CrossRefGoogle ScholarPubMed
Berkhout, R. P., Lambalk, C. B., Huirne, J., Mijatovic, V., Repping, S., Hamer, G., et al. High-quality human preimplantation embryos actively influence endometrial stromal cell migration. J Assist Reprod Genet. 2018;35(4):659–67.CrossRefGoogle ScholarPubMed
Orlando, J., Coulam, C.. Is superfertility associated with recurrent pregnancy loss? Am J Reprod Immunol. 2014;72(6):549–54.CrossRefGoogle ScholarPubMed
ESHRE Working Group on Recurrent Implantation Failure, Cimadomo, D., de Los Santos, M. J., Griesinger, G., Lainas, G., Le Clef, N., et al. ESHRE good practice recommendations on recurrent implantation failure. Hum Reprod Open. 2023;2023(3):hoad023.Google ScholarPubMed
Moser, G., Huppertz, B.. Implantation and extravillous trophoblast invasion: from rare archival specimens to modern biobanking. Placenta. 2017;56:19–26.CrossRefGoogle ScholarPubMed
Noyes, R. W., Hertig, A. T., Rock, J.. Reprint of: dating the endometrial biopsy. Fertil Steril. 2019;112(4 Suppl 1):e93–115.CrossRefGoogle ScholarPubMed
Capalbo, A., Poli, M., Rienzi, L., Girardi, L., Patassini, C., Fabiani, M., et al. Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial. Am J Hum Genet. 2021;108(12):2238–47.CrossRefGoogle Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×