Addition of Prednisolone and Heparin in Patients Undergoing IVF With Failed IVF Cycles

Addition of Prednisolone and Heparin in Patients With Repeated Implantation Failures: a Prospective Clinical Study

The addition of heparin and prednisolone increases pregnancy outcome parameters in women undergoing In Vitro Fertilisation (IVF) with failed IVF cycles.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Prednisolone and Heparin during COH for IVF; Drug: COH for IVF

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Greece
  • Chaidari, Attica
    • Athens, Chaidari, Attica, Greece, 12642
      • Assisted Reproduction Unit, 3rd Department of Obstetrics & Gynecology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• personal history of ≥2 failed IVF/ICSI cycles
• age <45 years
• availability of fresh ejaculate sperm for IVF/ICSI procedures
• confirmation of normal uterine cavity
• presence of good quality (Grade I or II) embryos for transfer

Exclusion Criteria:

• endocrine disorders
• immune disorders
• coagulation disorders

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: Prednisolone and Heparin during COH for IVF	Drug: Prednisolone and Heparin during COH for IVF; Low Molecular Weight Heparin (LMWH) (Enoxaparin Sodium, Clexane, Sanofi-Aventis, Australia) at a dose of 1 mg/kg/day and 5 mg prednisolone p.os (Prezolon; Nycomed Hellas SA) were to be initiated on the first day of injections in both protocols until the pregnancy test. In cases of pregnancy, prednisolone and enoxaparin were to be continued up to the 12th and 34th week, respectively
Active Comparator: COH for IVF	Drug: COH for IVF; Both GnRH agonists (long, starting at day 2 or 21) with Triptorelin acetate 0.1 mg (Gonapetpyl daily; Ferring, Kiel, Germany) and antagonists' with ganirelix 0.25 mg (Orgalutran; Organon, Oss, The Netherlands) or cetrorelix 0.25 mg (Cetrotide; Serono, Rome, Italy) protocols will be used; for ovarian stimulation both recombinant FSH (Puregon; Organon, Oss, Netherlands or Gonal F; Serono, Rome, Italy) and human menopausal gonadotrophin (Menopur; Ferring Pharmaceuticals, Langley, Berkshire, UK) will be used. Ovarian response will be monitored by ultrasonography, oocyte retrieval will be performed 36-38 hours after the hCG triggering and for luteal phase support 600 mg progesterone tablets (Utrogestan; Laboratoires Besins- Iscovesco, Paris, France) or gel 8% intravaginally (Vasclor; Verisfield Ltd, UK) will be applied.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
clinical pregnancy rate	finding of a fetal heart at >6 gestational weeks / 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
miscarriage rate	through study completion, an average of 2 years
live birth rate	through study completion, an average of 2 years
biochemical pregnancy rate	through study completion, an average of 2 years
OHSS	through study completion, an average of 2 years
multiple pregnancy rate	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Investigators: Principal Investigator: Charalampos Siristatidis, MD, PhD, National and Kapodistrian University of Athens

Publications and helpful links

General Publications

• Urman B, Ata B, Yakin K, Alatas C, Aksoy S, Mercan R, Balaban B. Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial. Hum Reprod. 2009 Jul;24(7):1640-7. doi: 10.1093/humrep/dep086. Epub 2009 Apr 8.
• Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005996. doi: 10.1002/14651858.CD005996.pub2.
• Nelson SM, Greer IA. The potential role of heparin in assisted conception. Hum Reprod Update. 2008 Nov-Dec;14(6):623-45. doi: 10.1093/humupd/dmn031. Epub 2008 Aug 12.
• Primi MP, Senn A, Montag M, Van der Ven H, Mandelbaum J, Veiga A, Barri P, Germond M. A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of an immunosuppressive/antibiotic treatment in different patient populations. Hum Reprod. 2004 Oct;19(10):2325-33. doi: 10.1093/humrep/deh430. Epub 2004 Jul 29.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: April 30, 2012
• First Submitted That Met QC Criteria: May 1, 2012
• First Posted (Estimate): May 2, 2012

Study Record Updates

• Last Update Posted (Estimate): July 19, 2016
• Last Update Submitted That Met QC Criteria: July 17, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Low molecular weight heparin; Prednisolone; Glucocorticoids; Pregnancy rate; Recurrent implantation failure
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anticoagulants; Prednisolone; Heparin
• Other Study ID Numbers: 123123