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Ghasemzadeh, A., Dopour Faliz, M., Farzadi, L., Navali, N., Bahramzadeh, B., Fadavi, A., Hakimi, P., Tehrani-ghadim, S., Abdollahi fard, S., & Hamdi, K. (2020). Effect of oral Utrogestan in comparison with Cetrotide on preventing luteinizing hormone surge in IVF cycles: A randomized controlled trial. International Journal of Reproductive BioMedicine (IJRM), 18(1), 41-46. https://doi.org/10.18502/ijrm.v18i1.6197
https://doi.org/10.18502/ijrm.v18i1.6197
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- Cited by 2 articles
authors
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Alieh Ghasemzadeh
Alieh Ghasemzadeh
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Masumeh Dopour Faliz
Masumeh Dopour Faliz
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Laya Farzadi
Laya Farzadi
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Nazli Navali
Nazli Navali
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Behzad Bahramzadeh
Behzad Bahramzadeh
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Arash Fadavi
Arash Fadavi
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Parvin Hakimi
Parvin Hakimi
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Sepideh Tehrani-ghadim
Sepideh Tehrani-ghadim
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Sedigheh Abdollahi fard
Sedigheh Abdollahi fard
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Kobra Hamdi
Kobra Hamdi
Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Published Date
- Jan 26, 2020
Effect of oral Utrogestan in comparison with Cetrotide on preventing luteinizing hormone surge in IVF cycles: A randomized controlled trial
Abstract
Background: Oral progesterone is recommended as an alternative to gonadotropin-releasing hormone (GnRH) agonists and antagonists to prevent luteinizing hormone (LH) surge in assisted reproductive technology (ART) cycles. However, there are little data regarding its use.
Objective: We aimed to compare the effect of oral Utrogestan and Cetrotide (a GnRH antagonist) on preventing LH surge in ART cycles.
Materials and Methods: In this randomized clinical trial, 100 infertile women undergoing ART who received recombinant follicle-stimulating hormone (FSH) at 150- 225 IU/day were randomly assigned to receive either Utrogestan 100 mg twice a day (case group) or GnRH antagonist protocol (control group) from cycle day 3 until the trigger day. Triggering was performed with 10,000 IU hCG) when there were at least three mature follicles. Viable embryos were cryopreserved for transfer in the next cycle for both groups. The number of oocytes retrieved and transferred embryos were compared between groups.
Results: The case group had significantly higher progesterone levels on triggering day, more follicles of >14 mm with higher maturity, and more oocytes retrieved with a higher rate of embryos transferred. A small increase in the pregnancy rate was observed in the case group, with no significant between-group differences. The most important result was the lack of premature LH surge in either group upon serum LH assessment on the triggering day.
Conclusion: Utrogestan is an alternative treatment that could reduce the LH surge rate and increase the ART outcomes including the number of oocytes retrieved and transferred embryos compared with GnRH agonists and antagonists.
Key words: In vitro fertilization, Premature luteinization, Utrogestan.
References
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[2] Hamdi K, Pia H, Hakimi P, Chaichi P. Relationship between thickness and pattern of endometrium and pregnancy rate in in vitro fertilization-intracytoplasmic. J Anal Res Clin Med 2018; 6: 22–27.
[3] Stimpfel M, Vrtacnik-Bokal E, Pozlep B, Virant-Klun I. Comparison of GnRH agonist, GnRH antagonist, and GnRH antagonist mild protocol of controlled ovarian hyperstimulation in good prognosis patients. Int J Endocrinol 2015; 2015: 385049.
[4] Dawood AS, Algergawy A, Elhalwagy A. Reduction of the cetrorelix dose in a multiple-dose antagonist protocol and its impact on pregnancy rate and affordability: A randomized controlled multicenter study. Clin Exp Reprod Med 2017; 44: 232–238.
[5] Rabati BK, Zeidi SN. Investigation of pregnancy outcome and ovarian hyper stimulation syndrome prevention in agonist and antagonist gonadotropin-releasing hormone protocol. J Res Med Sci 2012; 17: 1063–1066.
[6] Zhu X, Zhang X, Fu Y. Utrogestan as an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Medicine 2015; 94: e909.
[7] Zhu XX, Zhang XL, Fu YL. Effect of progesterone used to prevent LH surges in controlled ovarian stimulation. Reprod Contra 2015; 35: 384–388.
[8] Hutchens EG, Ramsey KA, Howard LC, Abshire MY, Patrie JT, McCartney CR. Progesterone has rapid positive feedback actions on LH release but fails to reduce LH pulse frequency within 12 h in estradiol-pretreated women. Physiol Rep 2016; 4: e12891.
