Cover
Vol. 10 No. 1 (2020)

Published: December 31, 2020

Pages: 67-82

Research Article

Comparison Between Preovulatory Follicular Pulsed Doppler Indices Under the Effect of Mild Ovarian Stimulation by Clomiphene Citrate vs Letrozole

Abstract

It was observed that embryos from oocytes resulting from well-vascularized follicles had a higher implantation rate than those from oocytes developed in poorly vascularized follicles. Neovascularization was recognized as primary in terms of ovulatory follicles growth and selection. Vascular endothelial growth factor serum level has a positive correlation with perifollicular blood flow. The 2D Color and Pulsed Doppler ultrasounds that allow visual observation of the flux of the blood in a limited part of the wall of the preovulatory follicles can be easily measured. To study the preovulatory follicle's blood flow parameters in infertile women undergoing different ovulation induction protocols. 50 infertile female patients who had undergone Intrauterine Insemination (IUI) procedures were classified into two groups which were letrozole or clomiphene citrate groups as induction protocol. Another ultrasound was performed on cycle day 11, 12, or 13 to evaluate growth follicles, also a Doppler study was done to measure perifollicular blood flow and endometrial thickness at the same time blood sample to measure vascular endothelial growth factor were taken. Human chorionic gonadotropin was injected and then after 36-40 hrs. IUI Procedure is done and follows up with the patient to do a pregnancy test after 14 days. The number of dominant follicles, endometrial thickness at HCG trigger, Perifollicular doppler blood flow vascular endothelial growth factor level, pregnancy rates were all measured in both groups. There were significant differences in Perifollicular RI (p<0.001) but there were no significant differences in Perifollicular PI (p=0.476). Regarding pregnancy rate, the letrozole group has a higher although not significant pregnancy rate (32%), if compared with those using CC (20%).

