Effect of Endometrial Biopsy on in Vitro Fertilization Pregnancy Rates - a Multicenter Study (EndoBx-IVF)
Animal and clinical studies have suggested that local tissue trauma can promote the process of an embryo implanting in the uterine cavity. The clinical studies have been performed in patients with a history of previously failed treatments using in vitro fertilization; a process of stimulating many eggs from a women and removing them from the body, to allow fertilisation with sperm to occur in a laboratory setting. The embryos are then replaced into the uterine cavity.
This study questions whether endometrial biopsy (placing a small straw like catheter through the cervix and into the uterine cavity to take a sample of tissue via suction into the bore of the catheter), within 5-10 days of starting a cycle of in vitro fertilization, will improve pregnancy outcome for patients in the first or second cycle of treatment. The hypothesis is that endometrial biopsy will improve pregnancy outcome.
The study is a randomized multicentre study involving 3 Canadian fertility centres.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Endometrial Biopsy on in Vitro Fertilization Pregnancy Rates - a Randomized, Multicenter Study|
- Clinical Pregnancy Rate [ Time Frame: Five weeks gestation, as dated from the egg retrieval ] [ Designated as safety issue: No ]Clinical pregnancy rate, defined as transvaginal ultrasound documentation of fetal heartbeat at five weeks gestation.
- Implantation Rate [ Time Frame: Five weeks gestation, as dated from the egg retrieval ] [ Designated as safety issue: No ]The number of gestational sacs seen at ultrasound, divided by the total number of embryos transferred
- Live Birth Delivery Rate [ Time Frame: Within twelve months of the cycle start date ] [ Designated as safety issue: No ]Live birth delivery rate will be the number of live birth deliveries expressed per 100 initiated cycles, aspiration cycles or embryo transfer cycles, for which the denominator (initiated, aspirated or embryo transfer cycles) will be specified. Live birth delivery will include deliveries that resulted in at least one live birth. The delivery of a singleton, twin or other multiple births will be registered as one delivery.
- Fertilization Rate [ Time Frame: 24 hours after egg retrieval ] [ Designated as safety issue: No ]Fertilization rate will be the number of zygotes resulting from insemination by IVF or injection by intracytoplasmic sperm injection, expressed as a ratio to the total number of oocytes inseminated or injected.
- Normal Fertilization Rate [ Time Frame: 24 Hours from egg retrieval ] [ Designated as safety issue: No ]Normal fertilization rate will be the number of normal zygotes resulting from insemination by IVF or injection by ICSI, expressed as a ratio to the total number of oocytes inseminated or injected.
- Endometrial Thickness [ Time Frame: Day of administration of human chorionic gonadotropin (8-12 days into ovarian stimulation) ] [ Designated as safety issue: No ]As assessed by transvaginal ultrasound, the maximum dimension of the endometrial cavity echo in an antero-posterior plane.
- Endometrial Pattern [ Time Frame: Day of administration of human chorionic gonadotropin (8-12 days into ovarian stimulation) ] [ Designated as safety issue: No ]The endometrial pattern will be categorised as either trilaminar (triple stipe pattern) or hyperechoic (diffusely echogenic)at the time of transvaginal ultrasound assessment.
- Percentage of subjects with embryos cryopreserved [ Time Frame: At the latest, day 6 after egg retrieval ] [ Designated as safety issue: No ]Total number of participants with embryos in excess, that met criteria for cryopreservation
- The number of embryos cryopreserved per subject [ Time Frame: At the latest, day 6 after egg retrieval ] [ Designated as safety issue: No ]The number of embryos each individual participant had in excess, meeting criteria for cryopreservation
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Endometrial Biopsy
Endometrial biopsy performed within 5-10 days prior to starting controlled ovarian stimulation, as part of in vitro fertilization treatment.
Device: Endometrial Biopsy
An endometrial biopsy is performed using a sampling device known as a pipelle catheter which is introduced into the uterine cavity. The inner core is withdrawn creating suctional pressure into the hollow bore of the cavity, which allows acquisition of endometrial tissue upon rotation in the cavity. This is removed and the tissue sent for pathologic examination.
No Intervention: Without Biopsy
Those proceeding with in vitro fertilization routinely, without an endometrial biopsy.
Although the data are preliminary, there are studies suggesting that mild endometrial trauma in the cycle preceding IVF increases pregnancy rates, at least in women with recurrent implantation failure. Whether endometrial biopsy could promote implantation and improve pregnancy rates in the larger population of women undergoing IVF has yet to be explored. The present study will address this question and examine the impact of endometrial biopsies on IVF outcomes in the context of a randomized controlled trial.
The optimal timing of the endometrial biopsy in the cycle preceding IVF has not been determined, but the majority of the studies have included a biopsy in the mid-luteal phase of the preceding cycle. In order to allow an adjuvant therapy to IVF that would be considered tolerable to a subject, and applicable to a large infertile women population, it was determined that a single endometrial biopsy, performed approximately 1 week prior to the start of controlled ovarian hyperstimulation (COH) in an IVF cycle, would be the simplest, most flexible, and generalizable intervention to study its effects on pregnancy rates. All other components of the IVF treatment will remain constant with approximately 8-12 days of ovarian stimulation, human chorionic gonadotrophin (HCG) trigger being administered in that time frame and oocyte retrieval occuring 36 hours later from trigger. The embryo transfer will take place either day 3 or day 5 after oocyte retrieval.
|Contact: Jon C Havelock, MD, FRCSC||1-604-422-7276||JHavelock@pacificfertility.ca|
|Contact: Kimberly Liu, MD, FRCSC||1-416-586-5367||KLiu@mtsinai.on.ca|
|Canada, British Columbia|
|Pacific Centre for Reproductive Medicine||Recruiting|
|Vancouver, British Columbia, Canada, V5G 4X7|
|Contact: Jon Havelock, MD FRCSC 604-422-7276 JHavelock@pacificfertility.ca|
|Contact: Heather Abbey, RN BScN 604-422-7276 ext 121 HAbbey@pacificfertility.ca|
|Principal Investigator: Jon Havelock, MD FRCSC|
|Mt. Sinai Hospital Centre for Fertility and Reproductive Health||Not yet recruiting|
|Toronto, Ontario, Canada, M5T 2Z5|
|Contact: Kimberly Liu, MD FRCSC 1-416-586-5367 KLiu@mtsinai.on.ca|
|Contact: Nurun Chowdhury, RN NChowdhury@mtsinai.on.ca|
|Principal Investigator: Kim Liu, MD, FRCSC|
|Principal Investigator:||Jon C Havelock, MD||Pacific Centre for Reproductive Medicine and University of British Columbia|