Oral Versus Vaginal Progesterone in the Luteal Support in Cryo-warmed Embryo Transfer Cycles

Oral Dydrogesterone Versus Vaginal Progesterone in the Luteal Phase Support in Cryo-warmed Embryo Transfer Cycles: Randomized Controlled Trial

In IVF/ICSI cycles, the progesterone levels induced by ovarian stimulation are low, therefore the luteal phase is supported by progesterone. The use of progestogens in IVF is associated with an improvement in the live birth rate Standard protocol for luteal phase support has not yet been established. Currently vaginal progesterone is widely used, since the classic oral progesterone seems to result in a low bioavailability and a lower pregnancy rate. However, vaginal administration of progesterone is associated with vaginal irritation, discharge and bleeding. For all these reasons, there is a need for an effective, well tolerated, and safe treatment that can improve patient satisfaction and compliance.

Many studies have observed similar pregnancy rate results with dydrogesterone and micronized vaginal progesterone. A new RCT including a total of 1143 patients by Tournaye, showed that dydrogesterone treatment had a similar safety profile to micronized vaginal progesterone (MVP) for luteal support as part of ART treatment. The crude pregnancy rates at 12 weeks were 37.6% and 33.1% in the dydrogesterone and MVP treatment groups respectively.

Regarding the administration route of progesterone, intramuscular and transvaginal routes are the two conventional progesterone administration techniques. However, very few studies have compared the advantages of oral dydrogestrone with vaginal progesterone for luteal support in ART cycles.

The objective of the investigator's study is to demonstrate the superiority of oral dydrogesterone (Duphaston) 10 over MVP (Utrogestan) used for luteal supplementation in cryo-warmed embryo transfer cycles. Upon consent, 224 patients women will be randomly allocated into either one of the study groups using a simple randomization method by computer-generated random numbers. Group I will receive the oral dydrogesterone, while group II will receive the vaginal microprogesterone.

Study Overview

• Status: Completed
• Conditions: Infertility; Sterility
• Intervention / Treatment: Drug: Progesterone

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Johnny Awwad, M.D; Phone Number: 5606 009613500; Email: jawwad@aub.edu.lb

Study Locations

• Lebanon
  • Beirut, Lebanon
    • American University of Beirut Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Normal uterine cavity
• Normal Hormonal investigation: TSH,PRL,FBS
• Frozen embryo transfer cycles: at least 2 embryos
• Primary or secondary infertility: tubal occlusion, male factor, unexplained, endometriosis, ovarian factors…
• Body mass index (BMI) ≥18 to ≤30 kg/m2

Exclusion Criteria:

• Preexisting untreated medical condition (thyroid disease, diabetes mellitus, hypertension, pulmonary conditions, cardiac condition…)
• History of three or more consecutively failed In Vitro Fertilization (IVF) cycles after embryo transfer
• History of three or more miscarriages
• Previous allergy reactions to progesterone products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Dydrogesterone; Oral dydrogesterone (Duphaston 10 mg) will be given orally four times daily : will be continued till the pregnancy test, and till at least 12 weeks of gestation in case of a positive pregnancy test.	Drug: Progesterone; Patients will be randomly assigned during the treatment follow up, at the time of addition of progesterone to the regimen, following computerized random number generator in procedure, to one of the study groups. Patients will be aware of the allocated arm since the treatment drugs have different route of administration. Group I will receive the oral dydrogesterone, while group II will receive the vaginal microprogesterone.
Experimental: Vaginal microprogesterone; Vaginal progesterone (Utrogestan 200 mg) will be given vaginally four times daily: will be continued till the pregnancy test, and till at least 12 weeks of gestation in case of a positive pregnancy test	Drug: Progesterone; Patients will be randomly assigned during the treatment follow up, at the time of addition of progesterone to the regimen, following computerized random number generator in procedure, to one of the study groups. Patients will be aware of the allocated arm since the treatment drugs have different route of administration. Group I will receive the oral dydrogesterone, while group II will receive the vaginal microprogesterone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live births per embryo transferred	Number of live births per number of embryos transferred	until date of delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing or Clinical pregnancy rate per started treatment cycle (CPR)	The presence of a viable fetus at 20 weeks gestation or fetal heart beat on transvaginal ultrasound after 6-7 weeks of gestation	20 weeks from Last Menstrual Period (LMP)
Implantation rate (IR)	Number of intrauterine gestational sacs observed on transvaginal ultrasound divided by the number of transferred embryos	7 weeks from LMP
Miscarriage rates	Pregnancy loss prior to 12 weeks of gestation	From a positive pregnancy test till 12 weeks gestation
Multiple gestation rate	More than one intra-uterine gestation sac at 6 weeks of gestation	6-7 weeks of gestation

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: August 3, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Assisted Reproductive Technology; Luteal Phase Support; Cryo-warmed Embryo Transfer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: AmericanUBMC-CWET

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No