Clinical trial NCT02863198: Endometrial Injury for Unexplained Infertility
Official title: Endometrial Injury for Unexplained Infertility: Randomized Case-control Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: unexplained infertility
endometrial injury
pregnancy
Lead sponsor: Benha University
Sponsor class: OTHER
First posted: 2016-08-11
Enrollment: 120
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: Measurement of Uterine Artery Pulsatility Index
timeFrame: one week
measure: Measurement of Uterine Artery Resistance Index
timeFrame: one week
measure: Appearance of Sub Endometrial Blood Flow in All Patients
timeFrame: one week
measure: Spiral Artery Pulsatility Indices in All Patients
timeFrame: one week
measure: Spiral Artery Doppler Resistance Indices in All Patients
timeFrame: one week
Secondary outcomes:
measure: Pregnancy Rate Between the Study and the Control Group
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Benha
country: Egypt
facility: Benha university hospitalا
state: Alqalubia
Study officials:
affiliation: Benha University
name: khalid M salama
role: STUDY_DIRECTOR
References:
citation: 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.