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Endometrial Injury for Unexplained Infertility

Endometrial Injury for Unexplained Infertility: Randomized Case-control Study

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02863198
Enrollment
120
Registered
2016-08-11
Start date
2013-10-31
Completion date
2016-07-31
Last updated
2017-03-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Infertility

Keywords

unexplained infertility, endometrial injury, pregnancy

Brief summary

One hundred and twenty women with unexplained infertility were included in the study. Divided randomly into two groups: Group I: (60 patients): (control group) Group II (60 patients): (study group) All the patients received (CC) and human menopausal gonadotropin. On day 5 of the cycle, Doppler examination was performed to all patients. Also on day 5, but only for group (II) patients, local endometrial injury was performed. Doppler studies was repeated, for all our patients, on the same day of prescribing human chorionic gonadotropin

Detailed description

This randomized case-control study was performed at the Obstetrics and Gynecology Department of University Hospital, during the period between October 2013 till July 2015. One hundred and twenty women with unexplained infertility were included in the study. Written, informed, consent, was taken from all women after explaining the nature and the aim of the study. The 120 patients were divided randomly into two groups (based on each alternate week referral to the clinic). All the patients received Clomiphene citrate (CC) and, Human menopausal gonadotrophin, according to the following protocol: Clomiphene Citrate (Clomiphene tablets, Clomiphene citrate 50 mg), 100 mg/day for 5 consecutive days, with therapy initiated on cycle day 3. Human menopausal gonadotrophin (Merional 75 international unit), was injected intra-muscularly, in a dose of 150 iu/day, on the days 3, 5, 7, 9 of the menstrual cycle. Serial transvaginal ultra sound was performed for all patients starting from day 10 and repeated every other day. Human menopausal gonadotrophin was continued daily, in the same dose, until follicles reached 18-22 mm. When the dominant follicles reached 18-22 mm, as measured by transvaginal ultrasound, human chorionic gonadotropin (5000 international unit) was injected intramuscularly, in a dose of 5,000 - 10,000 IU, and timed intercourse was advised, 36 h after human chorionic gonadotropin injection and the days after. Vaginal ultrasound was done about 60 h after human chorionic gonadotropin injection to confirm follicular rupture. On day 5 of the cycle, Doppler examination was performed to all patients. Also on day 5, but only for group II patients, local endometrial injury was performed. Doppler studies was repeated, for all our patients, on the same day of prescribing human chorionic gonadotropin. Technique of trans vaginal ultrasound: Trans vaginal sonography examination was performed with patient in the lithotomy position using transvaginal transducer with color Doppler facility, a longitudinal view of the uterus was obtained then, the color Doppler mode was activated. The endometrial and subendometrial blood flow distribution pattern was determined by demonstrating pulsatile color signals in the sub endometrial and endometrial regions. Doppler sonography was performed on the vessels with the highest color intensity within the innermost endometrial and sub endometrial area. The insonation angle was kept at 0° to identify the course of the small spiral arteries. After confirming that waveforms were continuous, an average of three to five cardiac cycles were selected for calculation of resistance index (RI), pulsatility index (PI). The vessel with the lowest PI was considered for further statistical analysis. Uterine circulation was assessed simultaneously in each examination; bilateral uterine arteries were sampled lateral to the cervix near the internal os. Mean levels of both uterine RI and PI were used for analysis.on the day of human chorionic gonadotropin administration the endometrial thickness was measured, and reported. on the same day The endometrial pattern was evaluated and described as a multilayered or a non-multilayered endometrium. A trilaminar endometrium presented as a triple-line pattern in which hyperechogenic outer lines and a well-defined central echogenic line with hypoechogenic or black areas between these lines. A non trilaminar endometrium consisted of homogeneous endometrial patterns, characterized by either hyperechogenic or isoechoic endometrium. Technique of endometrial injury: Endometrial injury was done only for patient of the study group. It was done on day 5, under complete aseptic conditions, no anesthesia, was given in most of cases. Endometrial local injury was performed on the posterior wall, midline, and 10-15 mm from the fundus using pipelle endometrial sampling (Pipelle).

