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

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

Detailed Description
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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.

Official Title
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Comparison of Live Birth Rate (> 24 Weeks) in Natural Cycle (NC) Single Euploid Frozen Embryo Transfers (FET) With Versus Without Luteal Phase Support (LPS)

Conditions
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Pregnancy Related, Infertility, Female

Intervention / Treatment
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* Diagnostic Test: Transvaginal ultrasound
* Diagnostic Test: Serial serum LH, E2, P4
* Drug: Progesterone 100 Mg Vaginal Insert
* Diagnostic Test: Serum P4 day of ET - Control Group
* Diagnostic Test: Serum P4 day of ET - Study Group
* Procedure: Embryo transfer
* Diagnostic Test: Serum hCG 10 days after ET
* Diagnostic Test: Serum P4 10 days after ET


Participation Criteria
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Eligibility Criteria
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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….)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Study Group<br>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. | Diagnostic Test: Transvaginal ultrasound<br>* Intermittent transvaginal ultrasound throughout the cycle to monitor follicular growth<br>Diagnostic Test: Serial serum LH, E2, P4<br>* Serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4 )levels throughout the cycle to determine ovulation. LH-surge is identified when a rise of 180% above the previous level occurred and ovulation is confirmed with a decrease in E2 concentration, and a rise of progesterone level to ≥ 1.0 ng/ml (Irani et al., 2017).<br>Diagnostic Test: Serum P4 day of ET - Study Group<br>* Serum P4 will be drawn when study group participants are admitted to the clinic for the ET procedure.<br>Procedure: Embryo transfer<br>* The procedure in which embryo is placed in the uterus.<br>* Other names: ET;Diagnostic Test: Serum hCG 10 days after ET<br>* Pregnancy will be confirmed / excluded by measurement of serum hCG 10 days after ET procedure and a level of > 15 IU will be regarded as positive result. The definitions of biochemical, ectopic, clinical and ongoing pregnancy follow the ICMART criteria (Zegers-Hochschild, 2006)<br>Diagnostic Test: Serum P4 10 days after ET<br>* Serum P4 will be drawn on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure<br>|
| Other: Control Group<br>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. | Diagnostic Test: Transvaginal ultrasound<br>* Intermittent transvaginal ultrasound throughout the cycle to monitor follicular growth<br>Diagnostic Test: Serial serum LH, E2, P4<br>* Serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4 )levels throughout the cycle to determine ovulation. LH-surge is identified when a rise of 180% above the previous level occurred and ovulation is confirmed with a decrease in E2 concentration, and a rise of progesterone level to ≥ 1.0 ng/ml (Irani et al., 2017).<br>Drug: Progesterone 100 Mg Vaginal Insert<br>* On day of ET procedure, to administer 200 mg of vaginal progesterone and increase to 300 mg/day from the day after the ET onwards until the pregnancy test. In case of an implantation, vaginal P4 will be continued until 7 weeks of pregnancy<br>* Other names: Progesterone 100Mg Vag Tab;Diagnostic Test: Serum P4 day of ET - Control Group<br>* Serum P4 will be drawn before starting LPS in form of vaginal progesterone on the day of ET procedure<br>Procedure: Embryo transfer<br>* The procedure in which embryo is placed in the uterus.<br>* Other names: ET;Diagnostic Test: Serum hCG 10 days after ET<br>* Pregnancy will be confirmed / excluded by measurement of serum hCG 10 days after ET procedure and a level of > 15 IU will be regarded as positive result. The definitions of biochemical, ectopic, clinical and ongoing pregnancy follow the ICMART criteria (Zegers-Hochschild, 2006)<br>Diagnostic Test: Serum P4 10 days after ET<br>* Serum P4 will be drawn on day 5 or day 6 after the ET procedure and together with the hCG 10 days after ET procedure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate | 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). | 2 months | 
| Clinical pregnancy rate | hCG > 15 Iu/ml and ultrasound confirmation of a gestational sac | 2 months | 
| Live birth rate | Number of deliveries that resulted in a live born neonate, expressed per 100 embryo transfers (Zegers-Hochschild et al., 2009) | 41 weeks | 
| Serum P4 levels on ET day | Progesterone level on the day of embryo transfer | 1 day | 
| Serum E2 and P4 levels on day 5 or 6 after ET procedure | Estradiol and Progesterone levels on day 5 or 6 after embryo transfer | 6 days | 
| Serum E2 and P4 levels on day 10 after ET procedure | Estradiol and Progesterone levels on day 10 after embryo transfer | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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luteal phase support, implantation rate, infertility, pregnancy rate, natural cycle, live birth, progesterone