Volume 47, Issue 1 , Pages 66-74, March 2008
Comparisons of Different Dosages of Gonadotropin-Releasing Hormone (GnRH) Antagonist, Short-acting Form and Single, Half-dose, Long-acting Form of GnRH Agonist During Controlled Ovarian Hyperstimulation and in vitro Fertilization
Article Outline
Summary
Objective
Both gonadotropin-releasing hormone (GnRH) analogs and antagonists have been used for pituitary desensitization during controlled ovarian hyperStimulation (COH). We aimed to determine the minimum effective daily dose of GnRH antagonist in women undergoing COH. We also compared the efficiency of a GnRH antagonist and a GnRH agonist.
Materials and Methods
Women undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer were divided into five groups: (1) cetrorelix 0.25mg(n = 86); (2) cetrorelix 0.2mg(n = 28); (3) cetrorelix 0.15 mg (n = 30); (4) leuprolide acetate (LA) 0.5 mg/day (n = 58); (5) single half-dose LA depot 1.88mg (n = 49). Cetrorelix was administered daily from menstrual day 8 until the day of human chorionic gonadotropin administration. LA or LA depot was started on day 21 of the previous menstrual cycle.
Results
We observed lower gonadotropin (Gn) dosages, estradiol (E2) levels and reduced risk of ovarian hyper-stimulation syndrome (OHSS) in the GnRH antagonist groups. A higher risk of luteinizing hormone (LH) surge was noted in cetrorelix0.2 and 0.15 mggroups. Gn dosages (IU)/E2 levels (pg/mL) in each group were: (1) 1,949.4/ 1,191.1; (2) 1,869.6/1,010.8; (3) 1,856.7/1,023.6; (4) 2,184.5/1,323.6; and (5) 2,103.5/1,313.5, respectively. LH/OHSS risks were: (1) 3.5%/5.8%; (2) 7.1%/3.6%; (3) 13.3%/3.3%; (4) 3.4%/8.6%; and (5) 2%/8.2%, respectively. Number of oocytes/embryos/grade I, II embryos were: (1) 9.4/7.9/5.8; (2) 7.5/4.2/3.6; (3) 6.3/4.1/3.1; (4) 12.3/ 8.9/6.6; and (5) 11.8/8.4/6.1, respectively. There was no significant difference in terms of clinical outcomes between groups 1, 4 and 5, except for higher abortion rates (AR) in group 1. Pregnancy rate (PR)/implantation rate (IR) ratios in groups 1, 4, and 5 were statistically higher than those in groups 2 and 3. Chemical PR/IR/AR were: (1) 30.2%/ 5.9%/7%; (2) 21.4%/5.1%/7.1%; (3) 16.7%/4.1%/10%; (4) 32.8%/5.5%/8.6%; and (5) 30.6%/5.7%/8.2%, respectively.
Conclusion
The lowest effective dosage of cetrorelix for pituitary desensitization during COH luteolysis is 0.25 mg, resulting in a comparable PR but a higher AR when compared with GnRH agonist.
