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

CRG UZ Brussel

Status and phase: Terminated; Phase 4

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

Treatments: Drug: Micronized progesterone; Drug: Estradiol Valerate

Study type: Interventional

Funder types: Other

Identifiers

NCT03976544

HRT_NC-FET

2018-003156-20 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 362 patients

Sex: Female

Ages: 18 to 42 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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362 participants in 2 patient groups

Natural cycle

No Intervention group

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.

Hormone replacement therapy cycle

Experimental group

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.

Treatment:

Drug: Estradiol Valerate

Drug: Micronized progesterone