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Semin Reprod Med 2010; 28(6): 486-492
DOI: 10.1055/s-0030-1265675
© Thieme Medical Publishers

Withholding Gonadotropins Until Human Chorionic Gonadotropin Administration

Rony Abdallah1 , Isaac Kligman1 , Owen Davis1 , Zev Rosenwaks1
  • 1The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York
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Publication History

Publication Date:
16 November 2010 (online)

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ABSTRACT

Withholding gonadotropins in women who exhibit high estradiol responses before follicles reach full maturation is called “coasting.” Coasting, or suspending gonadotropin administration, can be an effective strategy for decreasing the risk of ovarian hyperstimulation syndrome (OHSS) while reducing cancelation rates. In in vitro fertilization cycles, mechanistically it is believed that withholding gonadotropins starves smaller follicles, induces apoptosis, and decreases the potential for these follicles to elaborate vascular endothelial growth factor, a known mediator of OHSS. It is generally accepted that coasting should be initiated when the estradiol (E2) level is >3000 pg/mL in the setting of immature follicles. The human chorionic gonadotropin (hCG) trigger should be administered when the E2 level subsequently drops to a “safe” level. Cycle cancellation should be considered if, after 3 to 4 days of coasting, the E2 level remains excessively elevated. Oocyte retrieval may also be cancelled if the E2 level on the day after hCG trigger drops precipitously. In gonadotropin-releasing hormone agonist (GnRHa)-based protocols, one can consider withholding GnRHa administration if the E2 level continues to increase after a few days of coasting. Current data seem to show that the coasting period is short and/or is less likely to be required in GnRH-antagonist protocols as compared with GnRHa-based protocols. Large randomized control trials are still needed to establish the relative efficacy of coasting versus embryo cryopreservation in the context of OHSS prevention.

