Vitamin D Receptor DefectNCT05885633
Endometrial Vitamin D Receptor in PCOS
A study testing endometrial sampling with pipelle in people with Vitamin D Receptor Defect, run by Uşak University at 1 site in Turkey (Türkiye).
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. Read more about this study
- Who is it for?
- Ages 26 to 32 years, women only
- Conditions the study is for
- Vitamin D Receptor Defect
- What is being tested?
- endometrial sampling with pipelle
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 21 Oct 2022to 29 Apr 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 26 to 32 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Clinical diagnosis of PCOS
- Approval for IVF/ICSI and total embryo freezing
- Consent to endometrial sampling
Who cannot join
- Women with hyperandrogenism or ovulatory dysfunction due to non-PCOS etiologies.
- Patients taking vitamin D, insulin sensitizers, lipid-lowering or other hormonal drugs in the last three months were not included.
- Those with a history of mechanical endometrial injury, polypectomy, hysteroscopic myomectomy, endometrioma resection, dilatation/curettage, ovarian drilling and salpingectomy were also excluded.
- Participants with premalignant or malignant endometrial pathology, those with a history of tubal factor infertility, congenital uterine anomaly or any chronic systemic diseases were not included.
- Azoospermia patients were excluded from the study because we preferred ejaculate sperm for ICSI in patients in the control group.
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Usak University Training and Research Hospital
Uşak, 64200
About this study
Official title: Phenotypic Components of Polycystic Ovary Syndrome Determine Endometrial Vitamin D Receptor mRNA Expression Pattern
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.
Read the detailed 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.
- Conditions
- Vitamin D Receptor Defect
- Being tested
- endometrial sampling with pipelle
- Keywords
- PCOS, Vitamin D, Endometrium, VD receptor, Hyperandrogenemia, Insulin resistance
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
endometrial sampling with pipelleProcedure or surgery
Following oocyte retrieval while the patient was under anesthesia, endometrial tissue sampling was performed with the help of pipelle cannula. A portion of the endometrial tissue was put into RNA stabilization buffer (RNAlater) to be used in qPCR and stored at -20°C until the analysis. The remaining endometrial tissue was first fixed with 10% formalin, followed by paraffin blocking and prepared for immunohistochemical analysis.
| Study group | Role | What they receive |
|---|---|---|
| PCOS | Active comparator | Infertile PCOS patients (n=44) Receives: Procedure: endometrial sampling with pipelle |
| Non-PCOS control | Active comparator | Non-PCOS control with male factor infertility Receives: Procedure: endometrial sampling with pipelle |
| Phenotype A | Active comparator | Phenotype A: HA+OD+PCOM (classical/complete, n=17) Receives: Procedure: endometrial sampling with pipelle |
| Phenotype B | Active comparator | phenotype B: HA+OD (classical/non-PCOM, n=10) Receives: Procedure: endometrial sampling with pipelle |
| Phenotype C | Active comparator | phenotype C: HA+PCOM (ovulatory, n=9) Receives: Procedure: endometrial sampling with pipelle |
| Phenotype D | Active comparator | phenotype D: OD+PCOM (non-hyperandrogenic, n=8). Receives: Procedure: endometrial sampling with pipelle |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary aim of the study was to investigate whether there is a difference in VDR expression in the endometrium of PCOS patients compared to controls by qPCR and immunohistochemical methods
The VDR expression pattern in the endometrium of PCOS patients who underwent IVF/ICSI and total embryo freezing because they did not respond to first-line ovulation stimulation was analyzed at both mRNA and immunohistochemical levels. Endometrial VDR mRNA expression levels were measured by qPCR method. In addition, samples were stained immunohistochemically to determine the distribution and intensity of VDR in the endometrial tissue. In order to compare the possible relationship between progesterone receptor (PR) distribution and VDR distribution, endometrial samples were also stained immunohistochemically with PR antibody.
Measured: first 3 months
Secondary outcomes (2)
To reveal the effects of insulin resistance, HA, OD, and PCOM on endometrial VDR mRNA expression using correlation analyses.
Participants in the PCOS group were divided into four groups as phenotype A (HA+OD+PCOM), phenotype B (HA+OD), phenotype C (HA+PCOM) and phenotype D (OD+PCOM) and which phenotypic variable affected VDR mRNA was analyzed.
Measured: First three months
Clinical pregnancy and miscarriage rates
. Clinical pregnancy was defined as the presence of an intrauterine gestational sac in the transvaginal ultrasonography examination (Clinical pregnancy rate (CPR) = total number of clinical pregnancies/total number of ET cycles × 100%). Fetal loss before 12 weeks of gestation was defined as miscarriage (Miscarriage rate = total number of miscarriages/total number of clinical pregnancies × 100%).
Measured: three months following the first three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2023
- Study start21 Oct 2022
- Primary completion25 Jan 2023
- Study completion29 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vitamin D Receptor DefectStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- While the study group consisted of PCOS patients, the control group was selected from non-PCOS patients with male factor infertility.
