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

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

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.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: subcutaneous progesterone; Drug: vaginal progesterone

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain, 03016
    • Instituto Bernabeu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolutex; Subcutaneous progesterone	Drug: subcutaneous progesterone; subcutaneous progesterone 25 mg/day; Other Names: Protulex
Active Comparator: Progeffik; Vaginal progesterone	Drug: vaginal progesterone; vaginal progesterone in capsules 200 mg/3 times a day; 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of uterine contractions per minute	number of uterine contractions per minute on the day of embryo transfer	day 5

Collaborators and Investigators

• Sponsor: Instituto Bernabeu
• Investigators: Principal Investigator: Joanquin Llacer, Ph, Instituto Bernabeu

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: February 12, 2015
• First Posted (Estimate): February 13, 2015

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Infertility; Reproductive Techniques; Reproductive Techniques Assisted
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: BER-PRO-2014-01