Subcutaneous Progesterone Versus Vaginal Progesterone Tablets for Luteal Phase Support in In Vitro Fertilization (IVF)

Efficacy and Tolerability of Subcutaneous Progesterone (IBSA) Versus Vaginal Progesterone for Luteal Phase Support in Patients Undergoing In Vitro Fertilization (IVF)

Prospective, open, randomized, parallel, multicenter, two-arm trial to evaluate the efficacy and tolerability of a new progesterone formulation to be used for luteal support in IVF (Progesterone-IBSA) administered subcutaneously at a daily dose of 25 mg versus Progesterone tablets administered intravaginally at 100 mg twice daily for a total dose of 200 mg.

Study Overview

• Status: Completed
• Conditions: In Vitro Fertilization
• Intervention / Treatment: Drug: Progesterone; Drug: Progesterone

• Study Type: Interventional
• Enrollment (Actual): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Redondo Beach, California, United States, 90277
      • Reproductive Partners Medical Group, Inc.
    • San Jose, California, United States, 95124
      • Fertility Physicians of Northern California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
    • Thousand Oaks, California, United States, 91360
      • Fertility and Surgical Associates of California
  • Florida
    • Orlando, Florida, United States, 32804
      • Center for Reproductive Medicine
  • Idaho
    • Boise, Idaho, United States, 83702
      • Idaho Center for Reproductive Medicine
  • Texas
    • Bedford, Texas, United States, 76022
      • Center for Assisted Reproduction
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Reproductive Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient has given written informed consent;
• BMI < 30 kg/m2;
• Age 18 - 42 (upon starting COH);
• <3 prior ART cycles (IVF, ICSI and related procedures);
• Baseline (day 2-3 of cycling) FSH <15 IU/L and E2 <80 pg/mL;
• Normal uterine cavity as per recent hysterosalpingogram, sonohysterogram or hysteroscopic exam (i.e. no polyps or protruding submucosal fibroids);
• Patients must have at least three retrieved oocytes.

Exclusion Criteria:

• Intramural uterine fibroids that distort the uterine cavity or polyps >1 cm;
• Stage III or IV endometriosis (no endometriomas);
• Hydrosalpinges;
• History of past poor response to COH resulting in canceling ART;
• Use of thawed/donated oocytes;
• Use of thawed/donated embryos;
• Gestational carrier;
• Patients affected by pathologies associated with any contraindication of being pregnant;
• Hypersensitivity to study medication;
• Uncontrolled adrenal or thyroid dysfunction;
• History of conditions (i.e. toxic shock syndrome) that would contraindicate use of a vaginal progesterone product;
• History of arterial disease;
• Patients with hepatic impairment (liver function tests > 2x upper limits of normal);
• Patients with dermatologic disease;
• Patients with renal impairment (estimated creatinine clearance <60 mL/min/1.73 m2);
• Neoplasias (current) or history of neoplasia that may be responsive to progesterone;
• High grade cervical dysplasia;
• History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages, wherein pregnancy developed to a minimum of a gestational sac on TVUS;
• Participation in a concurrent clinical trial or in another trial within the past 2 months;
• Use of concomitant medications that might interfere with the study evaluation;
• Pre-implantation genetic diagnosis/screening

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: Progesterone SC	Drug: Progesterone; 25 mg, once a day, SC; Drug: Progesterone; 100 mg, twice a day, vaginally
Active Comparator: Progesterone Tablets	Drug: Progesterone; 25 mg, once a day, SC; Drug: Progesterone; 100 mg, twice a day, vaginally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ongoing Pregnancy Rate	10 weeks after treatment start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation Rate	Implantation rate was defined as the number of gestational sacs divided by the number of embryos transferred (%). This value was calculated for all the patients who had at least one embryo transferred.	4-5 weeks after treatment start
Delivery Rate		nearly 9 months after treatment start

Collaborators and Investigators

• Sponsor: IBSA Institut Biochimique SA

Publications and helpful links

General Publications

• Griesinger G, Trevisan S, Cometti B. Endometrial thickness on the day of embryo transfer is a poor predictor of IVF treatment outcome. Hum Reprod Open. 2018 Jan 29;2018(1):hox031. doi: 10.1093/hropen/hox031. eCollection 2018.
• Baker VL, Jones CA, Doody K, Foulk R, Yee B, Adamson GD, Cometti B, DeVane G, Hubert G, Trevisan S, Hoehler F, Jones C, Soules M. A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization. Hum Reprod. 2014 Oct 10;29(10):2212-20. doi: 10.1093/humrep/deu194. Epub 2014 Aug 6.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: January 22, 2009
• First Submitted That Met QC Criteria: January 22, 2009
• First Posted (Estimate): January 23, 2009

Study Record Updates

• Last Update Posted (Estimate): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 28, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Luteal support in IVF
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 07USA/Prg05