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uşak University
- Sponsor type
- University, hospital or other
- Collaborators
- Bahçeşehir University, Firat University
- Responsible party
- Sponsor
- Investigators
- nur DE gungor, assoc. prof., Principal investigator, BAU IVF-Centeraynur A ersahin, assoc. prof, Principal investigator, BAU IVF-Centerarzu yurci, assoc. prof., Principal investigator, Memorial IVF-CenterUlun ulug, prof, Principal investigator, Halic Universitymeltem yardım, specialist, Principal investigator, Yerkoy State Hospitalnilufer celik, assoc. prof., Principal investigator, Dr. Behcet Uz Children's Hospitalahmet tektemur, assoc. prof, Principal investigator, Firat UniversityTuncay Kuloglu, Assoc. prof, Principal investigator, Firat University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05885633
- Sponsor's protocol ID
- UsakUn
- Status last verified
- May 2023
- First submitted
- 10 May 2023
- Last updated
- 2 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Carmina E, Longo RA. Increased Prevalence of Elevated DHEAS in PCOS Women with Non-Classic (B or C) Phenotypes: A Retrospective Analysis in Patients Aged 20 to 29 Years. Cells. 2022 Oct 17;11(20):3255. doi: 10.3390/cells11203255.
PubMed 36291122
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenotypic Components of Polycystic Ovary Syndrome Determine Endometrial Vitamin D Receptor mRNA Expression Pattern
- ClinicalTrials.gov ID
- NCT05885633
- Acronym / sponsor ID
- UsakUn
- Conditions
- Vitamin D Receptor Defect
- Keywords
- PCOS, Vitamin D, Endometrium, VD receptor, Hyperandrogenemia, Insulin resistance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Uşak UniversityUniversity, hospital or other
- Collaborators
- Bahçeşehir University, Firat University
- Study start
- 21 Oct 2022 (actual)
- Primary completion
- 25 Jan 2023 (actual)
- Study completion
- 29 Apr 2023 (actual)
- First posted
- 2 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- While the study group consisted of PCOS patients, the control group was selected from non-PCOS patients with male factor infertility.
| Arm | Type | Receives |
|---|---|---|
| PCOS | Active comparator | Procedure: endometrial sampling with pipelleInfertile PCOS patients (n=44) |
| Non-PCOS control | Active comparator | Procedure: endometrial sampling with pipelleNon-PCOS control with male factor infertility |
| Phenotype A | Active comparator | Procedure: endometrial sampling with pipellePhenotype A: HA+OD+PCOM (classical/complete, n=17) |
| Phenotype B | Active comparator | Procedure: endometrial sampling with pipellephenotype B: HA+OD (classical/non-PCOM, n=10) |
| Phenotype C | Active comparator | Procedure: endometrial sampling with pipellephenotype C: HA+PCOM (ovulatory, n=9) |
| Phenotype D | Active comparator | Procedure: endometrial sampling with pipellephenotype D: OD+PCOM (non-hyperandrogenic, n=8). |
Who may qualify
- Ages
- 26 to 32 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Clinical diagnosis of PCOS
- Approval for IVF/ICSI and total embryo freezing
- Consent to endometrial sampling
Key exclusion criteria (5 listed)
- Women with hyperandrogenism or ovulatory dysfunction due to non-PCOS etiologies.
- Patients taking vitamin D, insulin sensitizers, lipid-lowering or other hormonal drugs in the last three months were not included.
- Those with a history of mechanical endometrial injury, polypectomy, hysteroscopic myomectomy, endometrioma resection, dilatation/curettage, ovarian drilling and salpingectomy were also excluded.
- Participants with premalignant or malignant endometrial pathology, those with a history of tubal factor infertility, congenital uterine anomaly or any chronic systemic diseases were not included.
- Azoospermia patients were excluded from the study because we preferred ejaculate sperm for ICSI in patients in the control group.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| endometrial sampling with pipelleFollowing oocyte retrieval while the patient was under anesthesia, endometrial tissue sampling was performed with the help of pipelle cannula. A portion of the endometrial tissue was put into RNA stabilization buffer (RNAlater) to be used in qPCR and stored at -20°C until the analysis. The remaining endometrial tissue was first fixed with 10% formalin, followed by paraffin blocking and prepared for immunohistochemical analysis. | Procedure or surgery | Non-PCOS control, PCOS, Phenotype A, Phenotype B, Phenotype C, Phenotype D |
Primary outcome
The primary aim of the study was to investigate whether there is a difference in VDR expression in the endometrium of PCOS patients compared to controls by qPCR and immunohistochemical methods
Time frame: first 3 months
The VDR expression pattern in the endometrium of PCOS patients who underwent IVF/ICSI and total embryo freezing because they did not respond to first-line ovulation stimulation was analyzed at both mRNA and immunohistochemical levels. Endometrial VDR mRNA expression levels were measured by qPCR method. In addition, samples were stained immunohistochemically to determine the distribution and intensity of VDR in the endometrial tissue. In order to compare the possible relationship between progesterone receptor (PR) distribution and VDR distribution, endometrial samples were also stained immunohistochemically with PR antibody.
2 secondary outcomes
To reveal the effects of insulin resistance, HA, OD, and PCOM on endometrial VDR mRNA expression using correlation analyses.
Time frame: First three months
Clinical pregnancy and miscarriage rates
Time frame: three months following the first three months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2023.
- Results publication: PubMed 36291122Carmina E, Longo RA. Increased Prevalence of Elevated DHEAS in PCOS Women with Non-Classic (B or C) Phenotypes: A Retrospective Analysis in Patients Aged 20 to 29 Years. Cells. 2022 Oct 17;11(20):3255. doi: 10.3390/cells11203255.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
nur DE gungor, assoc. prof. principal investigator
BAU IVF-Center
aynur A ersahin, assoc. prof principal investigator
BAU IVF-Center
arzu yurci, assoc. prof. principal investigator
Memorial IVF-Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing endometrial sampling with pipelle in people with Vitamin D Receptor Defect, run by Uşak University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary aim of the study was to investigate whether there is a difference in VDR expression in the endometrium of PCOS patients compared to controls by qPCR and immunohistochemical methods (time frame: first 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05885633, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2023.