Thin endometrium in ART cycles — definition, diagnosis, causes, and pathogenesis. Part 1 (literature review)

Close metadata

Recommended articles:

The role of intergenic interactions in the formation of perinatal complications of gestational diabetes mellitus in pregnant women after assisted reproductive technologies. Russian Journal of Human Reproduction. 2024;(2):51-61

Assisted reproductive technologies and the risk of placenta accreta. Russian Journal of Human Reproduction. 2024;(3):43-49

Calcium-phosphorus metabolism and assisted reproductive technologies: intersection points. Russian Journal of Human Reproduction. 2024;(4):19-28

The dilemma of management of patients with endometrioma and infertility. Russian Journal of Human Reproduction. 2024;(4):29-37

The place of GnRH antagonists in modern ART programs: the possibilities of using of new drug of ganirelix. Russian Journal of Human Reproduction. 2024;(4):38-50

Regulatory control of gestagens use in Russia in the era of individualized luteal phase support for assisted reproduction cycles. Russian Journal of Human Reproduction. 2024;(4):59-70

Correlation dependence of tissue inhibitor of metalloproteinase-1 levels and follicular fluid morphology in patients with combined (uterine myoma and endometriosis) infertility in the ART-programs. Russian Bulletin of Obstetrician-Gynecologist. 2024;(4):21-28

Significance of cell therapy in treatment of patients with thin endometrium and Asherman’s syndrome. Russian Bulletin of Obstetrician-Gynecologist. 2024;(5):42-48

Comparative analysis of oocyte quality in patients with tubal-peritoneal genesis of infertility in assisted reproductive technology programs. Russian Bulletin of Obstetrician-Gynecologist. 2024;(6):41-49

The experience of using the nasal form of GnRH agonists in in vitro fertilization programs. Russian Bulletin of Obstetrician-Gynecologist. 2024;(6):79-84

Implanting a good quality blastocyst into the receptive endometrium is the key to a successful pregnancy. Poor susceptibility of the endometrium, along with insufficient thickness of the endometrium, is considered one of the main reasons for the lack of embryo implantation and one of the most difficult problems in the treatment of infertility using assisted reproductive technologies. The purpose of the literature review is to present up-to-date data on the definition, diagnosis and causes of thin endometrium, as well as on the pathogenesis of concomitant embryo implantation failures.

Keywords:

thin endometrium

assisted reproductive technology

endometrial receptivity

Authors:

Isakova E.V.

International center for reproductive medicine

ORCID: 0000-0003-4462-6606

Savina V.A.

International center for reproductive medicine

ORCID: 0000-0002-3252-0727

Received:

27.08.2020

Accepted:

01.11.2020

List of references:

Davidson LM, Coward K. Molecular mechanisms of membrane interaction at implantation. Birth Defects Research. Part C, Embryo Today: Reviews. 2016;108(1):19-32. https://doi.org/10.1002/bdrc.21122
Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nature Medicine. 2012;18(12):1754-1767. https://doi.org/10.1038/nm.3012
Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertility and Sterility. 2012;97(5):1039-1043. https://doi.org/10.1016/j.fertnstert.2012.03.010
Wilcox AJ, Baird DD, Weinberg CR. Time of Implantation of the Conceptus and Loss of Pregnancy. New English Journal of Medicine. 1999;340(23):1796-1799. https://doi.org/10.1056/NEJM199906103402304
Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Human Reproduction Update. 2012; 17(2):242-253. https://doi.org/10.1093/humupd/dmq037
Edwards RG. Human implantation: the last barrier in assisted reproduction technologies? Reproduction Biomedicine Online. 2006; 13(6):887-904. https://doi.org/10.1016/s1472-6483(10)61039-5
Liu KE, Hartman M, Hartman A, Luo Z-C, Mahutte N. The impact of a thin endometrial lining on fresh and frozen — thaw IVF outcomes: an analysis of over 40 000 embryo transfers. Human Reproduction. 2018;33(10):1883-1888. https://doi.org/10.1093/humrep/dey281
Wu Y, Gao X, Lu X, Xi J, Jiang S, Sun Y, Xi X. Endometrial thickness affects the outcome of in vitro fertilization and embryo transfer in normal responders after GnRH antagonist administration. Reproductive Biology and Endocrinology. 2014;12:96. https://doi.org/10.1186/1477-7827-12-96
Bu Z, Sun Y. The impact of endometrial thickness on the day of human chorionic gonadotrophin (hCG) administration on ongoing pregnancy rate in patients with different ovarian response. Public Library of Science One. 2015;10(12):e0145703. https://doi.org/10.1371/journal.pone.0145703
Liu KE, Hartman M, Hartman A. Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society. Reproductive Biomedicine Online. 2019;39(1):49-62. https://doi.org/10.1016/j.rbmo.2019.02.013
Zhao J, Huang G, Sun H, et al. Chinese expert consensus on diagnosis and management of abnormal endometrium in assisted reproductive technology. Journal of Reproductive Medicine. 2018;27: 1057-1064.
Kasius A, Smit JG, Torrance HL, Eijkemans MJ, Mol BW, Opmeer BC, Broekmans FJM. Endometrial thickness and pregnancy rates after IVF: A systematic review and meta-analysis. Human Reproduction Update. 2014;20(4):530-541. https://doi.org/10.1093/humupd/dmu011
Check JH, Dietterich C, Check ML, Katz Y. Successful delivery despite conception with a maximal endometrial thickness of 4 mm. Clinical and Experemental Obstetrics and Gynecology. 2003;30(2-3): 93-94.
Sundström P. Establishment of a successful pregnancy following in-vitro fertilization with an endometrial thickness of no more than 4 mm. Human Reproduction. 1998;13(6):1550-1552. https://doi.org/10.1093/humrep/13.6.1550
Holden EC, Dodge LE, Sneeringer R, Moragianni VA, Penzias AS, Hacker MR. Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women. Human Fertility Cambridge. 2018;21(4):298-293. https://doi.org/10.1080/14647273.2017.1334130
Craciunas L, Gallos I, Chu J, Bourne T, Quenby S, Brosens JJ, Coomarasamy A. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Human Reproduction Update. 2019;25(2):202-223. https://doi.org/10.1093/humupd/dmy044
Gallos ID, Khairy M, Chu J, Rajkhowa M, Tobias A, Campbell A, Dowell K, Fishel S, Coomarasamy A. Optimal endometrial thickness to maximize live births and minimize pregnancy losses: Analysis of 25,767 fresh embryo transfers. Reproductive BioMedicine Online. 2018;37(5):542-548. https://doi.org/10.1016/j.rbmo.2018.08.025
