Luteal Phase Estradiol Support for In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles

NCT02677259 | Unknown Phase 2

• 1 other identifier: 0564
• Study Type: interventional
• Target: 506
• Locations: 0 countries
• Sites: N/A

Brief Summary

Optimizing in vitro fertilization (IVF) success is more important than ever, in light of new public funding of IVF in Ontario, Canada. In patients undergoing IVF using gonadotropin-releasing hormone (GnRH) analogues, the luteal phase appears to be compromised, which may be a result of controlled-ovarian hyperstimulation, significant fluctuations in hormone levels, the impact of the oocyte retrieval process, or direct compromise of the corpus luteum. Progesterone support is definitely necessary during the luteal phase to facilitate implantation but whether estrogen supplementation is also needed remains unclear. The present study aims to determine whether estradiol support during the luteal phase improves clinical pregnancy rate in patients undergoing IVF.

Conditions

IVF

Keywords

luteal phase; estradiol; pregnancy rate

Outcome Measures

Primary Outcomes (1)

• Clinical Pregnancy

  Presence of fetal heart activity on ultrasound at or beyond 6 weeks gestation.

  Assessed at 6 weeks gestation

Secondary Outcomes (5)

• Ongoing Pregnancy Rate

  Assessed at 12+1 weeks gestation

• Implantation Rate

  Assessed at 6 weeks gestation

• Luteal phase serum estradiol and progesterone concentration

  Performed at oocyte retrieval, 10 days after retrieval, and at the time of serum pregnancy testing, i.e. 17 days after retrieval

• Miscarriage Rate

  Assessed at 6 - 20 weeks gestation

• Ectopic Pregnancy Rate

  Assessed at 6 weeks gestation

Study Arms (2)

Estradiol + Standard Luteal Phase Support

EXPERIMENTAL

1. 17-beta estradiol 3 mg PO/PV BID from day of oocyte retrieval until 6 weeks gestation 2. Micronized progesterone 200 mg PV TID from day of oocyte retrieval until 10 weeks gestation

Drug: 17-beta estradiol; Drug: Micronized progesterone

Standard Luteal Phase Support

ACTIVE COMPARATOR

1\. Micronized progesterone 200 mg PV TID from day of oocyte retrieval until 10 weeks gestation

Drug: Micronized progesterone

Interventions

17-beta estradiol DRUG

Also known as: Estrace

Estradiol + Standard Luteal Phase Support

Micronized progesterone DRUG

Also known as: Endometrin

Estradiol + Standard Luteal Phase Support; Standard Luteal Phase Support

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Indications for IVF/ICSI include male factor, diminished ovarian reserve, tubal factor, ovulatory dysfunction and unexplained infertility.

You may not qualify if:

• none

Sponsors & Collaborators

• One Fertility: lead

Related Publications (21)

• Jee BC, Suh CS, Kim SH, Kim YB, Moon SY. Effects of estradiol supplementation during the luteal phase of in vitro fertilization cycles: a meta-analysis. Fertil Steril. 2010 Feb;93(2):428-36. doi: 10.1016/j.fertnstert.2009.02.033. Epub 2009 Apr 1.

  PMID: 19342034 BACKGROUND

• Smitz J, Devroey P, Camus M, Deschacht J, Khan I, Staessen C, Van Waesberghe L, Wisanto A, Van Steirteghem AC. The luteal phase and early pregnancy after combined GnRH-agonist/HMG treatment for superovulation in IVF or GIFT. Hum Reprod. 1988 Jul;3(5):585-90. doi: 10.1093/oxfordjournals.humrep.a136750.

  PMID: 3139698 BACKGROUND

• Smith EM, Anthony FW, Gadd SC, Masson GM. Trial of support treatment with human chorionic gonadotrophin in the luteal phase after treatment with buserelin and human menopausal gonadotrophin in women taking part in an in vitro fertilisation programme. BMJ. 1989 Jun 3;298(6686):1483-6. doi: 10.1136/bmj.298.6686.1483.

  PMID: 2503080 BACKGROUND

• Belaisch-Allart J, De Mouzon J, Lapousterle C, Mayer M. The effect of HCG supplementation after combined GnRH agonist/HMG treatment in an IVF programme. Hum Reprod. 1990 Feb;5(2):163-6. doi: 10.1093/oxfordjournals.humrep.a137062.

  PMID: 2108990 BACKGROUND

• van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2015 Jul 7;2015(7):CD009154. doi: 10.1002/14651858.CD009154.pub3.

  PMID: 26148507 BACKGROUND

• Fritz MA, Westfahl PK, Graham RL. The effect of luteal phase estrogen antagonism on endometrial development and luteal function in women. J Clin Endocrinol Metab. 1987 Nov;65(5):1006-13. doi: 10.1210/jcem-65-5-1006.

  PMID: 3667871 BACKGROUND

• Goldstein D, Zuckerman H, Harpaz S, Barkai J, Geva A, Gordon S, Shalev E, Schwartz M. Correlation between estradiol and progesterone in cycles with luteal phase deficiency. Fertil Steril. 1982 Mar;37(3):348-54.

  PMID: 7060785 BACKGROUND

• Ganesh A, Goswami S, Chattopadhyay R, Chakraborty C, Chaudhury K, Chakravarty BN. Luteal phase estradiol level: a potential predictive marker for successful pregnancy in in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2009 Apr;91(4):1018-22. doi: 10.1016/j.fertnstert.2008.01.074. Epub 2008 Mar 21.

