Endometrial injury for unexplained infertility: Arandomized case-control study

PATIENTS AND METHODS:

This randomized case-control study was performed at the Obstetrics and Gynecology Department of Benha University Hospital ,during the period between October 2013 till July 2015.One hundred and twenty women with unexplained infertility were included in the study ,these patients were recruited from Outpatient Clinic of Benha University, with the following criteria: age Between 20 - 35 years ,Body mass index 18-29 kg/m^2, ,Complaining of primary infertility for more than two years, and planning for IVF/ICSI trial , All factors which may contribute to infertility were excluded .Normal ovulation confirmed by previous folliculometry, Normal hormonal profile FSH, LH, and prolactin ,Antimullerian hormone (AMH) more than 1 ng/ml ,Normal Hysterosalpingography,Normal laparoscoic finding. . All the male partners had normal semen analysis, according to WHO 2010.

Primary exclusion Criteria:The patients with any of the following criteria were excluded from the study: Absence of inclusion criteria ,History of previous laparotomy ,Patients with history which may suggest endometriosis and Associated chronic medical conditions e.g. cardic disease, diabetes, renal disease … etc.

Awritten, 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 recieved Clomiphene citrate (CC) and, Human menopausal gonadotrophin ,according to the following protocol :Clomiphene Citrate(Clomiphene tablets, Clomiphene citrate 50 mg, The Arab Drug Company, ADCO, Egypt), 100 mg/day for 5 consecutive days, with therapy initiated on cycle day 3 . Human menopausal gonadotrophin (Merional 75IU, IBSA InstitutBiochimique SA, Switzerland), 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 folliculometry 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 ,HCG(Choriomon 5000 IU, IBSA Institut Biochimique SA ,Switzerland) was injected intramuscularly , in a dose of 5,000 – 10,000 IU, and timed intercourse was advised, 36 h after HCG injection and the days after. Vaginal ultrasound was done about 60 h after HCG injection to confirm follicular rupure. 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 prescriping HCG.

Technique of trans vaginal ultrasound:Trans vaginal sonography examination was performed with patient in the lithotomy position using a 7.5 -9 MHz, transvaginal transducer with color Doppler facility, using the Voluson 730 PRO V‐ G E, Health care USA.On ultrasound, 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 HCG 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 isoechogenic 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; Gynetics Medical Products, Hamont-Achel, Belgium).