Assessment of endometrial and subendometrial three-dimensional power Doppler angiography evaluated by the VOCAL method in frozen-thawed embryo transfer cycles on hormone replacement therapy

Abstract

BACKGROUND: The effectiveness of in vitro fertilization cycles / frozen-thawed embryo transfer cycles depends on a number of factors, the endometrial one being of great importance. Adequate endometrial and subendometrial blood supply is considered necessary for successful implantation. Currently, the possibilities of non-invasive assessment of the implantation properties of the endometrium are limited to the use of ultrasound.

AIM: The aim of this study was to assess the performance of endometrial and subendometrial three-dimensional power Doppler angiography combined with the Virtual Organ Computer-aided Analysis (VOCAL) method in frozen-thawed embryo transfer cycles on hormone replacement therapy and compare the obtained data among the women examined.

MATERIALS AND METHODS: This prospective study included 20 women. Doppler measurements were carried out three times — on the day of progesterone initiation, the day before embryo transfer and on the day of embryo transfer. The VOCAL software assessed the endometrial and subendometrial volume and blood flow indices such as vascularization index, flow index, and vascularization flow index. Patients were divided into two study groups depending on the onset of clinical pregnancy.

RESULTS: On the day of progesterone initiation among patients who got pregnant, we observed higher vascularization (3.52 ± 1.99 vs. 1.05 ± 1.36; p = 0.03) and vascularization flow (1.54 ± 0.98 vs. 0.63 ± 0.55; p = 0.03) indices compared to women with a negative result. Moreover, endometrial vascularization index on the day of progesterone initiation was positively correlated with the estrogen dose among both pregnant (r = 0.61; p = 0.04) and non-pregnant (r = 0.9; p = 0.0008) women. No differences in subendometrial blood flow indices depending on the onset of pregnancy were obtained, just as endometrial blood flow indices the day before embryo transfer and on the day of embryo transfer were comparable between women in the both study groups.

CONCLUSIONS: Three-dimensional power Doppler angiography evaluated by the Virtual Organ Computer-aided Analysis (VOCAL) method is a promising tool for non-invasive assessment of endometrial receptivity in frozen-thawed embryo transfer programs. However, further studies are required on a larger patient sample to form conclusions that are more accurate.

Keywords

three-dimensional power Doppler angiography / cryotransfer / vascularization index / flow index / vascularization flow index / endometrium / subendometrium / VOCAL

References

[1] Jinno M, Ozaki T, Iwashita M, et al. Measurement of endometrial tissue blood flow: a novel way to assess uterine receptivity for implantation. Fertil Steril. 2001;76(6):1168–1174. doi: 10.1016/s0015-0282(01)02897-7

[2] Jinno M., Ozaki T., Iwashita M., et al. Measurement of endometrial tissue blood flow: a novel way to assess uterine receptivity for implantation // Fertil Steril. 2001. Vol. 76, N. 6. P. 1168–1174. doi: 10.1016/s0015-0282(01)02897-7

[3] Wang L, Qiao J, Li R, et al. Role of endometrial blood flow assessment with color Doppler energy in predicting pregnancy outcome of IVF-ET cycles. Reprod Biol Endocrinol. 2010;18(8):122. doi: 10.1186/1477-7827-8-122

[4] Wang L., Qiao J., Li R., et al. Role of endometrial blood flow assessment with color Doppler energy in predicting pregnancy outcome of IVF-ET cycles // Reprod Biol Endocrinol. 2010. Vol. 18, N. 8. P. 122. doi: 10.1186/1477-7827-8-122

[5] Jokubkiene L, Sladkevicius P, Rovas L, et al. Assessment of changes in endometrial and subendometrial volume and vascularity during the normal menstrual cycle using three-dimensional power Doppler ultrasound. Ultrasound Obstet Gynecol. 2006;27(6):672–679. doi: 10.1002/uog.2742

[6] Jokubkiene L., Sladkevicius P., Rovas L., et al. Assessment of changes in endometrial and subendometrial volume and vascularity during the normal menstrual cycle using three-dimensional power Doppler ultrasound // Ultrasound Obstet Gynecol. 2006. Vol. 27, N. 6. P. 672–679. doi: 10.1002/uog.2742

