Impact of the presence of the corpus luteum on pregnancies obtained through frozen embryo transfer(FET): a prospective randomizedcontrolled study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Phenomena and Processes [G] - Chemical Phenomena [G02]

Trial duration

10 Dec 2024 → ongoing

Decision date (initial)

2024-10-23

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Instituto de Salud Carlos III

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

In pregnancies achieved through programmed frozen embryo transfer cycle (PC-FET) and modified natural frozen embryo transfer (mNC-FET), to determine whether there are differences in endothelial and placental function, maternal cardiovascular function, fetal growth and fetal cardiovascular and cerebral programming and to assess whether there is an association between these differences and the plasma concentrations of the main secretion products of the Corpus Luteum (CL) with vasoactive and angiogenic action.

Secondary objectives 5

1. To investigate whether there are differences in endothelial and placental function during the luteal phase and throughout ​the pregnancy ​​ ​and to determine whether the absence of CL and its secretion products is associated with a subsequent imbalance in ​the ​placental production of angiogenic and vasoactive substances related to the development of pre-eclampsia.
2. To study whether there are differences in maternal cardiovascular function between the study groups and to analyze their association with the plasma​tic​ concentration​s​ of vasoactive substances produced by the Corpus Luteum.
3. To determine whether the changes associated with fetal cardiovascular and cerebral programming in in vitro fertilization (IVF) ​are milder​​ ​in ​mNC-FET​​ pregnancies compared to PC-FET.
4. To study the​ ​fetal growth ​trajectories ​throughout ​the pregnancy​​ in both study groups and the correlation of fetal growth parameters with the plasma concentration of relaxin-2 in the first trimester of gestation.
5. To investigate whether different ​maternal ​pregestational lifestyle factors ​have an impact on the observed changes in maternal endothelial and cardiovascular function and fetal development in these pregnancies.

Conditions and MedDRA coding

Infertility

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Female patients ​18-​​​37 years o​ld​​​(both included)​ at the time of oocyte retrieval and less than 41 years of age at the time of embryo transfer.​
2. Regular menstrual cycle​s​ between 24 and 35 days.
3. Availability of cryopreserved blastocysts from own gametes
4. Indication for ​​single embryo​ transfer​.

Exclusion criteria 6

1. ​​​Recurrent pregnancy loss (3 or more).​​
2. ​Recurrent implantation failure in previous IVF treatments (3 or more unsuccessful embryo transfers)
3. Diagnosis of polycystic ovarian syndrome, diabetes mellitus, chronic arterial hypertension, maternal heart disease and autoimmune disease​s (Systemic Lupus Erythematosus (SLE) or Antiphospholipid syndrome (APS))
4. Active treatment with ​aspirin, heparin or other anticoagulant​ therapy, antihypertensives or other drugs ​used to treat circulation or coagulation disorders ​.
5. Indication for PGT (Preimplantation Genetic Testing).
6. Multiple ​pregnancy​.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Maternal: Relaxin-2 plasma concentration​s​.
2. -Fetal: Mitral annular plane systolic excursión (MAPSE) assessed by echocardiography.

Secondary endpoints 22

1. Angiogenic/vasoactive function of ​CL​​ and placenta: plasma concentration​s​ of VEGF-A, sFlt-1, PlGF progesterone, beta-hCG.​ ​
2. Maternal endothelial function:​​ ​​plasma concentration​s​ of VCAM-1 and endoglin.
3. ICAM-1 and VCAM-1 on the endothelial cells (EC) surface, VE-Cadherin at the EC junctions, intracellular endothelial nitric oxide synthase in EC, von Willebrand Factor in the extracellular matrix (ECM), thrombomodulin in ECM, tissue factor in ECM
4. Intracellular activation of ERK1/2, p38MAPK, SAPK/JNL and AKT. Fluorescent microspheres (permeability assay). EC proliferation-tube formation (angiogenesis assay).
5. Maternal cardiovascular function: Plasma NT-proBNP concentration.
6. Systolic, diastolic and mean arterial blood pressure (mmHg).
7. Carotid artery intima-media thickness (mm).
8. Maternal echocardiography: cardiac output (L/min), left ventricular remodeling parameters and total vascular resistance (dyn/sec/cm5).
9. Fetal programming: Cardiac: sphericity index, longitudinal and transverse heart diameter (mm).
10. Transverse and longitudinal diameters and sphericity index of atria and ventricles. Tricuspid annular plane systolic excursion (TAPSE)(mm). Tricuspid annulus tissue Doppler [E', A' and S' wave (cms/s)]. Isovolumetric relaxation time (IRT)
11. Cerebral cortex development: Depth of parietooccipital, cingulate and calcarine sulci (mm) corrected by DBP x 100. ​​
12. Fetal growth. First trimester: fetal crown-rump length (CRL), nuchal translucency (NT), ductus venosus pulsatility index (DV-PI), mean uterine artery pulsatility index (mUt-PI).
13. Fetal growth ultrasound (second and third trimester): 1) Biometry (mm): biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femoral length (FL).
14. 2) Estimated fetal weight (g) and centile.
15. 3) Doppler study of umbilical artery (UA), middle cerebral artery (MCA) and mUt-PI.
16. 4) Study of Fetal Limb Volume (FLV) by 3D-echo (ml). ​​
17. Neonatal data: Apgar 5', umbilical artery pH, gender, birth weight and centile based on our population normality
18. Placental study: Pregnancy: location of placenta (anterior, posterior, lateral or previa) and signs of placenta accreta spectrum disorders. Anatomopathologycal study of the placenta: weight (fresh, gr.) and histopathology
19. Preconceptional parameters: ​​ ​​​Both parents: age, ethnicity, socioeconomic status, education level, BMI, chronic diseases, smoking, alcohol consumption, illicit substance abuse.
20. Infertility and IVF data: number of previous pregnancies, previous obstetric complications, smoking during pregnancy, alcohol or illicit drugs consumption during pregnancy, infertility etiology, infertility length, number of previous unsuccessful embryo transfers
21. Ovarian stimulation protocol, gonadotrophin dose, ovarian stimulation duration, estradiol at trigger day, number of follicles at trigger, number of oocytes, number of MII, fertilization technique
22. Number of embryos, number of blastocysts, period of vitrification, transferred blastocyst quality. ​Lifestyle questionaries: PREDIMED, IPAQ, WHO-5, PSS-14, PSQI, , HDRS, FertiQol.​​

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Sponsor organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Address

Calle Rosellon 149-153

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Contact name

Gemma Casals

Public contact point

Organisation

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Contact name

Gemma Casals

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications