Адекватная толщина и структура эндометрия в период окна имплантации считается одним из основных требований для успешного наступления беременности в программах вспомогательных репродуктивных технологий. Однако значение прогностической роли толщины эндометрия, а также его пороговое значение, определяющее эффективность имплантации, до сих пор является спорным вопросом.
Цель настоящего обзора – проведение систематического анализа данных, имеющихся в современной литературе, по изучению значения и диагностики тонкого эндометрия в клинике вспомогательных репродуктивных технологий.
Thickness and structure of endometrium during the implantation window is one of the main characteristics of IVF efficacy. However, the prediction role and the threshold of endometrial thickness, which contributes to implantation success, is still the controversial question.
Objectives. To study the role and diagnosis of thin endometrium in IVF practice on the base of systematic literature review.
1. Отчеты регистра РАРЧ 2002–2011 гг. http://www.rahr.ru
2. Richter KS, Bugge KR, Bromer JG, Levy MJ. Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril 2007; 87: 53–9.
3. Gonen Y, Casper RF, Jacobson W, Blankier J. Endometrial thickness and growth during ovarian stimulation: A possible predictor of implantation in in vitro fertilization. Fertil Steril 1989; 52: 44650.
4. Alam V, Bernardini L, Gonzales J et al. A prospective study of echographic endometrial characteristics and pregnancy rates during hormonal replacement cycles. JARG 1993; 10: 215–9.
5. Noyes N, Liu HC, Sultan K et al. Endometrial thickness appears to be a significant factor in embryo implantation in in-vitro fertilization. J Hum Reprod 1995; 10 (4): 919–22.
6. Rinaldi L, Lisi F, Floccari AU et al. Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection. J Hum Reprod 1996; 11 (7): 1538–41.
7. Weissman A, Gotlieb L, Casper RF. The detrimental effect of increased endometrial thickness on implantation and pregnancy rates and outcome in an in vitro fertilization program. Fertil Steril 1999; 71: 147–9.
8. Bassil S. Changes in endometrial thickness, thickness, length and pattern in predicting pregnancy outcome during ovarian stimulation in in vitro fertilization. Ultrasound Obstet Gynecol 2001; 18: 258–63.
9. Kovacs P, Matyas S, Boda K, Kaali SG. The effect of endometrial thicknesson IVF/ICSI outcome. Hum Reprod 2003; 18 (11): 2337–41.
10. Dain L, Bider D, Levron J et al. Thin endometrium in donor oocyte recipients: enigma or obstacle for implantation? Fertil Steril 2013; 100 (5): 1289–95.
11. Miwa I, Tamura H, Takasaki A et al. Pathophysiologic features of «thin» endometrium. Fertil Steril 2009; 91: 998–1004.
12. Takasaki A, Tamura H, Taketani T et al. A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment.
J Ovarian Res 2013; 6 (1): 94.
13. Esmailzadeh S, Faramarzi M. Endometrial thickness and pregnancy outcome after intrauterine insemination. Fertil Steril 2007; 88: 432–7.
14. Sharara FI, Lim J, McClamrock HD. Endometrial pattern on the day of oocyte retrieval is more predictive of implantation success than the pattern or thickness on the day of hCG administration. JARG 1999; 16: 523–8.
15. Sereepapong W, Suwajanakorn S, Triratanachat S et al. Effects of clomiphene citrate on the endometrium of regularly cycling women. Fertil Steril 2000; 73: 287–9.
16. Isaacs JD Jr, Wells CS, Williams DB et al. Endometrial thickness is a valid monitoring parameter in cycles of ovulation induction with menotropins alone. Fertil Steril 1996; 65: 262–6.
17. Kuć P, Kuczyńska A, Topczewska M et al. The dynamics of endometrial growth and the triple layer appearance in three different controlled ovarian hyperstimulation protocols and their influence on IVF outcomes. Gynecol Endocrinol 2011; 27 (11): 867–73.
18. Apparao KBC, Lovely LP, Gui Y et al. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod 2002; 66: 297–304.
19. O’Donnell RL, Warner P, Lee RJ et al. Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen. Hum Reprod 2012; 27 (4): 1130–8.
20. Fatemi HM, Popovic-Todorovic B, Ameryckx L et al. In vitro fertilization pregnancy in a patient with proven chronic endometritis. Fertil Steril 2009; 91: 9–11.