Key Words: cetrorelix , GnRH agonist , GnRH antagonist , leuprolide acetate , pituitary suppression
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References
- . Effects of gonadotrophinreleasing hormone agonists (GnRHa) on follicle and oocyte quality . Hum Reprod . 1993;8:511–518
- . Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation in patients undergoing IVF: a randomized comparative study . Hum Reprod . 1993;8:2052–2055
- . The long-acting gonadotropin-releasing hormone analogues impaired the implantation rate . Fertil Steril . 1996;65:122–126
- . Comparison of a single half-dose, long-acting form of gonadotropin-releasing hormone analog (GnRH-a) and a short-acting form of GnRH-a for pituitary suppression in a controlled ovarian hyperstimulation program . Fertil Steril . 2000;73:817–820
- . Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation . Fertil Steril . 1993;59:596–600
- . Triggering of ovulation by a gonadotropin-releasing hormone (GnRH) agonist in patients pretreated with a GnRH antagonist . Fertil Steril . 1996;66:151–153
- Suppression of the endogenous luteinizing hormone surge by the gonadotrophinreleasing hormone antagonist Cetrorelix during ovarian stimulation . Hum Reprod . 1994;9:788–791
- Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages . J Assist Reprod Genet . 1996;13:216–222
- . The European Orgalutran Study Group. Treatment with the gonadotrophin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: results of a controlled, randomized, multicentre trial . Hum Reprod . 2000;15:1490–1498
- . Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation . Fertil Steril . 1997;67:917–922
- . Luteal phase and clinical outcome after human menopausal gonadotrophin/gonadotrophin releasing hormone antagonist treatment for ovarian stimulation in in-vitro fertilization/intracytoplasmic sperm injection cycles . Hum Reprod . 1999;14:1426–1430
- Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study . Hum Reprod . 2004;19:1993–2000
- . Ovarian response and follicular development for single-dose and multiple-dose protocols for gonadotropin-releasing hormone antagonist administration . Fertil Steril . 2005;83:1700–1707
- . First established pregnancy after controlled ovarian hyperstimulation with recombinant follicle stimulating hormone and the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) . Hum Reprod . 1998;13:294–295
- . Minimal stimulation using recombinant follicle-stimulating hormone and a gonadotropin-releasing hormone antagonist in women of advanced age . Fertil Steril . 2004;81:1002–1006
- . Improvement of in vitro fertilisation after treatment with buserelin, an agonist of luteinising hormone releasing hormone . Br Med J (Clin Res Ed) . 1988;296:1765–1768
- . Psychosocial stress as a cause of infertility . Fertil Steril . 1993;59:685–689
- . Prospective randomized study of D-Trp6-LHRH versus buserelin in long desensitization protocols for medically assisted conception cycles . Hum Reprod . 1994;9:220–225
- . Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles . Cochrane Database Syst Rev . 2002;(3):CD002808
- . Comparison between depot and standard release triptoreline in in vitro fertilization: pituitary sensitivity, luteal function, pregnancy outcome, and perinatal results . Fertil Steril . 1994;62:126–132
- . Prospective randomized study of clomiphene citrate and gonadotrophins versus goserelin and gonadotrophins for follicular stimulation in assisted reproduction . Hum Reprod . 1995;10:791–796
- . The use of long- and short-acting forms of gonadotrophinreleasing hormone analogues in women undergoing oocyte donation . Hum Reprod . 1998;13:1148–1151
- . A comparison of three gonadotrophin-releasing hormone analogues in an in-vitro fertilization programme: a prospective randomized study . Hum Reprod . 1999;14:288–293
- . A comparison between a standard and reduced dose of D-Trp-6-luteinizing hormone-releasing hormone administered after pituitary suppression for in-vitro fertilization . Hum Reprod . 1994;9:1813–1817
- . Pituitary-ovarian suppression by the standard and half-doses of D-Trp-6-luteinizing hormone-releasing hormone depot . Hum Reprod . 1992;7:1230–1234
- . Subcutaneous low dose leuprolide acetate depot versus leuprolide acetate for women undergoing ovarian stimulation for in-vitro fertilization . Hum Reprod . 1995;10:2909–2912
- . Gonadotropin-releasing hormone and reproductive medicine . J Obstet Gynaecol Can . 2003;25:98–113
- . Dose-related suppression of serum luteinizing hormone in women by a potent new gonadotropin-releasing hormone antagonist (Ganirelix) administered by intranasal spray . Fertil Steril . 1997;67:469–473
- . Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part II. Dose-proportionality and gonadotropin suppression after multiple doses of ganirelix in healthy female volunteers . Fertil Steril . 1999;72:1006–1012
