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

NCT ID: NCT04454749

Last Updated: 2021-03-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

3 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-11-09

Study Completion Date

2021-03-04

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Endometrial Disorder Infertility, Female IVF Pregnancy Early

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Blood test

Intervention Type DIAGNOSTIC_TEST

Mesurement of E2, P4, LH, FSH hormones

Ultrasound

Intervention Type DIAGNOSTIC_TEST

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.

Blood test

Intervention Type DIAGNOSTIC_TEST

Mesurement of E2, P4, LH, FSH hormones

Ultrasound

Intervention Type DIAGNOSTIC_TEST

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).

Blood test

Intervention Type DIAGNOSTIC_TEST

Mesurement of E2, P4, LH, FSH hormones

Ultrasound

Intervention Type DIAGNOSTIC_TEST

Follicular measurement and endometrium measurement

Interventions

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Blood test

Mesurement of E2, P4, LH, FSH hormones

Intervention Type DIAGNOSTIC_TEST

Ultrasound

Follicular measurement and endometrium measurement

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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ART Fertility Clinics LLC

OTHER

Sponsor Role lead

Responsible Party

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Barbara Lawrenz

Scientific Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Barbara Lawrenz, PhD

Role: PRINCIPAL_INVESTIGATOR

IVI Middle East Fertility Clinic LLC

Locations

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IVI Middle East Fertility Clinic

Abu Dhabi, , United Arab Emirates

Site Status

Countries

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United Arab Emirates

References

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Bu Z, Sun Y. The Impact of Endometrial Thickness on the Day of Human Chorionic Gonadotrophin (hCG) Administration on Ongoing Pregnancy Rate in Patients with Different Ovarian Response. PLoS One. 2015 Dec 30;10(12):e0145703. doi: 10.1371/journal.pone.0145703. eCollection 2015.

Reference Type RESULT
PMID: 26717148 (View on PubMed)

Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.

Reference Type RESULT
PMID: 20097333 (View on PubMed)

Haas J, Smith R, Zilberberg E, Nayot D, Meriano J, Barzilay E, Casper RF. Endometrial compaction (decreased thickness) in response to progesterone results in optimal pregnancy outcome in frozen-thawed embryo transfers. Fertil Steril. 2019 Sep;112(3):503-509.e1. doi: 10.1016/j.fertnstert.2019.05.001. Epub 2019 Jun 24.

Reference Type RESULT
PMID: 31248618 (View on PubMed)

Irani M, Robles A, Gunnala V, Reichman D, Rosenwaks Z. Optimal parameters for determining the LH surge in natural cycle frozen-thawed embryo transfers. J Ovarian Res. 2017 Oct 16;10(1):70. doi: 10.1186/s13048-017-0367-7.

Reference Type RESULT
PMID: 29037231 (View on PubMed)

Kasius A, Smit JG, Torrance HL, Eijkemans MJ, Mol BW, Opmeer BC, Broekmans FJ. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update. 2014 Jul-Aug;20(4):530-41. doi: 10.1093/humupd/dmu011. Epub 2014 Mar 23.

Reference Type RESULT
PMID: 24664156 (View on PubMed)

La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update. 2014 Jan-Feb;20(1):124-40. doi: 10.1093/humupd/dmt037. Epub 2013 Sep 29.

Reference Type RESULT
PMID: 24077980 (View on PubMed)

Lawrenz B, Labarta E, Fatemi H, Bosch E. Premature progesterone elevation: targets and rescue strategies. Fertil Steril. 2018 Apr;109(4):577-582. doi: 10.1016/j.fertnstert.2018.02.128.

Reference Type RESULT
PMID: 29653703 (View on PubMed)

Liu KE, Hartman M, Hartman A, Luo ZC, Mahutte N. The impact of a thin endometrial lining on fresh and frozen-thaw IVF outcomes: an analysis of over 40 000 embryo transfers. Hum Reprod. 2018 Oct 1;33(10):1883-1888. doi: 10.1093/humrep/dey281.

Reference Type RESULT
PMID: 30239738 (View on PubMed)

Liu Y, Ye XY, Chan C. The association between endometrial thickness and pregnancy outcome in gonadotropin-stimulated intrauterine insemination cycles. Reprod Biol Endocrinol. 2019 Jan 23;17(1):14. doi: 10.1186/s12958-019-0455-1.

Reference Type RESULT
PMID: 30674305 (View on PubMed)

Testart J, Frydman R, Feinstein MC, Thebault A, Roger M, Scholler R. Interpretation of plasma luteinizing hormone assay for the collection of mature oocytes from women: definition of a luteinizing hormone surge-initiating rise. Fertil Steril. 1981 Jul;36(1):50-4. doi: 10.1016/s0015-0282(16)45617-7.

Reference Type RESULT
PMID: 7250407 (View on PubMed)

Vaegter KK, Lakic TG, Olovsson M, Berglund L, Brodin T, Holte J. Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers. Fertil Steril. 2017 Mar;107(3):641-648.e2. doi: 10.1016/j.fertnstert.2016.12.005. Epub 2017 Jan 17.

Reference Type RESULT
PMID: 28108009 (View on PubMed)

Yuan X, Saravelos SH, Wang Q, Xu Y, Li TC, Zhou C. Endometrial thickness as a predictor of pregnancy outcomes in 10787 fresh IVF-ICSI cycles. Reprod Biomed Online. 2016 Aug;33(2):197-205. doi: 10.1016/j.rbmo.2016.05.002. Epub 2016 May 13.

Reference Type RESULT
PMID: 27238372 (View on PubMed)

Zhao J, Zhang Q, Wang Y, Li Y. Endometrial pattern, thickness and growth in predicting pregnancy outcome following 3319 IVF cycle. Reprod Biomed Online. 2014 Sep;29(3):291-8. doi: 10.1016/j.rbmo.2014.05.011. Epub 2014 Jun 13.

Reference Type RESULT
PMID: 25070912 (View on PubMed)

Other Identifiers

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2003-ABU-002-BL

Identifier Type: -

Identifier Source: org_study_id

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