21. Polisseni F, Bambirra EA, Camargos AF. Detection of chronic endometritis by diagnostic hysteroscopy in asymptomatic infertile patients. Gynecol Obstet Invest 2003; 55: 205–10.
22. Kasius JC, Broekmans FJM, Sie-Go DMDS et al. The reliability of the histological diagnosis of endometritis in asymptomatic IVF cases: a multicenter observer study. Hum Reprod 2012; 27: 153–8.
23. Schlaff WD, Hurst BS. Preoperative sonographic measurement of endometrial pattern predicts outcome of surgical repair in patients with severe Asherman’s syndrome. Fertil Steril 1995; 63: 410–3.
24. Le AW, Wang ZH, Yuan R et al. Association of the estrogen receptor-b gene RsaI and AluI polymorphisms with human idiopathic thin endometrium. Genet Mol Res 2013; 12 (4): 5978–85.
25. Godinjak Z, Bilalovic N. Estrogen and progesterone receptors in endometrium in women with unexplained Infertility. Mater Sociomed 2014; 26 (1): 51–2.
26. Nikas G. Pinopodes as markers of endometrial receptivity in clinical practice. Hum Reprod 1999; 2: 99–106.
27. Bentin-Ley U, Sjögren A, Nilsson L et al. Presence of uterine pinopodes at the embryo-endometrial interface during human implantation in vitro. Hum Reprod 1999; 14: 515–20.
28. Quinn С, Ryan E, Claessens EA et al. The presence of pinopodes in the human endometrium does not delineate the implantation window. Fertil Steril 2007; 87: 1015–21.
29. Kashida S, Sugino N, Takiguchi S et al. Regulation and role of vascular endothelial growth factor in the corpus luteum during mid-pregnancy in rats. Biol Reprod 2001; 64: 317–23.
30. Torry DS, Torry RJ. Angiogenesis and the expression of vascular endothelial growth factor in endometrium and placenta. Am J Reprod Immunol 1997; 37 (1): 21–9.
31. Meduri G, Bausero P, Perrot-Applanat M. Expression of vascular endothelial growth factor receptors in the human endometrium: modulation during the menstrual cycle. Biol Reprod 2000; 62 (2): 439–47.
32. Natoli AK et al. Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression. Hypertension 2005; 46: 1129–34.
33. Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Аnnu Rev Cell Dev Biol 2001; 17: 463–516.
34. Inagaki N, Stern C, McBain J et al. Analysis of intra-uterine cytokine concentration and matrix-metalloproteinase activity in women with recurrent failed embryo transfer. Hum Reprod 2003; 18 (3): 608–15.
35. Mirkin S, Arslan M, Churikov D et al. In search of candidate genes critically expressed in the human endometrium during the window of implantation. Hum Reprod 2005; 20: 2104–17.
36. Simon C, Bellver J, Vidal C et al. Similar endometrial development in oocyte donors treated with high- or low-dose GnRH480 antagonist compared to GnRH-agonist treatment and natural cycles. Hum Reprod 2005; 12: 3318–27.
37. Dıaz-Gimeno P, Horcajadas JA, Martınez-Conejero JA. A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil Steril 2011; 95: 50–60.
38. Демидов В.Н., Гус. А.И. Ультразвуковая диагностика гиперпластических и опухолевых процессов эндометрия. Под ред. В.В.Митькова, М.В.Медведева. Клиническое руководство по ультразвуковой диагностике. В 3 т. М.: Видар, 1997; с. 120–31.
39. 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). Hum Reprod 1991; 6: 232–7.
40. Lindhard A, Ravn V, Bentin-Ley U et al. Ultrasound characteristics and histological dating of the endometrium in a natural cycle in infertile women compared with fertile controls. Fertil Steril 2006; 86: 1344–55.
41. Puerto B, Creus M, Carmona F et al. Ultrasonography as a predictor of embryo implantation after in vitro fertilization: a controlled study. Fertil Steril 2003; 79: 101522.
42. Merce LT, Barco MJ, Bau S, Troyano J. Are endometrial parameters by three dimensional ultrasound and power Doppler angiography related to in vitro fertilization/embryo transfer outcome? Fertil Stril 2008; 89: 111–7.
