Trial record 3 of 96 for:    Open Studies | "Fertilization in Vitro"

Synchronization of Ovarian Stimulation for in Vitro Fertilization With Follicular Wave Emergence

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by University of Sao Paulo General Hospital
Sponsor:
Information provided by (Responsible Party):
University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:
NCT01668056
First received: August 6, 2012
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

Ovarian stimulation is an important phase of in vitro fertilization (IVF) treatments. The harvest of a larger number of viable eggs per cycle compensate eventual laboratory difficulties and allow for the selection of embryos with higher implantation potential. In the current protocols, based on the most prevailing theory of ovarian follicular development, stimulation drugs are usually started on the second or third day after the beginning of menses. The follicular phase of the menstrual cycle is believed to be the only favorable moment for follicular development.

In the early 2000's a new model of human ovarian follicular development (follicular waves) has been proposed based on frequent transvaginal ultrasound observations between two ovulations. It has been shown that ovarian antral follicles develop in synchronous groups, two to three times in a cycle. In fact the follicular wave phenomenon has been initially described in the 80's on domestic animals, like the mare and the cow. Moreover, studies in these animals have shown that synchronizing the start of the ovarian stimulation drugs with the beginning of a follicular wave yields better results for assisted reproductive treatments. Consequently in ovarian stimulation protocols for animal assisted reproduction it is important to control the initiation of a follicular wave.

Current protocols of ovarian stimulation for IVF in women do not consider the start of a follicular wave to begin drug administration. Therefore the purpose of this study is to evaluate two methods to control the emergence of a follicular wave (ovulation induction and dominant follicle aspiration) and to investigate the effects of synchronizing ovarian stimulation for IVF with follicular wave emergence in women compared to one of the current stimulation protocols (flexible GnRH protocol).


Condition Intervention
Infertility
Drug: Ovulation induction with choriogonadotropin alfa
Procedure: Aspiration of the dominant follicle
Other: Control

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of Controlling Follicular Wave Emergence to Synchronize Ovarian Stimulation for in Vitro Fertilization

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo General Hospital:

Primary Outcome Measures:
  • Emergence of an ovarian follicular wave after dominant follicle aspiration or hCG administration [ Time Frame: One year ] [ Designated as safety issue: No ]

    Evaluate if the aspiration of the dominant follicle is able to induce a follicular wave to emerge.

    Evaluate if administration of hCG is able to induce ovulation of a dominant follicle larger than 16mm and to induce a follicular wave to emerge.

    A follicular wave emergence is defined as an increase in the number of ovarian follicles smaller than 10mm seen at the transvaginal ultrasound scan after the interventions


  • Follicular growth pattern on ultrasound scan [ Time Frame: One year ] [ Designated as safety issue: No ]
    Evaluate with periodic transvaginal ultrasound scan the size (mm), number and growth rate (mm/day) of ovarian follicles in each of the three groups


Secondary Outcome Measures:
  • Estradiol and progesterone levels during ovarian stimulation [ Time Frame: One year ] [ Designated as safety issue: No ]
    Evaluate blood levels of estradiol (pg/mL) and progesterone (ng/mL) during ovarian stimulation in each of the three groups at each visit to evaluate the progress of treatment.

  • Number of mature oocytes retrieved [ Time Frame: One year ] [ Designated as safety issue: No ]
    Evaluate the number of metaphase II oocytes retrieved in each of the three groups

  • Total dose of gonadotrophins used [ Time Frame: One year ] [ Designated as safety issue: No ]
    Total dose of gonadotrophins (in international units) necessary to stimulate the ovaries (from the first day of stimulation until the last dose of recombinant FSH administered before the oocyte retrieval)

  • Fertilization rate [ Time Frame: One year ] [ Designated as safety issue: No ]
    Number of embryos formed in relation with the number of oocytes inseminated

  • Pregnancy rate [ Time Frame: One year ] [ Designated as safety issue: No ]
    Positive beta hCG determination on blood 10 days after embryo transfer


