الفهرس 
COVEROnly 14 pages are availabe for public view
 |  | from | 146 |  |  |
| | | from | 146 | | |
Abstract
Recent developments in fertility treatments have further diminished the consequences of male factor infertility. Yet, despite these changes, success rates in in-vitro fertilization (IVF) remain low, providing distress both for the individual concerned and for the economics of women’s health. The weak link in this, otherwise successful regulation of the female reproductive system, is the endometrium. Also, failed implantation remains a significant cause of reproductive failure in both spontaneous and assisted menstrual cycles. Genetic reasons are suspected, but the underlying gene alterations are not understood.
The limited implantation rate remains an unsolved problem in human reproductive medicine. The poor implantation rate of embryos also limits the utility of in-vitro fertilization and embryo transfer.
Uterine receptivity is believed to play an important role for achievement of normal pregnancy in ART cycles. The study of uterine receptivity in women relies primarily on non-invasive methods, such as ultrasonography. However, the predictive value and the reproducibility of these methods remain limited, and new methods of assessing uterine receptivity are needed.
Clearly, an important part of the study of implantation failure is the identification of specific growth factors or cytokines which are necessary for successful implantation.
TGFβ2 is one of the growth factors that have been described in the endometrium by many researchers, either in animal models or in humans, to indicate its role in reproduction which revealed its important role in both implantation process and early steps of embryonic development.
The difference of the endometrial TGFβ2 expression may play a significant role in the pathological processes involving improper implantation and infertility. Potentially functional deregulation of TGFβ2 gene expression infrequently occur in women with repeated failed ICSI and may play a role in the etiology of embryonic implantation failure.
The aim of this prospective case-control study was to evaluate the possible relationship between TGFβ2 expression within the endometrial tissue and failure of embryonic implantation in patients with failed ICSI through comparison of endometrial TGFβ2 expression in glands, luminal epithelium and stroma during secretory phases between patients with failed ICSI.
In this study, 50 patients ,whose attended in infertility clinic in Ain Shams University Maternity Hospital, with previous failed one or more ICSI trials, with easy transfer of 3 embryos at least of grade A, constituted the study group, all of them were 20-35 years old, having primary infertility, with no history of debilitating disease or recent PID or pelvic operations, having regular cycles, with no hormonal treatment in the month before the study and with normal basal (CD3) FSH, LH, TSH & prolactin and hysterosalpingography.
All patients were subjected to the following:
1- History taking, abdominal and pelvic examination.
2- Trans-vaginal U/S for:
a. Folliculometry (exclusion if abnormal).
b. Exclusion of any ovarian or uterine pathology.
c. Measurement of pre-ovulatory endometrial thickness.
3- Measurement of cycle day 18-21 serum progesterone.
4- Endometrial sampling using uterine biopsy on cycle day 18-23 was done.
All endometrial biopsies were fixed in 10% formaldehyde, embedded in paraffin blocks, and stained with Haematoxylin and Eosin for histopathological assessment and histological dating, together with morphometric analysis, then Immunohistochemical staining for TGFβ2 using monoclonal antibody.
In this study, TGFβ2 expression was evaluated in the endometrium of secretory phases by immunohistochemistry with scoring through two independent observers regarding intensity of immunostaining in each of glandular epithelium, luminal epithelium and stroma as well as spread (total surface area) of immune reaction.
After sample taking: All cases in the study group have undergone one cycle of ovarian stimulation completed by intracytoplasmic sperm injection (ICSI).
The study group (50 infertile women) divided in to 2 groups according to the success in the undergone ICSI:
Group A: Included 12 infertile women who became pregnant with next ICSI.
Group B: Included 38 infertile women who had another failed ICSI cycle.
Results were compared between group A (n=12) and group B (n=38).
Our results showed a non-significant difference (p>0.05) between both groups regarding the mean age of patients, BMI, basal FSH and LH, TSH, Prolactin and progesterone (CD 18-21) but highly significant difference (p>0.01) in endometrial thickness.
Moreover, each of age, BMI, basal FSH, LH and progesterone (CD 18-21) levels were not significantly correlated to TGFβ2 immunostaining (p>0.05) in the study group.
As regards endometrial thickness; it shows high significant correlation (p˂0.01) with TGFβ2 immunostaining intensity in luminal epithelium, glandular epithelium, stromal cells and total surface area staining.
As regard the prolactin it shows high significant correlation (p˂0.01) with serum TGFβ2 immunostaining intensity of glandular epithelium, stromal cells and the total surface area immunostaining, but there is no significant with luminal epithelium.
Also there is significant correlation (p˂0.05) between TSH and TGFβ2 immunostaining of stromal epithelium.
There is a highly significant difference (p˂0.01) between both groups as regards TGF2β immunostaining intensity in luminal epithelium, stromal epithelium and also in total surface area, while, it is significant difference (p<0.05) for glandular epithelium.
In our study we calculate the sensitivity and specificity of failure in TGFβ2 immunostaining, we found that specificity failure percent in luminal epithelium, glandular epithelium, stromal cells and total surface area, in score ≥ 2.50, it was 90%, while sensitivity failure in luminal epithelium, glandular epithelium, and total surface area, it was 87.7%.
In score ≥ 0.50 we found specificity failure 0% in glandular epithelium and total surface area with sensitivity failure 50%.
We conclude the deregulation and overexpression of TGFβ2 gene at window of implantation time might be a contributing factor leading to the impairment of implantation, clarifies the importance of this factor in reproduction.
Endometrial TGFβ2 expression can be used as an investigation for couples with repeated failed ICSI. It can be also used as a marker for optimal implantation, especially before ICSI trials.