Endometrial Preparation in Frozen Embryo Transfer Cycles

IVF Clinical Trial

Official title:

Hormonal Replacement Therapy Plus Letrozole Incorporation Versus Letrozole Mild Ovarian Stimulation in Endometrial Preparation for Frozen Embryo Transfer: A Randomised Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06181305
• Other study ID #: endometrial preparation
• Status: Recruiting
• Phase: Phase 4
• Start date: February 24, 2024
• Est. completion date: December 25, 2024

Study information

• Verified date: February 2024
• Source: Rahem Fertility Center
• Contact: Noha Moustafa El-hibishy, MSc
• Phone: 00201067411131
• Email: nohaesmaeelobgyn[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: December 25, 2024
• Est. primary completion date: November 25, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 37 Years

Eligibility

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.

Related Conditions & MeSH terms

• IVF

Intervention

Drug:
• estradiol valerate and letrozole
hormone replacement therapy by estradiol valerate plus letrozole incorporation .
• letrozole 2,5 mg tablet
mild ovarian stimulation

Locations

Country	Name	City	State
Egypt	Rahem fertility center	Zagazig

Sponsors (1)

Lead Sponsor	Collaborator
Rahem Fertility Center

Country where clinical trial is conducted

Egypt, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ongoing pregnancy rate (OPR)	Number of pregnant women with viable fetus at 12 weeks gestation per woman randomized	12 weeks
Secondary	Clinical pregnancy rate (CPR)	Number of gestational sacs with evident fetal pulsations per woman randomized,ectopic pregnancy is also includded pregnancy is aslo included	5 weeks after embryo transfer
Secondary	Ectopic pregnancy	pregnancy outside the uterine cavity diagnosed by ultrasound ,surgical visualization or histopathology	7 week
Secondary	Miscarriage rate	Number of miscarriages per woman with positive pregnancy tests	12 weeks
Secondary	Implantation rate	Number of gestational sac recognized by ultrasound in uterus 3 weeks after embryo transfer	21 days after embryo transfer
Secondary	live birth rate	The complete expulsion or extraction from a woman of a product of fertilization,after 22 complete weeks of gestational age;which,after such separation,breathes or shows any other evidence of life,such as heart beat,umblical cord pulsation or definite movement of voluntary muscles,irrespective of whether the umblical cord has been cut or the placenta is attached.A birth weight of 500 grams or more can be used if gestational age is unknown.Live births refer to the individual newborn ;for example,a twin delivery represents two live births	22 completed weeks of gestational age
Secondary	Number of participants with Hypertensive disorders of pregnancy	gestational hypertension or preeclampsia	20 weeks gestation till postpartum
Secondary	Number of participants with Large for gestational age	A birth weight greater than the 90th centile of the sex-specific birth weight for a given gestational age reference	from gestation till delivery