Endometrial Injury for Unexplained Infertility

• ClinicalTrials.gov Identifier: NCT02863198
• Recruitment Status: Completed
• First Posted: August 11, 2016
• Results First Posted: March 14, 2017
• Last Update Posted: March 14, 2017
• Sponsor: Benha University
• Information provided by (Responsible Party): khalid mohammed salama, Benha University

Study Description

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

Condition or disease	Intervention/treatment	Phase
Infertility	Device: endometrial injury	Not Applicable

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Endometrial Injury for Unexplained Infertility: Randomized Case-control Study
• Study Start Date: October 2013
• Actual Primary Completion Date: February 2016
• Actual Study Completion Date: July 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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).	Device: 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).
No Intervention: non endometrial injury; non endometrial injury was done only for patient of the control group

Outcome Measures

Primary Outcome Measures :

1. Measurement of Uterine Artery Pulsatility Index [ Time Frame: one week ]
   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.
2. Measurement of Uterine Artery Resistance Index [ Time Frame: one week ]
   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.
3. Appearance of Sub Endometrial Blood Flow in All Patients [ Time Frame: one week ]
   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 .
4. Spiral Artery Pulsatility Indices in All Patients [ Time Frame: one week ]
   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
5. Spiral Artery Doppler Resistance Indices in All Patients [ Time Frame: one week ]
   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.

Secondary Outcome Measures :

1. Pregnancy Rate Between the Study and the Control Group [ Time Frame: 3 weeks ]
   detection of serum pregnancy tests for both groups( study and the control group)

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 35 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Egypt

Benha university hospitalا

Benha, Alqalubia, Egypt

Sponsors and Collaborators

Benha University

Investigators

• Study Director: khalid M salama; Benha University

More Information

Additional Information:

infertility 

Publications:

Maged AM, Al-Inany H, Salama KM, Souidan II, Abo Ragab HM, Elnassery N. Endometrial Scratch Injury Induces Higher Pregnancy Rate for Women With Unexplained Infertility Undergoing IUI With Ovarian Stimulation: A Randomized Controlled Trial. Reprod Sci. 2016 Feb;23(2):239-43. doi: 10.1177/1933719115602776. Epub 2015 Sep 3.

• Responsible Party: khalid mohammed salama, director clinical research, Benha University
• ClinicalTrials.gov Identifier: NCT02863198
• Other Study ID Numbers: Khalid 3
• First Posted: August 11, 2016
• Results First Posted: March 14, 2017
• Last Update Posted: March 14, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by khalid mohammed salama, Benha University:

unexplained infertility; endometrial injury; pregnancy

Additional relevant MeSH terms:

Infertility