Optimizing Ovulation Induction in the Poor Responder - Full Text View

Purpose

The purpose of this randomized controlled trial is to compare the efficacy and effect of luteal estradiol and combined oral contraceptive pills (COPC) on follicle recruitment and synchrony in a poor responder population. The randomized groups consist of: 1. patients receiving luteal estradiol prior to ovulation induction; and 2. patients receiving COCPs for 1 month prior to ovulation induction. Follicle characteristics and serum biomarkers will be followed and compared in each group. Coefficient of variation will be used to evaluate follicle size discrepancy. Chi square analysis will be used to compare categorical variables between treatment groups. Both estradiol and COPCs are used clinically in assisted reproduction, so this study affords no additional risks to the participants.

Condition	Intervention
IVF Poor Responders	Drug: Estradiol Drug: Oral Contraceptive Pills (OCP)

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Optimizing Ovulation Induction in the Poor Responder: a Randomized Clinical Trial of Luteal Phase Estradiol Versus Combined Oral Contraceptive Pill on Ovarian Morphology and Biomarkers Prior to Ovulation Induction

Resource links provided by NLM:

Drug Information available for: Estradiol Estradiol cypionate Estradiol valerate Estradiol acetate Estradiol hemihydrate Ethynylestradiol mixture with norethindrone Ethinyl estradiol mixture with norethindrone

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Follicular response and synchrony [ Time Frame: 2 years ] [ Designated as safety issue: No ]
We will measure follicular response and synchrony following adminstration of extradiol patches or oral contraceptive pills.

Secondary Outcome Measures:

IVF outcomes [ Time Frame: 2 years ] [ Designated as safety issue: No ]
We will compare IVF outcomes in the estradiol patch and OCP groups.

Enrollment:	0
Study Start Date:	October 2010
Estimated Study Completion Date:	October 2012
Estimated Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Estradiol Patch This group of patients will receive estradiol patches prior to the IVF cycle.	Drug: Estradiol This group of patients will receive estradiol patches prior to the IVF cycle. Other Names: Vivelle-Dot Climara
Active Comparator: Oral Contraceptive Pills (OCP) This group of patients will receive OCP's prior to the IVF cycle.	Drug: Oral Contraceptive Pills (OCP) This group of patients will receive OCP's prior to the IVF cycle. Other Names: Loestrin Ortho-Novum

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Eligibility

Ages Eligible for Study:	20 Years to 50 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Antral follicle count < 8
Antimullerian hormone (AMH) <1.3
Follicle stimulating hormone (FSH)>10
History of follicular dysynchrony or poor response

Exclusion Criteria:

Menopause
FSH >40
Age > 50
Contraindication to estradiol or COCP (including pre-existing cardiovascular disease, familial thrombophilia (factor V Leiden), severe hypercholesterolemia, smoker over age 35) Ovulation induction during month of estradiol treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01200537

Locations

United States, North Carolina
Duke Fertility Center
Durham, North Carolina, United States, 27713

Sponsors and Collaborators

Duke University

Emory University

Investigators

Principal Investigator:	Susannah D Copland, MD	Duke University
Principal Investigator:	Donna Sessions, MD	Emory University

More Information

Publications:

Stephen EH, Chandra A. Updated projections of infertility in the United States: 1995-2025. Fertil Steril. 1998 Jul;70(1):30-4.

Keay SD, Liversedge NH, Mathur RS, Jenkins JM. Assisted conception following poor ovarian response to gonadotrophin stimulation. Br J Obstet Gynaecol. 1997 May;104(5):521-7. Review. No abstract available.

Fanchin R, Cunha-Filho JS, Schonäuer LM, Kadoch IJ, Cohen-Bacri P, Frydman R. Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens. Fertil Steril. 2003 Feb;79(2):316-21.

Fanchin R, Cunha-Filho JS, Schonäuer LM, Righini C, de Ziegler D, Frydman R. Luteal estradiol administration strengthens the relationship between day 3 follicle-stimulating hormone and inhibin B levels and ovarian follicular status. Fertil Steril. 2003 Mar;79(3):585-9.

Fanchin R, Salomon L, Castelo-Branco A, Olivennes F, Frydman N, Frydman R. Luteal estradiol pre-treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists. Hum Reprod. 2003 Dec;18(12):2698-703.

Fanchin R, Castelo Branco A, Kadoch IJ, Hosny G, Bagirova M, Frydman R. Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation. Fertil Steril. 2004 Jun;81(6):1554-9.

Dragisic KG, Davis OK, Fasouliotis SJ, Rosenwaks Z. Use of a luteal estradiol patch and a gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation for in vitro fertilization in poor responders. Fertil Steril. 2005 Oct;84(4):1023-6.

Check JH, Nowroozi K, Chase JS, Nazari A, Shapse D, Vaze M. Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea. Fertil Steril. 1990 May;53(5):811-6.

