Progesterone Supplementation on Women Having Low Progesterone Levels on Transfer Day

Study Overview
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Brief Summary
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The main objective of this study is to compare clinical pregnancy rates between two groups of women who have progesterone levels below 10 ng/mL on the day of frozen embryo transfer: group 1 (vaginal micronized progesterone supplemented with progesterone intramuscular 50 mg per day) and group 2 (vaginal micronized progesterone with no supplementation)

Detailed Description
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Trial Design: Single center, longitudinal, randomized, interventional, controlled, pharmacological study, enrolling women attending clinical Centers of medically assisted reproduction (ART). The study protocol consists in the record of all the diagnostic and clinical outcome parameters, according to clinical practice, for the following patient cohorts: The patients who are undergoing frozen embryo transfers with blastocyst or cleavage stage embryos and have progesterone levels below 10 ng/mL on the day of embryo transfer Study groups Group supplemented with progesterone intramuscular 50 mg per day until the day of beta-hcg testing (Intervention group); Group with no supplementation (Control group). Endometrial cycle is started with estradiol valerate dose of 4 mg to 8 mg per day, the patients then are appointed to have ultrasound scan of their endometrium every 3 to 7 days and the dose of estradiol may be increased to 16 mg per day maximum depends on the thickness of endometrium; when their endometrium reach 8 mm or higher and duration of endometrial preparation is ≥ 12 days, the embryo transfer will be planned and transvaginal progesterone are prescribed according to the day of transfer. If this is the first cycle of embryo transfer and she is < 35 years of age, 1 grade 1 embryo is transferred, otherwise 2 embryos are transferred. In the morning of embryo-transferred day, all patients will have their blood tested for progesterone levels, if their levels below 10 ng/mL, they will be recruited into the study and randomized into two groups. In the study group, the patients will be prescribed with intramuscular progesterone supplemetation 50 mg + 800mg vaginal micronized progesterone per day for 14 days, until the day of beta-hcg testing. In the control group, the patients will continue their regular medications (800mg vaginal micronized progesterone per day) until the day of beta-hcg testing without any progesterone supplementation. If the beta-hcg test is positive, the patients will be continued their prescriptions depending on study or control group as mentioned above till 7 weeks of pregnancy when the fetal heart can be confirmed, then the patients will be followed up till 11 - 12 weeks of pregnancy

Official Title
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Effectiveness of Progesterone Supplementation for Women Having Low Progesterone Levels on the Day of Frozen Embryo Transfer

Conditions
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Assisted Reproductive Technology

Intervention / Treatment
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* Procedure: Progesterone supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergone ART with frozen embryo transfer, blastocyst or cleavaged stage embryo transfer, from 18-45 years of age Normal BMI HRT for Endometrial preparation in FET cycles Exclusion Criteria: Oocyte donor cycles Surrogacy IVM PGT Abnormal Uterine (firbroids 0 -> 3 according to FIGO classification, polyp, adenomyosis, congenital malformation) Uterus fibroids type 4,5 (Figo classification) > 4cm History of recurrent implantation failure Endometrial thickness <7mm on the day of ET Cesarean scar defect (isthmocele)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients who have progesterone levels below 10 ng/mL on the day of embryo transfer will be randomized into 2 groups: Those who will be supplemented with intramuscular progesterone 50mg per day till day of beta-hcg testing Those who will continue their regular medications
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>In the control group, the patients will be indicated with standard protocol, micronized progesterone (Cyclogest pessary) 400mg two times per day for 14 days, without any progesterone supplementation. If the beta-hcg test is positive, the patients will be treated with the same protocol and followed till 7 weeks of pregnancy when the fetal heart can be confirmed | |
| Experimental: Study group<br>In the interventional group,the patients will be indicated with standard protocol, micronized progesterone (Cyclogest pessary) 400mg x 2 per day for 14 days, supplemented with intramuscular progesterone (Progesterone 25mg/ml) 25 mg x 2 at one time per day for 14 days. If the beta-hcg test is positive, the patients will be treated with the same protocol and followed till 7 weeks of pregnancy when the fetal heart can be confirmed | Procedure: Progesterone supplementation<br>* This procedure is to add more progesterone on those who have low progesterone levels on the day of embryo transfer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate | defined as the pregnancy completed 11 - 14 weeks of gestation and having vital fetus | week 11 - 14 of pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| implantation rate | the percentage of embryos which successfully undergo implantation compared to the number of embryos transferred in a given period | 3 weeks after embryo transfer | 
| Pregnancy rate | beta-hCG test is positive | 2 weeks after embryo transfer | 
| clinical pregnancy rate | pregnancy when fetal heart can be confirmed | 3 weeks after embryo transfer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low progesterone levels, progesterone supplementation, clinical pregnancy