Bu Z, Wang K, Dai W, Sun Y. Endometrial Thickness Significantly Affects Clinical Pregnancy and Live Birth Rates in Frozen-Thawed Embryo Transfer Cycles. Gynecology and Endocrinology. 2016;32(7): 524-528. https://doi.org/10.3109/09513590.2015.1136616
Simón C, Gómez C, Cabanillas S, Vladimirov I, Castillón G, Giles J, Boynukalin K, Findikli N, Bahçeci M, Ortega I, Vidal C, Funabiki M, Izquierdo A, López L, Portela S, Frantz N, Kulmann M, Taguchi S, Labarta E, Colucci F, Mackens S, Santamaría X, Muñoz E,. Barrera S, García-Velasco JA, Fernández M, Ferrando M, Ruiz M, Mol BW, Valbuena D; ERA-RCT Study Consortium Group. A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reproductive Biomedicine Online. 2020;41(3):402-415.
Mahajan N. Endometrial receptivity array: Clinical application. Journal of Human Reproductive Sciences. 2015;8(3):121-129. https://doi.org/10.4103/0974-1208.165153
Bassil R, Casper R, Samara N, Hsieh TB, Barzilay E, Orvieto R, Haas J. Does the endometrial receptivity array really provide personalized embryo transfer? Journal of Assisted Reproduction and Genetics. 2018;35(7):1301. https://doi.org/10.1007/s10815-018-1190-9
Mahajan N, Sharma S. The endometrium in assisted reproductive technology: How thin is thin? Journal of Human Reproductive Sciences. 2016;9(1):3-8. https://doi.org/10.4103/0974-1208.178632
Bonilla-Musoles F, Raga F, Osborne NG, Castillo JC, Bonilla F. Endometrial receptivity: Evaluation with ultrasound. Ultrasound Quarterly. 2013;29(1):3-20. https://doi.org/10.1097/RUQ.0b013e318281b60a
Barker MA, Boehnlein LM, Kovacs P, Lindheim SR. Follicular and luteal phase endometrial thickness and echogenic pattern and pregnancy outcome in oocyte donation cycles. Journal of Assisted Reproduction and Genetics. 2009;26(5):243-249. https://doi.org/10.1007/s10815-009-9312-z
Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, Kolibianakis E, Kunicki M, La Marca A, Lainas G, Le Clef N, Massin N, Mastenbroek S, Polyzos N, Sunkara S, Timeva T, Töyli M, Urbancsek J, Vermeulen N, Broekmans F. Guideline of the European Society of Human Reproduction and Embryology. Ovarian stimulation for IVF/ICSI. Human Reproduction Open. 2020;2020(2): hoaa009. https://doi.org/10.1093/hropen/hoaa009
Puente E, Alonso L, Laganà AS, Ghezzi F, Casarin J, Carugno J. Chronic Endometritis: Old Problem, Novel Insights and Future Challenges. Fertility and Sterility. 2020;13(4):250-256. https://doi.org/10.22074/ijfs.2020.5779
Hooker AB, de Leeuw R, van de Ven PM, Bakkum EA, Thurkow AL, Vogel NEA, van Vliet HAAM, Bongers MY, Emanuel MH, Verdonkschot AEM, Brölmann HAM, Huirne JAF. Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: short-term outcomes of a multicenter, prospective randomized controlled trial. Fertility and Sterility. 2017;107(5): 1223-1231. https://doi.org/10.1016/j.fertnstert.2017.02.113
Strohmer H, Obruca A, Radner KM, Feichtinger W. Relationship of the individual uterine size and the endometrial thickness in stimulated cycles. Fertility and Sterility. 1994;61(5):972-975. https://doi.org/10.1016/S0015-0282(16)56716-8
Di Spiezio Sardo A, Calagna G, Scognamiglio M, O’Donovan P, Campo R, de Wilde RL. Prevention of intrauterine post-surgical adhesions in hysteroscopy. A systematic review. European Journal of Obstetrics and Gynecology and Reproducrive Biology. 2016;203: 182-192. https://doi.org/10.1016/j.ejogrb.2016.05.050
Heger A, Sator M, Walch K, Pietrowski D. Smoking Decreases Endometrial Thickness in IVF/ICSI Patients. Geburtshilfe und Frauenheilkunde. 2018;78(1):78-82. https://doi.org/10.1055/s-0043-123762
