Study of Dual Trigger Ovulation in Oocyte Donors

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Prospective Trial of Dual Trigger Ovulation in Oocyte Donors

Conditions
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Infertility

Intervention / Treatment
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* Drug: HCG
* Drug: Lupron Trigger
* Drug: Dual Trigger


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: hCG<br>standard dose of hCG for ovulation trigger | Drug: HCG<br>* hCG Trigger<br>|
| Active Comparator: Lupron Trigger<br>Leuprolide acetate 2 mg ovulation trigger | Drug: Lupron Trigger<br>* leuprolide acetate 2 mg SQ<br>|
| Experimental: Dual Trigger<br>Lupron and hCG combined ovulation trigger | Drug: Dual Trigger<br>* a combination of the two drugs in low dosage (leuprolide acetate 2 mg and hCG 1500 IU).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 1 month | 
| 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. | 7 days post retrieval | 
| 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. | 7 days post retrieval | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Mature Oocytes Retrieved | Number of mature oocytes retrieved will assess the efficacy of the intervention | 1 day post ovulation | 
| 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. | 4 weeks post retrieval | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oocyte donor, oocyte recipient, ovulation trigger