[7] Raine-Fenning NJ, Campbell BK, Kendall NR, et al. Quantifying the changes in endometrial vascularity throughout the normal menstrual cycle with three-dimensional power Doppler angiography. Hum Reprod. 2004;19(2):330–338. doi: 10.1093/humrep/deh056

[8] Raine-Fenning N.J., Campbell B.K., Kendall N.R., et al. Quantifying the changes in endometrial vascularity throughout the normal menstrual cycle with three-dimensional power Doppler angiography // Hum Reprod. 2004. Vol. 19, N. 2. P. 330–338. doi: 10.1093/humrep/deh056

[9] Raine-Fenning N. Doppler assessment of uterine artery blood flow for the prediction of pregnancy after assisted reproduction treatment. Ultrasound Obstet Gynecol. 2008;31(4):371–375. doi: 10.1002/uog.5321

[10] Raine-Fenning N. Doppler assessment of uterine artery blood flow for the prediction of pregnancy after assisted reproduction treatment // Ultrasound Obstet Gynecol. 2008. Vol. 31, N. 4. P. 371–-375. doi: 10.1002/uog.5321

[11] 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(2):245–251. doi: 10.1016/s0015-0282(02)03223-5

[12] Chien L.W., Au H.K., Chen P.L., 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. Vol. 78, N. 2. P. 245–251. doi: 10.1016/s0015-0282(02)03223-5

[13] Nakai A, Yokota A, Koshino T, et al. Assessment of endometrial perfusion with Doppler ultrasound in spontaneous and stimulated menstrual cycles. J Nippon Med Sch. 2002;69(4):328–332. doi: 10.1272/jnms.69.328

[14] Nakai A., Yokota A., Koshino T., et al. Assessment of endometrial perfusion with Doppler ultrasound in spontaneous and stimulated menstrual cycles // J Nippon Med Sch. 2002. Vol. 69, N. 4. P. 328–332. doi: 10.1272/jnms.69.328

[15] Zaidi J, Campbell S, Pittrof R, et al. Endometrial thickness, morphology, vascular penetration and velocimetry in predicting implantation in an in vitro fertilization program. Ultrasound Obstet Gynecol. 1995;6(3):191–198. doi: 10.1046/j.1469-0705.1995.06030191.x

[16] Zaidi J., Campbell S., Pittrof R., et al. Endometrial thickness, morphology, vascular penetration and velocimetry in predicting implantation in an in vitro fertilization program // Ultrasound Obstet Gynecol. 1995. Vol. 6, N. 3. P. 191–198. doi: 10.1046/j.1469-0705.1995.06030191.x

[17] Friedler S, Schenker JG, Herman A, et al. The role of ultrasonography in the evaluation of endometrial receptivity following assisted reproductive treatments: a critical review. Hum Reprod Update. 1996;2(4):323–335. doi: 10.1093/humupd/2.4.323

[18] Friedler S., Schenker J.G., Herman A., et al. The role of ultrasonography in the evaluation of endometrial receptivity following assisted reproductive treatments: a critical review // Hum Reprod Update. 1996. Vol. 2, N. 4. P. 323-335. doi: 10.1093/humupd/2.4.323

[19] Hsieh YY, Chang FC, Tsai HD. Doppler evaluation of the uterine and spiral arteries from different sampling sites and phases of the menstrual cycle during controlled ovarian hyperstimulation. Ultrasound Obstet Gynecol. 2000;16(2):192–196. doi: 10.1046/j.1469-0705.2000.00196.x

[20] Hsieh Y.Y., Chang F.C., Tsai H.D. Doppler evaluation of the uterine and spiral arteries from different sampling sites and phases of the menstrual cycle during controlled ovarian hyperstimulation // Ultrasound Obstet Gynecol. 2000. Vol. 16, N. 2. P. 192–196. doi: 10.1046/j.1469-0705.2000.00196.x

[21] Pierson RA. Imaging the endometrium: are there predictors of uterine receptivity? J Obstet Gynaecol Can. 2003;25(5):360–368. doi: 10.1016/s1701-2163(16)30578-3

