The thin endometrium in the aspect of reproductive failures: The current problem or hyperdiagnosis?

Efendieva Z.N., Apolikhina I.A., Kalinina E.A.

1) I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia 2) Acad. V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia
The authors have carried out a systematic analysis of the data given in the world literature on the role of the thin endometrium in the aspect of reproductive failures. The review includes the results of studies and metaanalyses published in the PubMed journals on this topic. Modern literature presents various data on the minimum endometrial thickness necessary for pregnancy during the implantation window. The absence of a universal marker of endometrial receptivity and a set of many factors influencing the effectiveness of embryo-endometrial interactions make it difficult to analyze and identify the true causes of reproductive failures in patients with endometrial thinning, which requires further investigations in this area.

Keywords

thin endometrium
implantation failures
endometrial receptivity
infertility
in vitro fertilization

References

  1. Федеральная служба государственной статистики. Демография. Численность и состав населения. Электронный ресурс. Доступ: [Federal’naya sluzhba gosudarstvennoi statistiki. Demografiya. Chislennost’ i sostav naseleniya. Elektronnyi resurs. Dostup: http://www.gks.ru(In Ruaaian)]
  2. Корнеева И.Е. Современная концепция диагностики и лечения бесплодия в браке: автореф. дисс. … д-ра мед. наук. М., 2006. [Korneeva I.E. Sovremennaya kontseptsiya diagnostiki i lecheniya besplodiya v brake: avtoref. diss. … d-ra med. nauk. M., 2006. (In Russian)
  3. Maekawa R., Taketani T., Mihara Y., Sato S., Okada M et al. Thin endometrium transcriptome analysis reveals a potential mechanism of implantation failure. Reprod Med Biol 2017; 16: 206-227.
  4. Miwa I., Tamura H., Takasaki A., Yamagata Y., Shimamura K., Sugino N. Pathophysiologic features of «thin» endometrium. Fertil Steril. 2009; 91: 998-1004.
  5. Wu Y., Gao X., Lu X. et al. Endometrial thickness affects the outcome of in vitro fertilization and embryo transfer in normal responders after GnRH antagonist administration. Reprod Biol Endocrinol. 2014; 12: 96.
  6. Ginsburg E.S., Racowsky C. (eds). In Vitro Fertilization: A comprehensive guide. New York: Springer + Business Media. N.Y., 2012.
  7. Amui J., Check J.H., Cohen R. Successful twin pregnancy in a donor oocyte recipient despite a maximum endometrial thickness in the late proliferative phase of 4 mm. Clin Exp Obstet Gynecol. 2011; 38: 328-329.
  8. Shufaro Y., Simon A., Laufer N., Fatum M. Thin unresponsive endometrium – a possible complication of surgical curettage compromising ART outcome. J. Assist Reprod Genet. 2008; 25: 421-425.
  9. Basir G.S., O W.S., So W.W., Ng E.H., Ho P.C. Evaluation of cycle-to-cycle variation of endometrial responsiveness using transvaginal sonography in women undergoing assisted reproduction. Ultrasound Obstet Gynecol. 2002; 19(5): 484-489.
  10. Barker M.A., Boehnlein L.M., Kovacs P., Lindheim S.R. Follicular and luteal phase endometrial thickness and echogenic pattern and pregnancy outcome in oocyte donation cycles. J Assist Reprod Genet. 2009; 26: 243-249.
  11. Kasius A., Smit J.G., Torrance H.L., Eijkemans M.J., Mol B.W., Opmeer B.C., et al. Endometrial thickness and pregnancy rates after IVF: A systematic review and meta-analysis. Hum Reprod Update. 2014; 20: 530-541.
  12. Coelho Neto M.A., Martins W.P., Lima M.L. S., Barbosa M.A.P., Nastri C.O., Ferriani R.A. et al. Ovarian response is a better predictor of clinical pregnancy rate following embryo transfer than is thin endometrium or presense of an endometrioma. Ultrasound Obstet Gynecol. 2015; 46;501-505.
  13. Amir W., Micha B., Ariel H., Liat L.G., Jehoshua D., Adrian S. Predicting factors for endometrial thickness during treatment with assisted reproductive technology. Fertil Steril. 2007; 87: 799-804.
  14. Dix E., Check J.H. Successful pregnancies following embryo transfer despite very thin late proliferative endometrium. Clin Exp Obstet Gynecol. 2010; 37(1): 15-16.
  15. Check J.H., Cohen R. Live fetus following embryo transfer in a woman with diminished egg reserve whose maximal endometrial thickness was less than 4 mm. Clin Exp Obstet Gynecol. 2011; 38: 330-332.
  16. Check J.H., Cohen R., Wilson C. et al. Very thin endometrial in the late proliferative phase is more associated with poor pregnancy rates following controlled ovarian hyperstimulation than graduated estradiol regimens used for frozen embryo transfer. Fertil Steril. 2014; 101: e21.
