Down-regulated Hormonally Controlled Cycles for Vitrification-warmed Blastocyst Transfers

Study Overview
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Brief Summary
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Currently all patients that have freeze-all ICSI treatment cycles have the start of their FET cycle scheduled with the use of OCP. While an excellent pregnancy rate (75%) for the patients that have a blastocyst transfer has been maintained over time, 15% of started FET cycles are being cancelled because of premature luteinization, and the treatment (to transfer) takes approximately 89 days. The use of a Lucrin depot may reduce the number of cycles cancelled and reduce the treatment time to approximately 69 days. The use of no drugs and allowing the normal menstrual cycle to determine the time to start the FET cycle may suit some patients. Whether these benefits can be obtained while still maintaining the current FET pregnancy rate will be the main focus of the trial.

Detailed Description
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The patients will undergo standard assisted conception procedures; controlled ovarian stimulation (COS), oocyte pickup procedure (OPU), ICSI, embryo culture, blastocyst vitrification and frozen embryo transfer. If sufficient (>2) viable blastocyst develop from the in vitro culture of their embryos, all viable blastocysts will be cryopreserved using a routine vitrification procedure. This is the eligible patient population. On the day the last blastocyst(s) are frozen the patients will be given a further opportunity to ask questions and if satisfied they will be asked to complete a trial consent. At this point patients will be randomized by numeric code and given a schedule and drug prescription for scheduling the start of their hormone supplemented frozen embryo transfer cycle. During the scheduling period the patients will follow the drug prescription provided . After the completion of their treatment - the transfer of one or two vitrified-warmed blastocyst - the patients from both groups will receive identical luteal support drug schedules and prescriptions. A blood test will be performed on the 15th day of progesterone supplementation, to determine the βhCG blood concentration. Currently at Antalya IVF, approximately 75% of patients who have blastocysts transferred in a frozen embryo transfer cycle have a positive biochemical pregnancy test, >29 international units per litre (IU/L) of human chorionic gonadotropin (βhCG). If pregnant, patients will continue using estrogen and progesterone supplementation for a further 8 weeks. At 7 weeks of gestation (5 weeks after embryo transfer ) the patients will receive a transvaginal ultrasound scan (TVUS) to check for pregnancy viability (fetal sac with cardiac activity). Thereafter the patients will have regular TVUS to follow fetal development. At 20 weeks of gestation a TVUS will be performed to confirm an ongoing pregnancy (normal fetal development). All drug packs are delivered to the clinic by the pharmacy after receiving the prescription. A staff member will verify the code on the prescription with randomization code allocated to the patient. The pack will then be given to the patient after verbally confirming patient identity. The packs will also contain a drug use instruction sheet and a trial information sheet.

Official Title
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Down-regulated Hormonally Controlled Cycles for Vitrification-warmed Blastocyst Transfers: Reduces Time to Transfer and Cycle Cancellation

Conditions
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Pregnancy

Intervention / Treatment
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* Drug: Lucrin depot
* Drug: OCP
* Other: Natural


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: If patients have >2 blastocysts vitrified Exclusion Criteria: All patients not willing to participate in the study Patients with any known adverse reaction to one or the other of the drugs prescribed All patients that have no surviving blastocysts for transfer

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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All

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lucrin depot, artificial cycle start<br>intramuscular administration of Lucrin depot (half dose of 3.75mg) on the 5th day following oocyte retrieval | Drug: Lucrin depot<br>* scheduling the start of the artificial cycle and hormone down regulation during the artificial cycle<br>|
| Active Comparator: OCP active, artificial cycle start<br>to take active OCP tablets (1 per day) from the 10th day following oocyte retrieval for at least 21 days | Drug: OCP<br>* to schedule the start of the artificial cycle<br>|
| Experimental: Natural, menstrual period<br>to wait for the second bleed to commence the artificial FET cycle | Other: Natural<br>* to use the normal menstrual period to schedule treatment start<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cycle cancellation | blood progesterone concentration (>2nmol/L) as a measure of premature luteinization | On day 14 of estrogen supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate | TVUS normal fetal development >20 weeks of gestation, in case of a pregnancy | 20 weeks of gestation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy,, Lucrin depot,, frozen embryo transfer,, artificial cycle,, cancellation