KEYWORDS

In vitro fertilization - OHSS - coasting - VEGF - GnRH agonist - GnRH antagonist

REFERENCES

  • 1 Rabinovici J, Kushnir O, Shalev J, Goldenberg M, Blankstein J. Rescue of menotrophin cycles prone to develop ovarian hyperstimulation.  Br J Obstet Gynaecol. 1987;  94(11) 1098-1102
    PubMedGoogle Scholar
  • 2 Sher G, Salem R, Feinman M, Dodge S, Zouves C, Knutzen V. Eliminating the risk of life-endangering complications following overstimulation with menotropin fertility agents: a report on women undergoing in vitro fertilization and embryo transfer.  Obstet Gynecol. 1993;  81(6) 1009-1011
    PubMedGoogle Scholar
  • 3 Fluker M R, Hooper W M, Yuzpe A A. Withholding gonadotropins (“coasting”) to minimize the risk of ovarian hyperstimulation during superovulation and in vitro fertilization-embryo transfer cycles.  Fertil Steril. 1999;  71(2) 294-301
    CrossrefPubMedGoogle Scholar
  • 4 Wang T H, Horng S G, Chang C L et al. Human chorionic gonadotropin-induced ovarian hyperstimulation syndrome is associated with up-regulation of vascular endothelial growth factor.  J Clin Endocrinol Metab. 2002;  87(7) 3300-3308
    CrossrefPubMedGoogle Scholar
  • 5 Krasnow J S, Berga S L, Guzick D S, Zeleznik A J, Yeo K T. Vascular permeability factor and vascular endothelial growth factor in ovarian hyperstimulation syndrome: a preliminary report.  Fertil Steril. 1996;  65(3) 552-555
    PubMedGoogle Scholar
  • 6 Ravindranath N, Little-Ihrig L, Phillips H S, Ferrara N, Zeleznik A J. Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary.  Endocrinology. 1992;  131(1) 254-260
    CrossrefPubMedGoogle Scholar
  • 7 Neulen J, Yan Z, Raczek S et al. Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome.  J Clin Endocrinol Metab. 1995;  80(6) 1967-1971
    CrossrefPubMedGoogle Scholar
  • 8 Tozer A J, Iles R K, Iammarrone E, Gillott C M, Al-Shawaf T, Grudzinskas J G. The effects of ‘coasting’ on follicular fluid concentrations of vascular endothelial growth factor in women at risk of developing ovarian hyperstimulation syndrome.  Hum Reprod. 2004;  19(3) 522-528
    CrossrefPubMedGoogle Scholar
  • 9 García-Velasco J A, Zúñiga A, Pacheco A et al. Coasting acts through downregulation of VEGF gene expression and protein secretion.  Hum Reprod. 2004;  19(7) 1530-1538
    CrossrefPubMedGoogle Scholar
  • 10 Tortoriello D V, McGovern P G, Colón J M, Skurnick J H, Lipetz K, Santoro N. “Coasting” does not adversely affect cycle outcome in a subset of highly responsive in vitro fertilization patients.  Fertil Steril. 1998;  69(3) 454-460
    CrossrefPubMedGoogle Scholar
  • 11 Dhont M, Van der Straeten F, De Sutter P. Prevention of severe ovarian hyperstimulation by coasting.  Fertil Steril. 1998;  70(5) 847-850
    CrossrefPubMedGoogle Scholar
  • 12 Waldenström U, Kahn J, Marsk L, Nilsson S. High pregnancy rates and successful prevention of severe ovarian hyperstimulation syndrome by ‘prolonged coasting’ of very hyperstimulated patients: a multicentre study.  Hum Reprod. 1999;  14(2) 294-297
    CrossrefPubMedGoogle Scholar
  • 13 Egbase P E, Sharhan M A, Grudzinskas J G. Early unilateral follicular aspiration compared with coasting for the prevention of severe ovarian hyperstimulation syndrome: a prospective randomized study.  Hum Reprod. 1999;  14(6) 1421-1425
    CrossrefPubMedGoogle Scholar
  • 14 Benadiva C A, Davis O, Kligman I, Moomjy M, Liu H C, Rosenwaks Z. Withholding gonadotropin administration is an effective alternative for the prevention of ovarian hyperstimulation syndrome.  Fertil Steril. 1997;  67(4) 724-727
    CrossrefPubMedGoogle Scholar
  • 15 Yilmaz N, Uygur D, Ozgu E, Batioglu S. Does coasting, a procedure to avoid ovarian hyperstimulation syndrome, affect assisted reproduction cycle outcome?.  Fertil Steril. 2010;  94(1) 189-193
    CrossrefPubMedGoogle Scholar
  • 16 Egbase P E, Al-Sharhan M, Grudzinskas J G. ‘Early coasting’ in patients with polycystic ovarian syndrome is consistent with good clinical outcome.  Hum Reprod. 2002;  17(5) 1212-1216
    CrossrefPubMedGoogle Scholar
  • 17 Chen C D, Chao K H, Yang J H, Chen S U, Ho H N, Yang Y S. Comparison of coasting and intravenous albumin in the prevention of ovarian hyperstimulation syndrome.  Fertil Steril. 2003;  80(1) 86-90
    PubMedGoogle Scholar
