Optimizing Ovulation Induction in the Poor Responder

NCT01200537 | Withdrawn

• 1 other identifier: Pro00022374
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

IVF Poor Responders

Keywords

IVF; poor responders; follicle synchrony; IVF response; estrogen; estradiol (E2); oral contraceptive pill (OCP); birth control pill (BCP)

Outcome Measures

Primary Outcomes (1)

• Follicular response and synchrony

  We will measure follicular response and synchrony following adminstration of extradiol patches or oral contraceptive pills.

  2 years

Secondary Outcomes (1)

• IVF outcomes

  2 years

Study Arms (2)

Estradiol Patch

ACTIVE COMPARATOR

This group of patients will receive estradiol patches prior to the IVF cycle.

Drug: Estradiol

Oral Contraceptive Pills (OCP)

ACTIVE COMPARATOR

This group of patients will receive OCP's prior to the IVF cycle.

Drug: Oral Contraceptive Pills (OCP)

Interventions

Estradiol DRUG

This group of patients will receive estradiol patches prior to the IVF cycle.

Also known as: Vivelle-Dot, Climara

Estradiol Patch

Oral Contraceptive Pills (OCP) DRUG

This group of patients will receive OCP's prior to the IVF cycle.

Also known as: Loestrin, Ortho-Novum

Oral Contraceptive Pills (OCP)

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Emory University: collaborator

Study Sites (1)

Duke Fertility Center

Durham, North Carolina, 27713, United States

Location

Related Publications (24)

• Stephen EH, Chandra A. Updated projections of infertility in the United States: 1995-2025. Fertil Steril. 1998 Jul;70(1):30-4. doi: 10.1016/s0015-0282(98)00103-4.

  PMID: 9660416 BACKGROUND

• 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. doi: 10.1111/j.1471-0528.1997.tb11525.x. No abstract available.

  PMID: 9166190 BACKGROUND

• Fanchin R, Cunha-Filho JS, Schonauer 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. doi: 10.1016/s0015-0282(02)04574-0.

  PMID: 12568840 BACKGROUND

• Fanchin R, Cunha-Filho JS, Schonauer 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. doi: 10.1016/s0015-0282(02)04757-x.

  PMID: 12620444 BACKGROUND

• 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. doi: 10.1093/humrep/deg516.

  PMID: 14645194 BACKGROUND

• 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. doi: 10.1016/j.fertnstert.2003.11.037.

  PMID: 15193476 BACKGROUND

• 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. doi: 10.1016/j.fertnstert.2005.04.031.

  PMID: 16213865 BACKGROUND

• 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. doi: 10.1016/s0015-0282(16)53514-6.

  PMID: 2110073 BACKGROUND

• Gonen Y, Jacobson W, Casper RF. Gonadotropin suppression with oral contraceptives before in vitro fertilization. Fertil Steril. 1990 Feb;53(2):282-7. doi: 10.1016/s0015-0282(16)53282-8.

  PMID: 2105244 BACKGROUND

• 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. doi: 10.1093/oxfordjournals.humrep.a136491.

  PMID: 3106405 BACKGROUND

• 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. doi: 10.1023/a:1020381310860.

  PMID: 9866068 BACKGROUND

• 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. doi: 10.1007/BF02066431.

  PMID: 8947826 BACKGROUND

• 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. doi: 10.1016/s0015-0282(16)56700-4.

  PMID: 8174725 BACKGROUND

• 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. doi: 10.1016/s0015-0282(97)81862-6.

  PMID: 8986690 BACKGROUND

• 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. doi: 10.1093/humrep/12.11.2359.

  PMID: 9436663 BACKGROUND

• 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. doi: 10.1210/jcem.86.6.7605.

  PMID: 11397852 BACKGROUND

• Merce LT, Gomez 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. doi: 10.7863/jum.2005.24.9.1279.

  PMID: 16123188 BACKGROUND

• 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. doi: 10.1046/j.1469-0705.2002.00787.x.

  PMID: 12230451 BACKGROUND

• Pohl 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. doi: 10.1023/a:1009448810413.

  PMID: 11042827 BACKGROUND

• 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. doi: 10.1093/humrep/12.2.220.

  PMID: 9070699 BACKGROUND

• 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. doi: 10.1093/humrep/deg019.

  PMID: 12525438 BACKGROUND

• Fanchin R, Louafi N, Mendez Lozano DH, Frydman N, Frydman R, Taieb J. Per-follicle measurements indicate that anti-mullerian 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. doi: 10.1016/j.fertnstert.2005.01.115.

  PMID: 16009173 BACKGROUND

• Fanchin R, Mendez Lozano DH, Louafi N, Achour-Frydman N, Frydman R, Taieb J. Dynamics of serum anti-Mullerian hormone levels during the luteal phase of controlled ovarian hyperstimulation. Hum Reprod. 2005 Mar;20(3):747-51. doi: 10.1093/humrep/deh669. Epub 2004 Dec 23.

  PMID: 15618255 BACKGROUND

• 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. doi: 10.1093/humrep/deh688. Epub 2005 Jan 7.

  PMID: 15640257 BACKGROUND

MeSH Terms

Interventions

Estradiol; norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination; Norinyl

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

Study Officials

• Susannah D Copland, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Donna Sessions, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 23, 2010
• First Posted: September 13, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2012
• Last Updated: November 21, 2012

Record last verified: 2012-11

Locations

US (1)