  17. Zhang T., Li Z., Ren X., Huang B., Zhu G. et al. Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles. Medicine. 2018; 97: 4 (e9689).
  18. Kumbak B., Erden H.F., Tosun S. et al. Outcome of assisted reproduction treatment in patients with endometrial thickness less than 7 mm. Reprod Biomed Online. 2009; 18: 79-84.
  19. Merce L.T., Barco M.J., Bau S., Troyano J. Are endometrial parameters by three-dimensional ultrasound and power Doppler angiography related to in vitro fertilization/embryo transfer outcome? Fertil Steril. 2008; 89: 111-117.
  20. Chen S.L., Wu F.R., Luo C., Chen X., Shi X.Y., Zheng H.Y., Ni Y.P. Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertilization and embryo transfer: a retrospective cohort study. Reprod Biol Endocrinol. 2010; 24: 30.
  21. Таболова В.К., Корнеева И.Е., Донников А.Е., Бурменская О.В., Маслова М.А., Смольникова В.Ю. Профиль локальной экспрессии генов ростовых факторов и цитокинов в эндометрии периода «имплантационного окна» при хроническом эндометрите. Акушерство и гинекология. 2014; 12: 74-78. [Tabolova V.K., Korneeva I.E., Donnikov A.E., Burmenskaya O.V., Maslova M.A., Smol’nikova V.Yu. Profil’ lokal’noi ekspressii genov rostovykh faktorov i tsitokinov v endometrii perioda «implantatsionnogo okna» pri khronicheskom endometrite. Akusherstvo i ginekologiya. 2014; 12: 74-78.(In Russian)]
  22. Johnston‐MacAnanny E.B., Hartnett J., Engmann L.L., Nulsen J.C., Sanders M.M., Benadiva C.A. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril. 2010; 93: 437-441.
  23. Kaisus J.C., Broekmans F.J., Sie-Go D.M., Bourgain C., Eijkemans M.J., Fauser B.C. et al. The reliability of the histological diagnosis of endometritis in asymptomatic IVF cases: a multicenter observer study. Human Reprod. 2012; 27: 153-158.
  24. Sharma S., Rani G., Bose G., Saha I., Bathwal S.N. Tamoxifen is Better than Low-Dose Clomiphene or Gonadotropins in Women with Thin Endometrium (<7 mm) after Clomiphene in Intrauterine Insemination Cycles: A Prospective Study. J Hum Reprod Sci. 2018 Jan-Mar; 11 (1): 34-39.
  25. Casper R.F. It’s time to pay attention to the endometrium. Fertil Steril. 2011; 96 (3), 519-521.
  26. Боярский К.Ю., Гайдуков С.Н., Пальченко Н.А. Современный взгляд на проблему рецептивности и тонкого эндометрия в программах ВРТ (обзор литературы). Проблемы репродукции. 2013; 4: 51-60. [Boyarskii K.Yu.,Gaidukov S.N., Pal’chenko N.A. Sovremennyi vzglyad na problemu retseptivnosti i tonkogo endometriya v programmakh VRT (obzor literatury). Problemy reproduktsii. 2013; 4: 51-60. (In Russian)]
  27. Rossman I., Bartelmez G.W. The injection of the blood vascular system of the uterus. Anat Rec 1957; 128: 223-231.
  28. Catt J.W., Henman M. Toxic effects of oxygen on human embryo development. Hum Reprod. 2000; 15 (Suppl2): 199-206.
  29. Basir G.S., Lam T.P.,O W.S., Chau M.T., Ng E.H., Ho P.C. Cycle-to-cycle variation in utero-ovarian hemodynamic indices in ovarian stimulation cycles of the same women and its effects on the outcome of assisted reproduction treatment. Fertil Steril. 2002; 78: 1055-1060.
  30. Alfer J., Happel L., Dittrich R., Beckmann M.W., Hartmann A. et al. Insufficient angiogenesis: cause of abnormally thin endometrium in subfertile patients? Geburtsh Frauenheilk. 2017; 77: 756-764.
  31. Xu B., Zhang Q., Hao J., Xu D., Li Y. Two protocols to treat thin endometrium with grnulocyte colonystimulating factor during frozen embryo transfer cycles. Reprod. Biomed. Online. 2015; 30: 349-358.
  32. Львова А.В. Эффективность лечения «тонкого» эндометрия при маточной форме бесплодия и невынашивания беременности. Дисс. ... канд. мед. наук. М., 2018. [L’vova A.V. Effektivnost’ lecheniya «tonkogo» endometriya pri matochnoi forme besplodiya i nevynashivaniya beremennosti. Diss. ... kand. med. nauk. M., 2018. (In Russian)]
  33. Quinn C.E., Casper R.F. Pinopodes: a queslionable role in endometrial receptivity. Hum Reprod Update. 2009; 15: 229-236. (In Russian)]
  34. Quinn C., Ryan E., Claessens E.A., Greenblatt E., Hawrylyshyn P., Cruickshank B. et al. The presence of pinopodes in the human endometrium does not delineate the implantation window. Fertil Steril. 2007; 87: 1015-1021.
  35. Mahajan N. Endometrial receptivity array: clinical application. J Hum Reprod Sci. 2015; 8(3): 121–9.
  36. Применение эстрогенов в программах ВРТ. Научно-практические рекомендации. РАРЧ. 2015 г. [Primenenie estrogenov v programmakh VRT. Nauchno-prakticheskie rekomendatsii. RARCh. 2015 g. (In Russian)]
