Comparison of Live Birth Rate in Natural Cycle Single Euploid FET Versus Without Luteal Phase Support

Phase 1

Recruiting

• Conditions: Pregnancy Related; Infertility, Female
• Interventions: Diagnostic Test: Transvaginal ultrasound; Diagnostic Test: Serial serum LH, E2, P4; Drug: Progesterone 100 Mg Vaginal Insert; Diagnostic Test: Serum P4 day of ET - Study Group; Procedure: Embryo transfer; Diagnostic Test: Serum P4 day of ET - Control Group; Diagnostic Test: Serum hCG 10 days after ET; Diagnostic Test: Serum P4 10 days after ET

• Registration Number: NCT05969795
• Lead Sponsor: ART Fertility Clinics LLC

Brief Summary

To evaluate whether single euploid embryo transfer in NC without routinely administered LPS is non-inferior to NC with routinely administered LPS.

Detailed Description

In case the study will show that the live birth rate in single euploid NC frozen embryo transfer cycles without LPS is not inferior to NC cycles with LPS, treatment can be simplified, and participants comfort can be increased.

Study Timeline

• Study First Submitted: 2023-07-24
• Study First Submitted QC: 2023-07-24
• Study First Posted: 2023-08-01
• Study Start: 2023-09-05
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-09
• Primary Completion: 2026-04-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 342

Inclusion Criteria

• Age: 18 to 40 years
• Regular ovulatory cycles
• Availability of at least one euploid embryo after Trophectoderm biopsy for PGT-A on day 5 or day 6
• Detection of ovulation by P4 rise > 1.0 ng/ml after LH surge
• P4 value of at least 5 ng/ml on day 4 after ovulation

Exclusion Criteria

• History of repeated pre-menstrual spotting
• Factors affecting the implantation through anatomical changes of the uterus / ovaries or the tubes (adenomyosis, Asherman syndrome, endometriosis, uterine fibroids / polyps, isthmocele with intracavitary fluid presence, hydrosalpinx....)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Group	Transvaginal ultrasound	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Blood for P4 measurement will be drawn upon admission to the clinic for the ET procedure. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure.
Control Group	Transvaginal ultrasound	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Administer on FET day 200 mg of P4 and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. Blood for P4 measurement will be drawn before starting LPS in form of vaginal progesterone. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy.
Study Group	Serial serum LH, E2, P4	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Blood for P4 measurement will be drawn upon admission to the clinic for the ET procedure. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure.
Control Group	Progesterone 100 Mg Vaginal Insert	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Administer on FET day 200 mg of P4 and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. Blood for P4 measurement will be drawn before starting LPS in form of vaginal progesterone. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy.
Study Group	Serum P4 day of ET - Study Group	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Blood for P4 measurement will be drawn upon admission to the clinic for the ET procedure. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure.
Study Group	Embryo transfer	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Blood for P4 measurement will be drawn upon admission to the clinic for the ET procedure. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure.
Study Group	Serum hCG 10 days after ET	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Blood for P4 measurement will be drawn upon admission to the clinic for the ET procedure. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure.
Control Group	Embryo transfer	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Administer on FET day 200 mg of P4 and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. Blood for P4 measurement will be drawn before starting LPS in form of vaginal progesterone. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy.
Control Group	Serum P4 10 days after ET	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Administer on FET day 200 mg of P4 and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. Blood for P4 measurement will be drawn before starting LPS in form of vaginal progesterone. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy.
Study Group	Serum P4 10 days after ET	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Blood for P4 measurement will be drawn upon admission to the clinic for the ET procedure. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure.
Control Group	Serial serum LH, E2, P4	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Administer on FET day 200 mg of P4 and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. Blood for P4 measurement will be drawn before starting LPS in form of vaginal progesterone. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy.
Control Group	Serum P4 day of ET - Control Group	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Administer on FET day 200 mg of P4 and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. Blood for P4 measurement will be drawn before starting LPS in form of vaginal progesterone. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy.
Control Group	Serum hCG 10 days after ET	Intermittent ultrasound scans to monitor follicular growth and serial measurements of serum LH, E2 and P4 levels throughout the cycle to determine ovulation. Embryo transfer (ET) will be scheduled on the fifth day after ovulation. Administer on FET day 200 mg of P4 and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. Blood for P4 measurement will be drawn before starting LPS in form of vaginal progesterone. P4 will be measured on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy.

Primary Outcome Measures

Name	Time	Method
Serum P4 levels on ET day	1 day	Progesterone level on the day of embryo transfer
Clinical pregnancy rate	2 months	hCG \> 15 Iu/ml and ultrasound confirmation of a gestational sac
Implantation rate	2 months	Number of embryos which have produced ultrasonographic evidence of an intrauterine gestational sac per the total number of embryos transferred into the uterine cavity (Zegers-Hochschild et al., 2009).
Live birth rate	41 weeks	Number of deliveries that resulted in a live born neonate, expressed per 100 embryo transfers (Zegers-Hochschild et al., 2009)
Serum E2 and P4 levels on day 5 or 6 after ET procedure	6 days	Estradiol and Progesterone levels on day 5 or 6 after embryo transfer
Serum E2 and P4 levels on day 10 after ET procedure	10 days	Estradiol and Progesterone levels on day 10 after embryo transfer

Trial Locations

Locations (3)

ART Fertility Clinics Dubai; 🇦🇪 Dubai, United Arab Emirates

ART Fertility Clinics LLC; 🇦🇪 Abu Dhabi, United Arab Emirates

ART Fertility Clinics Al Ain; 🇦🇪 Al Ain, United Arab Emirates