  • 18 Chen D, Burmeister L, Goldschlag D, Rosenwaks Z. Ovarian hyperstimulation syndrome: strategies for prevention.  Reprod Biomed Online. 2003;  7(1) 43-49
    CrossrefPubMedGoogle Scholar
  • 19 Levinsohn-Tavor O, Friedler S, Schachter M, Raziel A, Strassburger D, Ron-El R. Coasting—what is the best formula?.  Hum Reprod. 2003;  18(5) 937-940
    CrossrefPubMedGoogle Scholar
  • 20 Moon H S, Joo B S, Moon S E, Lee S K, Kim K S, Koo J S. Short coasting of 1 or 2 days by withholding both gonadotropins and gonadotropin-releasing hormone agonist prevents ovarian hyperstimulation syndrome without compromising the outcome.  Fertil Steril. 2008;  90(6) 2172-2178
    CrossrefPubMedGoogle Scholar
  • 21 Ulug U, Ben-Shlomo I, Bahçeci M. Predictors of success during the coasting period in high-responder patients undergoing controlled ovarian stimulation for assisted conception.  Fertil Steril. 2004;  82(2) 338-342
    CrossrefPubMedGoogle Scholar
  • 22 García-Velasco J A, Isaza V, Quea G, Pellicer A. Coasting for the prevention of ovarian hyperstimulation syndrome: much ado about nothing?.  Fertil Steril. 2006;  85(3) 547-554
    CrossrefPubMedGoogle Scholar
  • 23 Atabekoglu C, Sonmezer M, Ozkavukcu S, Isbacar S. Unexpected pregnancy despite extremely decreased estradiol levels during ovarian stimulation.  Fertil Steril. 2008;  90(5) 2003. e5-e9
    PubMedGoogle Scholar
  • 24 Isaza V, Garcia-Velasco J A, Scheffer B, Remohi J, Simon C, Pellicer A. El coasting es eficaz en la prevención del síndrome de hiperestimulación ovárica y no afecta los resultados de la fecundación in vitro.  Progr Obstet Ginecol. 2001;  44 482-489
    PubMedGoogle Scholar
  • 25 Al-Shawaf T, Zosmer A, Hussain S et al. Prevention of severe ovarian hyperstimulation syndrome in IVF with or without ICSI and embryo transfer: a modified ‘coasting’ strategy based on ultrasound for identification of high-risk patients.  Hum Reprod. 2001;  16(1) 24-30
    CrossrefPubMedGoogle Scholar
  • 26 Isaza V, García-Velasco J A, Aragonés M, Remohí J, Simón C, Pellicer A. Oocyte and embryo quality after coasting: the experience from oocyte donation.  Hum Reprod. 2002;  17(7) 1777-1782
    CrossrefPubMedGoogle Scholar
  • 27 Ulug U, Bahçeci M, Erden H F, Shalev E, Ben-Shlomo I. The significance of coasting duration during ovarian stimulation for conception in assisted fertilization cycles.  Hum Reprod. 2002;  17(2) 310-313
    CrossrefPubMedGoogle Scholar
  • 28 Tilly J L, Kowalski K I, Johnson A L, Hsueh A JW. Involvement of apoptosis in ovarian follicular atresia and postovulatory regression.  Endocrinology. 1991;  129(5) 2799-2801
    CrossrefPubMedGoogle Scholar
  • 29 Erman Akar M, Oktay K. Falling FSH levels predict poor IVF pregnancy rates in patients whom the gonadotropins are withheld.  Arch Gynecol Obstet. 2009;  280(5) 761-765
    CrossrefPubMedGoogle Scholar
  • 30 Ranta T, Knecht M, Baukal A J, Korhonen M, Catt K J. GnRH agonist-induced inhibitory and stimulatory effects during ovarian follicular maturation.  Mol Cell Endocrinol. 1984;  35(1) 55-63
    CrossrefPubMedGoogle Scholar
  • 31 Ho Yuen B, Nguyen T A, Cheung A P, Leung P C. Clinical and endocrine response to the withdrawal of gonadotropin-releasing hormone agonists during prolonged coasting.  Fertil Steril. 2009;  92(2) 499-507
    CrossrefPubMedGoogle Scholar
  • 32 Delvigne A, Carlier C, Rozenberg S. Is coasting effective for preventing ovarian hyperstimulation syndrome in patients receiving a gonadotropin-releasing hormone antagonist during an in vitro fertilization cycle?.  Fertil Steril. 2001;  76(4) 844-846
    CrossrefPubMedGoogle Scholar
  • 33 Bahçeci M, Ulug U, Tosun S, Erden H F, Bayazit N. Impact of coasting in patients undergoing controlled ovarian stimulation with the gonadotropin-releasing hormone antagonist cetrorelix.  Fertil Steril. 2006;  85(5) 1523-1525
    CrossrefPubMedGoogle Scholar
  • 34 Farhi J, Ben-Haroush A, Lande Y, Sapir O, Pinkas H, Fisch B. In vitro fertilization cycle outcome after coasting in gonadotropin-releasing hormone (GnRH) agonist versus GnRH antagonist protocols.  Fertil Steril. 2009;  91(2) 377-382
    CrossrefPubMedGoogle Scholar
  • 35 Humaidan P, Papanikolaou E G, Tarlatzis B C. GnRHa to trigger final oocyte maturation: a time to reconsider.  Hum Reprod. 2009;  24(10) 2389-2394