[22] Pierson R.A. Imaging the endometrium: are there predictors of uterine receptivity? // J Obstet Gynaecol Can. 2003. Vol. 25, N. 5. P. 360–368. doi: 10.1016/s1701-2163(16)30578-3

[23] Ng EH, Chan CC, Tang OS, et al. Endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound in patients with small intramural uterine fibroids during IVF treatment. Hum Reprod. 2005;20(2):501–506. doi: 10.1093/humrep/deh594

[24] Ng E.H., Chan C.C., Tang O.S., et al. Endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound in patients with small intramural uterine fibroids during IVF treatment // Hum Reprod. 2005. Vol. 20, N. 2. P. 501–506. doi: 10.1093/humrep/deh594

[25] Raine-Fenning NJ, Campbell BK, Kendall NR, et al. Endometrial and subendometrial perfusion are impaired in women with unexplained subfertility. Hum Reprod. 2004;19(11):2605–2614. doi: 10.1093/humrep/deh459

[26] Raine-Fenning N.J., Campbell B.K., Kendall N.R., et al. Endometrial and subendometrial perfusion are impaired in women with unexplained subfertility // Hum Reprod. 2004. Vol. 19, N. 11. P. 2605–2614. doi: 10.1093/humrep/deh459

[27] Wu HM, Chiang CH, Huang HY, et al. Detection of the subendometrial vascularization flow index by three-dimensional ultrasound may be useful for predicting the pregnancy rate for patients undergoing in vitro fertilization-embryo transfer. Fertil Steril. 2003;79(3):507–511. doi: 10.1016/s0015-0282(02)04698-8

[28] Wu H.M., Chiang C.H., Huang H.Y., et al. Detection of the subendometrial vascularization flow index by three-dimensional ultrasound may be useful for predicting the pregnancy rate for patients undergoing in vitro fertilization-embryo transfer // Fertil Steril. 2003. Vol. 79, N. 3. P. 507–511. doi: 10.1016/s0015-0282(02)04698-8

[29] Schild RL, Holthaus S, d’Alquen J, et al. Quantitative assessment of subendometrial blood flow by three-dimensional-ultrasound is an important predictive factor of implantation in an in-vitro fertilization programme. Hum Reprod. 2000;15(1):89–94. doi: 10.1093/humrep/15.1.89

[30] Schild R.L., Holthaus S., d’Alquen J., et al. Quantitative assessment of subendometrial blood flow by three-dimensional-ultrasound is an important predictive factor of implantation in an in-vitro fertilization programme // Hum Reprod. 2000. Vol. 15, N. 1. P. 89–94. doi: 10.1093/humrep/15.1.89

[31] Raine-Fenning N. The role of three-dimensional ultrasound in assisted reproduction treatment. Ultrasound Obstet Gynecol. 2004;23(4):317–322. doi: 10.1002/uog.1028

[32] Raine-Fenning N. The role of three-dimensional ultrasound in assisted reproduction treatment // Ultrasound Obstet Gynecol. 2004. Vol. 23, N. 4. P. 317–322. doi: 10.1002/uog.1028

[33] Rizzatto GJ. Towards a more sophisticated use of breast ultrasound. Eur Radiol. 2001;11(12):2425–2435. doi: 10.1007/s00330-001-1165-5

[34] Rizzatto G.J. Towards a more sophisticated use of breast ultrasound // Eur Radiol. 2001. Vol. 11, N. 12. P. 2425–2435. doi: 10.1007/s00330-001-1165-5

[35] Mercé LT, Barco MJ, Bau S, et al. Are endometrial parameters by three-dimensional ultrasound and power Doppler angiography related to in vitro fertilization/embryo transfer outcome? Fertil Steril. 2008;89(1):111–117. doi: 10.1016/j.fertnstert.2007.02.029

[36] Mercé L.T., Barco M.J., Bau S., et al. Are endometrial parameters by three-dimensional ultrasound and power Doppler angiography related to in vitro fertilization/embryo transfer outcome? // Fertil Steril. 2008. Vol. 89, N. 1. P. 111–117. doi: 10.1016/j.fertnstert.2007.02.029

