Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT05885633 |
Other study ID # |
UsakUn |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
October 21, 2022 |
Est. completion date |
April 29, 2023 |
Study information
Verified date |
May 2023 |
Source |
Usak University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Vitamin D receptor (VDR) is widely expressed not only in tissues responsible for calcium
hemostasis, but also in reproductive organs, including the endometrium. The VDR, which is low
in the proliferative phase, starts to increase in the early secretory phase and decreases
again in the mid-secretory phase. Enzymes responsible for vitamin d (VD) production and
metabolism are expressed locally in the endometrium. Binding of active VD to VDR in nuclear
or plasma membrane increases receptivity gene expression and immunomodulators by activating
genomic and nongenomic pathways. VDR expression defect has been reported in the decidual
cells of recurrent miscarriages. There are no studies investigating the endometrial VDR
expression pattern in polycystic ovary syndrome (PCOS) and its phenotypes. The VDR expression
pattern in the endometrium of PCOS patients who underwent invitro fertilization
/intracytoplasmic sperm injection (IVF/ICSI) and total embryo freezing was analyzed at both
mRNA and immunohistochemical. The study group consisted of 44 PCOS patients who were referred
to IVF/ICSI because they did not respond to first-line treatment with letrozole or clomiphene
citrate (CC). Twenty patients who were scheduled for IVF/ICSI due to male factor infertility
and who were matched with the study group in terms of age and body mass index (BMI) were
included as the control group. Following egg collection, endometrial tissue was collected by
pipelle cannula while the patient was under anesthesia. All good quality blastocysts of both
groups were vitrified. The mRNA expression of vitamin D receptor transcript 2 (VDR-X2) and
vitamin D receptor transcript 4 (VDR-X4) were determined by quantitative polymerase chain
reaction (qPCR). The quantitative cycle equation method was used to calculate the differences
between VDR-mRNA expressions. Endometrial VDR and progesterone receptor (PR) immunoreactivity
were determined by immunohistochemistry.
Description:
Study question: How does the expression of endometrial vitamin D receptor vary according to
phenotypes in women with polycystic ovary syndrome (PCOS)?
What is known already: VDR is widely expressed not only in tissues responsible for calcium
hemostasis, but also in reproductive organs, including the endometrium. The VDR, which is low
in the proliferative phase, starts to increase in the early secretory phase and decreases
again in the mid-secretory phase. Enzymes responsible for VD production and metabolism are
expressed locally in the endometrium. Binding of active VD to VDR in nuclear or plasma
membrane increases receptivity gene expression and immunmodulators by activating genomic and
nongenomic pathways. VDR expression defect has been reported in the decidual cells of
recurrent miscarriage cases. There are no studies investigating the endometrial VDR
expression pattern in PCOS and its phenotypes.
Study design, size, duration: The study group consisted of 44 PCOS patients who were referred
to IVF/ICSI because they did not respond to first-line treatment with letrozole or clomiphene
citrate (CC). Twenty patients who were scheduled for IVF/ICSI due to male factor infertility
and who were matched with the study group in terms of age and BMI were included as the
control group. Those who met at least two of the criteria for hyperandrogenemia (HA),
ovulatory dysfunction (OD) and polycystic ovarian morphology (PCOM) determined by European
Society of Human Reproduction and Embryology/ American Society for Reproductive Medicine were
considered PCOS. Following egg collection, endometrial tissue was collected by pipelle
cannula while the patient was under anesthesia. All good quality blastocysts of both groups
were vitrified.
Participants/materials, setting, methods: The 44 participants in the PCOS group were divided
into four phenotypic groups as follows according to the National Institutes of Health (NIH)
consensus panel. Phenotype A: HA+OD+PCOM (classical/complete, n=17); phenotype B: HA+OD
(classical/non-PCOM, n=10); phenotype C: HA+PCOM (ovulatory, n=9); and phenotype D: OD+PCOM
(non-hyperandrogenic, n=8). The mRNA expression of vitamin D receptor transcript 2 (VDR-X2)
and vitamin D receptor transcript 4 (VDR-X4) were determined by qPCR. The quantitative cycle
equation method was used to calculate the differences between VDR-mRNA expressions.
Endometrial VDR and progesterone receptor (PR) immunoreactivity were determined by
immunohistochemistry. The histological score formula was used for the quantitative evaluation
of VDR and PR immunoreactivity.
Limitations, reasons for caution: The lack of an equal number of participants for each
phenotype is our first limitation. Due to the collection of endometrial samples in the
IVF/ICSI cycle, the possible effect of ovarian stimulation drugs and the associated increased
estrogen levels on the endometrium has not been excluded. Changes in endometrial VDR-mRNA
expression could not be confirmed by protein measurement.