The Accuracy of Endometrial Ultrasound to Predict Implantation

• ClinicalTrials.gov Identifier: NCT03860636
• Recruitment Status: Recruiting
• First Posted: March 4, 2019
• Last Update Posted: September 28, 2021
• Sponsor: University of Nottingham
• Information provided by (Responsible Party): Nick Raine Fenning, University of Nottingham

Study Description

Brief Summary:

To measure the accuracy of different ultrasound endometrial patterns to predict successful embryo implantation during assisted conception; in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

Condition or disease

Intervention/treatment

Infertility, Subfertility

Diagnostic Test: Endometrial Pattern on Ultrasound at ET; Diagnostic Test: Endometrial Pattern on Ultrasound at HCG; Diagnostic Test: Endometrial Pattern on Ultrasound at TVOR; Diagnostic Test: Endometrial Pattern on Ultrasound at co-ordination scan; Diagnostic Test: Endometrial thickness at HCG; Diagnostic Test: Endometrial thickness at TVOR; Diagnostic Test: Endometrial thickness at ET; Diagnostic Test: Endometrial thickness at coordination scan; Diagnostic Test: Endometrial volume at HCG; Diagnostic Test: Endometrial volume at TVOR; Diagnostic Test: Endometrial volume at ET; Diagnostic Test: Endometrial volume at coordination scan; Diagnostic Test: Blood test for progesterone at HCG; Diagnostic Test: Blood test for progesterone at TVOR; Diagnostic Test: Blood test for progesterone at ET; Diagnostic Test: Blood test for progesterone at coordination scan; Diagnostic Test: Change in endometrial pattern between TVOR and ET; Diagnostic Test: Blood test for estradiol at HCG; Diagnostic Test: Blood test for estradiol at TVOR; Diagnostic Test: Blood test for estradiol at ET; Diagnostic Test: Blood test for estradiol at coordination scan; Diagnostic Test: Endometrial blood flow (doppler) at HCG; Diagnostic Test: Endometrial blood flow (doppler) at TVOR; Diagnostic Test: Endometrial blood flow (doppler) at ET; Diagnostic Test: Endometrial blood flow (doppler) at coordination scan; Diagnostic Test: Contractility at embryo transfer on a subgroup of participants; Diagnostic Test: Change in endometrial pattern between coordination scan and ET; Diagnostic Test: Change in endometrial pattern between HCG and ET

Detailed Description:

Ultrasound appearance of the endometrium may predict successful implantation in assisted conception, but studies have yielded conflicting results.

The explanation may be different timing of, and classification systems for, the scan, different treatment protocols, and different definitions of success. Also scan quality has improved over time.

This is a prospective study looking at the endometrial pattern as a predictor of IVF/ICSI outcome, adjusting for embryo quality, ease of transfer, and fresh or frozen cycles. The study will focus on good quality single embryo transfer at the blastocyst stage. Other endometrial ultrasound parameters such as thickness, volume and Doppler will also be measured. Reliability studies will also be conducted to assess and account for inter- and intra-observer variation.

200 women will be recruited. They will include approximately 100 undergoing fresh and 100 undergoing frozen embryo transfer. There will be no change to routine clinical care. A single operator will analyse all ultrasound images to reduce inter-observer variation. When there is uncertainty about the pattern the chief investigator will be consulted to reach an agreement.