43. Chien LW, Au HK, Chen PL et al. Assessment of uterine receptivity by the endometrial-subendometrial blood flow distribution pattern in women undergoing in vitro fertilization-embryo transfer. Fertil Steril 2002; 78: 245–51.
44. Steer CV, Williams J, Zaidi J et al. Intra-observer, interobserver, interultrasound transducer and intercycle variation in colour Doppler assessment of uterine artery impedance. Hum Reprod 1995; 10 (2): 479–81.
45. Goswamy R, Steptoe PC. Doppler ultrasound studies of the uterine artery in spontaneous ovarian cycles. Hum Reprod 1989; 3: 721–5.
46. Scholtes MC, Wladimiroff JW, van Rijen HJ, Hop WC. Uterine and ovarian flow velocity waveforms in the normal menstrual cycle: a transvaginal Doppler study. Fertil Steril 1989; 52 (6): 981–5.
47. Ng EH, Chan CC, Tang OS et al. The role of endometrial and subendometrial vascularity measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during frozen-thawed embryo transfer cycles. Hum Reprod 2006; 21: 1612–7.
48. Chen MJ, Yang JH, Peng FH et al. Extended estrogen administration for women with thin endometrium in frozen-thawed in-vitro fertilization programs. JARG 2006; 23: 337–42.
49. Sher G, Fisch JD. Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod 2000; 15: 806–9.
50. Hsieh YY, Tsai HD, Chang CC et al. Low-dose aspirin for infertile women with thin endometrium receiving intrauterine insemination: a prospective, randomized study. JARG 2000; 17: 174–7.
51. Schlahsa L, Jaimes Y, Blasczyk R, Figueiredo C. Granulocyte colony-stimulatory factor: a strong inhibitor of natural killer cell function. Transfusion 2011; 51: 293–305.
52. Tesarik J, Hazout A, Mendoza-Tesarik R et al. Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles. Hum Reprod 2006; 21: 2572–9.
53. Qublah H, Amarin Z, Al-Quda M et al. Luteal phase support with GnRH-aim proves implantation and pregnancy rates in IVF cycles with endometrium of 7mm on day of egg retrieval. Hum Fertil (Camb) 2008; 11 (11): 43–7.
54. Li R, Hao G. Local injury to the endometrium: its effect on implantation. Curr Opin Obstet Gynecol 2009; 21: 236–9.
55. Narvekar SA, Gupta N, Shetty N et al. Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study. J Hum Reprod Sci 2010; 3: 15–9.
________________________________________________
1. Отчеты регистра РАРЧ 2002–2011 гг. http://www.rahr.ru
2. Richter KS, Bugge KR, Bromer JG, Levy MJ. Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril 2007; 87: 53–9.
3. Gonen Y, Casper RF, Jacobson W, Blankier J. Endometrial thickness and growth during ovarian stimulation: A possible predictor of implantation in in vitro fertilization. Fertil Steril 1989; 52: 44650.
4. Alam V, Bernardini L, Gonzales J et al. A prospective study of echographic endometrial characteristics and pregnancy rates during hormonal replacement cycles. JARG 1993; 10: 215–9.
5. Noyes N, Liu HC, Sultan K et al. Endometrial thickness appears to be a significant factor in embryo implantation in in-vitro fertilization. J Hum Reprod 1995; 10 (4): 919–22.
6. Rinaldi L, Lisi F, Floccari AU et al. Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection. J Hum Reprod 1996; 11 (7): 1538–41.
7. Weissman A, Gotlieb L, Casper RF. The detrimental effect of increased endometrial thickness on implantation and pregnancy rates and outcome in an in vitro fertilization program. Fertil Steril 1999; 71: 147–9.
8. Bassil S. Changes in endometrial thickness, thickness, length and pattern in predicting pregnancy outcome during ovarian stimulation in in vitro fertilization. Ultrasound Obstet Gynecol 2001; 18: 258–63.
9. Kovacs P, Matyas S, Boda K, Kaali SG. The effect of endometrial thicknesson IVF/ICSI outcome. Hum Reprod 2003; 18 (11): 2337–41.
10. Dain L, Bider D, Levron J et al. Thin endometrium in donor oocyte recipients: enigma or obstacle for implantation? Fertil Steril 2013; 100 (5): 1289–95.
