Comparison of Vaginal and Intramuscular Progesterone in Vitrified-warmed Blastocyst Transfer Cycles

Comparison of Vaginal Progesterone Gel (Crinone 8%®) and Intramuscular Progesterone in Vitrified-Warmed Blastocyst Transfer Cycles

The aim of this study is to test the hypothesis that the pregnancy rates of women (ages 18-50 years) undergoing transfer of vitrified-warmed blastocysts (frozen at less than 41 years of age) as part of their IVF treatment are not different with respect to the administration of progesterone (Crinone® 8% vaginal gel versus intramuscular progesterone).

Study Overview

• Status: Withdrawn
• Conditions: Infertility
• Intervention / Treatment: Drug: Vaginal progesterone gel (Crinone® 8%); Drug: Intramuscular Progesterone

Detailed Description

The hypothesis of this study is that the type of progesterone administered (intramuscular progesterone or Crinone® 8% vaginal gel) does not affect implantation and clinical pregnancy rates in women receiving cryo-thawed blastocysts that were produced using their own eggs and frozen before age 41 years. Both intramuscular progesterone (25-100 mg compounded in oil) or vaginal progesterone (Crinone® 8% vaginal progesterone gel) are widely used for luteal phase support in patients receiving vitrified-warmed embryos. Crinone® 8% is FDA approved for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency (FDA approval letter, 1997).

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Signed informed consent
• Patient age at time of embryo freezing: 18 to 40.9 years
• Patient age at embryo transfer: 18 to 50 years (i.e. women currently ages 18-50 years who are transferring embryos created using eggs retrieved from women aged 18-40.9 years)
• Blastocysts frozen by vitrification at Brigham and Women's Hospital
• Standard eligibility criteria for blastocyst transfer at Brigham and Women's Hospital

Exclusion Criteria:

• Fresh or cleavage-stage embryo transfer planned
• Gestational carrier cycles
• Natural and modified natural cycles
• Embryos frozen more than once or derived from thawed oocytes
• Embryos frozen at centers other than Brigham and Women's Hospital
• Embryos frozen using techniques other than vitrification (i.e. slow frozen)
• Patients with recurrent pregnancy loss, defined as failure of 3 or more clinical pregnancies
• Uterine factor infertility: Asherman's, submucosal fibroids, polyp greater than 1 cm at time of embryo transfer, uninterrupted hydrosalpinx
• Patients with three prior failed embryo transfers (fresh or frozen)
• BMI<18 or >40 kg/m2 at screening
• Currently breast feeding or pregnant
• Embryo biopsy performed
• Current smoking, alcohol or illicit drug use
• Allergy to study drugs
• Refusal or inability to adhere to study protocol
• Participation in other experimental drug trials concurrently within the past 60 days

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
Active Comparator: Vaginal progesterone gel (Crinone® 8%); Crinone® 8% (90 mg of micronized progesterone in a bioadhesive vaginal gel contained in a single use, one piece applicator) is administered once 5 days prior to embryo transfer, then twice per day until the pregnancy test is negative or until the 10th week of pregnancy.	Drug: Vaginal progesterone gel (Crinone® 8%); Crinone® 8% (90 mg of micronized progesterone in a bioadhesive vaginal gel contained in a single use, one piece applicator) is administered once 5 days prior to embryo transfer, then twice per day until the pregnancy test is negative or until the 10th week of pregnancy.; Other Names: vaginal progesterone; Crinone
Active Comparator: Intramuscular Progesterone; Progesterone-25 mg intramuscularly once 5 days prior to embryo transfer, then 50 mg once per day until the pregnancy test is negative or until the 10th week of pregnancy.	Drug: Intramuscular Progesterone; Progesterone-25 mg intramuscularly once 5 days prior to embryo transfer, then 50 mg once per day until the pregnancy test is negative or until the 10th week of pregnancy.; Other Names: progesterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	Percentage of patients with intrauterine gestational sac by ultrasound	5-6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	Maximum number of gestational sacs divided by total number of embryos transferred	5-6 weeks
Sustained implantation rate	maximum number of fetal heartbeats divided by total number of embryos transferred	7 weeks
Biochemical pregnancy	Positive serum b-hCG (above 5 IU/L) without subsequent ultrasound evidence of pregnancy	6 weeks
Ongoing pregnancy rate	Live intrauterine pregnancy at the time of transfer to obstetrical care	7-8 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Elena Yanushpolsky, MD, Assistant Professor, Harvard Medical School, Director of Reproductive Surgery at Brigham and Women's Hospital

Publications and helpful links

General Publications

• Wang Y, He Y, Zhao X, Ji X, Hong Y, Wang Y, Zhu Q, Xu B, Sun Y. Crinone Gel for Luteal Phase Support in Frozen-Thawed Embryo Transfer Cycles: A Prospective Randomized Clinical Trial in the Chinese Population. PLoS One. 2015 Jul 29;10(7):e0133027. doi: 10.1371/journal.pone.0133027. eCollection 2015.
• Lightman A, Kol S, Itskovitz-Eldor J. A prospective randomized study comparing intramuscular with intravaginal natural progesterone in programmed thaw cycles. Hum Reprod. 1999 Oct;14(10):2596-9. doi: 10.1093/humrep/14.10.2596.
• Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014 Aug;29(8):1706-11. doi: 10.1093/humrep/deu121. Epub 2014 May 20.
• Berger BM, Phillips JA. Pregnancy outcomes in oocyte donation recipients: vaginal gel versus intramuscular injection progesterone replacement. J Assist Reprod Genet. 2012 Mar;29(3):237-42. doi: 10.1007/s10815-011-9691-9. Epub 2012 Feb 4.

Helpful Links

• Drug information for progesterone

Study record dates

Study Major Dates

• Primary Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: May 11, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimate): May 13, 2016

Study Record Updates

• Last Update Posted (Actual): September 9, 2019
• Last Update Submitted That Met QC Criteria: September 6, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Infertility; In vitro fertilization; Progesterone; Embryo transfer; Blastocyst; Crinone
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: BWH2016progRCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No