Prolutex in Frozen Embryo Transfer Cycles at the Blastocyst Stage (PROGEX)

Study Overview
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Brief Summary
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The objective of this proof of concept clinical trial is to evaluate the impact of two different progesterone treatments for endometrial preparation (25 mg/twice-a-day, subcutaneous injection, and 200 mg/three times a day, vaginal administration) on the clinical pregnancy rate in women undergoing frozen embryo transfer (FET) at blastocyst stage.

Official Title
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A Proof of Concept, Randomized, Controlled Clinical Trial to Assess the Efficacy of Subcutaneous Progesterone (Prolutex) Versus Vaginal Progesterone (Progeffik) for Endometrial Preparation in Women Undergoing Frozen Embryo Transfer(FET) Cycles

Conditions
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Infertility

Intervention / Treatment
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* Drug: Progesterone subcutaneous
* Drug: Progesterone Vaginal Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women attending the clinics to undergo a frozen blastocyst embryo transfer, having given written informed consent, with the following characteristics: 18-49 years of age for subjects undergoing ET with donated oocytes (both inclusive); 18-37 years of age for subjects undergoing ET with autologous oocytes (both inclusive); BMI <32 kg/m2; Adequate endometrium preparation (Endometrial thickness > 7 mm) and E2 levels ( >100 pg/ml) on the day progesterone treatment is started; P4 levels <1.5 ng/ml on the day progesterone treatment is started; Transfer of 1 or 2 frozen embryos at blastocyst stage Transfer of frozen embryos of quality A and/or B according to Gardner criteria1; Semen from ejaculation either from the partner or from a bank ≤ 3 previous ET (frozen and fresh) with no pregnancy Normal uterine cavity (i.e. no polyp or protruding sub-mucosal fibroid). Exclusion Criteria: Presence of functional follicles > 10 mm of diameter on the day progesterone treatment is started; Intramural uterine fibroids that distort the uterine cavity or polyps >1 cm; Stage III or IV endometriosis (endometriomas); Hydrosalpinx; Pregnancy or lactation Malformations of the sexual organs incompatible with pregnancy; Patients affected by pathologies associated with any contraindication of being pregnant; Known allergy to progesterone preparations or their excipients; Uncontrolled adrenal or thyroid dysfunction; Undiagnosed vaginal haemorrhage; History of, or current arterial disease; Patients with hepatic impairment; HIV, Hepatitis B Virus or Hepatitis C Virus seropositive; Neoplasias (current) or history of neoplasia that may be responsive to progesterone; High grade cervical dysplasia; Active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders; Currently dependent on alcohol, drugs or psychotropic drugs History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages wherein pregnancy developed to a minimum of a gestational sac on transvaginal ultrasonography; Participation in a concurrent clinical trial or another trial within the past 2 months; Use of concomitant medications that might interfere with the study evaluation: hormonal treatments other than those used in the study, except thyroid hormones.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolutex<br> | Drug: Progesterone subcutaneous<br>* 25 mg/twice a day.<br>|
| Experimental: Progeffik<br> | Drug: Progesterone Vaginal Product<br>* 200 mg three times a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate |  | 4-5 weeks after progesterone treatment start. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum progesterone level |  | 19+/-2 days and 4-5 weeks after start progesterone treatment | 
| Frequency of uterine contractions | n of uterine contraction/min | on the day of Embryo transfer (i.e. 5 days after start progesterone treatment) | 
| Positive serum pregnancy (beta-hCG) test rate |  | 19+/-2 days after start progesterone treatment | 
| Implantation rate |  | 4-5 weeks after start progesterone treatment. | 
| Ongoing pregnancy rate |  | 9-11 weeks after start progesterone treatment. | 
| Abortion rate |  | 9 months after start progesterone treatment. |