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

NCT ID: NCT01367912

Last Updated: 2011-06-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

301 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-29

Study Completion Date

2008-11-30

Brief Summary

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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).

Detailed Description

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Several studies reported that elevated E2 may have a detrimental effect on endometrial receptivity and embryo. This conflict was the starting point of our study. The investigators thought that this luteal decrease in E2 level could be prevented by adding estradiol just before the receptivity window is open, instead of adding earlier in the luteal phase which could result in defective embryo implantation.

Conditions

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Infertility

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Progesterone only group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Progesterone+Early Estradiol group

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

Group Type ACTIVE_COMPARATOR

estradiol tablet

Intervention Type DRUG

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

Progesterone+Late estradiol group

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

Group Type ACTIVE_COMPARATOR

estradiol tablet

Intervention Type DRUG

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

Interventions

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estradiol tablet

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

Intervention Type DRUG

estradiol tablet

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

Intervention Type DRUG

Other Intervention Names

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estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark estrofem 2 mg tablet, Novo Nordisk, Bagsvaerd, Denmark

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

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

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Zekai Tahir Burak Women's Health Research and Education Hospital

OTHER

Sponsor Role lead

Responsible Party

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Zekai Tahir Burak Maternity and Teaching Hospital, Murat ÖZEL, M.D.

Principal Investigators

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Leyla Mollamahmutoğlu, MD

Role: STUDY_DIRECTOR

Zekai Tahir Burak Women's Health Research and Education Hospital

Locations

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Zekai Tahir Burak Maternity and Teaching Hospital

Ankara, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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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.

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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.

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Reference Type BACKGROUND
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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.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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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.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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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.

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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.

Reference Type BACKGROUND
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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.

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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.

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Reference Type 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.

Reference Type RESULT
PMID: 21067858 (View on PubMed)

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.

Reference Type 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.

Reference Type RESULT

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

Reference Type RESULT

Other Identifiers

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ZTB

Identifier Type: -

Identifier Source: org_study_id

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