Trial Information

Impact of Local Endometrial Injury on Implantation Rates in Fresh Embryo Transfer Cycles

HYPOTHESIS

1. Local endometrial injury improves implantation and pregnancy rates

2. Specifically, local endometrial injury during the follicular phase of an IVF cycle
improves the implantation and pregnancy rates in comparison to that in the luteal phase
prior to ovarian stimulation .

OBJECTIVES Primary objective

•To determine the impact of local endometrial injury on implantation rates in patients
undergoing fresh IVF cycles.

Secondary objectives

- To determine the impact of local endometrial injury on pregnancy outcomes (biochemical
pregnancy rate, clinical pregnancy rate, miscarriage rate and live birth rate) in
patients undergoing fresh IVF cycles.

- To determine the optimal timing for local endometrial injury (mid-luteal phase prior to
ovarian stimulation or early follicular phase during ovarian stimulation) to improve
pregnancy outcomes.

- To determine if there is a correlation between endometrial biopsy pathology and IVF
pregnancy outcomes among patients randomized to local endometrial injury.

STUDY DESIGN The study will be a randomized controlled study (RCT) and consists of patients
undergoing fertility treatment with their second fresh IVF cycle, which includes ovarian
stimulation with gonadotropin hormones ("microdose flare protocol"), an oocyte collection
procedure and a single embryo transfer.

The patient population will be randomized using computer-generated random table into three
arms:

- Luteal Phase Arm: LEI in mid-luteal phase (day 21-26) prior to the treatment cycle.

- Proliferative Phase Arm: LEI in early proliferative phase of current treatment cycle
(day 2-3).

- Control Arm: No LEI will be performed. Patients will undergo a routine fresh IVF
treatment cycle.

Other than the local endometrial injury, all patients will receive the same treatment and
follow up care as per standard practice at our clinic.

All patients in this study will undergo a "microdose flare protocol" fresh IVF cycle. As
part of this protocol patients are to take oral contraception pills for a month duration
prior to the start of the IVF cycle. Therefore the possibility of an undocumented pregnancy
at the time of the LEI in the luteal phase is minimized.

The LEI will be performed using the standard technique using a Pipelle sampling catheter in
the outpatient department. After a speculum examination is performed and the cervix is well
visualized, the Pipelle will be inserted gently through the cervical canal into the uterine
cavity and advanced slowly until resistance is noted. At this point the internal piston is
withdrawn to create negative suction and the Pipelle is gently maneuvered up and down
alongside the uterine cavity wall. The Pipelle catheter is then withdrawn gently and any
obtained specimen (uterine lining) will be sent for histopathological examination.

Both the embryologist who prepares the embryo and the physician who will transfer the embryo
will not be directly aware of which study arm the patient was allocated to. However all
procedures performed at our clinic, including a LEI, are documented on the patients chart
and therefore are accessible.

As per routine practice at our clinic, pregnancy tests will be performed by quantitative
serum beta-hCG level 12 days after embryo transfer. A clinical pregnancy will be confirmed
by using a transvaginal ultrasound 2 weeks after a positive pregnancy test (serum BHCG).