Sher G, Herbert C, Maassarani G, Jacobs MH. Assessment of the late proliferative phase endometrium by ultrasonography in patients undergoing in-vitro fertilization and embryo transfer (IVF/ET). Human Reproductive. 1991;6(2):232-237. https://doi.org/10.1093/oxfordjournals.humrep.a137312
Alfer J, Happel L, Dittrich R, Beckmann MW, Hartmann A, Gaumann A, Buck VU, Classen-Linke I. Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients? Geburtshilfe und Frauenheilkunde. 2017;77(7):756-764. https://doi.org/10.1055/s-0043-111899
Lessey BA, Damjanovich L, Coutifaris C, Castelbaum A, Albelda SM, Buck CA. Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. Journal of Clinical Investigation. 1992;90(1):188-195. https://doi.org/10.1172/JCI115835
Alfer J, Müller-Schöttle F, Classen-Linke I, von Rango U, Happel L, Beier-Hellwig K, Rath W, Beier HM. The endometrium as a novel target for leptin: differences in fertility and subfertility. Molecular Human Reproduction. 2000;6(7):595-601. https://doi.org/10.1093/humupd/4.5.539
Kojima K, Kanzaki H, Iwai M, Hatayama H, Fujimoto M, Inoue T, Horie K, Nakayama H, Fujita J, Mori T. Expression of leukemia inhibitory factor in human endometrium and placenta. Biology of Reproduction. 1994;50(4):882-887. https://doi.org/10.1095/biolreprod50.4.882
Gargett CE, Lederman FL, Lau TM, Taylor NH, Rogers PA. Lack of correlation between vascular endothelial growth factor production and endothelial cell proliferation in the human endometrium. Human Reproduction. 1999;14(8):2080-2088. https://doi.org/10.1093/humrep/14.8.2080
Miller PB, Parnell BA, Bushnell G, Tallman N, Forstein DA, Higdon HL 3rd, Kitawaki J, Lessey BA. Endometrial receptivity defects during IVF cycles with and without letrozole. Human Reproduction. 2012;27(3):881-888. https://doi.org/10.1093/humrep/der452
Serafini PC, Silva ID, Smith GD, Motta EL, Rocha AM, Baracat EC. Endometrial claudin-4 and leukemia inhibitory factor are associated with assisted reproduction outcome. Reproductive Biology and Endocrinology. 2009;7:30. https://doi.org/10.1186/1477-7827-7-30
Cascio S, Ferla R, D’Andrea A, Gerbino A, Bazan V, Surmacz E, Russo A. Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells. Journal of Cellular Physiology. 2009;221(1):189-194. https://doi.org/10.1002/jcp.21843
Adya R, Tan BK, Randeva HS. Differential effects of leptin and adiponectin in endothelial angiogenesis. Journal of Diabetes Research. 2015;2015:648239. https://doi.org/10.1155/2015/648239
Gonzalez RR, Leavis P. Leptin upregulates beta3-integrin expression and interleukin-1beta, upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures. Endocrine. 2001;16(1):21-28. https://doi.org/10.1385/ENDO:16:1:21
Carino C, Olawaiye AB, Cherfils S, Serikawa T, Lynch MP, Rueda BR, Gonzalez RR. Leptin regulation of proangiogenic molecules in benign and cancerous endometrial cells. The International Journal of Cancer. 2008;123(12):2782-2790. https://doi.org/10.1002/ijc.23887
Rosario GX, Hondo E, Jeong JW, Mutalif R, Ye X, Yee LX, Stewart CL. The LIF-mediated molecular signature regulating murine embryo implantation. Biology of Reproduction. 2014;91(3):66. https://doi.org/10.1095/biolreprod.114.118513
Kim EY, Choi HJ, Chung TW, Choi JY, Kim HS, Jung YS, Lee SO, Ha KT. Water-extracted Perilla frutescens increases endometrial receptivity though leukemia inhibitory factor-dependent expression of integrins. Journal of Pharmacological Science. 2016;131(4):259-266. https://doi.org/10.1016/j.jphs.2016.07.004
Senger DR, Ledbetter SR, Claffey KP, Papadopoulos-Sergiou A, Peruzzi CA, Detmar M. Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. The American Journal of Pathology. 1996;149(1):293-305.
