Endometrial Preparation in Frozen Embryo Transfer Cycles

NCT ID: NCT06181305

Last Updated: 2024-02-26

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-24

Study Completion Date

2024-12-25

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

In order to get optimal pregnancy rates after frozen embryo transfer (FET), the embryo stage and endometrium should be synchronized. Endometrial preparation is done by either natural, artificial (Hormonal replacement therapy HRT) , modified natural methods or mild ovarian stimulation. HRT cycle has a better schedualization however, there are some reports about higher rates of miscarriage, pregnancy induced hypertension (PIH) and preeclampsia (PET) in HRT cycles. A recent study has found that incorporation of the aromatase inhibitor (letrozole) to HRT cycles was associated with better FET outcomes in comparison to hormonal replacement therapy cycles alone. Meanwhile, mild ovarian stimulation protocol can be done either by oral drugs like letrozole or by letrozole plus gonadotropins . So this study aims to compare the reproductive outcomes in two endometrial preparation protocols for frozen embryo transfer cycles; letrozole mild ovarian stimulation versus HRT plus letrozole incorporation.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

In order to get optimal pregnancy rates after frozen embryo transfer (FET), the embryo stage and endometrium should be synchronized. This can be done by hormonal replacement therapy (HRT), natural cycles (NC), modified natural cycles or mild ovarian stimulation. In hormonal replacement therapy cycle, estrogen and progesterone are sequentially given to resemble the hormonal course of the natural cycle . Hormonal replacement therapy cycle has a better schedualization and is used for patients with irregular cycles as polycystic ovary syndrome ( PCOS). However, there are some reports about higher rates of miscarriage, pregnancy induced hypertension (PIH) and preeclampsia (PET) in HRT cycles.

A recent study has found that incorporation of the aromatase inhibitor (letrozole) to HRT cycles was associated with better FET outcomes in comparison to HRT cycles alone. Ongoing pregnancy rate (OPR) was higher in HRT plus letrozole group than HRT only group.

Letrozole is a third-generation aromatase inhibitor that leads to mono-ovulatory cycles with short half-life . Miller and his colleagues found that letrozole increased Integrin expression and improved pregnancy and implantation rates among women with endometrial receptivity defects . Another study found that ovarian stimulation with letrozole was associated with increase in the expression of uterine receptivity markers including integrin, leukemia inhibitory factor, and L-selectin.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

IVF

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Group A (HRT plus letrozole incorporation)

Exogenous oestradiol in the form of 2 mg oral oestradiol valerate , three times daily will be started on the 2nd or 3rd day of the cycle. Tri-laminar endometrium of ≥ 9 mm will be the targeted cut-off. If the endometrium does not yet reach the target, oestradiol supplementation will be continued with serial US assessment until the targeted cut-off will be reached. Upon reaching the target endometrium, oral letrozole tablets 2.5 mg will be started twice daily for 5 days only with continuation of 6 mg daily oestradiol supplementation. Then, daily intramuscular progesterone in oil (100 mg intramuscular progesterone) will be started once per day with continuation of 6 mg oestradiol

interventions:

Drug:estradiol valertae

Drug :letrozole 2.5 mg tablet

Group Type EXPERIMENTAL

estradiol valerate and letrozole

Intervention Type DRUG

hormone replacement therapy by estradiol valerate plus letrozole incorporation .

Group B (Letrozole mild ovarian stimulation)

Oral letrozole 2.5-5 mg daily on cycle day(3-7) will be added . TVS will be performed from cycle day 8-10 to make sure that a dominant follicle has been recruited with the endometrium thickness ≥ 7 mm . Upon reaching the dominant follicle (18-20mm) , endometrial thickness will be measured on the day of ovulation trigger and blood sample will be withdrawn from each patient for assessment of E2 , P4 and LH levels. Patients with low LH level , high E2 level , low P4 level (\<1 ng/ml) will continue in the RCT; 10,000unit HCG will be injected as ovulation trigger

intervention :

Drug :letrozole 2.5mg tablet

procedure: on the day of ovulation trigger blood sample will be withdrawn from each patient for assessment of E2 , P4 and LH levels.

Group Type ACTIVE_COMPARATOR

letrozole 2,5 mg tablet

Intervention Type DRUG

mild ovarian stimulation

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

estradiol valerate and letrozole

hormone replacement therapy by estradiol valerate plus letrozole incorporation .

