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Abstract
Summary
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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
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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
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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
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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.