الفهرس | Only 14 pages are availabe for public view |
Abstract Summary 153 Summary 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 stubbornly 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 noninvasive methods, such as ultrasonography. However, the predictive value and the reproducibality 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 cytokines which are necessary for successful implantation. Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine that has been described in the endometrium by many researchers, either in animal models or in humans, to indicate Summary 154 its role in reproduction which revealed its important role in both implantation process and early steps of embryonic development. The impairments of the endometrial LIF expression may play a significant role in the pathological processes involving improper implantation and infertility. Potentially functional mutations in the LIF gene do infrequently occur in women with unexplained infertility and may play a role in the etiology of infertility. The aim of this prospective case-control study was to evaluate the concentration of leukaemia inhibitory factor in uterine flushings in patients with unexplained infertility compaired to fertile controls. In this study, 30 patients with unexplained infertility constituted the study group, all of them were 25-37 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 serum day 3 FSH, LH, TSH, prolactin, and day 21 progesterone and hysterosalpingography. While, the control group included 30 fertile women as proved by previous successful pregnancy, all were 22-43 years old, with no use of hormonal contraception or IUD, with no history of debilitating disease, PID or pelvic operations, with regular menstrual cycles, with no hormonal treatment in the month before the study and with normal basal FSH, LH, TSH, prolactin and progesterone, and attending the family planning clinic in Ain Shams University Maternity Hospital, for the use of contraceptive method. All patients were subjected to the following: Summary 155 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 endometrial thickness. 3- Measurement of cycle day 18-21 serum progesterone. 4- Endometrial sampling using uterine flushing on cycle day 18-23 was done. 5- Leukemia inhibitory factor quantification in the uterine flush was done using the ELISA technique. 6- One cycle of ovarian stimulation completed by IUI or ICSI. In this study, LIF concentration was evaluated in the endometrium of members of both groups. 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, cycle day 18-21 progesterone and endometrial thickness. Moreover, each of age, basal FSH & LH, TSH, Prolactin and progesterone levels were not significantly correlated to LIF concentration (p>0.05) in the study group. LIF concentration was significantly positively correlated (p<0.05) with endometrial thickness for study group. When comparing cases and controls for LIF concentration in secretory phase; the difference was highly significant showing more LIF concentration in controls (p<0.01). With a Cut-off value for LIF of 88pg/ml we achieved 96.7% specificity and sensitivity of 83.3%, and efficacy 90%. After one cycle of ovarian stimulation for the study group; 27 patients failed to become pregnant (Failed ART); and 3 patients became pregnant (Successful ART). Summary 156 There was no statistically significant difference (p>0.05) between both groups regarding age, BMI, Serum level FSH, LH, TSH, Prolactin and progesterone. There was highly significant difference regarding LIF concentration between both groups being higher in successful group. It was found in previous studies that exposure of murine blastocysts to LIF at the time of trans-cervical transfer, resulted in pronounced positive effects on implantation and pregnancy rates without affecting fetal development later. We conclude that endometrial LIF expression is markedly decreased in cases of unexplained infertility than in fertile women. Also, the increase in expression in luteal phase with maximal expression at the time of embryonic implantation, clarifies the importance of this factor in reproduction and so, lacking this factor in the endometrium may be a cause of infertility. Endometrial LIF expression can be used as an investigation for couples with unexplained infertility. It can be also used as a marker for optimal implantation, especially before ICSI trials. Finally, further studies, including larger number of cases, are recommended to confirm the role of LIF in implantation and to confirm that recombinant LIF may be a potential therapeutic tool where its administration to patients with failed implantation during embryonic transfer can be used as a possible replacement therapy to increase their chances of successful implantation and so, may affect the results of ICSI trials. |