Natural Cycle Versus Hormone Replacement Therapy Cycle for a Frozen-thawed Embryo Transfer in PGT Patients

Phase 4

Terminated

• Conditions: Miscarriage; Frozen Embryo Transfer; Natural Cycle; Hormone Replacement Therapy Cycle; Preimplantation Genetic Screening; Euploid Embryos
• Interventions: Drug: Estradiol Valerate; Drug: Micronized progesterone

• Registration Number: NCT03976544
• Lead Sponsor: CRG UZ Brussel

Brief Summary

The aim of the current study is to compare miscarriage rates (before 8 weeks) between a true natural cycle (awaiting spontaneous LH surge) and a hormone replacement therapy cycle prior to blastocyst transfer in preimplantation genetic testing (PGT) patients, with biopsy on day 5 of embryonic development. The advantage of performing the study in PGT patients is the exclusion of aneuploidy as a cause of miscarriage.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-25
• Study First Submitted: 2019-06-04
• Study First Submitted QC: 2019-06-05
• Study First Posted: 2019-06-06
• Status Verified: 2025-01
• Primary Completion: 2025-01-01
• Study Completion: 2025-01-01
• Last Update Submitted: 2025-01-25
• Last Update Posted: 2025-01-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 362

Inclusion Criteria

• BMI under 35 kg/m2
• Regular menstrual cycle pattern (i.e. 24-35 days cycle)
• First, second and third ICSI-PGT cycle
• First frozen embryo transfer cycle following a fresh ICSI-PGT attempt
• PGT with trophectoderm biopsy on day 5 of embryonic development
• Signed informed consent

Exclusion Criteria

• Oligo-amenorrhea
• BMI above 35
• Contraindications for the use of hormonal replacement therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hormone replacement therapy cycle	Estradiol Valerate	Patients are asked to perform a blood sample, with evaluation of serum estradiol (E2), progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) on the first or second day of the menstrual cycle. If these values are considered basal for the beginning of the follicular phase, estrogen supplementation (Estradiol valerate, Progynova® 3x2mg/day) is started to induce proliferation of the endometrium. Blood sample and transvaginal ultrasound are thereafter performed ten to fourteen days later. If the endometrium is considered adequate (generally considered if triple line and above 6,5 mm thickness), embryo transfer is scheduled on the sixth day of progesterone (vaginal micronized progesterone, Utrogestan® 2x200mg twice a day) supplementation. In case of escape spontaneous ovulation embryo transfer will be performed considering the presumable time of ovulation.
Hormone replacement therapy cycle	Micronized progesterone	Patients are asked to perform a blood sample, with evaluation of serum estradiol (E2), progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) on the first or second day of the menstrual cycle. If these values are considered basal for the beginning of the follicular phase, estrogen supplementation (Estradiol valerate, Progynova® 3x2mg/day) is started to induce proliferation of the endometrium. Blood sample and transvaginal ultrasound are thereafter performed ten to fourteen days later. If the endometrium is considered adequate (generally considered if triple line and above 6,5 mm thickness), embryo transfer is scheduled on the sixth day of progesterone (vaginal micronized progesterone, Utrogestan® 2x200mg twice a day) supplementation. In case of escape spontaneous ovulation embryo transfer will be performed considering the presumable time of ovulation.

Primary Outcome Measures

Name	Time	Method
Miscarriage rate before 8 weeks of gestation	8 weeks	a spontaneous loss of a clinical pregnancy before 8 weeks of gestational age, in which the embryo(s) is/are nonviable and is/are (not) spontaneously absorbed or expelled from the uterus per initiated embryo transfer cycle and per positive hCG

Secondary Outcome Measures

Name	Time	Method
Miscarriage rate after 8 weeks of gestation	22 weeks	a spontaneous loss of a clinical pregnancy after 8 weeks but before 22 completed weeks of gestational age, in which the embryo(s) or fetus(es) is/are nonviable and is/are not spontaneously absorbed or expelled from the uterus per initiated embryo transfer cycle and per positive hCG
Clinical pregnancy rate	7 weeks	a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy per initiated embryo transfer cycles
Ongoing pregnancy rate	20 weeks	the number of pregnancies after 20 weeks of gestation per initiated embryo transfer cycle

Trial Locations

Locations (1)

Centre for Reproductive Medicine UZ Brussel; 🇧🇪 Brussels, Belgium