[9] Nayot D, Klachook S, Casper RF. Nimodipine, a calcium channel blocker, delays the spontaneous LH surge in women with regular menstrual cycles: a prospective pilot study. Reprod Biol Endocrinol 2013; 11: 7.
[10] Reichman DE, Zakarin L, Chao K, Meyer L, Davis OK, Rosenwarks Z. Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing hormone antagonist failure resulting in breakthrough luteinizing hormone surges in in vitro fertilization cycles. Fertil Steril 2014; 102: 99–102.
[11] Messinis IE, Vanakara P, Zavos A, Verikouki C, Georgoulias P, Dafopoulos K. Failure of the GnRH antagonist ganirelix to block the positive feedback effect of exogenous estrogen in normal women. Fertil Steril 2010; 94: 1554–1556.
[12] Dong J, Wang Y, Chai WR, Hong QQ, Wang NL, Sun LH, et al. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. BJOG 2017; 124: 1048–1055.
[13] Huang CY, Chen GY, Shieh ML, Li HY. An extremely patient-friendly and efficient stimulation protocol for assisted reproductive technology in normal and high responders. Reprod Biol Endocrinol 2018; 16: 18.
[14] Wang Y, Chen Q, Wang N, Chen H, Lyu Q, Kuang Y. Controlled ovarian stimulation using Medroxyprogesterone acetate and hMG in patients with polycystic ovary syndrome treated for IVF: a double-blind randomized crossover clinical trial. Medicine (Baltimore) 2016; 95: e2939.
[15] Clarke BL, Khosla S. Female reproductive system and bone. Arch Biochem Biophys 2010; 503: 118–128.
[16] Denis-Robichaud J, LeBlanc SJ, Jones-Bitton A, Silper BF, Aoki Cerri RL. Pilot study to evaluate the association between the length of the luteal phase and estrous activity detected by automated activity monitoring in dairy cows. Front Vet Sci 2018; 5: 210.
[17] Child T, Leonard SA, Evans JS, Lass A. Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted reproductive technology cycles. Reprod Biomed Online 2018; 36: 630–645.
[18] Zhu X, Ye H, Fu Y. The utrogestan and hMG protocol in patients with polycystic ovarian syndrome undergoing controlled ovarian hyperstimulation during IVF/ICSI treatments. Medicine (Baltimore) 2016; 95: e4193.
[19] Bergh C, Lindenberg S, Nordic Crinone Study Group. A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection. Hum Reprod 2012; 27: 3467–3473.
[20] Biberoglu EH, Tanrikulu F, Erdem M, Erdem A, Biberoglu KO. Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg intravaginal progesterone tablet. Gynecol Endocrinol 2016; 32: 55–57.
[21] Wei M, Mahady GB, Liu D, Zheng ZS, Lu Y. Astragalin, a flavonoid from morus alba (mulberry) increases endogenous estrogen and progesterone by inhibiting ovarian granulosa cell apoptosis in an aged rat model of menopause. Molecules 2016; 21: doi: 10.3390/molecules21050675. 1–15.
[22] Peluso JJ, Pru JK. Non-canonical progesterone signaling in granulosa cell function. Reproduction 2014; 147: R169–R178.
[23] Wang Y, Chen Q, Wang N, Chen H, Lyu Q, Kuang Y. Controlled ovarian stimulation using medroxyprogesterone acetate and hmg in patients with polycystic ovary syndrome treated for ivf: a double-blind randomized crossover clinical trial. Medicine (Baltimore) 2016; 95: e2939.
[24] Kim SH, Burt Solorzano CM, McCartney CR. Progesterone administration does not acutely alter LH pulse secretion in the mid-follicular phase in women. Physiol Rep 2018; 6: e13680.
[2] Hamdi K, Pia H, Hakimi P, Chaichi P. Relationship between thickness and pattern of endometrium and pregnancy rate in in vitro fertilization-intracytoplasmic. J Anal Res Clin Med 2018; 6: 22–27.
[3] Stimpfel M, Vrtacnik-Bokal E, Pozlep B, Virant-Klun I. Comparison of GnRH agonist, GnRH antagonist, and GnRH antagonist mild protocol of controlled ovarian hyperstimulation in good prognosis patients. Int J Endocrinol 2015; 2015: 385049.
[4] Dawood AS, Algergawy A, Elhalwagy A. Reduction of the cetrorelix dose in a multiple-dose antagonist protocol and its impact on pregnancy rate and affordability: A randomized controlled multicenter study. Clin Exp Reprod Med 2017; 44: 232–238.
