تقييم بعض العوامل الهرمونية والجزيئية عند النساء اللواتي يعانين من الإجهاض المتكرر ويتلقين عقار الديدروجستيرون في محافظة كربلاء

Evaluation of Some Hormonal and Molecular Factors in Women with Recurrent Abortion Receiving Dydrogesterone Drug in Karbala Province

abstract

Recurrent Pregnancy Loss (RPL) is a condition that is defined as three
consecutive pregnancy losses before 20 weeks from the last menstrual
period; RPL may be caused, in part, by low progesterone levels during the
luteal phase. Dydrogesterone (DYD), a synthetic progestogen, aims to
enhance endometrial receptivity and prevent pregnancy loss.
This study included (106) women from the Gynecology and Obstetrics
Teaching Hospital, Khadija Al-Kubra Hospital, and Outpatient infertility
clinics in Karbala Province. The participants were divided into three groups:
the first group involved 35 patients with recurrent pregnancy loss who
received dydrogesterone for six months, the second group included 35
patients with recurrent pregnancy loss without treatment, and the third group
comprised 36 healthy women as a control group. All participants in the study
were matched by age, ranging from 25 to 38 years, and body mass index.
The present study was applied to evaluate the concentrations of some
hormonal (progesterone, estradiol, prolactin, follicle-stimulating hormone,
luteinizing hormone, and testosterone; biochemical factors (progesteroneinduced
blocking factor and epithelial-cadherin) and relative gene expression
of progesterone receptors (nuclear and membrane progesterone receptors for
all study subjects.
Progesterone and estradiol levels decreased significantly (p ≤ 0.05) in
RPL patients untreated compared to the control group. No significant
difference in progesterone levels between RPL patients receiving treatment
and the control group, but a statistically significant increase (p ≤ 0.05) was
noted in progesterone concentration among RPL patients with treatment
compared to those without treatment. Also, a positive correlation (r = 0.522)
between progesterone and estradiol in RPL patients untreated.
B
The study estimated the concentrations of prolactin, follicle-stimulating
hormone, luteinizing hormone and testosterone in RPL women, these
parameters are non-significantly different (p ≤ 0.05) among all groups of this
study. The correlation has shown an inverse correlation between
progesterone and FSH concentration in RPL patients without treatment and
with treatment (r = – 0.46, r= – 0.390., respectively).
Data on Progesterone Induce Blocking Factor (PIBF) and Epithelial-
Cadherin (E-Cad) concentrations indicated a significant decrease (p ≤ 0.05)
in RPL patients without treatment compared to the control group. However,
there was a notable rise in PIBF and E-Cad levels between untreated RPL
patients and those undergoing treatment. Furthermore, a significant positive
correlation between Progesterone and PIBF was observed in both untreated
RPL patients and those receiving treatment.
The results of relative gene expression for progesterone membrane
receptor (mPRα) have indicated significantly increased gene expression (p ≤
0.05) in RPL patients without treatment and control group. Also found the
same result between RPL patients with treatment and without treatment. An
inverse relationship was found between mPRα gene expression and
Progesterone concentration in untreated RPL patients and RPL patients with
treatment (r = – 0.132, r= – 0.014., respectively). The results of patients who
had repeated miscarriages without receiving dydrogesterone therapy showed
a significantly lower expression of progesterone membrane receptors
(mPRß) in their endometrial tissue. Additionally, there was a significant
increase in gene expression of mPRß between RPL patients receiving
treatment and those without treatment (p ≤ 0.05). Results of the correlation
have shown a significantly positive correlation (r= 0.380) between mPRß
gene expression and Progesterone in RPL patients without treatment and in
RPL patients with treatment (r = 0.156).
C
The analysis of gene expression levels of NPR showed that there was
very little variation between untreated patients and the control groups. The
same findings were observed when comparing the gene expression of NPR
in treated and untreated patients. There was a positive correlation (r = 0.319)
between NPR gene expression and Progesterone concentration in RPL
patients without treatment and in RPL patients with treatment (r = 0.346).
The findings suggest a reduction of gene expression of membrane
progesterone receptor ß (mPRβ) and elevated gene expression of membrane
progesterone receptor α (mPRα) in RPL patients may play an important role
in the pathogenesis of RPL; and the reduction of mPRα and increased of
mPRβ after treatment with the dydrogesterone, that suggest to the
dydrogesterone direct effected on endometrial gene expression of
.progesterone receptors