11. Miwa I, Tamura H, Takasaki A et al. Pathophysiologic features of «thin» endometrium. Fertil Steril 2009; 91: 998–1004.
12. Takasaki A, Tamura H, Taketani T et al. A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment.
J Ovarian Res 2013; 6 (1): 94.
13. Esmailzadeh S, Faramarzi M. Endometrial thickness and pregnancy outcome after intrauterine insemination. Fertil Steril 2007; 88: 432–7.
14. Sharara FI, Lim J, McClamrock HD. Endometrial pattern on the day of oocyte retrieval is more predictive of implantation success than the pattern or thickness on the day of hCG administration. JARG 1999; 16: 523–8.
15. Sereepapong W, Suwajanakorn S, Triratanachat S et al. Effects of clomiphene citrate on the endometrium of regularly cycling women. Fertil Steril 2000; 73: 287–9.
16. Isaacs JD Jr, Wells CS, Williams DB et al. Endometrial thickness is a valid monitoring parameter in cycles of ovulation induction with menotropins alone. Fertil Steril 1996; 65: 262–6.
17. Kuć P, Kuczyńska A, Topczewska M et al. The dynamics of endometrial growth and the triple layer appearance in three different controlled ovarian hyperstimulation protocols and their influence on IVF outcomes. Gynecol Endocrinol 2011; 27 (11): 867–73.
18. Apparao KBC, Lovely LP, Gui Y et al. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod 2002; 66: 297–304.
19. O’Donnell RL, Warner P, Lee RJ et al. Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen. Hum Reprod 2012; 27 (4): 1130–8.
20. Fatemi HM, Popovic-Todorovic B, Ameryckx L et al. In vitro fertilization pregnancy in a patient with proven chronic endometritis. Fertil Steril 2009; 91: 9–11.
21. Polisseni F, Bambirra EA, Camargos AF. Detection of chronic endometritis by diagnostic hysteroscopy in asymptomatic infertile patients. Gynecol Obstet Invest 2003; 55: 205–10.
22. Kasius JC, Broekmans FJM, Sie-Go DMDS et al. The reliability of the histological diagnosis of endometritis in asymptomatic IVF cases: a multicenter observer study. Hum Reprod 2012; 27: 153–8.
23. Schlaff WD, Hurst BS. Preoperative sonographic measurement of endometrial pattern predicts outcome of surgical repair in patients with severe Asherman’s syndrome. Fertil Steril 1995; 63: 410–3.
24. Le AW, Wang ZH, Yuan R et al. Association of the estrogen receptor-b gene RsaI and AluI polymorphisms with human idiopathic thin endometrium. Genet Mol Res 2013; 12 (4): 5978–85.
25. Godinjak Z, Bilalovic N. Estrogen and progesterone receptors in endometrium in women with unexplained Infertility. Mater Sociomed 2014; 26 (1): 51–2.
26. Nikas G. Pinopodes as markers of endometrial receptivity in clinical practice. Hum Reprod 1999; 2: 99–106.
27. Bentin-Ley U, Sjögren A, Nilsson L et al. Presence of uterine pinopodes at the embryo-endometrial interface during human implantation in vitro. Hum Reprod 1999; 14: 515–20.
28. Quinn С, Ryan E, Claessens EA et al. The presence of pinopodes in the human endometrium does not delineate the implantation window. Fertil Steril 2007; 87: 1015–21.
29. Kashida S, Sugino N, Takiguchi S et al. Regulation and role of vascular endothelial growth factor in the corpus luteum during mid-pregnancy in rats. Biol Reprod 2001; 64: 317–23.
30. Torry DS, Torry RJ. Angiogenesis and the expression of vascular endothelial growth factor in endometrium and placenta. Am J Reprod Immunol 1997; 37 (1): 21–9.
31. Meduri G, Bausero P, Perrot-Applanat M. Expression of vascular endothelial growth factor receptors in the human endometrium: modulation during the menstrual cycle. Biol Reprod 2000; 62 (2): 439–47.
32. Natoli AK et al. Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression. Hypertension 2005; 46: 1129–34.
33. Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Аnnu Rev Cell Dev Biol 2001; 17: 463–516.
34. Inagaki N, Stern C, McBain J et al. Analysis of intra-uterine cytokine concentration and matrix-metalloproteinase activity in women with recurrent failed embryo transfer. Hum Reprod 2003; 18 (3): 608–15.
