Clinical trial NCT03877939: Detection of Kisspeptins and miRNAs in Patients With Non-viable Pregnancy
Official title: Detection of Kisspeptins and miRNAs in Patients With Non-viable Pregnancy
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Non-Viable Pregnancy
Keywords: Ectopic pregnancy
non-viable pregnancy
miRNA
Kisspeptin
β-HCG
biomarkers
Lead sponsor: Vida Recoletas Sevilla
Sponsor class: OTHER
Collaborators: name: IVI Madrid
name: Instituto Valenciano de Infertilidad, IVI VALENCIA
name: IVI Barcelona
First posted: 2019-03-18
Enrollment: 433
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Those patient that have made a pre-embryonic transfer in the IVI RMA Seville, IVI RMA Madrid, IVI RMA Valencia, and IVI RMA Barcelona clinics will constitute patient population.

Brief summary: Ectopic pregnancy (EP) is a pathology that affects 3%-16% of pregnancies in humans, being the main cause of morbidity and maternal mortality in the first trimester of pregnancy worldwide. The relevance of this problem has led to a demand on the scientific community, to obtain specific and early biomarkers in the determination of EP. In this context, the investigator's group has previously confirmed that both kisspeptin 54 and miR-324-3p are specific, selective and precise biomarkers to identify those patients suffering an EP. However, the utility of a diagnostic test using both biomarkers and other related ones in a population with other types of non-viable pregnancies should still be analysed.

Detailed description: This is a pilot study in which we intend to determine the moment in which biomarkers begin to be detected in non-viable pregnancies, in order to subsequently be able to develop specific studies focused on that moment. The following visits will be required:

SCREENING VISIT: To be performed before β-hCG test. After recruitment and signing informed consent, patients will be assigned with a three-letter code identifying the clinic and three numbers indicating the order in which the patient is recruited by each clinic.

β-hCG VISIT: To be performed the day of the β-hCG test (week 4):

- Peripheral blood samples will be collected for Progesterone (P4), Kisspeptin 54 and miR-324-3p analysis.

In case of negative result, patient will be out of the study. In case of positive result, β-hCG test \> 10 UI/L, patient will continue with the following visits.

SUBSEQUENT BLOOD EXTRACTION VISITS: To be performed on Mondays and Thursdays or Tuesdays and Fridays of each week from β-hCG test until non-viable pregnancy is confirmed or between weeks 6 and 8 when viable pregnancy is confirmed (a maximum of 10 blood sample extractions):

* Peripheral blood samples will be collected Progesterone (P4), Kisspeptin 54 and miR-324-3p will be analysed in these samples. Blood collection will be performed each day in a different arm, allowing a period between extractions in each arm of one week.
* In addition, an optional transvaginal ultrasound scan will be performed before each blood sample if patient wishes.

In case of pregnancy of unknown location (PUL), protocol will continue until VP or NVP is confirmed.

If NVP is confirmed before clinical pregnancy visit, patient will undergo an end of study visit.

CLINICAL PREGNANCY VISIT: To be performed between weeks 5+2 and 5+6, the same day that one of the subsequent blood extractions:

- A transvaginal ultrasound scan will be performed before the blood sample extraction.

In case of non-viable pregnancy, patient will perform the end of study visit. In case of clinical pregnancy, patient will continue with the following visits.

ONGOING PREGNANCY VISIT: To be performed between weeks 6 and 8, the same day that one of the subsequent blood extractions:

- A transvaginal ultrasound scan will be performed before the blood sample extraction. VP will be confirmed with this ultrasound scan.

In case of non-viable pregnancy, patient will undergo the end of study visit. In case of viable pregnancy, patient will undergo the end of study visit in week 10 of pregnancy.

END OF STUDY VISIT: To be performed after an ultrasound scan when NVP is confirmed or in week 10 of pregnancy. The following samples will be collected:

In case of ectopic pregnancy:

- Peripheral blood samples for Progesterone (P4), Kisspeptin 54 and miR-324-3p analysis.

In case of clinical miscarriage:

- Peripheral blood samples for Progesterone (P4), Kisspeptin 54 and miR-324-3p analysis.

In case of Biochemical pregnancy:

* Peripheral blood samples for Progesterone (P4), Kisspeptin 54 and miR-324-3p analysis.
* Blood sample for KIR typing.
* Blood samples of patient and partner for HLA-C typing. If partner does not attend to this visit, his sample may be collected in the following 3 weeks.
* Blood samples for detection of miRNAs related with insulin resistance, miR-424-5p and miR-15b.
* Oral glucose tolerance test (OGTT), including blood sample analysis before 75 g of glucose consumption and after 1h and 2 h.
* Uterine biopsy in the month in which the biochemical pregnancy is confirmed or in the following month (in P + 5) for detection of miRNAs related with insulin resistance, miR-424-5p and miR-15b.

In case of viable pregnancy in week 10 of gestation:

* Peripheral blood samples for Progesterone (P4), Kisspeptin 54 and miR-324-3p analysis.
* Blood sample for KIR typing.
* Blood samples of patient and partner for HLA-C typing. If partner does not attend to this visit, his sample may be collected in the following 3 weeks.
* Blood samples for detection of miRNAs related with insulin resistance, miR-424-5p and miR-15b.
* Data of an oral glucose tolerance test (OGTT) that patients perform routinely in the first trimester of pregnancy will be required.

Eligibility criteria: Inclusion Criteria:

* Patients who will perform SET.
* Patients using own oocytes.

Exclusion Criteria:

* Complicated uterine cavity.

Primary outcomes:
measure: Level of Kisspeptin 54
timeFrame: Mar 2019 - Oct 2021
measure: Level of miR-324-3p
timeFrame: Mar 2019 - Oct 2021
Secondary outcomes:
measure: Level of progesterone
timeFrame: Mar 2019 - Oct 2021
measure: Level of hormone β-hCG
timeFrame: Mar 2019 - Oct 2021
measure: Level of miRNAs related with insulin resistance, miR-424-5p and miR-15b
timeFrame: Mar 2019 - Oct 2021
measure: Level of miRNAs related with insulin resistance, miR-424-5p and miR-15b
timeFrame: Mar 2019 - Oct 2021
measure: KIR typing
timeFrame: Mar 2019 - Oct 2021
measure: HLA-C typing
timeFrame: Mar 2019 - Oct 2021
measure: Oral glucose tolerance test (OGTT)
timeFrame: Mar 2019 - Oct 2021
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: IVI RMA Madrid
city: Seville
country: Spain
facility: IVI RMA Seville
Study officials:
affiliation: IVI RMA Seville
name: Manuel Fernández-Sánchez, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: