The Outcome of Two Protocols Used to Prepare Endometrium for Frozen Embryo Transfer

NCT04507022 | Completed Phase 4

• 1 other identifier: RFC041120190008
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

This is a RCT to test the outcome of two protocols used for preparation of the endometrium for frozen blastocyst embryo transfer

Conditions

Infertility; Infertility, Female; Infertility, Male

Outcome Measures

Primary Outcomes (1)

• Ongoing Pregnancy Rate

  visualization of fetal cardiac pulsation by ultrasound

  at 12 weeks of gestation

Secondary Outcomes (7)

• endometrial compaction

  from the end of estradiol phase to the day of embryo transfer up to 11 days

• clinical pregnancy rate

  6 weeks gestation

• Live birth rate

  24 weeks

• Implantation rate

  6 weeks gestation

• Number of participants with Hypertensive disorders of pregnancy

  20 weeks gestation till postpartum

Study Arms (2)

HRT Plus Aromatase Inhibitor

EXPERIMENTAL

Hormone replacement treatment (HRT) will be used in all cases. Exogenous estradiol will be started on day 2 or 3 of the cycle. In all participants, 2 mg oral estradiol valerate, will be administered three times daily. Ultrasound evaluation of endometrium will be performed 10 to 12 days after starting E2. Trilaminar endometrium of 9 mm will be the targeted cutoff . If not yet ready, E2 supplementation will be continued with serial US assessment until the desired cutoff is achieved. Thereafter, participants will be randomized to two groups: Group A (HRT plus AI): will be given aromatase inhibitor for 5 days only (2.5 mg twice daily), along with the oral 6 mg E2. Then, daily intramuscular (IM) P in oil (100 mg IM P) will be started in addition to the daily dose of oral 6 mg E2. In both groups, embryos will be warmed on the 6th day of P supplementation. Before undergoing FET, endometrial thickness will be re-evaluated. IM P and 6mg E2 will be continued thereafter.

Drug: Estradiol Valerate; Drug: Progesterone; Drug: Aromatase inhibitor

HRT Only

ACTIVE COMPARATOR

Hormone replacement treatment (HRT) will be used in all cases. Exogenous estradiol will be started on day 2 or 3 of the cycle. In all participants, 2 mg oral estradiol valerate, will be administered three times daily. Ultrasound evaluation of endometrium will be performed 10 to 12 days after starting E2. Trilaminar endometrium of 9 mm will be the targeted cutoff . If not yet ready, E2 supplementation will be continued with serial US assessment until the desired cutoff is achieved. Thereafter, participants will be randomized to two groups Group B (HRT only): will be administered daily intramuscular (IM) P in oil (100 mg IM P) in addition to the daily dose of oral 6 mg E2. In both groups, embryos will be warmed on the 6th day of P supplementation. Before undergoing FET, endometrial thickness will be re-evaluated. IM P and 6mg E2 will be continued thereafter.

Drug: Estradiol Valerate; Drug: Progesterone

Interventions

Estradiol Valerate DRUG

2mg three times daily

HRT Only; HRT Plus Aromatase Inhibitor

Progesterone DRUG

100 mg daily intramuscular

HRT Only; HRT Plus Aromatase Inhibitor

Aromatase inhibitor DRUG

2.5 mg twice daily for 5 days

HRT Plus Aromatase Inhibitor

Eligibility Criteria

• Age: 18 Years - 37 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged from18 - 37 years old undergoing FET using good quality blastocysts vitrified on day 5(3 BB and more) (according to Gardner and Schoolcraft 1999) (8).
• Participants having at least one good quality blastocyst (3BB and more) available for transfer after warming.
• Participants having trilaminar endometrium of 9 mm after E2 preparation.

You may not qualify if:

• Women younger than 18 or older than 37 years old.
• Women who have uterine abnormality or pathology.
• Women who will refuse to participate in in the study.

Sponsors & Collaborators

• Rahem Fertility Center: lead

Study Sites (1)

Rahem Fertility Center

Zagazig, Sharqia Province, 44519, Egypt

Location

Related Publications (8)

• Mackens S, Santos-Ribeiro S, van de Vijver A, Racca A, Van Landuyt L, Tournaye H, Blockeel C. Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum Reprod. 2017 Nov 1;32(11):2234-2242. doi: 10.1093/humrep/dex285.

  PMID: 29025055 BACKGROUND

• Sekhon L, Feuerstein J, Pan S, Overbey J, Lee JA, Briton-Jones C, Flisser E, Stein DE, Mukherjee T, Grunfeld L, Sandler B, Copperman AB. Endometrial preparation before the transfer of single, vitrified-warmed, euploid blastocysts: does the duration of estradiol treatment influence clinical outcome? Fertil Steril. 2019 Jun;111(6):1177-1185.e3. doi: 10.1016/j.fertnstert.2019.02.024. Epub 2019 Apr 24.

  PMID: 31029432 BACKGROUND

• 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.

  PMID: 30239738 BACKGROUND

• Pan Y, Hao G, Wang Q, Liu H, Wang Z, Jiang Q, Shi Y, Chen ZJ. Major Factors Affecting the Live Birth Rate After Frozen Embryo Transfer Among Young Women. Front Med (Lausanne). 2020 Mar 24;7:94. doi: 10.3389/fmed.2020.00094. eCollection 2020.

  PMID: 32266278 BACKGROUND

• 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.

  PMID: 31248618 BACKGROUND

• Devine K, Richter KS, Widra EA, McKeeby JL. Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomized controlled noninferiority trial. Fertil Steril. 2018 Feb;109(2):266-275. doi: 10.1016/j.fertnstert.2017.11.004. Epub 2018 Jan 17.

  PMID: 29338855 BACKGROUND

• Miller PB, Parnell BA, Bushnell G, Tallman N, Forstein DA, Higdon HL 3rd, Kitawaki J, Lessey BA. Endometrial receptivity defects during IVF cycles with and without letrozole. Hum Reprod. 2012 Mar;27(3):881-8. doi: 10.1093/humrep/der452. Epub 2012 Jan 13.

  PMID: 22246449 BACKGROUND

• Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999 Jun;11(3):307-11. doi: 10.1097/00001703-199906000-00013.

  PMID: 10369209 BACKGROUND

MeSH Terms

Conditions

Infertility; Infertility, Female; Infertility, Male

Interventions

Estradiol; Progesterone; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Male; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Physiological Effects of Drugs

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2020
• First Posted: August 10, 2020
• Study Start: August 12, 2020
• Primary Completion: February 5, 2021
• Study Completion: February 5, 2021
• Last Updated: April 27, 2022

Record last verified: 2020-10

Locations

EG (1)