[37] 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(6):1612–1617. doi: 10.1093/humrep/dei502

[38] Ng E.H., Chan C.C., Tang O.S., 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. Vol. 21, N. 6. P. 1612–1617. doi: 10.1093/humrep/dei502

[39] Ng EH, Chan CC, Tang OS, et al. The role of endometrial and subendometrial blood flows measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during IVF treatment. Hum Reprod. 2006;21(1):164–170. doi: 10.1093/humrep/dei277

[40] Ng E.H., Chan C.C., Tang O.S., et al. The role of endometrial and subendometrial blood flows measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during IVF treatment // Hum Reprod. 2006. Vol. 21, N. 1. P. 164–170. doi: 10.1093/humrep/dei277

[41] Ng EH, Chan CC, Tang OS, et al. Factors affecting endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound during IVF treatment. Hum Reprod. 2006;21(4):1062-1069. doi: 10.1093/humrep/dei442

[42] Ng E.H., Chan C.C., Tang O.S., et al. Factors affecting endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound during IVF treatment // Hum Reprod. 2006. Vol. 21, N. 4. P. 1062–1069. doi: 10.1093/humrep/dei442

[43] Ng EH, Chan CC, Tang OS, et al. Relationship between uterine blood flow and endometrial and subendometrial blood flows during stimulated and natural cycles. Fertil Steril. 2006;85(3):721–727. doi: 10.1016/j.fertnstert.2005.09.051

[44] Ng E.H., Chan C.C., Tang O.S., et al. Relationship between uterine blood flow and endometrial and subendometrial blood flows during stimulated and natural cycles // Fertil Steril. 2006. Vol. 85, N. 3. P. 721–727. doi: 10.1016/j.fertnstert.2005.09.051

[45] Ng EH, Chan CC, Tang OS, et al. Changes in endometrial and subendometrial blood flow in IVF. Reprod Biomed Online. 2009;18(2):269–275. doi: 10.1016/s1472-6483(10)60265-9

[46] Ng E.H., Chan C.C., Tang O.S., et al. Changes in endometrial and subendometrial blood flow in IVF // Reprod Biomed Online. 2009. Vol. 18, N. 2. P. 269–275. doi: 10.1016/s1472-6483(10)60265-9

[47] Gardner DK, Sakkas D. Assessment of embryo viability: the ability to select a single embryo for transfer – a review. Placenta. 2003;24(B):S5–S12. doi: 10.1016/s0143-4004(03)00136-x

[48] Gardner D.K., Sakkas D. Assessment of embryo viability: the ability to select a single embryo for transfer--a review // Placenta. 2003. Vol. 24, N. B. P. S5–S12. doi: 10.1016/s0143-4004(03)00136-x

[49] Peek M, Landgren BM, Johannisson E. The endometrial capillaries during the normal menstrual cycle: a morphometric study. Hum Reprod. 1992;7(7):906–911. doi: 10.1093/oxfordjournals.humrep.a137767

[50] Peek M., Landgren B.M., Johannisson E. The endometrial capillaries during the normal menstrual cycle: a morphometric study // Hum Reprod. 1992. Vol. 7, N. 7. P. 906–911. doi: 10.1093/oxfordjournals.humrep.a137767

[51] Gannon BJ, Carati CJ, Verco CJ. Endometrial perfusion across the normal human menstrual cycle assessed by laser Doppler fluxmetry. Hum Reprod. 1997;12(1):132–139. doi: 10.1093/humrep/12.1.132

[52] Gannon B.J., Carati C.J., Verco C.J. Endometrial perfusion across the normal human menstrual cycle assessed by laser Doppler fluxmetry // Hum Reprod. 1997. Vol. 12, N. 1. P. 132–139. doi: 10.1093/humrep/12.1.132

[53] Ng EH, Chan CC, Tang OS, et al. Comparison of endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound between stimulated and natural cycles in the same patients. Hum Reprod. 2004;19(10):2385–2390. doi: 10.1093/humrep/deh384