Interventions

Endometrial injury was done only for patient of the study group. It was done on day 5, under complete aseptic conditions, no anesthesia, was given in most of cases. Endometrial local injury was performed on the posterior wall, midline, and 10-15 mm from the fundus using pipelle endometrial sampling (Pipelle).

Sponsors

Benha University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)

Eligibility

Sex/Gender
FEMALE
Age
20 Years to 35 Years
Healthy volunteers
No

Inclusion criteria

* age Between 20 - 35 years * Body mass index 18-29 kg/m2 * primary infertility for more than two years, and planning for IVF/intracytoplasmic sperm injection trial * Normal ovulation confirmed by previous US * Normal hormonal profile follicle stimulating hormone, luteinizing hormone, and prolactin, Antimullerian hormone (AMH) more than 1 ng/ml * Normal hysterosalpingography * Normal laparoscopic finding * normal semen analysis, according to World Health Organization 2010

Exclusion criteria

* Absence of inclusion criteria * History of previous laparotomy * Patients with history which may suggest endometriosis * Associated chronic medical conditions e.g. cardiac disease, diabetes, renal disease… etc.

Design outcomes

Primary

MeasureTime frameDescription
Spiral Artery Doppler Resistance Indices in All Patientsone weekSpiral artery Doppler resistance indices between study and control groups on the day of human chorionic gonadotropin administration.it is an indicator of resistance of Spiral artery to perfusion . In ultrasonography,it can be calculated from the peak systolic velocity and end diastolic velocity of blood flow and is calculated with the following formula: (peak systolic velocity - end diastolic velocity)/peak systolic velocity.lower values are better than higher values.
Measurement of Uterine Artery Pulsatility Indexone weekmeasurement of uterine artery pulsatility index at day of human chorionic gonadotropin administration.Pulsatility index is a measure of the variability of blood velocity in a vessel, and was calculated as the difference between the peak systolic and end diastolic velocities divided by the mean velocity during the cardiac cycle. Higher values are indicative of increased vascular resistance.
Measurement of Uterine Artery Resistance Indexone weekmeasurement of uterine artery resistance index at day of human chorionic gonadotropin administration.it is an indicator of resistance of uterine artery to perfusion . In ultrasonography, it can be calculated from the peak systolic velocity and end diastolic velocity of blood flow and is calculated with the following formula: (peak systolic velocity - end diastolic velocity)/peak systolic velocity.lower values are better than higher values.
Appearance of Sub Endometrial Blood Flow in All Patientsone weekAppearance of sub endometrial blood flow between patients of study and control groups on the day of human chorionic gonadotropin administration. subendometrial blood flow distribution pattern was determined by demonstrating pulsatile color signals in the sub endometrial area.The number of patients demonstrating subendometrial blood flow distribution pattern are collected .
Spiral Artery Pulsatility Indices in All Patientsone weekSpiral artery Doppler pulsatility indices between study and control groups on the day of human chorionic gonadotropin administration.Pulsatility index is a measure of the variability of blood velocity in a vessel, and was calculated as the difference between the peak systolic and end diastolic velocities divided by the mean velocity during the cardiac cycle. Higher values are indicative of increased vascular resistance

Secondary

MeasureTime frameDescription
Pregnancy Rate Between the Study and the Control Group3 weeksdetection of serum pregnancy tests for both groups( study and the control group)

Countries

Egypt

Participant flow

Participants by arm

ArmCount
Endometrial Injury
Endometrial injury was done only for patient of the study group. It was done on day 5, under complete aseptic conditions, no anesthesia, was given in most of cases. Endometrial local injury was performed on the posterior wall, midline, and 10-15 mm from the fundus using pipelle endometrial sampling (Pipelle). endometrial injury: Endometrial injury was done only for patient of the study group. It was done on day 5, under complete aseptic conditions, no anesthesia, was given in most of cases. Endometrial local injury was performed on the posterior wall, midline, and 10-15 mm from the fundus using pipelle endometrial sampling (Pipelle).
60
Non Endometrial Injury
non endometrial injury was done only for patient of the control group
60
Total120

Baseline characteristics

CharacteristicEndometrial InjuryNon Endometrial InjuryTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
60 Participants60 Participants120 Participants
Region of Enrollment
Egypt
60 participants60 participants120 participants
Sex: Female, Male
Female
60 Participants60 Participants120 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 600 / 60
serious
Total, serious adverse events
0 / 600 / 60

Outcome results

Primary

Appearance of Sub Endometrial Blood Flow in All Patients

Appearance of sub endometrial blood flow between patients of study and control groups on the day of human chorionic gonadotropin administration. subendometrial blood flow distribution pattern was determined by demonstrating pulsatile color signals in the sub endometrial area.The number of patients demonstrating subendometrial blood flow distribution pattern are collected .

