Impact of Endometrial Compaction in Euploid Frozen Embryo Transfers

Sponsor

Boston IVF (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04330066

Collaborator

(none)

187

Enrollment

Location

21.9

Anticipated Duration (Months)

8.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this pilot study is to evaluate whether a decrease in endometrial thickness (compaction) prior to progesterone exposure (endogenous or exogenous) to the day before a single frozen embryo transfer has an impact on the clinical pregnancy rate with euploid embryos in exogenous hormone and modified natural thaw cycles. Information derived from this study may give insight on ways to improve pregnancy rates in cryo-thaw cycles.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Female	Diagnostic Test: Abdominal ultrasound measurement of the endometrial lining

Detailed Description

Methods: Study participation will not influence any element of IVF treatment and all participants will be receiving the standard of care at Boston IVF. Potential participants will be identified by a member of the research team, who will review the appointment log and medical records to ensure eligibility. Eligible participants interested in participating in the study will have an abdominal ultrasound endometrial thickness measurement on the day of the participants embryo transfer (T2). This abdominal ultrasound is part of routine clinical care necessary for the embryo transfer. The eligible participant will provide verbal consent to a member of the research team prior to the ultrasound. Baseline demographic data will be obtained from the electronic medical record including: age, race, education level, partner status, height, weight, gravidity, and parity.

Two groups of thaw cycles will be included: (1) exogenous hormone replacement thaw cycles and (2) modified natural thaw cycle. Both groups will follow the standard of care for cycle preparation at Boston IVF. Ultrasound measurements of the endometrial lining (T1) will only be used if they were within 1 day of the initiation of progesterone (group 1) or ovulation trigger injection (group 2). At T1, multiple endometrial lining measurements will be made per standard protocol, but only the optimal image and measurement will be saved. At T2, only a single endometrial thickness measurement will be measured by the sonographer and will be recorded on a study log. Images should include a longitudinal view of the endometrium and cervix. Measurements from the T2 ultrasound will be blinded from the participant and they will not be used to make any clinical decisions. Both groups will have a comparison of the difference in endometrial thickness measurement between T1 and T2.

Sample Size Justification: Given the limited data on this specific topic, the study will be an observational pilot study. Given the available resources, the researchers will aim to have 100 participants per cycle preparation group, for a total of 200 participants.

Data Analysis: Descriptive data will be presented as the proportion, mean with standard deviation, or median with interquartile range. Comparisons will be made using the chi-square or Fisher's exact test for categorical variables and parametric or non-parametric tests for continuous variables based on data distribution. Logistic regression analysis will be performed for multivariate analysis. All data will be analyzed with SAS 9.4 (SAS Institute Inc., Cary, NC, USA). All tests will be two sided and a P value < 0.05 will be required to confer significance.

Study Design

Study Type:

Observational

Actual Enrollment :

187 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Impact of Endometrial Compaction in Euploid Frozen Embryo Transfers: a Prospective Observational Pilot Study

Actual Study Start Date :

Sep 1, 2020

Anticipated Primary Completion Date :

May 30, 2022

Anticipated Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Exogenous hormone replacement thaw cycle Participants in this group will follow Boston IVF's standard exogenous hormone replacement protocol. Participants will take Estrace 3mg twice daily by mouth for endometrial preparation. After 16-18 days of Estrace, endometrial thickness will be measured by transvaginal ultrasound but medication and ultrasounds will be continued until the endometrial lining is ≥ 7 mm. Once the final endometrial lining is ≥ 7 mm (T1), the doctor of record will start the participant the following day with intramuscular progesterone daily or intramuscular progesterone every 3 days with daily vaginal progesterone. Frozen embryo transfers would occur on the sixth day of progesterone.	Diagnostic Test: Abdominal ultrasound measurement of the endometrial lining On the day of the participants frozen embryo transfer, an endometrial thickness measurement (T2) will obtained from an abdominal ultrasound during the embryo transfer.
Natural thaw cycle Participants in this group will follow Boston IVF's standard natural thaw cycle protocol. Participants will be coming for blood and transvaginal ultrasound monitoring around day 11 of the participants cycle. Once the participant has a final measurement of the endometrial lining ≥ 7 mm (T1), a 17mm ovarian follicle, and a progesterone < 1.2 ng/mL, the doctor of record will schedule the patient to receive a trigger injection to induce ovulation followed by an embryo transfer 6-7 days later. Participants may be started on vaginal progesterone 4 days after the trigger injection for added supplementation per the doctor of record.	Diagnostic Test: Abdominal ultrasound measurement of the endometrial lining On the day of the participants frozen embryo transfer, an endometrial thickness measurement (T2) will obtained from an abdominal ultrasound during the embryo transfer.

Arm

Intervention/Treatment

Exogenous hormone replacement thaw cycle

Participants in this group will follow Boston IVF's standard exogenous hormone replacement protocol. Participants will take Estrace 3mg twice daily by mouth for endometrial preparation. After 16-18 days of Estrace, endometrial thickness will be measured by transvaginal ultrasound but medication and ultrasounds will be continued until the endometrial lining is ≥ 7 mm. Once the final endometrial lining is ≥ 7 mm (T1), the doctor of record will start the participant the following day with intramuscular progesterone daily or intramuscular progesterone every 3 days with daily vaginal progesterone. Frozen embryo transfers would occur on the sixth day of progesterone.

Diagnostic Test: Abdominal ultrasound measurement of the endometrial lining

On the day of the participants frozen embryo transfer, an endometrial thickness measurement (T2) will obtained from an abdominal ultrasound during the embryo transfer.

Natural thaw cycle

Participants in this group will follow Boston IVF's standard natural thaw cycle protocol. Participants will be coming for blood and transvaginal ultrasound monitoring around day 11 of the participants cycle. Once the participant has a final measurement of the endometrial lining ≥ 7 mm (T1), a 17mm ovarian follicle, and a progesterone < 1.2 ng/mL, the doctor of record will schedule the patient to receive a trigger injection to induce ovulation followed by an embryo transfer 6-7 days later. Participants may be started on vaginal progesterone 4 days after the trigger injection for added supplementation per the doctor of record.

Diagnostic Test: Abdominal ultrasound measurement of the endometrial lining

On the day of the participants frozen embryo transfer, an endometrial thickness measurement (T2) will obtained from an abdominal ultrasound during the embryo transfer.

Outcome Measures

Primary Outcome Measures

Clinical pregnancy rate [through study completion, an average of 1 year]
defined as confirmation of gestational sac with fetal heart beat on ultrasound between 6 - 9 weeks gestation

Secondary Outcome Measures

Biochemical pregnancy rate [through study completion, an average of 1 year]
defined as positive beta-hCG but no gestational sac visualized
Live birth rate [through study completion, an average of 1 year]
defined as delivery > 23 weeks gestation
Miscarriage rate [through study completion, an average of 1 year]
defined as the loss of a pregnancy prior to 12 weeks per total number of pregnancies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 44 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Single euploid frozen embryo transfer
≥ 7 mm endometrial lining on transvaginal ultrasound
1st or 2nd frozen embryo transfer

Exclusion Criteria:

Obesity with body mass index > 40
Underweight with body mass index < 18.5
Utilization of a gestational carrier
History of recurrent pregnancy loss (≥ 2 spontaneous abortions)
Uterine factors (history of uterine adhesions, uterine surgery, fibroids, polyps)
History of an endometrial receptivity assay (ERA) biopsy