Maximal Stimulation and Delayed Fertilization for Diminished Ovarian Reserve: a Randomized Pilot Study

• Sponsor: Atrium Health
• Information provided by (Responsible Party): Brad Hurst, Atrium Health

Study Description

Brief Summary:

The purpose of the study is (A) to determine if the following novel approach improves the live birth rate with In-Vitro Fertilization (IVF) for women with a poor prognosis due to diminished ovarian reserve:

• ovarian stimulation with medications that are effective in women with diminished ovarian reserve but adversely affect the endometrium
• oocyte retrieval and vitrification
• fertilization and embryo transfer in a subsequent cycle with controlled endometrial preparation B) To determine the optimal stimulation protocol for women with diminished ovarian reserve incorporating oocyte vitrification

Women who are not eligible to participate in the Carolinas Medical Center (CMC) Assisted Reproductive Therapy program because of an extremely poor prognosis will be recruited for a prospective, randomized, open-label study to determine if a novel approach improves the live birth rate with traditional IVF "poor prognosis" stimulation protocols. The novel approach will incorporate one of two protocols utilizing medications that provide maximal ovarian stimulation but have a temporary detrimental fertility-reducing effect on the endometrium. If ovarian stimulation is adequate, oocyte retrieval will be performed and viable oocytes vitrified (stored in a "glass-like" state in liquid nitrogen). At a later time, oocyte warming and fertilization will be performed in a subsequent cycle, in which the endometrium has been prepared.

Key points include:

• Randomization to one of two ovarian stimulation protocols that have been shown to have a detrimental effect on the endometrium, and therefore are rarely used in a "fresh" IVF cycle
• Oocyte vitrification is considered to be an investigational procedure by the American Society of Reproductive Medicine (ASRM), and should only be performed under the supervision of an IRB. With oocyte vitrification, ovarian stimulation and oocyte retrieval can "unlinked" from embryo transfer, allowing embryo transfer to occur in a more optimal environment
• Endometrial preparation is routine for frozen embryo transfer

Condition or disease	Intervention/treatment	Phase
Infertility	Drug: clomiphene plus gonadotropins; Drug: Leuprolide flare	Phase 4

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Maximal Stimulation and Delayed Fertilization for Diminished Ovarian Reserve: a Randomized Pilot Study
• Study Start Date: January 2011
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: March 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: clomiphene plus gonadotropins; clomiphene plus gonadotropins	Drug: clomiphene plus gonadotropins; clomiphene plus gonadotropin ovulation induction; Other Name: Clomid. Serophene. Gonal f. Bravelle. Follistim. Menopur.
Active Comparator: Leuprolide flare; Leuprolide flare	Drug: Leuprolide flare; Leuprolide flare ovulation induction; Other Name: Lupron.

Outcome Measures

Primary Outcome Measures :

1. Oocytes [ Time Frame: up to 24 months ]
   Number of oocytes retrieved

Secondary Outcome Measures :

1. Number of Oocytes Vitrified [ Time Frame: up to 24 months ]

Other Outcome Measures:

1. Number of Embryos From Vitrified Oocytes [ Time Frame: up to 24 months ]
   per ovarian stimulation treatment protocol

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Basal FSH 17 IU/mL (highest ever)
• Basal FSH 15-17 (highest ever) and failed EFORT test
• Age > 43 at the time of expected retrieval
• Failure to conceive with a prior "poor prognosis" IVF stimulation protocol (microdose leuprolide flare or GnRH antagonist cycle) if administered because of evidence of diminished ovarian reserve
• Failure to conceive with 3 or more IVF cycles at CMC

Exclusion Criteria:

• Contraindications to IVF
• Contraindication to pregnancy
• Allergy or contraindication to medications used for IVF or embryo transfer
• Use for a gestational carrier
• Uncorrected or untreatable uterine infertility
• Smoking or substance abuse within 3 months of initiating stimulation for IVF

Contacts and Locations

Sponsors and Collaborators

Atrium Health

Investigators

• Principal Investigator: Bradley S Hurst, M.D.; Atrium Health

More Information

• Responsible Party: Brad Hurst, Director, Assisted Reproductive Therapies, Atrium Health
• ClinicalTrials.gov Identifier: NCT01921166 History of Changes
• Other Study ID Numbers: Diminished Ovarian Reserve
• First Posted: August 13, 2013
• Results First Posted: February 23, 2018
• Last Update Posted: February 23, 2018
• Last Verified: January 2018

Keywords provided by Brad Hurst, Atrium Health:

infertility; diminished ovarian reserve; fertilization in vitro; ovulation inducion; vitrification

Additional relevant MeSH terms:

Infertility; Genital Diseases, Male; Genital Diseases, Female; Clomiphene; Enclomiphene; Zuclomiphene; Leuprolide; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Antineoplastic Agents, Hormonal; Antineoplastic Agents