Study Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: The Prognostic Accuracy of Within Cycle, Pre-embryo Transfer, Ultrasound Endometrial Patterns, to Predict Implantation During Assisted Reproduction
• Actual Study Start Date: November 26, 2018
• Estimated Primary Completion Date: February 28, 2022
• Estimated Study Completion Date: April 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Fresh Embryo Transfer; Women will be invited to attend and have transvaginal ultrasound scans (TVUS) and blood tests at three different points during their treatments.; The day they receive their HCG trigger,; The day of transvaginal oocyte retrieval (TVOR) and; The day of embryo transfer (ET).	Diagnostic Test: Endometrial Pattern on Ultrasound at ET; Ultrasound scan; Diagnostic Test: Endometrial Pattern on Ultrasound at HCG; Ultrasound; Diagnostic Test: Endometrial Pattern on Ultrasound at TVOR; Ultrasound; Diagnostic Test: Endometrial thickness at HCG; Ultrasound; Diagnostic Test: Endometrial thickness at TVOR; Ultrasound; Diagnostic Test: Endometrial thickness at ET; Ultrasound scan; Diagnostic Test: Endometrial volume at HCG; Ultrasound scan; Diagnostic Test: Endometrial volume at TVOR; Ultrasound scan; Diagnostic Test: Endometrial volume at ET; Ultrasound scan; Diagnostic Test: Blood test for progesterone at HCG; Blood test; Diagnostic Test: Blood test for progesterone at TVOR; Blood test; Diagnostic Test: Blood test for progesterone at ET; Blood test; Diagnostic Test: Blood test for estradiol at HCG; Blood test; Diagnostic Test: Blood test for estradiol at TVOR; Blood test; Diagnostic Test: Blood test for estradiol at ET; Blood test; Diagnostic Test: Endometrial blood flow (doppler) at HCG; Ultrasound scan; Diagnostic Test: Endometrial blood flow (doppler) at TVOR; Ultrasound scan; Diagnostic Test: Endometrial blood flow (doppler) at ET; Ultrasound scan; Diagnostic Test: Contractility at embryo transfer on a subgroup of participants; Ultrasound scan; Diagnostic Test: Change in endometrial pattern between HCG and ET; Ultrasound scan
Frozen Embryo Transfer; Women will be invited to attend and have transvaginal ultrasound scans (TVUS) and blood tests at two different points during their treatments.; The day we coordinate with embryologist (day of progesterone +/-1); The day of embryo transfer (ET).	Diagnostic Test: Endometrial Pattern on Ultrasound at ET; Ultrasound scan; Diagnostic Test: Endometrial Pattern on Ultrasound at co-ordination scan; Ultrasound; Diagnostic Test: Endometrial thickness at ET; Ultrasound scan; Diagnostic Test: Endometrial thickness at coordination scan; Ultrasound scan; Diagnostic Test: Endometrial volume at ET; Ultrasound scan; Diagnostic Test: Endometrial volume at coordination scan; Ultrasound scan; Diagnostic Test: Blood test for progesterone at ET; Blood test; Diagnostic Test: Blood test for progesterone at coordination scan; Blood test; Diagnostic Test: Change in endometrial pattern between TVOR and ET; Ultrasound scan; Diagnostic Test: Blood test for estradiol at ET; Blood test; Diagnostic Test: Blood test for estradiol at coordination scan; Blood test; Diagnostic Test: Endometrial blood flow (doppler) at ET; Ultrasound scan; Diagnostic Test: Endometrial blood flow (doppler) at coordination scan; Ultrasound scan; Diagnostic Test: Contractility at embryo transfer on a subgroup of participants; Ultrasound scan; Diagnostic Test: Change in endometrial pattern between coordination scan and ET; Ultrasound scan

Outcome Measures

Primary Outcome Measures :

1. Number of clinical pregnancies [ Time Frame: Within 12 weeks after embryo transfer (usually scan performed at 6-7 weeks gestation) ]
   Intrauterine pregnancy with fetal heart detected on ultrasound arising from the treatment cycle

Secondary Outcome Measures :

1. Number of ectopic pregnancies [ Time Frame: Within 10 weeks after embryo transfer ]
   Ectopic pregnancy resulting from the treatment cycle
2. Number of biochemical pregnancies [ Time Frame: Within 6 weeks after embryo tranfer ]
   Biochemical pregnancy resulting from the treatment cycle
3. Number of miscarriages [ Time Frame: Within 12 weeks after embryo transfer ]
   Miscarriage resulting from the treatment cycle
4. Number of live birth [ Time Frame: Within one year after embryo transfer ]
   Live birth resulting from the treatment cycle

Biospecimen Retention:   Samples Without DNA

Blood for progesterone and estradiol

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Female
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Women who are having in vitro fertilisation or intracytoplasmic sperm injection where a clear image of endometrial pattern can be obtained. In cases where we can't obtain a clear endometrial pattern due to pathology or uterine position, we will exclude these cases from analysis. In cases of failure of fertilisation where no embryo is available for transfer these cases will be excluded from analysis.

