Progesterone Supplementation in Frozen Embryo Transfer Cycles

Study Overview
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Brief Summary
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Recurrent implantation failure (RIF) occurs after women undergo in vitro fertilization and have multiple embryos transferred but no resulting pregnancies. RIF is a very challenging clinical entity for the reproductive physician and the patient. In fact, there is not even an agreed upon definition in the medical community. Many potential causes have been investigated over the past several years but no clear answer has emerged. Interest has recently turned to the endometrium, or the lining of the uterus. Studies have shown that the genes that are turned on in the endometrium vary based on how long this tissue has been exposed to progesterone, an important hormone that prepares the uterine lining for implantation of the growing embryo. In some women, it seems that they require longer periods of progesterone exposure to reach the same state of readiness. We hypothesize that an even larger proportion of women in RIF population will require longer treatments with progesterone. In this study, we will randomize women with RIF who are about to undergo a frozen embryo transfer to one of two groups. The first group will have their embryo transfer done on the standard sixth day of progesterone treatment. The other group will have their transfer done on the seventh day of progesterone. We will be comparing the clinical pregnancy rate of the two groups as well as the live birth rate and miscarriage rate. We expect that extending the progesterone treatment by one day will increase the pregnancy rate of women with RIF.

Official Title
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Assessing the Optimal Duration of Progesterone Supplementation Prior to Transfer of Frozen Embryos in the Recurrent Implantation Failure Population

Conditions
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Infertility Due to Nonimplantation, Infertility

Intervention / Treatment
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* Drug: Prometrium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient at Mount Sinai Fertility who wants to undertake a frozen embryo transfer History of recurrent implantation failure, defined as no pregnancy after three or more embryo transfers of four or more good quality blastocysts Exclusion Criteria: Previous testing with Endometrial Receptivity Assay (ERA) Unable understand/communicate in English

Ages Eligible for Study
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Minimum Age: 18 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: Control Group<br>This arm of the study will have their frozen-thawed embryo transfer take place on the sixth day of progesterone supplementation (Prometrium), which is the standard protocol in our clinic. | Drug: Prometrium<br>* The intervention will involve delaying the transfer of a frozen-thawed embryo into the uterus to increase the duration of progesterone exposure.<br>|
| Experimental: Experimental Group<br>This arm of the study will have their frozen-thawed embryo transfer take place on the seventh day of progesterone supplementation (Prometrium). | Drug: Prometrium<br>* The intervention will involve delaying the transfer of a frozen-thawed embryo into the uterus to increase the duration of progesterone exposure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical pregnancy rate | Rate of pregnancy, evidenced by clinical (fetal heartbeat) or ultrasound parameters (ultrasound visualization of a gestational sac, embryonic pole with heartbeat). It includes ectopic pregnancy. | 6 to 8 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate | Rate of birth in which a fetus is delivered with signs of life after complete expulsion or extraction from its mother, beyond 20 completed weeks of gestational age | Approximately 9 months after embryo transfer | 
| Miscarriage rate | Rate of natural death of embryo or fetus, after reaching clinical pregnancy stage and at or before 10 weeks gestation. | Approximately 3 months after embryo transfer |