Trial Outcomes & Findings for Endometrial Injury for Assisted Reproduction (NCT NCT01132144)

Results Overview

The complete expulsion or extraction from its mother of a product of fertilization, irrespective of the duration of the pregnancy, which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation, or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. Note: All allocated women will be used as denominator when assessing live birth rate.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

158 participants

Primary outcome timeframe

1 year

Results posted on

2014-02-17

Participant Flow

The recruitment occurred from July 2010 to March 2012 in the fertility clinic of an university hospital.

All women that fulfilled eligibility criteria were invited to participate. Those who agreed were included. No women was excluded.

Participant milestones

Participant milestones
Measure	Endometrial Injury Group Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation. The pipelle was introduced gently through the cervix up to the uterine fundus. The piston was then drawn back to the end of the biopsy cannula until it self-locks and creates a negative pressure. Aiming to wound the entire endometrium, the examiner applied regular back-and-forth movements while rotating the sampler covering the whole uterine cavity. This procedure was continued until fragments of uterine mucosa appeared within the sheath, which generally took 30 seconds.	Control Group Introduction of the speculum and wiping of the cervix with gaze for 30 seconds
Overall Study STARTED	79	79
Overall Study COMPLETED	79	79
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Endometrial Injury for Assisted Reproduction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Endometrial Injury Group n=79 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation. The pipelle was introduced gently through the cervix up to the uterine fundus. The piston was then drawn back to the end of the biopsy cannula until it self-locks and creates a negative pressure. Aiming to wound the entire endometrium, the examiner applied regular back-and-forth movements while rotating the sampler covering the whole uterine cavity. This procedure was continued until fragments of uterine mucosa appeared within the sheath, which generally took 30 seconds.	Control Group n=79 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.	Total n=158 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	79 Participants n=5 Participants	79 Participants n=7 Participants	158 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	32.4 years STANDARD_DEVIATION 3.2 • n=5 Participants	32.1 years STANDARD_DEVIATION 3.1 • n=7 Participants	32.2 years STANDARD_DEVIATION 3.2 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	79 Participants n=7 Participants	158 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Brazil	79 participants n=5 Participants	79 participants n=7 Participants	158 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: All women enrolled.

The complete expulsion or extraction from its mother of a product of fertilization, irrespective of the duration of the pregnancy, which, after such separation, breathes or shows any other evidence of life, such as heart beat, umbilical cord pulsation, or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. Note: All allocated women will be used as denominator when assessing live birth rate.

Outcome measures

Outcome measures
Measure	Endometrial Injury Group n=79 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Control Group n=79 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.
Live Birth	33 participants	18 participants

SECONDARY outcome

Timeframe: 3 months

Population: All women enrolled.

Pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. Multiple gestational sacs are counted as one clinical pregnancy. Note: All allocated women will be considered when assessing clinical pregnancy rate.

Outcome measures

Outcome measures
Measure	Endometrial Injury Group n=79 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Control Group n=79 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.
Clinical Pregnancy	39 participants	23 participants

SECONDARY outcome

Timeframe: 6 months

At least one fetus with heart beat after 12 weeks of gestational age. Note: All allocated women will be considered when assessing ongoing pregnancy rate.

Outcome measures

Outcome measures
Measure	Endometrial Injury Group n=79 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Control Group n=79 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.
Ongoing Pregnancy	33 participants	18 participants

SECONDARY outcome

Timeframe: 9 months

Population: The number of clinical pregnancies was used as denominator, since miscarriage is a harm that can only happen in pregnant women.

Loss of a clinical pregnancy before 20 completed weeks of gestational age (18 weeks after fertilization). Note: All allocated women will be considered when assessing miscarriage rate.

Outcome measures

Outcome measures
Measure	Endometrial Injury Group n=39 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Control Group n=23 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.
Miscarriage	6 Clinical pregnancies	5 Clinical pregnancies

SECONDARY outcome

Timeframe: 3 months

The number of gestational sacs observed divided by the number of embryos transferred.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 month

Population: Women that achieved at least one follicle \>17mm during ovarian stimulation.

The maximum distance perpendicular to the inter-endometrial interface from the endometrium-myometrium interface of the anterior to the posterior wall of the uterus assessed in the sagittal plane. This outcome will be assessed when at least one follicle ≥ 17mm is observed.

Outcome measures

Outcome measures
Measure	Endometrial Injury Group n=72 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Control Group n=74 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.
Endometrial Thickness	10.12 mm Standard Deviation 1.55	9.98 mm Standard Deviation 1.62

SECONDARY outcome

Timeframe: 1 month

Population: Women that achieved at least one follicle \>17mm during ovarian stimulation.

The total volume of endometrial tissue assessed by three-dimensional ultrasonography. This outcome will be assessed when at least one follicle ≥ 17mm is observed.

Outcome measures

Outcome measures
Measure	Endometrial Injury Group n=72 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Control Group n=74 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.
Endometrial Volume	6.18 cm³ Standard Deviation 1.63	6.01 cm³ Standard Deviation 1.48

SECONDARY outcome

Timeframe: 1 month

Population: Women that achieved at least one follicle \>17mm during ovarian stimulation.

Vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) assessed from endometrium using three-dimensional Power Doppler ultrasonography. This outcome will be assessed when at least one follicle ≥ 17mm is observed. Only VFI was reported as it is a combination of VI and FI (VFI = VI\*FI/100), and currently there are several concerns about the validity of these indices. Such indices have no scale.

Outcome measures

Outcome measures
Measure	Endometrial Injury Group n=72 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Control Group n=74 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.
Three-dimensional Doppler Indices From Endometrium (VFI)	0.97 index Standard Deviation 0.51	0.76 index Standard Deviation 0.40

SECONDARY outcome

Timeframe: Immediately after procedure

Population: All women enrolled.

Pain will be assessed using a Visual Analogue Scale (VAS). We will use a 10 cm length horizontal line, anchored by word descriptors at each end: "No Pain" = 0 cm and "Very Severe Pain" = 10 cm. This outcome will be assessed in both groups, just after endometrial injury or sham procedure.

Outcome measures

Outcome measures
Measure	Endometrial Injury Group n=79 Participants Endometrial biopsy was performed once with a pipelle de Cornier® in the month before initiating controlled ovarian stimulation.	Control Group n=79 Participants Introduction of the speculum and wiping of the cervix with gaze for 30 seconds.
Procedure Related Pain	6.42 cm Standard Deviation 2.35	1.82 cm Standard Deviation 1.52

Adverse Events

Endometrial Injury Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Control Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Wellington P Martins

University of Sao Paulo

Phone: 55162231

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place