References

  1. Petro EM, Leroy JL, Covaci A, Fransen E, De Neubourg D, Dirtu AC, De Pauw I, Bols PE. Endocrine- disrupting chemicals in human follicular fluid impair in vitro oocyte developmental competence. Human Reproduction. 2012 Apr 1;27(4):1025- 33. [Online Article Link]
  2. Singh M, Chaudhry P, Asselin E. Bridging endometrial receptivity and implantation: network of hormones, cytokines, and growth factors. Journal of Endocrinology. 2011 Jul 1;210(1):5- 14. [Online Article Link]
  3. Schulte MM, Tsai JH, Moley KH. Obesity and PCOS: the effect of metabolic derangements on endometrial receptivity at the time of implantation. Reproductive Sciences. 2015 Jan 1;22(1):6-14. [Online Article Link]
  4. Naredi N, Singh SK, Sharma R. Does perifollicular vascularity on the day of oocyte retrieval affect pregnancy outcome in an In Vitro fertilization cycle?. Journal of human reproductive sciences. 2017 Oct;10(4):281-87. [Online Article Link]
  5. Blankstein J, Aziz P, Malepati S, Amir J. Ultrasound in Follicle Monitoring for Ovulation Induction/IUI. In: Stadtmauer L, Tur-Kaspa I. (eds) Ultrasound Imaging in Reproductive Medicine. Springer, Cham. 2019:249- 271. [Online Article Link]
  6. Bassett DL. The changes in the vascular pattern of the ovary of the albino rat during the estrous cycle. American Journal of Anatomy. 1943 Sep;73(2):251-91. [Online Article Link]
  7. Vural F, Vural B, Doğer E, Çakıroğlu Y, Çekmen M. Perifollicular blood flow and its relationship with endometrial vascularity, follicular fluid EG-VEGF, IGF-1, and inhibin-a levels and IVF outcomes. Journal of assisted reproduction and genetics. 2016 Oct 1;33(10):1355-62. [Online Article Link]
  8. Stadtmauer LA, Tur-Kaspa I (eds.). Ultrasound Imaging in Reproductive Medicine, 17, Springer Science +Business Media, New York, USA, 2014. [Online Article Link]
  9. Han H, Mo X, Ma Y, Zhou Y, Zhang B. The Role of Blood Flow in Corpus Luteum Measured by Transvaginal Two-Dimensional and Three- Dimensional Ultrasound in the Prediction of Early Intrauterine Pregnancy Outcomes. Frontiers in Pharmacology. 2019;10:767. [Online Article Link]
  10. Huyghe S, Verest A, Thijssen A, Ombelet W. The prognostic value of perifollicular blood flow in the outcome after assisted reproduction: a systematic review. Facts, Views & Vision in Obgyn. 2017 Sep;9(3):153- 56. [Online Article Link]
  11. Tjon-Kon-Fat RI, Bensdorp AJ, Bossuyt PM, Koks C, Oosterhuis GJ, Hoek A, Hompes P, Broekmans FJ, Verhoeve HR, De Bruin JP, Van Golde R. Is IVF—served two different ways—more cost-effective than IUI with controlled ovarian hyperstimulation?. Human reproduction. 2015 Oct 1;30(10):2331- 9. [Online Article Link]
  12. Bryan J. Clomifene’s role in fertility treatment has never been usurped by its rivals. The Pharmaceutical Journal, 285:470,11034900. [Online Article Link]
  13. Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized double- blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertility and sterility. 2002 Aug 1;78(2):280-5. [Online Article Link]
  14. Walker MH, Tobler KJ. Female Infertility. InStatPearls [Internet] 2020 Mar 4. StatPearls Publishing. [Online Article Link]
  15. Nahuis M, van der Veen F, Oosterhuis J, Mol BW, Hompes P, van Wely M. Review of the safety, efficacy, costs and patient acceptability of recombinant folliclestimulating hormone for injection in assisting ovulation induction in infertile women. International Journal of Womens Health, 2010;1:205-211. [Online Article Link]
  16. Pourali L, Ayati S, Tavakolizadeh S, Soleimani H, Sani FT. Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: A randomized trial. International Journal of Reproductive BioMedicine. 2017 Jan;15(1):49-54. [Online Article Link]
  17. Hussein Z, Al-Obaidi MT, AL- Saadi WI, Selman MO. Comparison of the Effect of Clomiphene citrate and Letrozole on the Endometrial Parameters of PCOS Women. Journal of Pharmaceutical Sciences and Research. 2017 Nov 1;9(11):2291-5. [Online Article Link]
  18. Shrivastava U, Shrestha S, Dhakal R. Combined Clomiphene Citrate- Metformin Versus Letrozole- Metformin in Achieving Pregnancy among Women with Polycystic Ovary Syndrome. Gynecol Reprod Health. 2019;3(1):1-5. [Online Article Link]
  19. Zeinalzadeh M, Basirat Z, Esmailpour M. Efficacy of letrozole in ovulation induction compared to that of clomiphene citrate inpatients with polycystic ovarian syndrome. J Reprod Med. 2010;55:36–40. [Online Article Link]
  20. Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews. 2018 May; 2018(5):CD010287. [Online Article Link]
  21. Mitwally H, Mitwally K, Boyd B, Mitwally M. Clomiphene Citrate versus Aromatase Inhibitors: Mechanism of Action. In: Manual of Ovulation Induction & Ovarian Stimulation Protocols. Jaypee Brothers Medical Publishers (P) Ltd. 2016; 29,293. [Online Article Link]
  22. Gajjar A, Gajjar N, Neerjesh, Gajjar D, Raut S, Bhavna B. Glimpse on Splendid Aromatase Inhibitor– Letrozole-A Pragmatic Review. World Journal of Pharmaceutical Research. 2017. [Online Article Link]
  23. Ray PB, Ray A, Chakraborti PS. Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction in Indian women with polycystic ovarian syndrome. Archives of gynecology and obstetrics. 2012 Mar 1;285(3):873-7. [Online Article Link]
  24. Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. Comparison of letrozole with continuous gonadotropins and clomiphene- gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. Journal of assisted reproduction and genetics. 2009 Jan 1;26(1):19-24. [Online Article Link]
  25. Al-Fozan H, Al-Khadouri M, Tan SL, Tulandi T. A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation. Fertility and sterility. 2004 Dec 1;82(6):1561-3. [Online Article Link]
