Effect of Endometrial Biopsy on in Vitro Fertilization Pregnancy Rates - a Multicenter Study

NCT ID: NCT01983423

Last Updated: 2017-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2016-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Infertility Pregnancy

Keywords

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Endometrial Biopsy Endometrial Sampling In Vitro Fertilization Pregnancy Implantation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Endometrial Biopsy

Endometrial biopsy performed within 5-10 days prior to starting controlled ovarian stimulation, as part of in vitro fertilization treatment.

Group Type EXPERIMENTAL

Endometrial Biopsy

Intervention Type DEVICE

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.

Without Biopsy

Those proceeding with in vitro fertilization routinely, without an endometrial biopsy.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DEVICE

Other Intervention Names

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Endometrial pipelle biopsy Endometrial sampling

Eligibility Criteria

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Inclusion Criteria

Women undergoing first or second IVF cycle, with or without ICSI

* Age 18-39
* BMI 18-35 kg/m2
* Uterine cavity evaluation (hysterosalpingogram, sonohysterogram, hysteroscopy) in the preceding 24 months
* Early follicular phase (Day 2 or Day 3) serum FSH, evaluated in the preceding 6 months

ONE of the following:

* Non- oral contraceptive pill (non-OCP) subjects: Documented LH surge 9-11 days prior to enrollment
* Current OCP subjects: OCP use for ≥ 10 days
* Use of long GnRH agonist or GnRH antagonist protocol
* Subject able to give informed consent

Exclusion Criteria

* Prior enrolment in this study
* Any prior early follicular phase serum FSH level ≥12 IU/L
* Previous poor ovarian response, defined as prior IVF cycle cancelled for poor response, or ≤4 oocytes retrieved
* IVF for pre-implantation genetic diagnosis (PGD) or fertility preservation
* Diabetes mellitus or uncontrolled thyroid disease
* Abnormal uterine cavity, such as unresected submucosal fibroids, uterine septum, Mullerian anomaly such as bicornuate or unicornuate uterus or intrauterine adhesions
* Hydrosalpinx that has not been removed or surgically ligated
* Any contraindication to endometrial biopsy
* Office hysteroscopy or other uterine procedure planned or performed during cycle preceding IVF stimulation
* Use of surgically retrieved sperm
Minimum Eligible Age

18 Years

Maximum Eligible Age

39 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Jon Havelock

NETWORK

Sponsor Role lead

Responsible Party

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Jon Havelock

Principal investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Jon C Havelock, MD

Role: PRINCIPAL_INVESTIGATOR

Pacific Centre for Reproductive Medicine and University of British Columbia

Locations

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Pacific Centre for Reproductive Medicine

Vancouver, British Columbia, Canada

Site Status

Mt. Sinai Hospital Centre for Fertility and Reproductive Health

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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Lejeune B, Lecocq R, Lamy F, Leroy F. Changes in the pattern of endometrial protein synthesis during decidualization in the rat. J Reprod Fertil. 1982 Nov;66(2):519-23. doi: 10.1530/jrf.0.0660519.

Reference Type BACKGROUND
PMID: 7175806 (View on PubMed)

Humphrey KW. The effects of some anti-oestrogens on the deciduoma reaction and delayed implantation in the mouse. J Reprod Fertil. 1968 Jul;16(2):201-9. doi: 10.1530/jrf.0.0160201. No abstract available.

Reference Type BACKGROUND
PMID: 4298258 (View on PubMed)

Gnainsky Y, Granot I, Aldo PB, Barash A, Or Y, Schechtman E, Mor G, Dekel N. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril. 2010 Nov;94(6):2030-6. doi: 10.1016/j.fertnstert.2010.02.022. Epub 2010 Mar 24.

Reference Type BACKGROUND
PMID: 20338560 (View on PubMed)

Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I. Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril. 2003 Jun;79(6):1317-22. doi: 10.1016/s0015-0282(03)00345-5.

Reference Type BACKGROUND
PMID: 12798877 (View on PubMed)

Raziel A, Schachter M, Strassburger D, Bern O, Ron-El R, Friedler S. Favorable influence of local injury to the endometrium in intracytoplasmic sperm injection patients with high-order implantation failure. Fertil Steril. 2007 Jan;87(1):198-201. doi: 10.1016/j.fertnstert.2006.05.062.

Reference Type BACKGROUND
PMID: 17197286 (View on PubMed)

Karimzadeh MA, Ayazi Rozbahani M, Tabibnejad N. Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: a randomised clinical trial. Aust N Z J Obstet Gynaecol. 2009 Dec;49(6):677-80. doi: 10.1111/j.1479-828X.2009.01076.x.

Reference Type BACKGROUND
PMID: 20070722 (View on PubMed)

Zhou L, Li R, Wang R, Huang HX, Zhong K. Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates. Fertil Steril. 2008 May;89(5):1166-1176. doi: 10.1016/j.fertnstert.2007.05.064. Epub 2007 Aug 6.

Reference Type BACKGROUND
PMID: 17681303 (View on PubMed)

Karimzade MA, Oskouian H, Ahmadi S, Oskouian L. Local injury to the endometrium on the day of oocyte retrieval has a negative impact on implantation in assisted reproductive cycles: a randomized controlled trial. Arch Gynecol Obstet. 2010 Mar;281(3):499-503. doi: 10.1007/s00404-009-1166-1. Epub 2009 Jul 1.

Reference Type BACKGROUND
PMID: 19568761 (View on PubMed)

Katz VL. Diagnostic procedures. Imaging, endometrial sampling, endoscopy: indications and contraindications, complications. In: Katz VL, Lentz GM, Lobo RA, Gershenson DM, eds. Comprehensive Gynecology . 5th ed. Philadelphia, Pa: Mosby; 2007.

Reference Type BACKGROUND

Hilton J, Liu KE, Laskin CA, Havelock J. Effect of endometrial injury on in vitro fertilization pregnancy rates: a randomized, multicentre study. Arch Gynecol Obstet. 2019 Apr;299(4):1159-1164. doi: 10.1007/s00404-019-05044-9. Epub 2019 Jan 19.

Reference Type DERIVED
PMID: 30661093 (View on PubMed)

Other Identifiers

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EndoBx- IVF

Identifier Type: -

Identifier Source: org_study_id