Hambartsoumian E. Endometrial leukemia inhibitory factor (LIF) as a possible cause of unexplained infertility and multiple failures of implantation. The American Journal of Reproductive Immunology. 1998;39(2):137-143. https://doi.org/10.1111/j.1600-0897.1998.tb00345.x
Piccinni MP, Beloni L, Livi C, Maggi E, Scarselli G, Romagnani S. Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions. Nature Medicine. 1998;4(9):1020-1024. https://doi.org/10.1038/2006
Tawfeek MA, Eid MA, Hasan AM, Mostafa M, El-Serogy HA. Assessment of leukemia inhibitory factor and glycoprotein 130 expression in endometrium and uterine flushing: a possible diagnostic tool for impaired fertility. BMC Womens Health. 2012;12:10. https://doi.org/10.1186/1472-6874-12-10
Bouloumié A, Drexler HC, Lafontan M, Busse R. Leptin, the product of Ob gene, promotes angiogenesis. Circulation Research. 1998; 83(10):1059-1066. https://doi.org/10.1161/01.res.83.10.1059
Banerjee P, Jana SK, Pasricha P, Ghosh S, Chakravarty B, Chaudhury K. Proinflammatory cytokines induced altered expression of cyclooxygenase-2 gene results in unreceptive endometrium in women with idiopathic recurrent spontaneous miscarriage. Fertility and Sterility. 2013;99(1):179-187.e2. https://doi.org/10.1016/j.fertnstert.2012.08.034
Würfel W. Treatment with granulocyte colony-stimulating factor in patients with repetitive implantation failures and/or recurrent spontaneous abortions. Journal of Reproductive Immunology. 2015;108: 123-135. https://doi.org/10.1016/j.jri.2015.01.010
Zhao Y, Rong H, Chegini N. Expression and selective cellular localization of granulocyte-macrophage colony-stimulating factor (GM-CSF) and GM-CSF alpha and beta receptor messenger ribonucleic acid and protein in human ovarian tissue. Biology of Reproduction. 1995;53(4):923-930. https://doi.org/10.1095/biolreprod53.4.923
Giacomini G, Tabibzadeh SS, Satyaswaroop PG, Bonsi L, Vitale L, Bagnara GP, Strippoli P, Jasonni VM. Epithelial cells are the major source of biologically active granulocyte macrophage colony-stimulating factor in human endometrium. Human Reproductive. 1995;10(12):3259-3263. https://doi.org/10.1093/oxfordjournals.humrep.a135899
Cai L, Jeon Y, Yoon JD, Hwang SU, Kim E, Park KM, Kim KJ, Jin MH, Lee E, Kim H, Jeung EB, Hyun SH. The effects of human recombinant granulocyte-colony stimulating factor treatment during in vitro maturation of porcine oocyte on subsequent embryonic development. Theriogenology. 2015;84(7):1075-1087. https://doi.org/10.1016/j.theriogenology.2015.06.008
Rahmati M, Petitbarat M, Dubanchet S, Bensussan A, Chaouat G, Ledee N. Granulocyte-colony stimulating factor related pathways tested on an endometrial ex vivo model. Public Library of Science One. 2014;9(9):e102286. https://doi.org/10.1371/journal.pone.0102286
Salmassi A, Schmutzler AG, Schaefer S, Koch K, Hedderich J, Jonat W, Mettler L. Is granulocyte colony-stimulating factor level predictive for human IVF outcome? Human Reproduction. 2005; 20(9):2434-2440. https://doi.org/doi.org/10.1093/humrep/dei071
Maekawa R, Taketani T, Mihara Y, Sato S, Okada M, Tamura I, Jozaki K, Kajimura T, Asada H, Tamura H, Takasaki A, Sugino N. Thin endometrium transcriptome analysis reveals a potential mechanism of implantation failure. Reproductive Medicine and Biology. 2017;16(2):206-227. https://doi.org/10.1002/rmb2.12030
Le AW, Wang ZH, Yuan R, Shan LL, Xiao TH, Zhuo R, Shen Y. Association of the estrogen receptor-β gene RsaI and AluI polymorphisms with human idiopathic thin endometrium. Genetic and Molecular Research. 2013;12(4):5978-5985. https://doi.org/10.4238/2013.november.26.7

Close metadata