    CrossrefPubMedGoogle Scholar
  • 36 Hernández E R, Gómez-Palomares J L, Ricciarelli E. No room for cancellation, coasting, or ovarian hyperstimulation syndrome in oocyte donation cycles.  Fertil Steril. 2009;  91(4, Suppl) 1358-1361
    CrossrefPubMedGoogle Scholar
  • 37 Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study.  Fertil Steril. 2008;  89(1) 84-91
    CrossrefPubMedGoogle Scholar
  • 38 Huddleston H G, Racowsky C, Jackson K V, Fox J H, Ginsburg E S. Coasting vs. cryopreservation of all embryos for prevention of ovarian hyperstimulation syndrome in in vitro fertilization.  Fertil Steril. 2008;  90(4) 1259-1262
    CrossrefPubMedGoogle Scholar
  • 39 Tummon I S, Contag S A, Thornhill A R, Session D R, Dumesic D A, Damario M A. Cumulative first live birth after elective cryopreservation of all embryos due to ovarian hyperresponsiveness.  Fertil Steril. 2004;  81(2) 309-314
    CrossrefPubMedGoogle Scholar
  • 40 Asch R H, Ivery G, Goldsman M, Frederick J L, Stone S C, Balmaceda J P. The use of intravenous albumin in patients at high risk for severe ovarian hyperstimulation syndrome.  Hum Reprod. 1993;  8(7) 1015-1020
    PubMedGoogle Scholar
  • 41 Shalev E, Giladi Y, Matilsky M, Ben-Ami M. Decreased incidence of severe ovarian hyperstimulation syndrome in high risk in-vitro fertilization patients receiving intravenous albumin: a prospective study.  Hum Reprod. 1995;  10(6) 1373-1376
    PubMedGoogle Scholar
  • 42 Aboulghar M A, Evers J H, Al-Inany H. Intra-venous albumin for preventing severe ovarian hyperstimulation syndrome.  Cochrane Database Syst Rev. 2000;  2(2) CD001302
    PubMedGoogle Scholar
  • 43 McClelland D B. ABC of transfusion. Human albumin solutions.  BMJ. 1990;  300(6716) 35-37
    CrossrefPubMedGoogle Scholar
  • 44 Isik A Z, Gokmen O, Zeyneloglu H B, Kara S, Keles G, Gulekli B. Intravenous albumin prevents moderate-severe ovarian hyperstimulation in in-vitro fertilization patients: a prospective, randomized and controlled study.  Eur J Obstet Gynecol Reprod Biol. 1996;  70(2) 179-183
    CrossrefPubMedGoogle Scholar
  • 45 Aboulghar M, Evers J H, Al-Inany H. Intravenous albumin for preventing severe ovarian hyperstimulation syndrome: a Cochrane review.  Hum Reprod. 2002;  17(12) 3027-3032
    CrossrefPubMedGoogle Scholar
  • 46 Bellver J, Muñoz E A, Ballesteros A et al. Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation syndrome in high-risk IVF patients: a randomized controlled study.  Hum Reprod. 2003;  18(11) 2283-2288
    CrossrefPubMedGoogle Scholar
  • 47 Chen C D, Chao K H, Yang J H, Chen S U, Ho H N, Yang Y S. Comparison of coasting and intravenous albumin in the prevention of ovarian hyperstimulation syndrome.  Fertil Steril. 2003;  80(1) 86-90
    PubMedGoogle Scholar
  • 48 Sauer M V, Paulson R J, Lobo R A. Rare occurrence of ovarian hyperstimulation syndrome in oocyte donors.  Int J Gynaecol Obstet. 1996;  52(3) 259-262
    CrossrefPubMedGoogle Scholar
  • 49 Halme J, Toma S K, Talbert L M. A case of severe ovarian hyperstimulation in a healthy oocyte donor.  Fertil Steril. 1995;  64(4) 857-859
    PubMedGoogle Scholar
  • 50 Pennings G, de Wert G, Shenfield F, Cohen J, Tarlatzis B, Devroey P. ESHRE Task Forse on Ethics and Law . ESHRE Task Force on Ethics and Law 12: oocyte donation for non-reproductive purposes.  Hum Reprod. 2007;  22(5) 1210-1213
    CrossrefPubMedGoogle Scholar
  • 51 Acevedo B, Gomez-Palomares J L, Ricciarelli E, Hernández E R. Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates.  Fertil Steril. 2006;  86(6) 1682-1687
    CrossrefPubMedGoogle Scholar
  • 52 Shapiro B S, Daneshmand S T, Garner F C, Aguirre M, Ross R. Comparison of human chorionic gonadotropin and gonadotropin-releasing hormone agonist for final oocyte maturation in oocyte donor cycles.  Fertil Steril. 2007;  88(1) 237-239
    CrossrefPubMedGoogle Scholar
  • 53 Hernández E R, Gómez-Palomares J L, Ricciarelli E. No room for cancellation, coasting, or ovarian hyperstimulation syndrome in oocyte donation cycles.  Fertil Steril. 2009;  91(4, Suppl) 1358-1361
    CrossrefPubMedGoogle Scholar

Zev RosenwaksM.D. 

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College

1305 York Avenue, New York, NY 10021

Email: rta9002@med.cornell.edu

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