Criteria

Inclusion Criteria:

• Female undergoing in vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI)
• Own or donated eggs
• Informed consent

Exclusion Criteria:

• Known pathology affecting the endometrial cavity (polyp, submucosal fibroid)
• Septate uterus or more complex uterine abnormality.

Contacts and Locations

Contacts

Contact: Nicholas Raine-Fenning, MBChB MRCOG PhD; +441158961900; nick.raine-fenning@nottingham.ac.uk

Contact: Hiba Elhassan, MBBS BSc (Hons) MRCOG; hiba.elhassan@nottingham.ac.uk

Locations

United Kingdom

Nurture Fertility; Recruiting

Nottingham, Nottinghamshire, United Kingdom, NG10 5QG

Contact: Nicholas Raine-Fenning, MBChB PhD nick.raine-fenning@nottingham.ac.uk

Contact: Hiba Elhassan, MBBS BSc (Hons) MRCOG hiba.elhassan@nottingham.ac.uk

Principal Investigator: Nicholas Raine-Fenning, MBChB PhD

Sub-Investigator: Hiba Elhassan, MBBS BSc MRCOG

Sub-Investigator: Jim Thornton, Prof of Obs & Gynae, MD, FRCOG

Sub-Investigator: Walid Maalouf, PhD

Sponsors and Collaborators

University of Nottingham

Investigators

• Principal Investigator: Nicholas Raine-Fenning, MBChB MRCOG PhD; University of Nottingham, Nurture Fertility Director

More Information

Publications of Results:

Coats E, Carden H, Zujovic L, Maalouf W, Hopkisson J, Raine-Fenning N. Qualifying the difficulty of embryo transfer with a visual analogue scale and assessing its impact on IVF outcomes. Hum Fertil (Camb). 2019 Sep;22(3):177-181. doi: 10.1080/14647273.2018.1434903. Epub 2018 Feb 19.

Richardson A, Brearley S, Ahitan S, Chamberlain S, Davey T, Zujovic L, Hopkisson J, Campbell B, Raine-Fenning N. A clinically useful simplified blastocyst grading system. Reprod Biomed Online. 2015 Oct;31(4):523-30. doi: 10.1016/j.rbmo.2015.06.017. Epub 2015 Jul 8.

Richardson A, Brearley S, Ahitan S, Chamberlain S, Davey T, Zujovic L, Hopkisson J, Campbell B, Raine-Fenning N. Temporal validation of a simplified blastocyst grading system. Hum Fertil (Camb). 2017 Jun;20(2):113-119. doi: 10.1080/14647273.2016.1255355. Epub 2016 Nov 28.

Raine-Fenning NJ, Campbell BK, Clewes JS, Kendall NR, Johnson IR. The reliability of virtual organ computer-aided analysis (VOCAL) for the semiquantification of ovarian, endometrial and subendometrial perfusion. Ultrasound Obstet Gynecol. 2003 Dec;22(6):633-9.

Raine-Fenning N, Campbell B, Collier J, Brincat M, Johnson I. The reproducibility of endometrial volume acquisition and measurement with the VOCAL-imaging program. Ultrasound Obstet Gynecol. 2002 Jan;19(1):69-75.

Jones NW, Raine-Fenning NJ, Mousa HA, Bradley E, Bugg GJ. Evaluating the intra- and interobserver reliability of three-dimensional ultrasound and power Doppler angiography (3D-PDA) for assessment of placental volume and vascularity in the second trimester of pregnancy. Ultrasound Med Biol. 2011 Mar;37(3):376-85. doi: 10.1016/j.ultrasmedbio.2010.11.018. Epub 2011 Jan 21.

• Responsible Party: Nick Raine Fenning, Chief Investigator, University of Nottingham
• ClinicalTrials.gov Identifier: NCT03860636
• Other Study ID Numbers: REC 87-1808
• First Posted: March 4, 2019
• Last Update Posted: September 28, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nick Raine Fenning, University of Nottingham:

In Vitro Fertilisation (IVF); Intra Cytoplasmic Injection (ICSI); Endometrial Pattern; Ultrasound

Additional relevant MeSH terms:

Infertility; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Progesterone; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins