Clinical trial NCT01983423: Effect of Endometrial Biopsy on in Vitro Fertilization Pregnancy Rates - a Multicenter Study
Official title: Effect of Endometrial Biopsy on in Vitro Fertilization Pregnancy Rates - a Randomized, Multicenter Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Infertility
Pregnancy
Keywords: Endometrial Biopsy
Endometrial Sampling
In Vitro Fertilization
Pregnancy
Implantation
Lead sponsor: Pacific Centre for Reproductive Medicine
Sponsor class: NETWORK
First posted: 2013-11-14
Enrollment: 52
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical Pregnancy Rate
timeFrame: Five weeks gestation, as dated from the egg retrieval
Secondary outcomes:
measure: Implantation Rate
timeFrame: Five weeks gestation, as dated from the egg retrieval
measure: Live Birth Delivery Rate
timeFrame: Within twelve months of the cycle start date
measure: Fertilization Rate
timeFrame: 24 hours after egg retrieval
measure: Normal Fertilization Rate
timeFrame: 24 Hours from egg retrieval
measure: Endometrial Thickness
timeFrame: Day of administration of human chorionic gonadotropin (8-12 days into ovarian stimulation)
measure: Endometrial Pattern
timeFrame: Day of administration of human chorionic gonadotropin (8-12 days into ovarian stimulation)
measure: Percentage of subjects with embryos cryopreserved
timeFrame: At the latest, day 6 after egg retrieval
measure: The number of embryos cryopreserved per subject
timeFrame: At the latest, day 6 after egg retrieval
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Pacific Centre for Reproductive Medicine
state: British Columbia
city: Toronto
country: Canada
facility: Mt. Sinai Hospital Centre for Fertility and Reproductive Health
state: Ontario
Study officials:
affiliation: Pacific Centre for Reproductive Medicine and University of British Columbia
name: Jon C Havelock, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.