Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT01921166 |
Other study ID # |
Diminished Ovarian Reserve |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
January 2011 |
Est. completion date |
March 2014 |
Study information
Verified date |
June 2021 |
Source |
Wake Forest University Health Sciences |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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
Description:
Women who are not eligible to participate in the CMC Assisted Reproductive Therapy (ART)
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 be "unlinked" from embryo transfer, allowing embryo transfer to occur in a
more optimal environment
- Endometrial preparation is routine for frozen embryo transfer Eligible patients will be
randomized to one of two protocols: clomiphene + HMG or leuprolide flare protocol.
All subjects must undergo pre-cycle IVF testing as per routine for the CMC ART program. In
general, the study will be comprised of subjects not eligible for IVF due to extremely poor
prognosis because of expected compromised ovarian stimulation (see inclusion criteria below).
Subjects are financially responsible for all treatments in this study. Randomized will be
performed by a random number generator after informed consent has been signed. Randomization
at this point will allow time to order and obtain required medications.
Cycle start requirements (performed cycle day 2 or 3):
- Basal Follicle Stimulating Hormone (FSH) 12 mIU/mL or less AND
- Basal estradiol 50 pg/mL or less AND
- Acceptable baseline ultrasound (no evidence of a condition for which IVF would be
contraindicated) If patient does not meet start requirements, delay and repeat cycle
start tests in the next IVF session.
Group 1: clomiphene + human menopausal gonadotropin Menopur ® (HMG)
- Clomiphene 100 mg cycle days 3-7 plus
- HMG 300 units daily beginning cycle day 3 and continued until day of HCG (Ovidrel)
administration
Group 2: leuprolide flare + HMG
- leuprolide acetate 0.5 mg twice daily beginning cycle day 3 and continued until day of
HCG (Ovidrel) administration
- HMG 300 units daily beginning cycle day 3 and continued until day of HCG (Ovidrel)
administration
Both groups:
- Follow-up ultrasound, estradiol cycle day 8. Cancel cycle if estradiol is < 200 pg/mL.
If estradiol is 200 pg/mL or higher, make HMG dose adjustments and schedule follow-up
estradiol and ultrasound visits as per routine IVF protocol.
- Administer Ovidrel 500 mg when 2nd largest follicle reaches a mean diameter of 18mm.
Cancel cycle if < 3 follicles 10mm or larger are recruited or if spontaneous ovulation
occurs.
- Retrieval: per standard IVF routine
- Vitrification: all viable oocytes will be vitrified on the day of oocyte retrieval.
- Remainder of stimulation cycle: no additional medications
- Stimulation and retrieval cycle may be repeated at patient request if < 5 oocytes are
vitrified to store additional oocytes for transfer cycle.
Transfer cycle:
- Programmed frozen embryo transfer protocol as per ART program routine: precycle
treatment with oral contraceptives (OCP), leuprolide administration during OCP, OCP
withdrawal bleeding, estrogen priming of endometrium, ultrasound assessment of
endometrium after 12-14 days, addition of daily progesterone when endometrial thickness
is 7mm or greater, oocyte warming/fertilization/transfer scheduled.
- Oocyte warming and intracytoplasmic sperm injection (ICSI): oocytes warmed on the 2nd
day of progesterone administration (example, if progesterone is started on Monday,
oocytes are warmed on Tuesday). Semen sample collected on day of warming and prepared
per IVF routine for ICSI. Mature viable oocytes undergo ICSI. Per ART laboratory
routine, oocytes are assessed for fertilization the following day. If embryos are
available for transfer, the embryo transfer procedure is performed according to standard
CMC ART program guidelines the 6-8 cell or blastocyst stage. If available, excess
embryos may be cryopreserved, at patients' request, as per CMC ART Program routine.
Follow-up hormonal therapy, pregnancy test(s), and ultrasound studies will be performed
per CMC ART program protocol.
Vitrified oocytes will be discarded or kept in storage according to the terms of our oocyte
storage agreement.
Crossover:
If a patient fails to conceive after the above, she may elect to cross-over into the opposite
treatment group