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

NCT03976544 | Terminated Phase 4 DMC

• 2 other identifiers: HRT_NC-FET2018-003156-20
• Study Type: interventional
• Target: 362
• Locations: 1 country
• Sites: 1

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.

Conditions

Miscarriage; Frozen Embryo Transfer; Natural Cycle; Hormone Replacement Therapy Cycle; Preimplantation Genetic Screening; Euploid Embryos

Keywords

frozen-thawed embryo transfer; FET; natural cycle; hormone replacement therapy cycle; miscarriage

Outcome Measures

Primary Outcomes (1)

• Miscarriage rate before 8 weeks of gestation

  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

  8 weeks

Secondary Outcomes (3)

• Miscarriage rate after 8 weeks of gestation

  22 weeks

• Clinical pregnancy rate

  7 weeks

• Ongoing pregnancy rate

  20 weeks

Study Arms (2)

Natural cycle

NO INTERVENTION

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 serum hormonal values are considered basal for the beginning of the follicular phase, patients are asked to come back on day 10 to 12 of the cycle for blood sample and transvaginal ultrasound scan in order to assess follicular growth. The timing of ovulation is determined based on a combination of ultrasonography features (the presence of a dominant follicle and adequate endometrium) and endocrine hormonal values in serum blood samples. Ovulation is generally defined as an, at least, 180% increase of LH compared to the mean level in the previous 24h. Frozen-warmed blastocyst transfer will take place six days following the spontaneous LH surge.

Hormone replacement therapy cycle

EXPERIMENTAL

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.

Drug: Estradiol Valerate; Drug: Micronized progesterone

Interventions

Estradiol Valerate DRUG

Estradiol valerate will be started in the beginning of the menstrual cycle in order to induce proliferation of the endometrium.

Also known as: Progynova

Hormone replacement therapy cycle

Micronized progesterone DRUG

If the endometrium is considered adequately proliferated, micronized progesterone is administered and frozen-thawed blastocyst transfer will take place on the 6th day of supplementation.

Also known as: Utrogestan

Hormone replacement therapy cycle

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• CRG UZ Brussel: lead

Study Sites (1)

Centre for Reproductive Medicine UZ Brussel

Brussels, 1090, Belgium

Location

MeSH Terms

Conditions

Abortion, Spontaneous

Interventions

Estradiol; Progesterone; Utrogestan

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; 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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical fellow

Model Details: Patients will be randomized to either natural cycle frozen-thawed embryo transfer (group A), or hormonal replacement therapy cycle frozen-thawed embryo transfer (group B).

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 6, 2019
• Study Start: May 25, 2019
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)