Endometrial Compaction and Its Influence on Pregnancy Rate in Frozen Embryo Cycle Regimes

March 4, 2021 updated by: Barbara Lawrenz, ART Fertility Clinics LLC
For a pregnancy to occur, an euploid embryo at blastocyst developmental stage, a receptive endometrium and the synchrony of both is crucial. Many studies lately investigated the influence of the endometrial thickness and pattern on the artificial reproductive technology (ART) outcome, however, with conflicting results.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Further on, the measurement of the endometrial thickness was mostly performed either on the day of final oocyte maturation in stimulated cycles with fresh embryo transfer or on the day of progesterone administration in FET cycles.

Progesterone is essential for the secretory transformation and compaction of the endometrium, prior to implantation. A recently published paper (Haas et al., 2019) however, evaluated the degree of endometrial compaction under the influence of progesterone in FET cycles and described, that a lack of certain endometrial compaction has a negative impact on the ongoing pregnancy rate. As in this study embryos of unknown ploidy status were transferred, the role of embryo ploidy on the outcome may bias the study results.

In the herein presented study protocol we aim to investigate the influence of endometrial compaction in FET cycles in which euploid embryos are transferred.

HYPOTHESIS: Lack of endometrial compaction after the start of progesterone leads to an impaired reproductive outcome.

Study Type

Observational

Enrollment (Actual)

3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Patients who are undergoing ovarian stimulation for IVF/ICSI with pre-implantation genetic screening and embryo vitrification, who are planned for their first FET transfer cycle.

Description

Inclusion Criteria:

  • Women aged 18 years to 40 years with regular menses (26-34 days)
  • Having 1 or 2 chromosomally normal cryopreserved blastocysts available for transfer after IVF / ICSI treatment
  • First frozen-thawed transfer cycle
  • Progesterone level < 1.5 ng/mL day of trigger injection in stimulation cycle from which embryos to be transferred were created.

Exclusion Criteria:

  • Polycystic ovarian syndrome
  • Poor ovarian responder in accordance with Bologna criteria
  • Uterine abnormality US / saline infusion sonohysterogram
  • Previous dilatation & curettage (D&C)
  • Hydrosalpinx
  • Asherman syndrome
  • History of endometriosis AFS ≥ 2
  • ICSI due to severe male factor with testicular sperm
  • Any known contraindications or allergy to oral estradiol or progesterone.
  • Discontinuation of HRT medication ( medication error in research HRT cycle )
  • Failure to detect ovulation in the research natural cycle
  • Ovulation after day 20 in a natural cycle
  • Duration of estradiol exposure ≥ 17 days and endometrium < 6mm
  • Spontaneous ovulation in HRT artificial cycle

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Stimulated cycles
Ovarian stimulation will be performed by standard protocols. Stimulation medication dosage will be individualised prior to stimulation start according to the ovarian reserve parameters and during ovarian stimulation according to the ovarian response and the measured levels of E2 and progesterone (P4), in order to avoid progesterone elevation during late follicular phase. Final oocyte maturation will be achieved by administration of either 10.000 IU of hCG, 0.3 mg of GnRH agonist (Triptorelin) or dual trigger (hCG and GnRH-analogue), as soon as ≥ 3 follicles ≥ 17 mm are present. Oocyte retrieval will be carried out 36 hours after administration of the trigger. Embryos will undergo PGT-A at blastocyst stage and be vitrified thereafter.
Diagnostic test: Blood test
Mesurement of E2, P4, LH, FSH hormones
Diagnostic test: Ultrasound
Follicular measurement and endometrium measurement
Artificial (HRT) Cycles

Start of estradiol valerate 4mg on day 2 of the cycle for three days. Increase E2 to 6mg on day 4 of E2 treatment. E2 dose may be increased according to clinician discretion based on endometrial thickness. Maximum time of E2 exposure will be 14 days. Transvaginally scan to monitor endometrial development and to exclude the presence of a dominant follicle. Serial measurements of serum LH, estradiol and progesterone levels. Commence the initial progesterone dose of 100mg at 22hrs (vaginal suppository) after ≥ 7 days and ≤ 16 days of estradiol administration when the minimal endometrial thickness achieved is 6mm with a trilaminar appearance. Subsequently increase progesterone administration to 100mg vaginally three times daily. Continue estradiol administration 6mg (3 tablets daily).

Blastocyst transfer is scheduled on the 5th full day of progesterone administration, following the initial initiation of progesterone.
Diagnostic test: Blood test
Mesurement of E2, P4, LH, FSH hormones
Diagnostic test: Ultrasound
Follicular measurement and endometrium measurement
Spontaneous natural cycles

Ultrasound scans to monitor follicular growth and serial measurements of serum LH, estradiol and progesterone levels to determine the timing of ovulation. The LH surge will be considered to have begun when the concentration rises by 180% above the most recent serum value and continues to rise thereafter.

Day 1 after the LH rise, a decrease in estradiol concentration is identified. Twenty four hours later progesterone concentrations rise with a level of greater than or equal to 1.5ng/ml confirming ovulation (day 0). This is considered as day 0 with initiation of vaginal progesterone 100mg (vaginal suppository) at 2200H. The following day (day 1) increases progesterone administration to 100mg vaginally three times daily (8 hourly) and continues this regime until 7 weeks gestation as per clinic protocol.

Embryo transfer is scheduled 5 days (day 5) following confirmation of ovulation (day 0).
Diagnostic test: Blood test
Mesurement of E2, P4, LH, FSH hormones
Diagnostic test: Ultrasound
Follicular measurement and endometrium measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing pregnancy rate
Time Frame: 12 weeks
Ongoing pregnancy rate (≥ 12 weeks) in patients with endometrial compaction compared to patients without endometrial compaction after frozen embryo transfer of 1 or 2 euploid blastocysts
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemical pregnancy rate in HRT cycle
Time Frame: 5 weeks
Positive hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen after embryo transfer in HRT-FET cycles with one or two euploid embryos, depending on the degree of compaction.
5 weeks
Biochemical pregnancy rate in spontaneous cycle
Time Frame: 5 weeks
positive hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen) after embryo transfer in NC-FET cycles with one or two euploid embryos, depending on the degree of compaction.
5 weeks
Clinical implantation rate in HRT cycle
Time Frame: 6 weeks
Number of gestational sacs observed by ultrasound at 6 weeks of gestation divided by the number of embryos transferred), defined by a ß-hCG of > 5 IU on day 12 after embryo transfer in HRT-FET cycles with one or two euploid embryos, depending on the degree of compaction
6 weeks
Clinical implantation rate in spontaneous cycle
Time Frame: 6 weeks
Number of gestational sacs observed by ultrasound at 6 weeks of gestation divided by the number of embryos transferred), defined by a ß-hCG of > 5 IU on day 12 after embryo transfer in NC-FET cycles with one or two euploid embryos, depending on the degree of compaction.
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ART Fertility Clinics LLC

Investigators

  • Principal Investigator: Barbara Lawrenz, PhD, IVI Middle East Fertility Clinic LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 9, 2020

Primary Completion (Actual)

February 25, 2021

Study Completion (Actual)

March 4, 2021

Study Registration Dates

First Submitted

June 28, 2020

First Submitted That Met QC Criteria

June 28, 2020

First Posted (Actual)

July 1, 2020

Study Record Updates

Last Update Posted (Actual)

March 8, 2021

Last Update Submitted That Met QC Criteria

March 4, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2003-ABU-002-BL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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