Gonen Y, Jacobson W, Casper RF. Gonadotropin suppression with oral contraceptives before in vitro fertilization. Fertil Steril. 1990 Feb;53(2):282-7.

Cohen J, Debache C, Solal P, Serkine AM, Achard B, Boujenah A, Pez JP, Paris X, Robert J, Loffredo V. Results of planned in-vitro fertilization programming through the pre-administration of the oestrogen-progesterone combined pill. Hum Reprod. 1987 Jan;2(1):7-9.

Biljan MM, Mahutte NG, Dean N, Hemmings R, Bissonnette F, Tan SL. Pretreatment with an oral contraceptive is effective in reducing the incidence of functional ovarian cyst formation during pituitary suppression by gonadotropin-releasing hormone analogues. J Assist Reprod Genet. 1998 Nov;15(10):599-604.

Lindheim SR, Barad DH, Witt B, Ditkoff E, Sauer MV. Short-term gonadotropin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation. J Assist Reprod Genet. 1996 Oct;13(9):745-7.

Scott RT, Navot D. Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonist during ovulation induction for in vitro fertilization. Fertil Steril. 1994 May;61(5):880-5.

Schoolcraft W, Schlenker T, Gee M, Stevens J, Wagley L. Improved controlled ovarian hyperstimulation in poor responder in vitro fertilization patients with a microdose follicle-stimulating hormone flare, growth hormone protocol. Fertil Steril. 1997 Jan;67(1):93-7.

Damario MA, Barmat L, Liu HC, Davis OK, Rosenwaks Z. Dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves in-vitro fertilization outcome in high responder patients. Hum Reprod. 1997 Nov;12(11):2359-65.

Dumesic DA, Damario MA, Session DR, Famuyide A, Lesnick TG, Thornhill AR, McNeilly AS. Ovarian morphology and serum hormone markers as predictors of ovarian follicle recruitment by gonadotropins for in vitro fertilization. J Clin Endocrinol Metab. 2001 Jun;86(6):2538-43.

Mercé LT, Gómez B, Engels V, Bau S, Bajo JM. Intraobserver and interobserver reproducibility of ovarian volume, antral follicle count, and vascularity indices obtained with transvaginal 3-dimensional ultrasonography, power Doppler angiography, and the virtual organ computer-aided analysis imaging program. J Ultrasound Med. 2005 Sep;24(9):1279-87.

Scheffer GJ, Broekmans FJ, Bancsi LF, Habbema JD, Looman CW, Te Velde ER. Quantitative transvaginal two- and three-dimensional sonography of the ovaries: reproducibility of antral follicle counts. Ultrasound Obstet Gynecol. 2002 Sep;20(3):270-5.

Pöhl M, Hohlagschwandtner M, Obruca A, Poschalko G, Weigert M, Feichtinger W. Number and size of antral follicles as predictive factors in vitro fertilization and embryo transfer. J Assist Reprod Genet. 2000 Jul;17(6):315-8.

Tomas C, Nuojua-Huttunen S, Martikainen H. Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization. Hum Reprod. 1997 Feb;12(2):220-3.

Yong PY, Baird DT, Thong KJ, McNeilly AS, Anderson RA. Prospective analysis of the relationships between the ovarian follicle cohort and basal FSH concentration, the inhibin response to exogenous FSH and ovarian follicle number at different stages of the normal menstrual cycle and after pituitary down-regulation. Hum Reprod. 2003 Jan;18(1):35-44.

Fanchin R, Louafi N, Méndez Lozano DH, Frydman N, Frydman R, Taieb J. Per-follicle measurements indicate that anti-müllerian hormone secretion is modulated by the extent of follicular development and luteinization and may reflect qualitatively the ovarian follicular status. Fertil Steril. 2005 Jul;84(1):167-73.

Fanchin R, Méndez Lozano DH, Louafi N, Achour-Frydman N, Frydman R, Taieb J. Dynamics of serum anti-Müllerian hormone levels during the luteal phase of controlled ovarian hyperstimulation. Hum Reprod. 2005 Mar;20(3):747-51. Epub 2004 Dec 23.

Fanchin R, Taieb J, Lozano DH, Ducot B, Frydman R, Bouyer J. High reproducibility of serum anti-Mullerian hormone measurements suggests a multi-staged follicular secretion and strengthens its role in the assessment of ovarian follicular status. Hum Reprod. 2005 Apr;20(4):923-7. Epub 2005 Jan 7.

Responsible Party:	Susannah Copland, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:	NCT01200537 History of Changes
Other Study ID Numbers:	Pro00022374
Study First Received:	August 23, 2010
Last Updated:	November 19, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Duke University:

IVF
poor responders
follicle synchrony
IVF response

estrogen
estradiol (E2)
oral contraceptive pill (OCP)
birth control pill (BCP)

Additional relevant MeSH terms:

Contraceptive Agents
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Norinyl
Contraceptives, Oral
Contraceptives, Oral, Combined
Estradiol
Polyestradiol phosphate

Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on May 19, 2013