Time frame: one week

ArmMeasureValue (NUMBER)
Endometrial InjuryAppearance of Sub Endometrial Blood Flow in All Patients33 participants
Non Endometrial InjuryAppearance of Sub Endometrial Blood Flow in All Patients12 participants
p-value: <0.05Chi-squared
Primary

Measurement of Uterine Artery Pulsatility Index

measurement of uterine artery pulsatility index at day of human chorionic gonadotropin administration.Pulsatility index is a measure of the variability of blood velocity in a vessel, and was calculated as the difference between the peak systolic and end diastolic velocities divided by the mean velocity during the cardiac cycle. Higher values are indicative of increased vascular resistance.

Time frame: one week

ArmMeasureValue (MEAN)Dispersion
Endometrial InjuryMeasurement of Uterine Artery Pulsatility Index2.40 indexStandard Deviation 0.23
Non Endometrial InjuryMeasurement of Uterine Artery Pulsatility Index2.35 indexStandard Deviation 0.28
p-value: <0.05t-test, 2 sided
Primary

Measurement of Uterine Artery Resistance Index

measurement of uterine artery resistance index at day of human chorionic gonadotropin administration.it is an indicator of resistance of uterine artery to perfusion . In ultrasonography, it can be calculated from the peak systolic velocity and end diastolic velocity of blood flow and is calculated with the following formula: (peak systolic velocity - end diastolic velocity)/peak systolic velocity.lower values are better than higher values.

Time frame: one week

ArmMeasureValue (MEAN)Dispersion
Endometrial InjuryMeasurement of Uterine Artery Resistance Index0.86 indexStandard Deviation 0.04
Non Endometrial InjuryMeasurement of Uterine Artery Resistance Index0.85 indexStandard Deviation 0.03
p-value: <0.05t-test, 2 sided
Primary

Spiral Artery Doppler Resistance Indices in All Patients

Spiral artery Doppler resistance indices between study and control groups on the day of human chorionic gonadotropin administration.it is an indicator of resistance of Spiral artery to perfusion . In ultrasonography,it can be calculated from the peak systolic velocity and end diastolic velocity of blood flow and is calculated with the following formula: (peak systolic velocity - end diastolic velocity)/peak systolic velocity.lower values are better than higher values.

Time frame: one week

ArmMeasureValue (MEAN)Dispersion
Endometrial InjurySpiral Artery Doppler Resistance Indices in All Patients0.62 indexStandard Deviation 0.06
Non Endometrial InjurySpiral Artery Doppler Resistance Indices in All Patients0.66 indexStandard Deviation 0.04
p-value: <0.05t-test, 2 sided
Primary

Spiral Artery Pulsatility Indices in All Patients

Spiral artery Doppler pulsatility indices between study and control groups on the day of human chorionic gonadotropin administration.Pulsatility index is a measure of the variability of blood velocity in a vessel, and was calculated as the difference between the peak systolic and end diastolic velocities divided by the mean velocity during the cardiac cycle. Higher values are indicative of increased vascular resistance

Time frame: one week

ArmMeasureValue (MEAN)Dispersion
Endometrial InjurySpiral Artery Pulsatility Indices in All Patients1.19 indexStandard Deviation 0.246
Non Endometrial InjurySpiral Artery Pulsatility Indices in All Patients1.01 indexStandard Deviation 0.25
p-value: <0.05t-test, 2 sided
Secondary

Pregnancy Rate Between the Study and the Control Group

detection of serum pregnancy tests for both groups( study and the control group)

Time frame: 3 weeks

ArmMeasureValue (NUMBER)
Endometrial InjuryPregnancy Rate Between the Study and the Control Group11 participants
Non Endometrial InjuryPregnancy Rate Between the Study and the Control Group4 participants
p-value: <0.05Chi-squared

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026