Effect of Letrozole on Hyaluronic Acid Concentration of the Endometrial Wash

widely throughout connective, epithelial, and neural tissues. The study included 40 infertile females. A full history taking, complete general examination, complete gynecological examination


Introduction
Infertility is a disease of the reproductive system, which is defined as the failure to achieve pregnancy after at least one year of regular unprotected sexual intercourse in women < 35 years who are not using contraception and after six months in women > 35 years or due to an impairment of a person's capacity to reproduce, either as an individual or with his/her partner, it affects about 10-15% of couples (Bergqvist, et al [1] , Campbell, S [2] ).
According to the World Health Organization (WHO) definition, a couple is considered infertile if, after 2 years of regular sexual intercourse, without contraception, the woman has not become pregnant (Chun, et al [3] ). Hyaluronic acid (HA) is an anionic, nonsulfated glycosaminoglycan that has a significant role in establishing the cellular microenvironment conducive to the development of the proliferative process.
The lack of hyaluronic acid synthase regulation genes causes abnormal production of HA and promotion of abnormal biological processes such as metastasis and pregnancy loss (Al-Hussaini and Shaaban [4] ).An increasing number of reports suggest the role of HA in female reproduction and interest in its application in assisted reproduction is rising.However, there are contrasting data about the effectiveness of adding HA to the embryo-transfer medium on improving pregnancy rates (Oats, et al [5] ).Several studies evaluated the co-administration of Letrozole during ovarian stimulation in patients suffering from a diminished ovarian reserve, yielding conflicting results.In these studies, Letrozole was started either concomitantly with or before gonadotropins, and was given for a total of 5 stimulation days (Elsedeek, et al [6] , Ahmied, M. [7] ).Hypothetically, extending the duration of letrozole co and Ahmeid [8] ).The study aims to evaluate the use of letrozole in the stimulation of infertile women in relation to hyaluronic acid levels in endometrium.

Materials and Methods
This

Results
In this study, the majority of women enrolled have belonged to rural area (60%) and below 30 years old (55%), parity was 0-5 but the majority were complaining of primary infertility (60%) and the infertility duration from 2 years to >7

Discussion
It is important to understand the host physiological and pathological mechanisms underlying events of the female reproductive tract, such as endometriosis, tumors, and infertility (González-Ramos, et al [9] ).There were very few declared studies regarding the relation of hyaluronic acid with infertility and no previous studies were done about the levels of HA in women who received letrozole plus Gonadotropin and who received Clomid plus Gonadotropin.A study done by (Simões, et al [10] ) indicated that there was an elevated concentration of hyaluronic acid in women endometrium in the proliferative phase and higher HAS1 and HAS2 reactivity when compared with normal women.In addition, (Nagyova, E [11] ) indicated that HA levels were increased in the endometrial stroma during the secretory phase of the menstrual cycle and fall to very low levels at menstruation, suggestive of a role in implantation.In different studies, (Gomes, et al [12] ) in the study the immune- (Mohey-Elsaeed, et al [13] ) reported spatiotemporal expression of RHAMM protein in mouse endometrium during the estrous cycle and peri-implantation period, suggesting its possible role in endometrial receptivity.HA has also been shown to improve the cryotolerance of blastocysts, which then leads to increased birth rates in cows (Lane, et al [14] ).
Moreover, HA was detected in oviductal fluids collected by catheterization during the estrous cycle in heifers and cows (Simon, et al [15] ) and was shown to be highest at ovulation (Stojkovic, et al [16] ).
Synthesis of HA is increased significantly in the uterus of mice on the day of implantation (Fouladi-Nashta, et al [17] ), and HA differential expression in the human endometrium during the menstrual cycle implies its involvement in implantation.In the human uterus, the peak expression of HAS and CD44 is in the mid-secretory stage (Afify, et al [18] ).
There is a plethora of data suggesting the beneficial roles for HA in human embryo implantation (Ahmeid M. [7] , González-Ramos, et al [9] ).

Conclusions
It was concluded that hyaluronic acid was elevated significantly in women who received ovulation stimulation drugs and letrozole was a good treatment for anovulatory cycle women.
-treatment may provide a more pronounced effect on intrafollicular androgens and circulating estrogen levels.Letrozole co-treatment during the entire stimulation course improves ovarian response in normal responders undergoing IVF-ET (Hameed .i1.r2 0 http://doi.org/10.28969/IJEIR.v1et al.AlJuboory, 22 Figure (1): Methodology of the study present study included aspiration of endometrial wash fluid on the day of trigger by putting the patient in the lithotomy position.Cleaning of the vagina was done by normal saline wash.Using a sterile IUI catheter connected to a disposable syringe; three ml of sterile normal saline was injected slowly into the endometrial cavity after passing the cervical mucus and re-aspirated after thirty seconds.This volume was chosen after making a pilot study since a larger amount might spill into the ovarian tubes and may go farther into the peritoneal cavity causing peritoneal irritation, a lesser amount might not cover the entire cavity and the samples will not be sufficient for measuring the hyaluronic acid concentration.Samples were transferred into a plain sterile tube for assessment of

Figure ( 2 ):Figure
Figure (2): Correlation between hyaluronic acid and LH of group A at day of follicles triggering expression of hyaluronic acid (HA) in the uterine horns of the mouse throughout the estrous cycle phases, their data showed that the highest concentration of HA in uterine horns occurred during diestrus compared with other phases.Moreover, .i1.r2 0 http://doi.org/10.28969/IJEIR.v1et al.AlJuboory, 30

Table ( 1
): General characteristics of females enrolled in the present study