Antral Follicle Priming Prior to ICSI (Intracytoplasmic Sperm Injection) in Previously Diagnosed Low Responders (FOLLPRIM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Instituto de Investigacion Sanitaria La Fe
ClinicalTrials.gov Identifier:
NCT01310647
First received: March 7, 2011
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

The aim of this study is to compare the effectiveness of testosterone,estradiol and a combined treatment with estrogens/progestagens prior to IVF-ICSI in previously diagnosed low responder patients.


Condition Intervention Phase
Ovarian Diseases
Drug: Testosterone
Drug: Estradiol
Drug: CombEq
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Randomized Controlled Trial of Antral Follicle Priming Prior to IVF-ICSI in Previously Diagnosed Low Responders.

Resource links provided by NLM:


Further study details as provided by Instituto de Investigacion Sanitaria La Fe:

Primary Outcome Measures:
  • Number of MII oocytes retrieved [ Time Frame: 36h after GnRH analogue administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total number of follicles punctured [ Time Frame: 36h after GnRH analogue administration ] [ Designated as safety issue: No ]
  • Total number of oocytes retrieved [ Time Frame: 36h after GnRH analogue administration ] [ Designated as safety issue: No ]
  • Total number of viable embryos [ Time Frame: 48h after follicular puncture ] [ Designated as safety issue: No ]
  • Serum and Follicular hormonal levels (testosterone, androstenedione, estradiol) [ Time Frame: 36h after GnRH analogue administration ] [ Designated as safety issue: No ]
  • Granulosa cells genetic expression profile [ Time Frame: 36h after GnRH analogue administration ] [ Designated as safety issue: No ]
  • Implantation rate [ Time Frame: 15 days after embryo transfer ] [ Designated as safety issue: No ]
  • Pregnancy rate [ Time Frame: 15 days after embryo transfer ] [ Designated as safety issue: No ]
  • Clinical pregnancy rate [ Time Frame: 5 weeks after embryo transfer ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: June 2011
Study Completion Date: February 2014
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Testosterone
Transdermal testosterone (20µg/day) from day 24 of the previous cycle until day 2 of the ICSI cycle
Drug: Testosterone
Transdermal testosterone (20µg/kg/day)from day 24 of the previous cycle to day 2 of the ICSI cycle
Other Name: Testopatch, Pierre Fabre Ibérica S.A.
Experimental: Estradiol
Transdermal estradiol (200µg/day)from day 20 of the previous cycle to day 3 of the ICSI cycle
Drug: Estradiol
Transdermal estradiol (200µg/day)from day 20 of the previous cycle to day 3 of the ICSI cycle
Other Name: Alcis 100, Chiesi España
Experimental: CombEq
  • (150µg Desogestrel + 30µg Ethinylestradiol)/day during the luteal phase of the two cycles prior to the ICSI
  • Estradiol valerate 4 mg/day during 10 days, starting the second day of the cycle prior to the ICSI cycle.
Drug: CombEq

(150µg Desogestrel + 30µg Ethinylestradiol)/day during the luteal phase of the two cycles prior to the ICSI.

Valerate estradiol 4mg/day during 10 days, starting the second day of the cycle prios to the ICSI cycle.

Other Names:
  • Microdiol, MERCK SHARP & DOHME
  • Meriestra 2mg, Novartis Farmacéutica, S.A.

Detailed Description:

During controlled ovarian hyperstimulation (COH), most of the early antral follicles are required to grow coordinately. Marked follicular size discrepancies during COH imply that an important number of follicles undergo unsatisfactory maturation. It has been proved that follicular priming with estradiol during the luteal phase of the cycle prior to COH or testosterone treatment during the early follicular phase of the COH cycle may increase the amount of oocytes and embryos retrieved. Nevertheless there are no prospective studies comparing such approaches. The present study consist of two phases:

The present study consists of two different phases:

  • Phase I: (Non randomized) Identification of confirmed low responder patients. Potential low responder patients will be subjected to an standardized ovarian hyperstimulation protocol
  • Phase II: (Randomized) those patients, once confirmed as low responders, will be offered the opportunity to enter the interventional part of the study, being randomized to three different treatment groups: estradiol, testosterone or combined progestagens and estrogens prior to the IVF-ICSI cycle. The previous cycle (phase I) will be used as a self-control for each patient.
  Eligibility

Ages Eligible for Study:   18 Years to 41 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Phase 1 (Non randomized. The patient must fit the first plus at least other 2 criteria)

    • Infertility requiring an IVF/ICSI treatment
    • Age ≥ 38 years
    • Basal FSH ≥ 10 mUI/ml (day 3 of the cycle)
    • Serum AMH ≤ 5 pmol/l
    • Antral follicular count ≤ 6 (day 3 of the cycle)
  2. Phase 2 (Randomized. The patient must fit at least one criterion regarding the day of GNRH analogue administration during the cycle performed in Phase 1)

    • Less than 4 follicles which mean diameter measuring more than 16mm
    • Serum estradiol levels ≤ 500 pg/ml
    • 4 MII or less than 4 MII oocytes retrieved

Exclusion Criteria:

  • Patients suffering of endometriosis
  • Patients having progesterone levels ≤ 4 ng/ml (day 21 of the cycle)
  • Patients having a partner affected by severe oligo/astheno/teratozoospermia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01310647

Locations
Spain
La Fe University Hospital. Department of Obstetrics and Gynecology
Valencia, Spain, 46026
Sponsors and Collaborators
Instituto de Investigacion Sanitaria La Fe
Investigators
Principal Investigator: César Díaz, M.D. La Fe University Hospital. Department of Obstetrics and Gynecology
Study Director: Antonio Pellicer, Professor La Fe University Hospital. Department of Obstetrics and Gynecology
Study Chair: Alicia Marzal, M.D. La Fe University Hospital. Department of Obstetrics and Gynecology
  More Information

Publications:
Responsible Party: Instituto de Investigacion Sanitaria La Fe
ClinicalTrials.gov Identifier: NCT01310647     History of Changes
Other Study ID Numbers: 2009-018009-26, 2009-018009-26
Study First Received: March 7, 2011
Last Updated: February 27, 2014
Health Authority: Spain: Spanish Agency of Medicines
European Union: European Medicines Agency

Keywords provided by Instituto de Investigacion Sanitaria La Fe:
estradiol
testosterone
combined oral contraceptive
low responders
ICSI

Additional relevant MeSH terms:
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Estradiol
Polyestradiol phosphate
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Estrogens
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on September 29, 2014