Estimated Enrollment: 30
Study Start Date: January 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control
Patients will be stimulated according to the conventional flexible GnRH antagonist protocol for IVF. Alfa follitropin (150IU a day) will be started on the third day of the menstrual cycle. Treatment monitoring will be done with transvaginal ultrasound scans and serum determinations of estradiol and progesterone 5 days after the start of gonadotropins and every each day thereafter. Once the leading follicle reaches 13 mm in mean diameter 0,25mg of cetrorelix acetate will be administered daily. Once at least two follicles reach 18mm or more in mean diameter 250 micrograms of choriogonadotropin alfa will be administered and 36 hours latter patients will undergo follicle aspiration for IVF. Embryos will be cryopreserved (vitrification) on the third or fifth day of development. Two months after women will undergo uterine preparation for embryo transfer.
Other: Control
Conventional flexible GnRH antagonist protocol of ovarian stimulation for in vitro fertilization, with gonadotropin star at the third day of a natural menstrual cycle.
Experimental: Ovulation induction
Patients will be monitored with daily transvaginal ultrasound scans from the tenth day of the menstrual cycle on. When the dominant follicle reaches a mean diameter of 16mm or more, patients will receive 250 micrograms of choriogonadotropin alfa subcutaneously. Daily transvaginal ultrasound scans will be done starting two days after the administration of the medication until a cohort of ovarian follicles between 4-6 mm is seen (follicular wave emergence). From this point on patients will undergo the same stimulation protocol as Controls, i.e., flexible GnRH antagonist protocol.
Drug: Ovulation induction with choriogonadotropin alfa
Administration of 250 micrograms of choriogonadotropin alfa subcutaneously when the dominant follicle of a natural menstrual cycle reaches 16mm or more of mean diameter. Verify if this intervention is able to induce follicular wave emergence and synchronize the start of the flexible GnRH antagonist protocol of ovarian stimulation with the start of a follicular wave.
Experimental: Dominant follicle aspiration
Patients will be monitored with daily transvaginal ultrasound scans from the tenth day of the menstrual cycle on. When the dominant follicle reaches a mean diameter of 16mm or more, patients will then undergo aspiration of the dominant and all follicles greater than 10mm in mean diameter. aspiration will be transvaginal ultrasound guided and under sedation, as for oocyte retrieval. Oocytes eventually obtained at this first aspiration will not be used for IVF. Daily transvaginal ultrasound scans will be done starting the day after the follicular aspiration until a cohort of follicles between 4-6 mm is seen (follicular wave emergence). From this point on patients will undergo the same stimulation protocol as Controls, i.e., flexible GnRH antagonist protocol.
Procedure: Aspiration of the dominant follicle
Aspiration of all follicles greater than 10mm in mean diameter when the dominant follicle of a natural menstrual cycle reaches 16mm or more of mean diameter. Aspiration will be guided by transvaginal ultrasound. Verify if this intervention is able to induce follicular wave emergence and synchronize the start of the flexible GnRH antagonist protocol of ovarian stimulation with the start of a follicular wave.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age < 35 years old
  • body mass index: 19-30 kg/m2
  • tubal or male factor infertility with indication of in vitro fertilization
  • antral follicle count: 10-20
  • normal uterus in transvaginal ultrasound scan
  • FSH on the third day of the menstrual cycle below 12mUI/mL and estradiol below 80pg/mL
  • male partner with at least 5 million motile sperm and 1% normal strict morphology on semen analyses

Exclusion Criteria:

  • ovarian factor infertility
  • non identification of one or both ovaries in the transvaginal ultrasound scan
  • non treated endocrine disorders
  • smoking habit
  • endometriosis stage III -IV
  • severe male factor infertility (less than one million sperm per mL of semen)
  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: NCT01668056

Contacts
Contact: Paulo HM Bianchi, MD paulobianchi35@gmail.com

Locations
Brazil
University of Sao Paulo General Hospital Recruiting
Sao Paulo, Brazil
Contact: Paulo HM Bianchi, MD       paulobianchi35@gmail.com   
Principal Investigator: Paulo HM Bianchi, MD         
Sponsors and Collaborators
University of Sao Paulo General Hospital
Investigators
Study Chair: Edmund c Baracat, PhD University of Sao Paulo Medical School
Study Director: Paulo C Serafini, PhD University of Sao Paulo Medical School
Principal Investigator: Paulo HM Bianchi, MD University of Sao Paulo Medical School
  More Information

Publications:
Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT01668056     History of Changes
Other Study ID Numbers: 1099/09
Study First Received: August 6, 2012
Last Updated: September 9, 2013
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Sao Paulo General Hospital:
in vitro fertilization
ovarian stimulation
follicular waves
luteal phase

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Chorionic Gonadotropin
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 01, 2014