Timing of Estrogen Support During the Luteal Phase of in Vitro Fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) Cycle

NCT01367912 | Completed

• 1 other identifier: ZTB
• Study Type: interventional
• Target: 301
• Locations: 1 country
• Sites: 1

Brief Summary

To test the hypothesis that adding estradiol (E2) to progesterone supplementation later in the luteal phase of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, rather than earlier in the luteal phase, improves clinical pregnancy rates (PRs).

Conditions

Infertility

Keywords

Luteal phase support; estradiol supplementation; IVF/ICSI; clinical pregnancy rate

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy rate

  Clinical pregnancies were detected with the confirmation of positive fetal cardiac activities by transvaginal sonography in the sixth gestational week.

  sixth gestational week.

Study Arms (3)

Progesterone only group

NO INTERVENTION

received a single daily application of vaginal progesterone gel beginning from the day of OPU and continued at least until pregnancy was ruled out by a negative serum ß-hCG measurement performed on the 14th day after embryo transfer with no E2 added

Progesterone+Early Estradiol group

ACTIVE COMPARATOR

received 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel

Drug: estradiol tablet

Progesterone+Late estradiol group

ACTIVE COMPARATOR

received 2 mg estradiol tablets orally two times daily beginning from the fifth day after hCG injection, in addition to vaginal progesterone gel

Drug: estradiol tablet

Interventions

estradiol tablet DRUG

received 2 mg estradiol tablets orally two times daily beginning from the first day after hCG injection, in addition to vaginal progesterone gel

Also known as: estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark

Progesterone+Early Estradiol group

Eligibility Criteria

• Age: Up to 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• All patients on long GnRH agonist protocol with controlled ovarian hyperstimulation who were seen in our IVF clinic between February and November 2008, and who have E2 levels on the day of hCG administration \>2500 pg/dl

You may not qualify if:

• Presence of azoospermia requiring testicular sperm extraction procedure
• endometriosis greater than stage II
• unilateral oophorectomy, polycystic ovarian syndrome (PCOS)
• secondary infertility

Sponsors & Collaborators

• Zekai Tahir Burak Women's Health Research and Education Hospital: lead

Study Sites (1)

Zekai Tahir Burak Maternity and Teaching Hospital

Ankara, 06220, Turkey (Türkiye)

Location

Related Publications (30)

• Ubaldi F, Bourgain C, Tournaye H, Smitz J, Van Steirteghem A, Devroey P. Endometrial evaluation by aspiration biopsy on the day of oocyte retrieval in the embryo transfer cycles in patients with serum progesterone rise during the follicular phase. Fertil Steril. 1997 Mar;67(3):521-6. doi: 10.1016/s0015-0282(97)80080-5.

  PMID: 9091341 BACKGROUND

• Kolibianakis EM, Devroey P. The luteal phase after ovarian stimulation. Reprod Biomed Online. 2002;5 Suppl 1:26-35. doi: 10.1016/s1472-6483(11)60214-9.

  PMID: 12537779 BACKGROUND

• Fauser BC, Devroey P. Reproductive biology and IVF: ovarian stimulation and luteal phase consequences. Trends Endocrinol Metab. 2003 Jul;14(5):236-42. doi: 10.1016/s1043-2760(03)00075-4.

  PMID: 12826330 BACKGROUND

• Devreker F, Govaerts I, Bertrand E, Van den Bergh M, Gervy C, Englert Y. The long-acting gonadotropin-releasing hormone analogues impaired the implantation rate. Fertil Steril. 1996 Jan;65(1):122-6.

  PMID: 8557126 BACKGROUND

• Daya S, Gunby J. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2004;(3):CD004830. doi: 10.1002/14651858.CD004830.

  PMID: 15266541 BACKGROUND

• Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002 Sep;17(9):2287-99. doi: 10.1093/humrep/17.9.2287.

  PMID: 12202415 BACKGROUND

• 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

• Gelbaya TA, Kyrgiou M, Tsoumpou I, Nardo LG. The use of estradiol for luteal phase support in in vitro fertilization/intracytoplasmic sperm injection cycles: a systematic review and meta-analysis. Fertil Steril. 2008 Dec;90(6):2116-25. doi: 10.1016/j.fertnstert.2007.10.053. Epub 2008 Jan 7.

  PMID: 18178194 BACKGROUND

• Kolibianakis EM, Venetis CA, Papanikolaou EG, Diedrich K, Tarlatzis BC, Griesinger G. Estrogen addition to progesterone for luteal phase support in cycles stimulated with GnRH analogues and gonadotrophins for IVF: a systematic review and meta-analysis. Hum Reprod. 2008 Jun;23(6):1346-54. doi: 10.1093/humrep/den115. Epub 2008 Apr 11.

  PMID: 18408017 BACKGROUND

• Buvat J, Marcolin G, Guittard C, Dehaene JL, Herbaut JC, Louvet AL. [Luteal support after administration of an LHRH analog for in vitro fertilization. Superiority of vaginal progesterone in comparison with oral progesterone]. Presse Med. 1990 Mar 24;19(11):527. No abstract available. French.

