Mono-menotropins Versus Mixed Gonadotropin/Menotropins Protocol on Embryo Quality
| Status: | Recruiting |
|---|---|
| Conditions: | Women's Studies, Infertility |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 21 - 38 |
| Updated: | 4/2/2016 |
| Start Date: | March 2015 |
| End Date: | October 2016 |
| Contact: | Eileen Davies |
| Email: | daviese@mainlinefertility.com |
| Phone: | 484-380-4861 |
A Prospective, Randomized Trial to Compare Mono-menotropins Protocol for Controlled Ovarian Stimulation (COS) Versus Mixed Gonadotropin/Menotropins Protocol on Embryo Quality Parameters
This study is for couples pursuing in vitro fertilization (IVF) with preimplantation genetic
screening (PGS) of embryos to achieve pregnancy. The objective of this clinical trial is to
study the effect of mono-menotropins for COS versus mixed protocol of
urofollitropin/menotropins on cleavage-stage and blastocyst embryo quality after IVF. Embryo
quality parameters include conventional embryo grade, early embryo viability assessment
(Eeva) time-lapse parameters, and chromosomal aneuploidy rates after PGS.
This pilot study is expected to significantly contribute to optimization of treatment
regimens and stimulation protocols to optimize embryo quality.
screening (PGS) of embryos to achieve pregnancy. The objective of this clinical trial is to
study the effect of mono-menotropins for COS versus mixed protocol of
urofollitropin/menotropins on cleavage-stage and blastocyst embryo quality after IVF. Embryo
quality parameters include conventional embryo grade, early embryo viability assessment
(Eeva) time-lapse parameters, and chromosomal aneuploidy rates after PGS.
This pilot study is expected to significantly contribute to optimization of treatment
regimens and stimulation protocols to optimize embryo quality.
This proposed study is a single-center, prospective, randomized experimental design.
One-hundred women between the ages of 21 to 38 (inclusive) pursuing IVF treatment for
infertility and preimplantation genetic screening (PGS).
Pre-medication All study patients will take oral contraception pills (OCP) starting between
day 2-4 of the menstrual cycle before controlled ovarian stimulation (COS) is started for
IVF, and they are continued for 21 days. Cycle preparation using an oral contraceptive pill
is thought to be important in improving follicular homogeneity.
Randomization Randomization of patients into the Stimulation Group 1 (Mono-Menotropin
Protocol) or Stimulation Group 2 (Mixed Urofollitropin/Menotropin Mixed Protocol) will occur
at OCP start using a computerized randomization program.
Ovarian Stimulation Stimulation Group 1: Mono-Menotropin Protocol Fifty patients will
undergo the standard of care COS for IVF using Menopur(Ferring, Parsippany, New Jersey (NJ)
USA) only. Patients will receive 300 IU of Menopur injected subcutaneously daily for the
first five days of stimulation. Thereafter, Menopur may be adjusted (to optimize ovarian
response by patient's physician) in 75 IU increments up to a total of 450 IU Menopur daily
up to and including day of hCG trigger.
Stimulation Group 2: Urofollitropin/Menotropin Mixed Protocol Fifty patients will undergo
the standard of care controlled ovarian stimulation (COS) for IVF using Bravelle (Ferring,
Parsippany, NJ) and Menopur (Ferring, Parsippany, NJ USA) mixed protocol. Bravelle and
Menopur are widely used in controlled ovarian stimulation cycles for the development of
multiple follicles in assisted reproductive technology (ART) programs. Patients will receive
a Bravelle/Menopur in a 3:1 ratio (225/75 IU) administered subcutaneously daily for the
first five days of stimulation. Thereafter, Menopur will continue to be administered at 75
IU daily, whereas Bravelle may be adjusted (to optimize ovarian response by the patient's
physician) in 75 IU increments up to a total of 450 IU daily up to and including day of hCG
trigger.
Luteinizing Hormone (LH)-surge Suppression Gonadotropin Releasing Hormone (GnRH) antagonist
will be used to suppress endogenous pituitary LH for the prevention of premature LH surges.
Patients will receive 0.25 mg/day of Ganirelix Acetate or Cetroelix Acetate when follicle
size reaches 12 mm and will continue up to and including day of hCG trigger.
HCG Trigger Human chorionic gonadotropin (hCG) (Novarel; Ferring, Parsippany, NY, USA) will
be used intramuscularly (IM) in both stimulation groups to induce oocyte maturation 36 hours
prior to the oocyte retrieval procedure
Cycle Monitoring Cycles will be monitored with follicular ultrasound measurements and serum
estradiol concentrations throughout ovarian stimulation. HCG will be given IM when at least
three follicles reach a diameter of ≥17 mm. Egg retrieval will be conducted by transvaginal
ultrasound 36 h after hCG administration.
Insemination All mature oocytes will have intracytoplasmic sperm injection (ICSI) to achieve
fertilization.
Embryo Development Two-pronuclei (2pn) embryos will be placed in the Eeva dish after
fertilization check at 16-18 hours post ICSI. To maintain a continuous and uninterrupted
imaging process from day 1 through day 3, no media changes or dish removal from the
incubator will be permitted. On day 3, imaging will be stopped just before routine embryo
grading will be performed according to Society for Assisted Reproductive Technology (SART)
standards. Cell number and quality score based on symmetry of cells and percent
fragmentation will be recorded. Embryos will be tracked individually. Software will
automatically measures cell division timings and provide quantitative information regarding
embryo development. Embryo grading day 5 will be performed according to standard operating
procedure. Blastocysts will be biopsied on day 5 or 6. Biopsies will be sent to a genetics
laboratory (Reprogenetics, New Jersey) for aCGH euploidy testing. Biopsied blastocysts will
be vitrified for future frozen embryo transfer (FET) cycle/s, in which euploid blastocyst/s
with the correct number of chromosomes will be thawed and transferred back to the uterus in
an attempt to achieve pregnancy.