- . Biological assessment criteria during antagonist protocols . J Gynecol Obstet Biol Reprod (Paris) . 2004;33:3S32–3S35 [In French]
- . Gonadotrophin-releasing hormone antagonists: will they replace the agonists? . Reprod Biomed Online . 2003;6:43–53
- . GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial . Hum Reprod . 2005;20:616–621
- . Depot GnRH agonist versus the single dose GnRH antagonist regimen (cetrorelix, 3mg) in patients undergoing assisted reproduction treatment . Reprod Biomed Online . 2003;7:185–189
- . Use of gonadotrophin releasing hormone (GnRH) antagonist (cetrotide) during ovarian stimulation for in-vitro fertilization treatment: multiple doses and single dose . J Obstet Gynaecol Res . 2001;27:261–265
- . A novel regimen of gonadotropin-releasing hormone (GnRH) antagonist plus pulsatile GnRH: controlled restoration of gonadotropin secretion and ovulation induction . Fertil Steril . 1990;54:1140–1145
- . The use of gonadotropin-releasing hormone antagonist in a flexible protocol: a pilot study . Am J Obstet Gynecol . 2003;189:444–446
- . Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol. Meta-analysis . Arch Gynecol Obstet . 2001;265:175–182
- . Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group . Hum Reprod . 2000;15:526–531
- . Effect of antagonists vs agonists on in vitro fertilization outcome . Clin Exp Obstet Gynecol . 2004;31:257–259
- Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin) . Fertil Steril . 2000;73:314–320
- . Gonadotropin-releasing hormone (GnRH)-antagonist versus GnRH-agonist in ovarian stimulation of poor responders undergoing IVF . J Assist Reprod Genet . 2003;20:455–460
- . A prospective randomized study comparing gonadotropin-releasing hormone agonists or gonadotropin-releasing hormone antagonists in couples with unexplained infertility and/or mild oligozoospermia . Fertil Steril . 2005;83:1354–1362
- . GnRH antagonist improved blastocyst quality and pregnancy outcome after multiple failures of IVF/ICSI-ET with a GnRH agonist protocol . J Assist Reprod Genet . 2004;21:317–322
- . A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon) . Hum Reprod . 1998;13:3023–3031
- . Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks . Hum Reprod . 1999;14:2681–2686
- Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist cetrorelix (Cetrotide) in controlled ovarian stimulation for assisted reproduction . Arch Gynecol Obstet . 2000;264:29–32
- . Gonadotrophin-releasing hormone antagonists for assisted conception . Cochrane Database Syst Rev . 2001;(4):CD001750
- . Comparable effectiveness using flexible single-dose GnRH antagonist (cetrorelix) and single-dose long GnRH agonist (goserelin) protocol for IVF cycles–a prospective, randomized study . Reprod Biomed Online . 2003;7:301–308
- . Gonadotropin-releasing hormone antagonist: new tools vs. old habits . Fertil Steril . 2000;73:18–20
- . Recombinant gonadotrophins associated with GnRH antagonist (cetrorelix) in ovarian stimulation for ICSI: comparison of r-FSH alone and in combination with r-LH . Eur J Obstet Gynecol Reprod Biol . 2006;126:212–216
- . LH stimulation of estrogen secretion by cultured rat granulosa cells . Mol Cell Endocrinol . 1981;24:17–28
- . Comparison of two different starting multiple dose gonadotropin-releasing hormone antagonist protocols in a selected group of in vitro fertilization-embryo transfer patients . Fertil Steril . 2004;81:562–566
- . No influence of body weight on pregnancy rate in patients treated with cetrorelix according to the single- and multipledose protocols . Reprod Biomed Online . 2003;6:482–487
- . GnRH antagonist in assisted reproduction: a Cochrane review . Hum Reprod . 2002;17:874–885
- Ovarian stimulation by clomiphene citrate and hMG in combination with cetrorelix acetate for ICSI cycles . Hum Reprod . 2003;18:45–49
- . Why is the clinical acceptance of gonadotropin-releasing hormone antagonist cotreatment during ovarian hyperstimulation for in vitro fertilization so slow? . Fertil Steril . 2005;83:1607–1611
- . Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of gonadotropin-releasing hormone agonists versus antagonists . Fertil Steril . 2004;82:167–171
- . The benefits of mid-luteal addition of human chorionic gonadotrophin in in-vitro fertilization using a downregulation protocol and luteal support with progesterone . Hum Reprod . 1996;11:1552–1557
- . Ovarian stimulation for in-vitro fertilization/intracytoplasmic sperm injection with gonadotrophins and gonadotrophin-releasing hormone analogues: agonists and antagonists . Hum Reprod . 1999;14(Suppl 1):207–221
PII: S1028-4559(08)60057-1
doi:10.1016/S1028-4559(08)60057-1
© 2008 Taiwan Association of Obstetric & Gynecology. Published by Elsevier Inc. All rights reserved.
Volume 47, Issue 1 , Pages 66-74, March 2008
