Endometrial Preparation in Frozen Embryo Transfer Cycles

NCT06181305 | Recruiting Phase 4

• 1 other identifier: endometrial preparation
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

IVF

Outcome Measures

Primary Outcomes (1)

• ongoing pregnancy rate (OPR)

  Number of pregnant women with viable fetus at 12 weeks gestation per woman randomized

  12 weeks

Secondary Outcomes (7)

• Clinical pregnancy rate (CPR)

  5 weeks after embryo transfer

• Ectopic pregnancy

  7 week

• Miscarriage rate

  12 weeks

• Implantation rate

  21 days after embryo transfer

• live birth rate

  22 completed weeks of gestational age

Study Arms (2)

Group A (HRT plus letrozole incorporation)

EXPERIMENTAL

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

Drug: estradiol valerate and letrozole

Group B (Letrozole mild ovarian stimulation)

ACTIVE COMPARATOR

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.

Drug: letrozole 2,5 mg tablet

Interventions

estradiol valerate and letrozole DRUG

hormone replacement therapy by estradiol valerate plus letrozole incorporation .

Group A (HRT plus letrozole incorporation)

letrozole 2,5 mg tablet DRUG

mild ovarian stimulation

Group B (Letrozole mild ovarian stimulation)

Eligibility Criteria

• Age: 18 Years - 37 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rahem Fertility Center: lead

Study Sites (1)

Rahem fertility center

Zagazig, 44511, Egypt

RECRUITING

Related Publications (7)

• 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.

  PMID: 35288021 BACKGROUND

• 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.

  PMID: 36344952 BACKGROUND

• 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.

  PMID: 36305795 BACKGROUND

• 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.

  PMID: 34305815 BACKGROUND

• 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.

  PMID: 31126712 BACKGROUND

• 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.

  PMID: 35863997 BACKGROUND

• 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.

  PMID: 36924405 BACKGROUND

MeSH Terms

Interventions

Estradiol; Letrozole

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; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Eman El-gindy, MD,PhD

  Rahem Fertility Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Noha Moustafa El-hibishy, MSc

CONTACT

00201067411131; nohaesmaeelobgyn@yahoo.com

Eman El-gindy, MD,PhD

CONTACT

00201227491143; eman_elgindy2013@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: doctor

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: December 26, 2023
• Study Start: February 24, 2024
• Primary Completion: November 25, 2024
• Study Completion: December 25, 2024
• Last Updated: February 26, 2024

Record last verified: 2024-02

Locations

EG (1)