  PMID: 2138757 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

• Bergh PA, Navot D. The impact of embryonic development and endometrial maturity on the timing of implantation. Fertil Steril. 1992 Sep;58(3):537-42. doi: 10.1016/s0015-0282(16)55259-5.

  PMID: 1521649 BACKGROUND

• Muasher S, Acosta AA, Garcia JE, Jones GS, Jones HW Jr. Luteal phase serum estradiol and progesterone in in vitro fertilization. Fertil Steril. 1984 Jun;41(6):838-43. doi: 10.1016/s0015-0282(16)47895-7.

  PMID: 6427017 BACKGROUND

• Yang JH, Chen HF, Lien YR, Chen SU, Ho HN, Yang YS. Elevated E2: oocyte ratio in women undergoing IVF and tubal ET. Correlation with a decrease in the implantation rate. J Reprod Med. 2001 May;46(5):434-8.

  PMID: 11396368 BACKGROUND

• Valbuena D, Martin J, de Pablo JL, Remohi J, Pellicer A, Simon C. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril. 2001 Nov;76(5):962-8. doi: 10.1016/s0015-0282(01)02018-0.

  PMID: 11704118 BACKGROUND

• Smitz J, Bourgain C, Van Waesberghe L, Camus M, Devroey P, Van Steirteghem AC. A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation. Hum Reprod. 1993 Jan;8(1):40-5. doi: 10.1093/oxfordjournals.humrep.a137871.

  PMID: 8458924 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

• Lewin A, Benshushan A, Mezker E, Yanai N, Schenker JG, Goshen R. The role of estrogen support during the luteal phase of in vitro fertilization-embryo transplant cycles: a comparative study between progesterone alone and estrogen and progesterone support. Fertil Steril. 1994 Jul;62(1):121-5. doi: 10.1016/s0015-0282(16)56826-5.

  PMID: 8005275 BACKGROUND

• Tay PY, Lenton EA. Inhibition of progesterone secretion by oestradiol administered in the luteal phase of assisted conception cycles. Med J Malaysia. 2003 Jun;58(2):187-95.

  PMID: 14569738 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

• Younis JS, Ezra Y, Sherman Y, Simon A, Schenker JG, Laufer N. The effect of estradiol depletion during the luteal phase on endometrial development. Fertil Steril. 1994 Jul;62(1):103-7. doi: 10.1016/s0015-0282(16)56823-x.

  PMID: 8005273 BACKGROUND

• Vlahos NF, Lipari CW, Bankowski B, Lai TH, King JA, Shih IeM, Fragakis K, Zhao Y. Effect of luteal-phase support on endometrial L-selectin ligand expression after recombinant follicle-stimulating hormone and ganirelix acetate for in vitro fertilization. J Clin Endocrinol Metab. 2006 Oct;91(10):4043-9. doi: 10.1210/jc.2006-0520. Epub 2006 Jul 25.

  PMID: 16868054 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

• 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

• Serna J, Cholquevilque JL, Cela V, Martinez-Salazar J, Requena A, Garcia-Velasco JA. Estradiol supplementation during the luteal phase of IVF-ICSI patients: a randomized, controlled trial. Fertil Steril. 2008 Dec;90(6):2190-5. doi: 10.1016/j.fertnstert.2007.10.021. Epub 2008 Jan 14.

  PMID: 18191847 BACKGROUND

• Pouly JL, Piekrishvili R, Beaume-BrugonF, Schubert B, Janny L. Luteal phase supplementation with oestrogens doesn't improve the IVF pregnancy rate: a randomized study. Hum Reprod 2005; 20:O- 195.

  RESULT

• Tonguc E, Var T, Ozyer S, Citil A, Dogan M. Estradiol supplementation during the luteal phase of in vitro fertilization cycles: a prospective randomised study. Eur J Obstet Gynecol Reprod Biol. 2011 Feb;154(2):172-6. doi: 10.1016/j.ejogrb.2010.10.003. Epub 2010 Nov 9.

  PMID: 21067858 RESULT

• Causio F, Leonetti T. Luteal phase support with estrogen and progesterone in in vitro fertilization cycles using GnRHa and FSH. Gior Ital Ostet Ginecol 1997; 19: 277-82.

  RESULT

• Rashidi BH, Asheghan H, Jafarabadi M, Tehrani NE. The role of estrogen supplementation during the luteal phase in in vitro fertilization-embryo transfer cycles: a comparative study between progesterone and estrogen plus progesterone support. Proceedings of the 18th World Congress on Fertility and sterility; 2004 May 23-28; Montreal, Canada. Internatioanal Congress Series; 2004.p.120-123.

  RESULT

• Elnashar AM, Aboul-Enein GI. Endometrial receptivity. Middle East Fertil Soc J 2004; 9 (1): 10-24).

  RESULT

MeSH Terms

Conditions

Infertility

Interventions

Estradiol; estradiol, estriol drug combination; Tablets

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

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; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Leyla Mollamahmutoğlu, MD

  Zekai Tahir Burak Women's Health Research and Education Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: June 7, 2011
• Study Start: February 1, 2008
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: June 7, 2011

Record last verified: 2008-11

Locations

TU (1)