Abnormal embryos (aneuploidy embryos with the incorrect number of chromosomes) may be
donated to research or discarded.
One-hundred women between the ages of 21 to 38 (inclusive) pursuing IVF treatment for
infertility and preimplantation genetic screening (PGS).
Pre-medication All study patients will take oral contraception pills (OCP) starting between
day 2-4 of the menstrual cycle before controlled ovarian stimulation (COS) is started for
IVF, and they are continued for 21 days. Cycle preparation using an oral contraceptive pill
is thought to be important in improving follicular homogeneity.
Randomization Randomization of patients into the Stimulation Group 1 (Mono-Menotropin
Protocol) or Stimulation Group 2 (Mixed Urofollitropin/Menotropin Mixed Protocol) will occur
at OCP start using a computerized randomization program.
Ovarian Stimulation Stimulation Group 1: Mono-Menotropin Protocol Fifty patients will
undergo the standard of care COS for IVF using Menopur(Ferring, Parsippany, New Jersey (NJ)
USA) only. Patients will receive 300 IU of Menopur injected subcutaneously daily for the
first five days of stimulation. Thereafter, Menopur may be adjusted (to optimize ovarian
response by patient's physician) in 75 IU increments up to a total of 450 IU Menopur daily
up to and including day of hCG trigger.
Stimulation Group 2: Urofollitropin/Menotropin Mixed Protocol Fifty patients will undergo
the standard of care controlled ovarian stimulation (COS) for IVF using Bravelle (Ferring,
Parsippany, NJ) and Menopur (Ferring, Parsippany, NJ USA) mixed protocol. Bravelle and
Menopur are widely used in controlled ovarian stimulation cycles for the development of
multiple follicles in assisted reproductive technology (ART) programs. Patients will receive
a Bravelle/Menopur in a 3:1 ratio (225/75 IU) administered subcutaneously daily for the
first five days of stimulation. Thereafter, Menopur will continue to be administered at 75
IU daily, whereas Bravelle may be adjusted (to optimize ovarian response by the patient's
physician) in 75 IU increments up to a total of 450 IU daily up to and including day of hCG
trigger.
Luteinizing Hormone (LH)-surge Suppression Gonadotropin Releasing Hormone (GnRH) antagonist
will be used to suppress endogenous pituitary LH for the prevention of premature LH surges.
Patients will receive 0.25 mg/day of Ganirelix Acetate or Cetroelix Acetate when follicle
size reaches 12 mm and will continue up to and including day of hCG trigger.
HCG Trigger Human chorionic gonadotropin (hCG) (Novarel; Ferring, Parsippany, NY, USA) will
be used intramuscularly (IM) in both stimulation groups to induce oocyte maturation 36 hours
prior to the oocyte retrieval procedure
Cycle Monitoring Cycles will be monitored with follicular ultrasound measurements and serum
estradiol concentrations throughout ovarian stimulation. HCG will be given IM when at least
three follicles reach a diameter of ≥17 mm. Egg retrieval will be conducted by transvaginal
ultrasound 36 h after hCG administration.
Insemination All mature oocytes will have intracytoplasmic sperm injection (ICSI) to achieve
fertilization.
Embryo Development Two-pronuclei (2pn) embryos will be placed in the Eeva dish after
fertilization check at 16-18 hours post ICSI. To maintain a continuous and uninterrupted
imaging process from day 1 through day 3, no media changes or dish removal from the
incubator will be permitted. On day 3, imaging will be stopped just before routine embryo
grading will be performed according to Society for Assisted Reproductive Technology (SART)
standards. Cell number and quality score based on symmetry of cells and percent
fragmentation will be recorded. Embryos will be tracked individually. Software will
automatically measures cell division timings and provide quantitative information regarding
embryo development. Embryo grading day 5 will be performed according to standard operating
procedure. Blastocysts will be biopsied on day 5 or 6. Biopsies will be sent to a genetics
laboratory (Reprogenetics, New Jersey) for aCGH euploidy testing. Biopsied blastocysts will
be vitrified for future frozen embryo transfer (FET) cycle/s, in which euploid blastocyst/s
with the correct number of chromosomes will be thawed and transferred back to the uterus in
an attempt to achieve pregnancy.
Abnormal embryos (aneuploidy embryos with the incorrect number of chromosomes) may be
donated to research or discarded.
Inclusion Criteria:
- Patients undergoing IVF in an attempt to achieve pregnancy.
- Day 2-4 Follicle Stimulating Hormone (FSH) < 10 IU/ml, LH< 12 IU/ml, and estradiol
<50 pg/ml on day 2-4 of menstrual cycle
- Antimullerian Hormone > 1.5
- Between 10 and 20 basal antral follicles on day 2-4 of the menstrual cycle
- Body weight >50 kg, with BMI > 18 and < 32 kg/m2
Exclusion Criteria:
- Smokers
- Polycystic ovarian disease
- Endometriosis greater than Stage I
- Testicular aspirated sperm
- Preimplantation Genetic Diagnosis (PGD) for single gene disorder
- Preimplantation Genetic Screening (PGS) banking cycles
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