[5] Rabati BK, Zeidi SN. Investigation of pregnancy outcome and ovarian hyper stimulation syndrome prevention in agonist and antagonist gonadotropin-releasing hormone protocol. J Res Med Sci 2012; 17: 1063–1066.
[6] Zhu X, Zhang X, Fu Y. Utrogestan as an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Medicine 2015; 94: e909.
[7] Zhu XX, Zhang XL, Fu YL. Effect of progesterone used to prevent LH surges in controlled ovarian stimulation. Reprod Contra 2015; 35: 384–388.
[8] Hutchens EG, Ramsey KA, Howard LC, Abshire MY, Patrie JT, McCartney CR. Progesterone has rapid positive feedback actions on LH release but fails to reduce LH pulse frequency within 12 h in estradiol-pretreated women. Physiol Rep 2016; 4: e12891.
[9] Nayot D, Klachook S, Casper RF. Nimodipine, a calcium channel blocker, delays the spontaneous LH surge in women with regular menstrual cycles: a prospective pilot study. Reprod Biol Endocrinol 2013; 11: 7.
[10] Reichman DE, Zakarin L, Chao K, Meyer L, Davis OK, Rosenwarks Z. Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing hormone antagonist failure resulting in breakthrough luteinizing hormone surges in in vitro fertilization cycles. Fertil Steril 2014; 102: 99–102.
[11] Messinis IE, Vanakara P, Zavos A, Verikouki C, Georgoulias P, Dafopoulos K. Failure of the GnRH antagonist ganirelix to block the positive feedback effect of exogenous estrogen in normal women. Fertil Steril 2010; 94: 1554–1556.
[12] Dong J, Wang Y, Chai WR, Hong QQ, Wang NL, Sun LH, et al. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. BJOG 2017; 124: 1048–1055.
[13] Huang CY, Chen GY, Shieh ML, Li HY. An extremely patient-friendly and efficient stimulation protocol for assisted reproductive technology in normal and high responders. Reprod Biol Endocrinol 2018; 16: 18.
[14] Wang Y, Chen Q, Wang N, Chen H, Lyu Q, Kuang Y. Controlled ovarian stimulation using Medroxyprogesterone acetate and hMG in patients with polycystic ovary syndrome treated for IVF: a double-blind randomized crossover clinical trial. Medicine (Baltimore) 2016; 95: e2939.
[15] Clarke BL, Khosla S. Female reproductive system and bone. Arch Biochem Biophys 2010; 503: 118–128.
[16] Denis-Robichaud J, LeBlanc SJ, Jones-Bitton A, Silper BF, Aoki Cerri RL. Pilot study to evaluate the association between the length of the luteal phase and estrous activity detected by automated activity monitoring in dairy cows. Front Vet Sci 2018; 5: 210.
[17] Child T, Leonard SA, Evans JS, Lass A. Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted reproductive technology cycles. Reprod Biomed Online 2018; 36: 630–645.
[18] Zhu X, Ye H, Fu Y. The utrogestan and hMG protocol in patients with polycystic ovarian syndrome undergoing controlled ovarian hyperstimulation during IVF/ICSI treatments. Medicine (Baltimore) 2016; 95: e4193.
[19] Bergh C, Lindenberg S, Nordic Crinone Study Group. A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection. Hum Reprod 2012; 27: 3467–3473.
[20] Biberoglu EH, Tanrikulu F, Erdem M, Erdem A, Biberoglu KO. Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg intravaginal progesterone tablet. Gynecol Endocrinol 2016; 32: 55–57.
[21] Wei M, Mahady GB, Liu D, Zheng ZS, Lu Y. Astragalin, a flavonoid from morus alba (mulberry) increases endogenous estrogen and progesterone by inhibiting ovarian granulosa cell apoptosis in an aged rat model of menopause. Molecules 2016; 21: doi: 10.3390/molecules21050675. 1–15.
[22] Peluso JJ, Pru JK. Non-canonical progesterone signaling in granulosa cell function. Reproduction 2014; 147: R169–R178.
[23] Wang Y, Chen Q, Wang N, Chen H, Lyu Q, Kuang Y. Controlled ovarian stimulation using medroxyprogesterone acetate and hmg in patients with polycystic ovary syndrome treated for ivf: a double-blind randomized crossover clinical trial. Medicine (Baltimore) 2016; 95: e2939.
[24] Kim SH, Burt Solorzano CM, McCartney CR. Progesterone administration does not acutely alter LH pulse secretion in the mid-follicular phase in women. Physiol Rep 2018; 6: e13680.