Impact of the Presence of the Corpus Luteum on Pregnancies Obtained Through Frozen Embryo Transfer(FET) (LUTI)

Impact of the Presence of the Corpus Luteum on Pregnancies Obtained Through Frozen Embryo Transfer(FET): a Prospective Randomized Controlled Study

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.

Study Overview

• Status: Recruiting
• Conditions: Embryo Transfer; Infertilities
• Intervention / Treatment: Drug: Estradiol + Progesterone; Drug: Ovitrelle ( Hcg 250 mcg)

• Study Type: Interventional
• Enrollment (Estimated): 334
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Laura B Burunat, Graduate; Phone Number: 4198 0034932275400; Email: burunat@recerca.clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Laura Burunat
    • Contact: Laura Burunat Ruesgas, Chemistry; Phone Number: 4198 0034932275400; Email: burunat@recerca.clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female patients 18- 37 years old (both included) at the time of oocyte retrieval and less than 41 years of age at the time of embryo transfer.
• Regular menstrual cycles between 24 and 35 days.
• Availability of cryopreserved blastocysts from own gametes
• Indication for single embryo transfer.
• Patients who will be included in the LUTI study are candidates for either of the two procedures under study, and will have no contraindications for either procedure.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PC-FET (endometrial preparation with absence of CL); Pregnancies with absence of corpus luteum	Drug: Estradiol + Progesterone; Pregnancies with absence of corpus luteum(PC-FET)
Active Comparator: NC-FET (natural cycle FET, endometrial preparation with presence of CL); Pregnancies with presence of corpus luteum	Drug: Ovitrelle ( Hcg 250 mcg); NC-FET(natural cycle FET, endometrial preparation with presence of CL)
No Intervention: Control Arm; Spontaneous pregnancies with no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maternal: Relaxin-2 plasma concentrations.	Up to 10 month
Fetal: Mitral annular plane systolic excursion (MAPSE) assessed by echocardiography.	Up to 10 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angiogenic/vasoactive function of corpus luteum and placenta		Up to 10 month
plasma concentrations of VCAM-1 and endoglin.		Up to 10 month
Maternal endothelial function		Up to 10 month
Maternal echocardiography: cardiac output (L/min)		Up to 10 month
Fetal programming	Cardiac: sphericity index, longitudinal and transverse heart diameter (mm).	Up to 10 month
Fetal programming	Cerebral cortex development: Depth of parietooccipital, cingulate and calcarine sulci (mm) corrected by DBP x 100	Up to 10 month
Fetal growth	Fetal crown-rump length (CRL)(cm)	At 12 week of gestation
Fetal growth	Biometry (mm)	At 20, 28, 32, and 36 week of gestation.
Neonatal data	Apgar 5' test(parameter/puntuation)	At Delivery
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	At Delivery
Preconceptional parameters	Both parents: age(years)	Visit 0 (Baseline)
Maternal Cardivascular Function	Plasma NT-proBNP concentration(pg/mL)	Up to 10 month
left ventricular remodeling parameters and total vascular resistance (dyn/sec/cm5).		Up to 10 month
Fetal programming	Transverse and longitudinal diameters and sphericity index of atria and ventricles(mm).	Up to 10 month
Fetal programming	Tricuspid annular plane systolic excursion (TAPSE)(mm).	Up to 10 month
Fetal programming	Tricuspid annulus tissue Doppler [E', A' and S' wave (cms/s)].	Up to 10 month
Fetal programming	Isovolumetric relaxation time (IRT)(mL/mmHg)	Up to 10 month
Fetal growth	Nuchal translucency (NT)(mm)	At 12 week of gestation
Fetal growth	ductus venosus pulsatility index (DV-PI)(pencentile)	At 12 week of gestation
Fetal growth	Mean uterine artery pulsatility index (mUt-PI)(percentile)	At 12 week of gestation
Fetal growth	Biparietal diameter (BPD)(cm)	At 20, 28, 32, and 36 week of gestation.
Fetal growth	Head circumference (HC)(cm)	At 20, 28, 32, and 36 week of gestation.
Fetal growth	Abdominal circumference (AC)(cm)	At 20, 28, 32, and 36 week of gestation.
Fetal growth	Femoral length (FL)(mm)	At 20, 28, 32, and 36 week of gestation.
Fetal growth	Estimated fetal weight (g) and centile.	At 20, 28, 32, and 36 week of gestation.
Fetal growth	Doppler study of umbilical artery (UA) middle cerebral artery (MCA) and mUt-PI (percentile)	At 20, 28, 32, and 36 week of gestation.
Fetal growth	Study of Fetal Limb Volume (FLV) by 3D-echo (ml)	At 20, 28, 32, and 36 week of gestation.
Neonatal data	Umbilical artery pH(range)	At Delivery
Preconceptional parameters	Both parents: ethnicity(descriptive)	Visit 0 (Baseline)
Preconceptional parameters	Both parents: socioeconomic status(descriptive)	Visit 0 (Baseline)
Preconceptional parameters	Both parents: education level(descriptive),	Visit 0 (Baseline)
Preconceptional parameters	Both parents: BMI(cm/kg)	Visit 0 (Baseline)
Preconceptional parameters	Both parents: chronic diseases(descriptive)	Visit 0 (Baseline)
Preconceptional parameters	Both parents: smoking(yes/no)	Visit 0 (Baseline)
Preconceptional parameters	Both parents: alcohol consumption(yes/No)	Visit 0 (Baseline)
Preconceptional parameters	Both parents: illicit substance abuse(Yes/No).	Visit 0 (Baseline)
Maternal Cardivascular Function	Systolic, diastolic and mean arterial blood pressure(mmHg)	Up to 10 month
Maternal Cardivascular Function	Carotid artery intima-media thickness(mm)	Up to 10 month
Neonatal data	Birth weight(kg)	At Delivery

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2025
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: December 5, 2024
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 26, 2025

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Progestins; Estradiol; Progesterone
• Other Study ID Numbers: 2024-513600-33-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No