Suboptimal subject recruitment

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.

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.

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