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

Primary Purpose

Miscarriage, Frozen Embryo Transfer, Natural Cycle

Status
Recruiting
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Estradiol Valerate
Micronized progesterone
Sponsored by
CRG UZ Brussel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Miscarriage focused on measuring frozen-thawed embryo transfer, FET, natural cycle, hormone replacement therapy cycle, miscarriage

Eligibility Criteria

18 Years - 42 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Centre for Reproductive Medicine UZ BrusselRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Natural cycle

Hormone replacement therapy cycle

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Miscarriage rate after 8 weeks of gestation
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
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
the number of pregnancies after 20 weeks of gestation per initiated embryo transfer cycle

Full Information

First Posted
June 4, 2019
Last Updated
September 13, 2023
Sponsor
CRG UZ Brussel
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1. Study Identification

Unique Protocol Identification Number
NCT03976544
Brief Title
Natural Cycle Versus Hormone Replacement Therapy Cycle for a Frozen-thawed Embryo Transfer in PGT Patients
Official Title
Natural Cycle Versus Hormone Replacement Therapy Cycle for a Frozen-thawed Embryo Transfer in PGT Patients: A Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2019 (Actual)
Primary Completion Date
September 1, 2025 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
CRG UZ Brussel

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
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).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
522 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Natural cycle
Arm Type
No Intervention
Arm Description
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.
Arm Title
Hormone replacement therapy cycle
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Estradiol Valerate
Other Intervention Name(s)
Progynova
Intervention Description
Estradiol valerate will be started in the beginning of the menstrual cycle in order to induce proliferation of the endometrium.
Intervention Type
Drug
Intervention Name(s)
Micronized progesterone
Other Intervention Name(s)
Utrogestan
Intervention Description
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.
Primary Outcome Measure Information:
Title
Miscarriage rate before 8 weeks of gestation
Description
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
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Miscarriage rate after 8 weeks of gestation
Description
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
Time Frame
22 weeks
Title
Clinical pregnancy rate
Description
a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy per initiated embryo transfer cycles
Time Frame
7 weeks
Title
Ongoing pregnancy rate
Description
the number of pregnancies after 20 weeks of gestation per initiated embryo transfer cycle
Time Frame
20 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
42 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Centre for Reproductive Medicine UZ Brussel
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elsie Nulens
Phone
+32 2 477 66 48
Email
Studieverpleegkundigen_CRG@UZBrussel.be
First Name & Middle Initial & Last Name & Degree
Christophe Blockeel, MD, PhD
First Name & Middle Initial & Last Name & Degree
Caroline Roelens, Dr

12. IPD Sharing Statement

Plan to Share IPD
No

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

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