Infertility
Conditions
Keywords
oocyte donor, oocyte recipient, ovulation trigger
Brief summary
The project is a randomized, controlled, prospective study of oocyte donors comparing the safety and efficacy of triggering ovulation using a combination of two drugs-GnRH agonist and very low dose hCG-versus triggering ovulation with a standard hCG dose alone or a standard GnRH trigger alone.
Detailed description
The study population will consist of young women, age 21 to 34, presenting to our facility with the desire to donate oocytes and who meet FDA and program requirements for donation. Participants will be randomized to one of the three treatment interventions for triggering ovulation: 1) a standard dose of hCG, 2) leuprolide acetate 2 mg alone, or 3) a combination of the two drugs in low dosage (leuprolide acetate 2 mg and hCG 1500 IU). Study participants who choose to repeat oocyte donation during the course of the study trial, and who consent to participate in the trial again, will be randomized in a cross-over manner for any subsequent trials. Following randomization, the clinical care of study subjects will be the same as for non-participant oocyte donors. Participants in all three study arms will undergo standard ovarian stimulation protocol with gonadotropins, standard individualized adjustment of medication dose, standard criteria for administration of the ovulation trigger dose, and standard egg retrieval procedure. The recipient population will be recruited from women, age 18 to 55, who present to our center wishing to become pregnant using donor oocytes. All prospective participants who meet the Center for Reproductive Medicine (CRM) criteria be recipients of donated eggs will be eligible to participate, should they wish to do so. If a prospective recipient consents to participate in the study, then she would be matched with either a donor who is not participating in the study (and is receiving one of our standard triggers for ovulation) or a donor who is participating in the study and whose medication to trigger ovulation has been randomized into one of three groups: standard dose hCG, Leuprolide acetate, or a combination of low dose hCG and Leuprolide acetate. A recipient who chooses to participate in the study will have no additional tests or procedures over the ones that she would normally do in order to receive donated eggs.
Interventions
DRUGHCG
hCG Trigger
DRUGLupron Trigger
leuprolide acetate 2 mg SQ
DRUGDual Trigger
a combination of the two drugs in low dosage (leuprolide acetate 2 mg and hCG 1500 IU).
Sponsors
Merck Sharp & Dohme LLC
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Donors * Young women, age 21 to 34, presenting to our facility with the desire to donate oocytes and meeting FDA and program requirements for donation. Recipients * Women, age 21 to 55, presenting to our facility with the desire to donate oocytes and meeting FDA and program requirements to be recipients of donated eggs.
Exclusion criteria
Donors * Less than 2 ovaries or any other significant ovarian abnormality * Does not meet current FDA or program requirements for donation. * A contraindication for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, clinically significant ovarian cysts) * A contraindication for the use of oral contraceptive pills (h/o thromboembolism, breast cancer, undiagnosed vaginal bleeding) * Known gene defects, genetic abnormalities or abnormal karyotype * Contraindication or hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol * Inability to give informed consent * Donors who, because of their place of residence or personal situation, would not be able to commit to all required time points including the one extra visit required by study participation. * The subject has a recent history of/or current epilepsy, thrombophilia, diabetes, cardiovascular, gastro-intestinal, hepatic, renal or pulmonary or auto-immune disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Having Adverse Events | 1 month | Any donor having a serious complication such as severe hyperstimulation syndrome, ovarian torsion, infection or peritoneal bleeding will be recorded |
| Number of Days Post Retrieval Until Subject is Able to Resume Her Usual Activities | 7 days post retrieval | Subjects will complete a brief questionnaire on post retrieval day 7. They will state how many days after retrieval they were able to resume their usual activities. |
| Ovarian Volume | 7 days post retrieval | Ovarian volume of both ovaries will be measured by ultrasound on post op day number 7. Measurements will be taken in three different dimensions and volume calculated from those measurements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Mature Oocytes Retrieved | 1 day post ovulation | Number of mature oocytes retrieved will assess the efficacy of the intervention |
| Pregnancies Per Transfer | 4 weeks post retrieval | Pregnancy rate per transfer will be assessed by hCG level on day 14 post retrieval and clinical pregnancy rate will be assessed by ultrasound on day 28 post retrieval. This will additionally assess efficacy of intervention. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Human Chorionic Gonadotropin standard dose of hCG for ovulation trigger
HCG: hCG Trigger | 9 |
| Lupron Trigger Leuprolide acetate 2 mg ovulation trigger
Lupron Trigger: leuprolide acetate 2 mg SQ | 9 |
| Dual Trigger Lupron and hCG combined ovulation trigger
Dual Trigger: a combination of the two drugs in low dosage (leuprolide acetate 2 mg and hCG 1500 IU). | 8 |
| Total | 26 |
Baseline characteristics
| Characteristic | Human Chorionic Gonadotropin | Lupron Trigger | Dual Trigger | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
| Region of Enrollment United States | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 0 / 9 |
| other Total, other adverse events | 0 / 9 | 0 / 8 | 1 / 9 |
| serious Total, serious adverse events | 0 / 9 | 1 / 8 | 0 / 9 |
Outcome results
Primary
Number of Days Post Retrieval Until Subject is Able to Resume Her Usual Activities
Subjects will complete a brief questionnaire on post retrieval day 7. They will state how many days after retrieval they were able to resume their usual activities.
Time frame: 7 days post retrieval
Population: Data was not completed by study participants so data was not analyzed for comparison
Primary
Number of Subjects Having Adverse Events
Any donor having a serious complication such as severe hyperstimulation syndrome, ovarian torsion, infection or peritoneal bleeding will be recorded
Time frame: 1 month
Population: Total of 26 participants were enrolled. Number of subjects enrolled in each arm were below targeted numbers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| hCG Trigger | Number of Subjects Having Adverse Events | 0 participants |
| Dual Trigger | Number of Subjects Having Adverse Events | 1 participants |
| Lupron Trigger | Number of Subjects Having Adverse Events | 0 participants |
Primary
Ovarian Volume
Ovarian volume of both ovaries will be measured by ultrasound on post op day number 7. Measurements will be taken in three different dimensions and volume calculated from those measurements.
Time frame: 7 days post retrieval
Population: data for ovarian volume was not collected by 3D ultrasound
Secondary
Number of Mature Oocytes Retrieved
Number of mature oocytes retrieved will assess the efficacy of the intervention
Time frame: 1 day post ovulation
Population: Data was not completed by study participants so data was not analyzed for comparison
Secondary
Pregnancies Per Transfer
Pregnancy rate per transfer will be assessed by hCG level on day 14 post retrieval and clinical pregnancy rate will be assessed by ultrasound on day 28 post retrieval. This will additionally assess efficacy of intervention.
Time frame: 4 weeks post retrieval
Population: Data was not completed by study participants so data was not analyzed for comparison