  PMID: 18359023 BACKGROUND

• Hutchinson-Williams KA, Lunenfeld B, Diamond MP, Lavy G, Boyers SP, DeCherney AH. Human chorionic gonadotropin, estradiol, and progesterone profiles in conception and nonconception cycles in an in vitro fertilization program. Fertil Steril. 1989 Sep;52(3):441-5. doi: 10.1016/s0015-0282(16)60915-9.

  PMID: 2776898 BACKGROUND

• Emperaire JC, Ruffie A, Audebert AJ, Verdaguer S. Early prognosis for IVF pregnancies through plasma oestrogens. Lancet. 1984 Nov 17;2(8412):1151. doi: 10.1016/s0140-6736(84)91577-0. No abstract available.

  PMID: 6150201 BACKGROUND

• Sharara FI, McClamrock HD. Ratio of oestradiol concentration on the day of human chorionic gonadotrophin administration to mid-luteal oestradiol concentration is predictive of in-vitro fertilization outcome. Hum Reprod. 1999 Nov;14(11):2777-82. doi: 10.1093/humrep/14.11.2777.

  PMID: 10548621 BACKGROUND

• Farhi J, Weissman A, Steinfeld Z, Shorer M, Nahum H, Levran D. Estradiol supplementation during the luteal phase may improve the pregnancy rate in patients undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril. 2000 Apr;73(4):761-6. doi: 10.1016/s0015-0282(99)00632-9.

  PMID: 10731538 BACKGROUND

• Lukaszuk K, Liss J, Lukaszuk M, Maj B. Optimization of estradiol supplementation during the luteal phase improves the pregnancy rate in women undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril. 2005 May;83(5):1372-6. doi: 10.1016/j.fertnstert.2004.11.055.

  PMID: 15866571 BACKGROUND

• Var T, Tonguc EA, Doganay M, Gulerman C, Gungor T, Mollamahmutoglu L. A comparison of the effects of three different luteal phase support protocols on in vitro fertilization outcomes: a randomized clinical trial. Fertil Steril. 2011 Mar 1;95(3):985-9. doi: 10.1016/j.fertnstert.2010.06.057. Epub 2010 Aug 2.

  PMID: 20674911 BACKGROUND

• Elgindy EA, El-Haieg DO, Mostafa MI, Shafiek M. Does luteal estradiol supplementation have a role in long agonist cycles? Fertil Steril. 2010 May 1;93(7):2182-8. doi: 10.1016/j.fertnstert.2009.01.066. Epub 2009 Feb 24.

  PMID: 19243745 BACKGROUND

• Gorkemli H, Ak D, Akyurek C, Aktan M, Duman S. Comparison of pregnancy outcomes of progesterone or progesterone + estradiol for luteal phase support in ICSI-ET cycles. Gynecol Obstet Invest. 2004;58(3):140-4. doi: 10.1159/000079115. Epub 2004 Jun 15.

  PMID: 15205566 BACKGROUND

• Engmann L, DiLuigi A, Schmidt D, Benadiva C, Maier D, Nulsen J. The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study. Fertil Steril. 2008 Mar;89(3):554-61. doi: 10.1016/j.fertnstert.2007.04.006. Epub 2007 Aug 2.

  PMID: 17678651 BACKGROUND

• Ceyhan ST, Basaran M, Kemal Duru N, Yilmaz A, Goktolga U, Baser I. Use of luteal estrogen supplementation in normal responder patients treated with fixed multidose GnRH antagonist: a prospective randomized controlled study. Fertil Steril. 2008 Jun;89(6):1827-30. doi: 10.1016/j.fertnstert.2007.08.029. Epub 2007 Dec 11.

  PMID: 18054930 BACKGROUND

• Huang N, Situ B, Chen X, Liu J, Yan P, Kang X, Kong S, Huang M. Meta-analysis of estradiol for luteal phase support in in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2015 Feb;103(2):367-73.e5. doi: 10.1016/j.fertnstert.2014.10.029. Epub 2014 Dec 6.

  PMID: 25492682 BACKGROUND

• Fatemi HM, Kolibianakis EM, Camus M, Tournaye H, Donoso P, Papanikolaou E, Devroey P. Addition of estradiol to progesterone for luteal supplementation in patients stimulated with GnRH antagonist/rFSH for IVF: a randomized controlled trial. Hum Reprod. 2006 Oct;21(10):2628-32. doi: 10.1093/humrep/del117. Epub 2006 Jul 20.

  PMID: 16857887 BACKGROUND

• Beckers NG, Macklon NS, Eijkemans MJ, Ludwig M, Felberbaum RE, Diedrich K, Bustion S, Loumaye E, Fauser BC. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment. J Clin Endocrinol Metab. 2003 Sep;88(9):4186-92. doi: 10.1210/jc.2002-021953.

  PMID: 12970285 BACKGROUND

MeSH Terms

Interventions

Estradiol; Progesterone

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners

Central Study Contacts

Evan Taerk, MD,MSc

CONTACT

4167372033; evantaerk@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Evan Taerk

Study Record Dates

• First Submitted: February 4, 2016
• First Posted: February 9, 2016
• Study Start: May 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: February 10, 2016

Record last verified: 2016-02