Uterine Junctional Zone and Its Relation to Adverse Obstetrical Outcomes in Assisted Reproductive Technology

Uterine Junctional Zone Evaluation on 3D Ultrasound and Its Relation to Major Adverse Obstetrical Outcomes in Assisted Reproductive Technology

The junctional zone (JZ) is an internal layer of the myometrium, with unique characteristics that allow its visualization as a hypoechogenic structure in three-dimensional (3D) ultrasound.

While there is a growing realization that the origins of major obstetrical complications associated with defective deep placentation, such as pre-term labour, fetal growth restriction and pre-eclampsia, may lie in the very early pregnancy events, the underlying mechanisms are not understood.

Study Overview

• Status: Recruiting
• Conditions: Infertility, Female

Detailed Description

During pregnancy, unique vascular changes occur, associated with decidualization of the maternal tissues in response to trophoblast invasion, first in the endometrium and subsequently in the myometrial JZ. The JZ broadly represents the inner third of the myometrium that, together with its overlying endometrium, is involved in placentation.

Defective deep placentation, defined by the absent or incomplete remodelling of the JZ segment of the spiral arteries, may be associated with a spectrum of obstetrical complications, ranging from late miscarriage and pre-term labour to fetal growth restriction and pre-eclampsia.

Thus, the primary site of vascular pathology in pregnancies lies not in the placenta or decidua but in the JZ. To understand how impaired remodelling of the myometrial JZ prior to conception may predispose to subsequent defective deep placentation, it is important to first describe the structural and functional changes in the JZ at the time of embryo implantation, and subsequently analyse the distinguishing features of defective deep placentation associated with different pregnancy disorders.

Thus, non-invasive assessment of the JZ prior to conception may turn out to be useful in identifying those women at risk of major obstetrical complications.

This project aims to evaluate the relationship between the characteristics of the ZJ in 3D ultrasound, and major adverse obstetrical outcomes in assisted reproductive technology (ART) treatments, namely in vitro fertilization cycles, intracytoplasmic sperm injection and frozen embryo transfer (FET).

In a prospective and observational study with the inclusion of 200 cases, a 3D ultrasound will be performed on the day on which the final oocyte maturation is triggered or, on FET, on the day prior to the administration of progesterone.

After the quality of visualization of the JZ is classified, its thickness will be measured and described as regular, irregular or interrupted.

The volume of the ZJ will be obtained by subtracting the endometrial volume from the volume of the junctional zone and the endometrium.

These characteristics will be related to major obstetrical adverse outcomes: pre-eclampsia, pre-term labour and fetal growth restriction. The relation with a high-risk first trimester screening for pre-eclampsia will also be accessed.

After explaining the study and obtaining written consent, a 3D ultrasound will be performed for uterine evaluation, on the day of the final oocyte maturation trigger in cases of IVF / ICSI. In cases of FET, the ultrasound evaluation will be carried out on the day before the start of the luteal phase support.

All ultrasounds will be performed in a standardized manner by the same operator. With an empty bladder, in a lithotomy position, a 2D transvaginal ultrasound will be performed using a GE Voluson 730 Expert® ultrasound, with an endovaginal probe with a 4-8MHz frequency. Identification of endometriosis lesions or acquired uterine abnormalities such as leiomyomas or adenomyosis will be exclusion criteria. After evaluating the number and maximum dimension of the ovarian follicles and the endometrial thickness, the three-dimensional volume box will be placed to encompass the entire uterus in longitudinal section, with minimal inclusion of para-uterine structures. A maximum acquisition angle of 90º and maximum quality will be used. To minimize artifacts, during the acquisition both the probe and the woman must remain immobile, being asked to hold their breath. Then, a three-dimensional volume will be generated by automatic 360º rotation of the transducer. For each case, two volumes will always be obtained.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Isabel B Pereira, M.D.; Phone Number: +351967053610; Email: isabelsofiapereira@yahoo.com
• Study Contact Backup: Name: Isabel B Pereira, M.D; Phone Number: +351967053610; Email: isabelsofiapereira@yahoo.com

Study Locations

• Portugal
  • Lisbon, Portugal
    • Recruiting
    • Centro Hospitalar Universitario Lisboa Norte
    • Contact: Isabel Barros Pereira, M.D.; Phone Number: 00351967053610
  • Lisbon, Portugal, 1600
    • Recruiting
    • Departamento de Obstetricia, Ginecologia e Medicina da Reprodução
    • Principal Investigator: Isabel Barros Pereira, M.D.
  • Madeira
    • Funchal, Madeira, Portugal, 9000
      • Not yet recruiting
      • Hospital Central do Funchal
      • Contact: Isabel B Pereira; Phone Number: +351967053610; Email: isabelsofiapereira@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Women included are followed in the fertility clinic aged between 18 and 40 years in cycles of IVF, ICSI or endometrial preparation for frozen embryo transfer

Description

Inclusion Criteria:

• Women followed in the infertility clinic aged between 18 and 42 years in cycles of IVF, ICSI or endometrial preparation for frozen embryo transfer

Exclusion Criteria:

• Myomas
• adenomyosis
• endometriosis

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-eclampsia	Pre-eclampsia rate	40 weeks
pre-term labour	pre-term labour rate	37 weeks
Fetal growth restriction	Fetal growth restriction rate	40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-risk first trimester screening for pre-eclampsia	High-risk first trimester screening for pre-eclampsia rate	12 weeks

Collaborators and Investigators

• Sponsor: Centro Hospitalar Lisboa Norte
• Investigators: Principal Investigator: Isabel B Pereira, M.D, Centro Hospitalar Lisboa Norte

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2023
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: infertility; 3D ultrasound; junctional zone
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Infertility; Infertility, Female
• Other Study ID Numbers: JZ OO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No