  37. Lazzarin N., Vaquero E., Exacoustos C. et al. Low-dose aspirin and omega-3 fatty acids improve uterine artery blood flow velocity in women with recurrent miscarriage due to impaired uterine perfusion. Fertil Steril. 2009; 92: 296-300.
  38. Takasaki A., Tamura H., Miwa I., Taketani T., Shimamura K., Sugino N. Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil Steril 2010; 93: 1851-1858.
  39. Acharya S., Yasmin E., Balen A.H. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies – a report of 20 cases. Hum Fertil (Camb). 2009 Dec; 12(4): 198-203.
  40. Marzieh Aghahosseini et al. Estradiol supplementation during the luteal phase in poor responder patients undergoing in vitro fertilization: a randomized clinical trial. J Assist Reprod Genet. 2011; 28: 785-790.
  41. Краснопольская К.В., Назаренко Т.А., Сесина Н.И., Ершова И.Ю., Александрова В.Р. Результаты программ ЭКО с донорскими ооцитами у пациенток с ультразвуковыми признаками «тонкого» эндометрия. Медицинский алфавит. 2017; 1 (12): 34-38. [Krasnopol’skaya K.V., Nazarenko T.A., Sesina N.I., Ershova I.Yu., Aleksandrova V.R. Rezul’taty programm EKO s donorskimi ootsitami u patsientok s ul’trazvukovymi priznakami «tonkogo» endometriya. Meditsinskii alfavit. 2017; 1 (12): 34-38. (In Russian)]
  42. Силантьева Е.С. Физические методы структурно-функционального ремоделирования эндометрия у женщин с нарушением репродуктивной функции. Дисс. ... докт. мед. наук. М., 2008. [Silant’eva E.S. Fizicheskie metody strukturno-funktsional’nogo remodelirovaniya endometriya u zhenshchin s narusheniem reproduktivnoi funktsii. Diss. dokt. med. nauk. M., 2008. (In Russian)]
  43. Шнейдерман М.Г., Левков Л.А., Калинина Е.А., Смольникова В.Ю., Павлович С.В., Мишиева Н.Г., Абубакиров А.Н., Алиева К.У., Казарян Л.М., Аксененко А.А., Куземин А.А., Дюжева Е.В., Беляева Н.А., Фатхудинов Т.Х., Макаров А.В., Афян А.И., Владимирова И.В. Новый способ прегравидарной подготовки «тонкого» эндометрия – альтернатива гормональному лечению. Акушерство и гинекология. 2015; 1: 51-57. [Shneiderman M.G., Levkov L.A., Kalinina E.A., Smol’nikova V.Yu., Pavlovich S.V., Mishieva N.G., Abubakirov A.N., Alieva K.U., Kazaryan L.M., Aksenenko A.A., Kuzemin A.A., Dyuzheva E.V., Belyaeva N.A., Fatkhudinov T.Kh., Makarov A.V., Afyan A.I., Vladimirova I.V. Novyi sposob pregravidarnoi podgotovki «tonkogo» endometriya – al’ternativa gormonal’nomu lecheniyu. Akusherstvo i ginekologiya. 2015; 1: 51-57. (In Russian)]
  44. Краснопольская К.В., Назаренко Т.А., Федоров А.А., Ершова И.Ю. Влияние на эффективность ЭКО эндометриального скретчинга, назначаемого пациенткам с ультразвуковыми признаками экстремально «тонкого» эндометрия. Медицинский алфавит. 2016; 3(27): 39-43. [Krasnopol’skaya K.V., Nazarenko T.A., Fedorov A.A., Ershova I.Yu. Vliyanie na effektivnost’ EKO endometrial’nogo skretchinga, naznachaemogo patsientkam s ul’trazvukovymi priznakami ekstremal’no „tonkogo” endometriya. Meditsinskii alfavit. 2016. 3(27): 39-43. (In Russian)]
  45. Potdar N., Gelbaya T., Nardo L.G. Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis. Reprod Biomed Online 2012; 25(6): 561-571.
  46. Papanikolaou E.G., Kyrou D., Zervakakou G., Paggou E., Humaidan P. Follicular HCG endometrium priming for IVF patients experiencing resisting thin endometrium. A proof of concept study. J Assist Reprod Genet 2013; 30:1341-1345.
  47. Mouhayar Y., Sharara F. Modern management of thin lining. Middle East Fertil Soc J. 2017; 22: 1-12.
  48. Li J., Mo S., Chen Y. The effect of G-CSF on infertile women undergoing IVF treatment: A meta-analysis. Systems Biology in Reproductive Medicine 2017; 63 (4): 239-247.
  49. Chang Y., Li J., Chen Y., Wei L., Yang X., Shi Y., Liang X. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med. 2015; 5: 1286–1290.
  50. Tandulwadkar S.R., Naralkar M.V., Surana A.D. et al. Autologous Intrauterine Platelet-Rich Plasma Instillation for Suboptimal Endometrium in Frozen Embryo Transfer Cycles: a Pilot Study. J Hum Reprod Sci. 2017;10 (3): 208-12.
  51. Molina A., Sánchez J., Sánchez W., Vielma V. Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium. JBRA Assist Reprod. 2018; 22 (1): 42–8.
  52. Chang Y., Li J., Wei Li-na, Pang J., Chen J., Liang X. Autologous platelet-rich plasma infusion improves clinical pregnancy rate in frozen embryo transfer cycles for women with thin endometrium. Medicine. 2019; 98: 3 (e14062).
  53. Santamaria X., Cabanillas S., Cervello I., Abrona C., Raga F., Ferro J. et al. Autologous cell therapy with CD133+ bone marrow-derived stem cells from refractory Asherman’s syndrome and endometrial atrophy: a pilot cohort study. Hum Reprod. 2016; 31 (5): 1087-1096.