  26. Al-Shoraky Mohamed S, El-Din Hussien H, Ahmed El-Desouky ES. Letrozole Versus Clomiphene Citrate for Ovulation Induction in Women with Polycytic Ovary Syndrome. Al- Azhar Medical Journal. 2020 Jan 1;49(1):209-18. [Online Article Link]
  27. Jirge PR, Patil RS. Comparison of endocrine and ultrasound profiles during ovulation induction with clomiphene citrate and letrozole in ovulatory volunteer women. Fertility and sterility. 2010 Jan 1;93(1):174-83. [Online Article Link]
  28. Garg N, Vanitha VG. A Comparative Study of Letrozole Vs Clomiphene Citrate as First Line for Anovulatory Infertility–An Institutional Experience. Asian Research Journal of Gynaecology and Obstetrics. 2019 Apr 11;2(1):1-8. [Online Article Link]
  29. Behnoud N, Farzaneh F, Ershadi S. The effect of clomiphene citrate versus letrozole on pregnancy rate in women with polycystic ovary syndrome: A randomized clinical trial. Crescent Journal of Medical and Biological Sciences. 2019;6(3):335-40. [Online Article Link]
  30. Pritts EA. Letrozole for ovulation induction and controlled ovarian hyperstimulation. Current Opinion in Obstetrics and Gynecology. 2010 Aug 1;22(4):289-94. [Online Article Link]
  31. Hashim HA, Shokeir T, Badawy A. Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Fertility and sterility. 2010 Sep 1;94(4):1405-9. [Online Article Link]
  32. Monteleone P, Artini PG, Simi G, Casarosa E, Cela V, Genazzani AR. Follicular fluid VEGF levels directly correlate with perifollicular blood flow in normoresponder patients undergoing IVF. Journal of Assisted Reproduction and Genetics. 2008 May 1;25(5):183-6. [Online Article Link]
  33. Lam PM, Haines C. Vascular endothelial growth factor plays more than an angiogenic role in the female reproductive system. Fertility and sterility. 2005 Dec 1;84(6):1775-8. [Online Article Link]
  34. Gordon JD, Mesiano S, Zaloudek CJ, Jaffe RB. Vascular endothelial growth factor localization in human ovary and fallopian tubes: possible role in reproductive function and ovarian cyst formation. The Journal of Clinical Endocrinology & Metabolism. 1996 Jan 1;81(1):353-9. [Online Article Link]
  35. Kudsy M, Alhalabi M, Al-Quobaili F. Follicular fluid Vascular Endothelial Growth Factor (VEGF) could be a predictor for pregnancy outcome in normo-responders and polycystic ovary syndrome women undergoing IVF/ICSI treatment cycles. Middle East Fertility Society Journal. 2016 Mar 1;21(1):52-6. [Online Article Link]
  36. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reproduction. 2018 Sep 1;33(9):1602-18. [Online Article Link]
  37. Fortune JE, Rivera GM, Yang MY. Follicular development: the role of the follicular microenvironment in selection of the dominant follicle. Animal reproduction science. 2004 Jul 1;82:109-26. [Online Article Link]
  38. Bhal PS, Pugh ND, Gregory L, O'Brien S, Shaw RW. Perifollicular vascularity as a potential variable affecting outcome in stimulated intrauterine insemination treatment cycles: a study using transvaginal power Doppler. Human Reproduction. 2001 Aug 1;16(8):1682-9. [Online Article Link]
  39. Oyesanya OA, Parsons JH, Collins WP, Campbell S. Prediction of oocyte recovery rate by transvaginal ultrasonography and color Doppler imaging before human chorionic gonadotropin administration in in vitro fertilization cycles. Fertility and sterility. 1996 Apr 1;65(4):806-9. [Online Article Link] Authors Biography Dr. Dalia Jasim Mahmood She received the M.B.CH.B. from the College of Medicine, Al- Mustansiriya University in 2007. She occupied the position of rotator house officer in Al-Yarmouk Teaching Hospital from 2008-2009. She worked in Baghdad during her permanency in obstetrics and gynecology 2011-2012. She started the residency program in 2013 at Al-Yarmouk Teaching Hospital and graduated as a specialist in Obstetrics and Gynecology in 2017 with F.I.C.O.G of Obst. & Gyne. She worked as a specialist in Al-Zaafranea General Hospital from 2017-2018. From 2018-2020 graduated as a specialist in infertility with Ph.D. from Al Nahrain University, the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies. Dr. Huda Ali Hussaini She received the M.B.Ch.B : Babylon University, College of Medicine, in 2000. The diploma in Radiology from the University of Baghdad in 2007. She is a fellow of the Iraqi Board for Medical Specialization, Council of Radiology since 2008. Currently, she is an assistant professor. Al Nahrain University, College of Medicine, department of surgery (specialist radiologist). She is a Member of staff in the high Institute of infertility diagnosis and ARTS. Including the ultrasound department in the institute since 2018. She has Participations in a lot of annual meetings, medical conferences. Seminars, continuous learning, and thesis discussion. She is a member of the Iraqi medical association, the Iraqi Society of Radiologists and medical imaging, the Iraqi Journal of Embryos infertility researches, European Society for Hybrid, Molecular, and translation imaging. She published more than 15 articles and has supervised many students. Dr. Wasan A. Abdulhameed She received M.B.CH.B. from the University of Baghdad, College of medicine in 1992, the diploma and the Arab Board in Gyn. and Obs. from Medical City, Baghdad in 1998. She worked at Al Sharjah University, UAE. She earned a laparoscopic surgery certificate from India in 2009. She was a Lactation consultant in Australia in 2010. She occupied many administrative positions She attended more than 20 academic congresses internationally. How to cite: Mahmood DJ; Hussaini HA; Abdulhameed WA. Comparison Between Preovulatory Follicular Pulse Doppler Indices Under the Effect of Mild Ovarian Stimulation by Clomiphene Citrate vs Letrozole; Iraqi Journal of Embryos and Infertility Researches (IJEIR), (2020); 10(1): 67-82. Doi: http://doi.org/10.28969/IJEIR.v10.i1.r5 © 2020 Author(s)