[54] Ng E.H., Chan C.C., Tang O.S., et al. Comparison of endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound between stimulated and natural cycles in the same patients // Hum Reprod. 2004. Vol. 19, N. 10. P. 2385–2390. doi: 10.1093/humrep/deh384

[55] Ng EH, Chan CC, Tang OS, et al. Endometrial and subendometrial vascularity is higher in pregnant patients with livebirth following ART than in those who suffer a miscarriage. Hum Reprod. 2007;22(4):1134–1141. doi: 10.1093/humrep/del458

[56] Ng E.H., Chan C.C., Tang O.S., et al. Endometrial and subendometrial vascularity is higher in pregnant patients with livebirth following ART than in those who suffer a miscarriage // Hum Reprod. 2007. Vol. 22, N. 4. P. 1134–1141. doi: 10.1093/humrep/del458

[57] Nastri CO, Ferriani RA, Raine-Fenning N, et al. Endometrial scratching performed in the non-transfer cycle and outcome of assisted reproduction: a randomized controlled trial. Ultrasound Obstet Gynecol. 2013;42(4):375–382. doi: 10.1002/uog.12539

[58] Nastri C.O., Ferriani R.A., Raine-Fenning N., et al. Endometrial scratching performed in the non-transfer cycle and outcome of assisted reproduction: a randomized controlled trial // Ultrasound Obstet Gynecol. 2013. Vol. 42, N. 4. P. 375–382. doi: 10.1002/uog.12539

[59] Martins WP, Raine-Fenning NJ, Ferriani RA, et al. Quantitative three-dimensional power Doppler angiography: a flow-free phantom experiment to evaluate the relationship between color gain, depth and signal artifact. Ultrasound Obstet Gynecol. 2010;35(3):361–368. doi: 10.1002/uog.7562

[60] Martins W.P., Raine-Fenning N.J., Ferriani R.A., et al. Quantitative three-dimensional power Doppler angiography: a flow-free phantom experiment to evaluate the relationship between color gain, depth and signal artifact // Ultrasound Obstet Gynecol. 2010. Vol. 35, N. 3. P. 361–368. doi: 10.1002/uog.7562

[61] Martins WP, Lima JC, Welsh AW, et al. Three-dimensional Doppler evaluation of single spherical samples from the placenta: intra- and interobserver reliability. Ultrasound Obstet Gynecol. 2012;40(2):200–206. doi: 10.1002/uog.11076

[62] Martins W.P., Lima J.C., Welsh A.W., et al. Three-dimensional Doppler evaluation of single spherical samples from the placenta: intra- and interobserver reliability // Ultrasound Obstet Gynecol. 2012. Vol. 40, N. 2. P. 200–206. doi: 10.1002/uog.11076

[63] Miyague AH, Raine-Fenning NJ, Polanski L, et al. Assessing repeatability of 3D Doppler indices obtained by static 3D and STIC power Doppler: a combined in-vivo/in-vitro flow phantom study. Ultrasound Obstet Gynecol. 2013;42(5):571–576. doi: 10.1002/uog.12419

[64] Miyague A.H., Raine-Fenning N.J., Polanski L., et al. Assessing repeatability of 3D Doppler indices obtained by static 3D and STIC power Doppler: a combined in-vivo/in-vitro flow phantom study // Ultrasound Obstet Gynecol. 2013. Vol. 42, N. 5. P. 571–576. doi: 10.1002/uog.12419

[65] Elsokkary M, Eldin AB, Abdelhafez M, et al. The reproducibility of the novel utilization of five-dimensional ultrasound and power Doppler in the prediction of endometrial receptivity in intracytoplasmic sperm-injected women: a pilot prospective clinical study. Arch Gynecol Obstet. 2019;299(2):551–558. doi: 10.1007/s00404-018-5001-4

[66] Elsokkary M., Eldin A.B., Abdelhafez M., et al. The reproducibility of the novel utilization of five-dimensional ultrasound and power Doppler in the prediction of endometrial receptivity in intracytoplasmic sperm-injected women: a pilot prospective clinical study // Arch Gynecol Obstet. 2019. Vol. 299, N. 2. P. 551–558. doi: 10.1007/s00404-018-5001-4

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