Subcutaneous Progesterone Versus Vaginal Progesterone for Endometrial Preparation in Fresh Donated Oocytes Recipients

Study Overview
=================
Brief Summary
-----------------
Randomised, prospective, investigator-blinded, controlled, single-centre study to assess the impact on the ongoing pregnancy rate with the use of two progesterones with different administration routes, in recipients of fresh embryos from donor oocytes, undergoing endometrial preparation for fresh embryo transfer.

Detailed Description
-----------------
Exploratory study with a control group treated according to our Service's usual therapeutic regimen for the transfer of embryos with donor oocytes. The controlled ovarian stimulation protocol in oocyte donors is always calculated according to the standard protocol at the Bernabeu Institute. Endometrial preparation will be carried out following the standard protocol of the Bernabeu Institute as follows: the oestrogen will be administered transdermally and patients with maintained ovarian function undergo medical hypophysectomy with depot GnRH agonists administered in the mid-luteal phase of the previous cycle. On the day of oocyte retrieval, the patient will be randomised: Group A will be administered subcutaneous progesterone 25 mg/day (Prolutex), and Group B will be administered vaginal progesterone in capsules 200 mg/3 times a day (Progeffik). The embryo transfer will be performed on day 5 of the embryo culture (Day +5). A biochemical pregnancy test beta- hCG and the P4 analysis will be performed 14 days after oocyte retrieval. All the cycles will be monitored according to the Department's standard criteria, using transvaginal ultrasound to assess embryonic development and endometrial thickness, as well as analytical controls. The study will be blinded to the investigator. The evaluating professionals will not know if the subject has been administered vaginal progesterone or subcutaneous progesterone. The medication will be delivered by a person who does not participate in the evaluations and who is dedicated to group assignment, to data centralisation, and to delivering the medication. The aim of this study is to determine if the ongoing pregnancy rate in patients undergoing a fresh embryo transfer cycle with donor oocytes is affected by the progesterone administration route.

Official Title
-----------------
Subcutaneous Progesterone (Prolutex) Versus Vaginal Progesterone Capsules (Progeffik) for Endometrial Preparation in Fresh Donated Oocytes Recipients: a Randomised, Prospective, Single-blind, Pilot Study

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Drug: subcutaneous progesterone
* Drug: vaginal progesterone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female, aged from 18 to 49 years (both inclusive) Woman who wishes to become pregnant Endometrial thickness greater 7 mm on the day of patient randomisation to one of the progesterone groups Six or more donor retrieved oocytes Patient programmed for fresh embryo transfer on day +5 of embryo culture BMI lower than 30 Kg/m2 Infertility that justifies treatment with donor oocytes Male with no known karyotype alterations Semen by ejaculation from either the partner or from a bank Uterus able to support embryo implantation and pregnancy Absence of pregnancy before starting the embryo transfer cycle Has given prior written consent Exclusion Criteria: - Important systemic diseases, endocrine-metabolic abnormalities involving the pituitary, thyroid, adrenals, pancreas, liver or kidney. HIV, HBV or HCV seropositivity Undiagnosed vaginal bleeding Pregnancy, breastfeeding or any contraindication to becoming pregnant Malformation of sexual organs incompatible with pregnancy Known allergy to progesterone preparations or their excipients Current dependence on alcohol, drugs or psychotropic medication Concurrent participation in another study Concomitant medication that could interfere with the study medication: different hormonal treatments used in the study, except thyroid hormones, antipsychotics, anxiolytics, hypnotics, sedatives, chronic treatment with prostaglandin inhibitors

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 48 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolutex<br>Subcutaneous progesterone | Drug: subcutaneous progesterone<br>* subcutaneous progesterone 25 mg/day<br>* Other names: Protulex;|
| Active Comparator: Progeffik<br>Vaginal progesterone | Drug: vaginal progesterone<br>* vaginal progesterone in capsules 200 mg/3 times a day<br>* Other names: Progeffik;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ongoing pregnancy rate at 12 weeks gestation | ongoing pregnancy rate at 12 weeks gestation using subcutaneous progesterone and using vaginal progesterone capsules | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progesterone level on the days of the transfer | progesterone level on the days of the transfer | 5 days | 
| progesterone level on biochemical pregnancy test beta-hCG | progesterone level on biochemical pregnancy test beta-hCG | 14 days | 
| endometrium thickness on the day of oocyte retrieval | endometrium thickness on the day of oocyte retrieval | 0 day | 
| endometrium thickness on the day of embryo transfer | endometrium thickness on the day of embryo transfer | 5 days | 
| endometrium morphology on the day of oocyte retrieval | endometrium morphology (trilaminar pattern and echogenicity) on the day of oocyte retrieval | 0 day | 
| endometrium morphology on the day of embryo transfer | endometrium morphology (trilaminar pattern and echogenicity) on the day of embryo transfer | 5 days | 
| implantation rate | number of embryo sacs at 4-5 weeks (by ultrasound) versus number of embryos transferred | 4-5 weeks | 
| positive biochemical pregnancy test beta- hCG rate | positive biochemical pregnancy test beta- hCG rate at 14 days | 14 days | 
| clinical pregnancy rate | rate of patients with embryo any sac with a heartbeat (by ultrasound) | 4-5 weeks | 
| miscarriage rate | miscarriage rate in patients with positive biochemical pregnancy test beta- hCG rate on day +14 | 10 weeks | 
| occurrence of side effects | occurrence of side effects associated with progesterone | day 5, day 14, 4-5 days, 10 weeks | 
| comfort in relation to the progesterone administration route | comfort in relation to the progesterone administration route | 10 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Reproductive Techniques, Infertility, Reproductive Techniques Assisted