Received 16.04.2019

Accepted 19.04.2019

About the Authors

Efendieva Zulphiya Nurudinovna, postgraduate student at the Depertment of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education
of the I.M. Sechenov First MSMU of Ministry of Health of Russia (Sechenov University). E-mail: efendievaz@yandex.ru
119991 Russia, Moscow, ul. Bolshaya Pirogovskaya, 2, p. 4.
Apolikhina Inna Anatolievna, MD, Head of the Department of Aesthetic Gynecology and Rehabilitation of National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov. Professor of the Depertment of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education of the I.M. Sechenov First MSMU of Ministry of Health of Russia (Sechenov University). E-mail: i_apolikhina@oparina4.ru
117997 Russia, Moscow, Ac. Oparina str. 4.
Kalinina Elena Anatolievna, MD., Ph.D., Head of Department of assistive technologies in infertility treatment. National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov Ministry of Health of Russia. E-mail: e_kalinina@oparina4.ru
117997 Russia, Moscow, Ac. Oparina str. 4.

For citation: Efendieva Z.N., Apolikhina I.A., Kalinina E.A. The thin endometrium in the aspect of reproductive failures: The current problem or hyperdiagnosis?
Akusherstvo i Ginekologiya. Obstetrics and gynecology. 2019; 9:32-9.(In Russian)
https://dx.doi.org/10.18565/aig.2019.9.32-39

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