35. Mirkin S, Arslan M, Churikov D et al. In search of candidate genes critically expressed in the human endometrium during the window of implantation. Hum Reprod 2005; 20: 2104–17.
36. Simon C, Bellver J, Vidal C et al. Similar endometrial development in oocyte donors treated with high- or low-dose GnRH480 antagonist compared to GnRH-agonist treatment and natural cycles. Hum Reprod 2005; 12: 3318–27.
37. Dıaz-Gimeno P, Horcajadas JA, Martınez-Conejero JA. A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil Steril 2011; 95: 50–60.
38. Демидов В.Н., Гус. А.И. Ультразвуковая диагностика гиперпластических и опухолевых процессов эндометрия. Под ред. В.В.Митькова, М.В.Медведева. Клиническое руководство по ультразвуковой диагностике. В 3 т. М.: Видар, 1997; с. 120–31.
39. 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). Hum Reprod 1991; 6: 232–7.
40. Lindhard A, Ravn V, Bentin-Ley U et al. Ultrasound characteristics and histological dating of the endometrium in a natural cycle in infertile women compared with fertile controls. Fertil Steril 2006; 86: 1344–55.
41. Puerto B, Creus M, Carmona F et al. Ultrasonography as a predictor of embryo implantation after in vitro fertilization: a controlled study. Fertil Steril 2003; 79: 101522.
42. Merce LT, Barco MJ, Bau S, Troyano J. Are endometrial parameters by three dimensional ultrasound and power Doppler angiography related to in vitro fertilization/embryo transfer outcome? Fertil Stril 2008; 89: 111–7.
43. Chien LW, Au HK, Chen PL et al. Assessment of uterine receptivity by the endometrial-subendometrial blood flow distribution pattern in women undergoing in vitro fertilization-embryo transfer. Fertil Steril 2002; 78: 245–51.
44. Steer CV, Williams J, Zaidi J et al. Intra-observer, interobserver, interultrasound transducer and intercycle variation in colour Doppler assessment of uterine artery impedance. Hum Reprod 1995; 10 (2): 479–81.
45. Goswamy R, Steptoe PC. Doppler ultrasound studies of the uterine artery in spontaneous ovarian cycles. Hum Reprod 1989; 3: 721–5.
46. Scholtes MC, Wladimiroff JW, van Rijen HJ, Hop WC. Uterine and ovarian flow velocity waveforms in the normal menstrual cycle: a transvaginal Doppler study. Fertil Steril 1989; 52 (6): 981–5.
47. Ng EH, Chan CC, Tang OS et al. The role of endometrial and subendometrial vascularity measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during frozen-thawed embryo transfer cycles. Hum Reprod 2006; 21: 1612–7.
48. Chen MJ, Yang JH, Peng FH et al. Extended estrogen administration for women with thin endometrium in frozen-thawed in-vitro fertilization programs. JARG 2006; 23: 337–42.
49. Sher G, Fisch JD. Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod 2000; 15: 806–9.
50. Hsieh YY, Tsai HD, Chang CC et al. Low-dose aspirin for infertile women with thin endometrium receiving intrauterine insemination: a prospective, randomized study. JARG 2000; 17: 174–7.
51. Schlahsa L, Jaimes Y, Blasczyk R, Figueiredo C. Granulocyte colony-stimulatory factor: a strong inhibitor of natural killer cell function. Transfusion 2011; 51: 293–305.
52. Tesarik J, Hazout A, Mendoza-Tesarik R et al. Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles. Hum Reprod 2006; 21: 2572–9.
53. Qublah H, Amarin Z, Al-Quda M et al. Luteal phase support with GnRH-aim proves implantation and pregnancy rates in IVF cycles with endometrium of 7mm on day of egg retrieval. Hum Fertil (Camb) 2008;
11 (11): 43–7.
54. Li R, Hao G. Local injury to the endometrium: its effect on implantation. Curr Opin Obstet Gynecol 2009; 21: 236–9.
55. Narvekar SA, Gupta N, Shetty N et al. Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study. J Hum Reprod Sci 2010; 3: 15–9.
Авторы
А.И.Афян, Н.В.Долгушина
ФГБУ Научный центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова Минздрава России, Москва