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

• ClinicalTrials.gov Identifier: NCT01590173
• Recruitment Status: Completed
• First Posted: May 2, 2012
• Last Update Posted: July 19, 2016
• Sponsor: National and Kapodistrian University of Athens
• Information provided by (Responsible Party): Siristatidis Charalampos, MD, PhD, National and Kapodistrian University of Athens

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Infertility	Drug: Prednisolone and Heparin during COH for IVF; Drug: COH for IVF	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Addition of Prednisolone and Heparin in Patients With Repeated Implantation Failures: a Prospective Clinical Study
• Study Start Date: January 2012
• Actual Primary Completion Date: July 2016
• Actual Study Completion Date: July 2016

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. clinical pregnancy rate [ Time Frame: finding of a fetal heart at >6 gestational weeks / 2 years ]

Secondary Outcome Measures :

1. miscarriage rate [ Time Frame: through study completion, an average of 2 years ]
2. live birth rate [ Time Frame: through study completion, an average of 2 years ]
3. biochemical pregnancy rate [ Time Frame: through study completion, an average of 2 years ]
4. OHSS [ Time Frame: through study completion, an average of 2 years ]
5. multiple pregnancy rate [ Time Frame: through study completion, an average of 2 years ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Greece

Assisted Reproduction Unit, 3rd Department of Obstetrics & Gynecology

Athens, Chaidari, Attica, Greece, 12642

Sponsors and Collaborators

National and Kapodistrian University of Athens

Investigators

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

More Information

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.

• Responsible Party: Siristatidis Charalampos, MD, PhD, Senior Lecturer, Director of the IVF Unit, National and Kapodistrian University of Athens
• ClinicalTrials.gov Identifier: NCT01590173
• Other Study ID Numbers: 123123
• First Posted: May 2, 2012
• Last Update Posted: July 19, 2016
• Last Verified: July 2016

Keywords provided by Siristatidis Charalampos, MD, PhD, National and Kapodistrian University of Athens:

Low molecular weight heparin; Prednisolone; Glucocorticoids; Recurrent implantation failure; Pregnancy rate

Additional relevant MeSH terms:

Infertility; Genital Diseases; Urogenital Diseases; Prednisolone; Heparin; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action