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

Ovarian Diseases Clinical Trial

— FOLLPRIM  

Official title:

Prospective Randomized Controlled Trial of Antral Follicle Priming Prior to IVF-ICSI in Previously Diagnosed Low Responders.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01310647
• Other study ID #: 2009-018009-26
• Secondary ID: 2009-018009-26
• Status: Completed
• Phase: Phase 2
• First received: March 7, 2011
• Last updated: February 27, 2014
• Start date: June 2011
• Est. completion date: February 2014

Study information

• Verified date: February 2014
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: February 2014
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 41 Years

Eligibility

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

Related Conditions & MeSH terms

• Ovarian Diseases

Intervention

Drug:
• Testosterone
Transdermal testosterone (20µg/kg/day)from day 24 of the previous cycle to day 2 of the ICSI cycle
• Estradiol
Transdermal estradiol (200µg/day)from day 20 of the previous cycle to day 3 of the ICSI cycle
• 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.

Locations

Country	Name	City	State
Spain	La Fe University Hospital. Department of Obstetrics and Gynecology	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Fábregues F, Peñarrubia J, Creus M, Manau D, Casals G, Carmona F, Balasch J. Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial. Hum Reprod. 2009 Feb;24(2):349-59. doi: 10.1093/humrep/den428. Epub 2008 Dec 3. — View Citation

Fanchin R, Salomon L, Castelo-Branco A, Olivennes F, Frydman N, Frydman R. Luteal estradiol pre-treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists. Hum Reprod. 2003 Dec;18(12):2698-703. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of MII oocytes retrieved		36h after GnRH analogue administration
Secondary	Total number of follicles punctured		36h after GnRH analogue administration
Secondary	Total number of oocytes retrieved		36h after GnRH analogue administration
Secondary	Total number of viable embryos		48h after follicular puncture
Secondary	Serum and Follicular hormonal levels (testosterone, androstenedione, estradiol)		36h after GnRH analogue administration
Secondary	Granulosa cells genetic expression profile		36h after GnRH analogue administration
Secondary	Implantation rate		15 days after embryo transfer
Secondary	Pregnancy rate		15 days after embryo transfer
Secondary	Clinical pregnancy rate		5 weeks after embryo transfer