Intervention Type DRUG

letrozole 2,5 mg tablet

mild ovarian stimulation

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Women aged between 18 and 37 years with either regular cycles or oligomenorrhoea or amenorrhoea.
* Women undergoing FET cycles.
* Participants should have at least one good-quality blastocyst available for vitrification and also for transfer after warming.
* Participants having optimal endometrium before starting luteal phase support

Exclusion Criteria

* Women who will refuse to participate in in the study.
* Women who will not reach the optimal endometrium.
* Participants that don't have at least one good-quality blastocyst for transfer after warming.
* PGT embryos will be excluded.
Minimum Eligible Age

18 Years

Maximum Eligible Age

37 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Rahem Fertility Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Eman Elgindy

doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Eman El-gindy, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Rahem Fertility Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Rahem fertility center

Zagazig, , Egypt

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Egypt

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Noha Moustafa El-hibishy, MSc

Role: CONTACT

00201067411131

Eman El-gindy, MD,PhD

Role: CONTACT

00201227491143

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Eman El-gindy, MD,PhD

Role: primary

00201227491143

Noha Moustafa El hibishy, MSc

Role: backup

00201067411131

References

Explore related publications, articles, or registry entries linked to this study.

Elgindy EA, Abdelghany AA, Sibai AbdAlsalam H, Mostafa MI. The novel incorporation of aromatase inhibitor in hormonal replacement therapy cycles: a randomized controlled trial. Reprod Biomed Online. 2022 Apr;44(4):641-649. doi: 10.1016/j.rbmo.2021.10.025. Epub 2021 Dec 20.

Reference Type BACKGROUND
PMID: 35288021 (View on PubMed)

Ezoe K, Fukuda J, Takeshima K, Shinohara K, Kato K. Letrozole-induced endometrial preparation improved the pregnancy outcomes after frozen blastocyst transfer compared to the natural cycle: a retrospective cohort study. BMC Pregnancy Childbirth. 2022 Nov 7;22(1):824. doi: 10.1186/s12884-022-05174-0.

Reference Type BACKGROUND
PMID: 36344952 (View on PubMed)

An BGL, Chapman M, Tilia L, Venetis C. Is there an optimal window of time for transferring single frozen-thawed euploid blastocysts? A cohort study of 1170 embryo transfers. Hum Reprod. 2022 Nov 24;37(12):2797-2807. doi: 10.1093/humrep/deac227.

Reference Type BACKGROUND
PMID: 36305795 (View on PubMed)

Mumusoglu S, Polat M, Ozbek IY, Bozdag G, Papanikolaou EG, Esteves SC, Humaidan P, Yarali H. Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review. Front Endocrinol (Lausanne). 2021 Jul 9;12:688237. doi: 10.3389/fendo.2021.688237. eCollection 2021.

Reference Type BACKGROUND
PMID: 34305815 (View on PubMed)

Zhang J, Liu H, Wang Y, Mao X, Chen Q, Fan Y, Xiao Y, Kuang Y. Letrozole use during frozen embryo transfer cycles in women with polycystic ovary syndrome. Fertil Steril. 2019 Aug;112(2):371-377. doi: 10.1016/j.fertnstert.2019.04.014. Epub 2019 May 21.

Reference Type BACKGROUND
PMID: 31126712 (View on PubMed)

Godiwala P, Makhijani R, Bartolucci A, Grow D, Nulsen J, Benadiva C, Grady J, Engmann L. Pregnancy outcomes after frozen-thawed embryo transfer using letrozole ovulation induction, natural, or programmed cycles. Fertil Steril. 2022 Oct;118(4):690-698. doi: 10.1016/j.fertnstert.2022.06.013. Epub 2022 Jul 19.

Reference Type BACKGROUND
PMID: 35863997 (View on PubMed)

Lawrenz B, Melado L, Fatemi HM. Frozen embryo transfers in a natural cycle: how to do it right. Curr Opin Obstet Gynecol. 2023 Jun 1;35(3):224-229. doi: 10.1097/GCO.0000000000000862. Epub 2023 Mar 14.

Reference Type BACKGROUND
PMID: 36924405 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

endometrial preparation

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Progesterone-modified Natural Cycle for FET
NCT06644794 NOT_YET_RECRUITING PHASE3