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

Infertility Clinical Trial

Official title:

The Role of Controlling Follicular Wave Emergence to Synchronize Ovarian Stimulation for in Vitro Fertilization

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01668056
• Other study ID #: 1099/09
• Status: Recruiting
• Phase: N/A
• First received: August 6, 2012
• Last updated: September 9, 2013
• Start date: January 2012
• Est. completion date: December 2014

Study information

• Verified date: September 2013
• Source: University of Sao Paulo General Hospital
• Contact: Paulo HM Bianchi, MD
• Email: paulobianchi35[@]gmail.com
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility

Intervention

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.

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.

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.

Locations

Country	Name	City	State
Brazil	University of Sao Paulo General Hospital	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

References & Publications (5)

Adams GP, Singh J, Baerwald AR. Large animal models for the study of ovarian follicular dynamics in women. Theriogenology. 2012 Nov;78(8):1733-48. doi: 10.1016/j.theriogenology.2012.04.010. Epub 2012 May 22. — View Citation

Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. — View Citation

Baerwald AR, Adams GP, Pierson RA. Characterization of ovarian follicular wave dynamics in women. Biol Reprod. 2003 Sep;69(3):1023-31. Epub 2003 May 14. — View Citation

Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012 Jan-Feb;18(1):73-91. doi: 10.1093/humupd/dmr039. Epub 2011 Nov 8. Review. — View Citation

de Mello Bianchi PH, Serafini P, Monteiro da Rocha A, Assad Hassun P, Alves da Motta EL, Sampaio Baruselli P, Chada Baracat E. Review: follicular waves in the human ovary: a new physiological paradigm for novel ovarian stimulation protocols. Reprod Sci. 2010 Dec;17(12):1067-76. doi: 10.1177/1933719110366483. Epub 2010 May 3. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Emergence of an ovarian follicular wave after dominant follicle aspiration or hCG administration	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	One year	No
Primary	Follicular growth pattern on ultrasound scan	Evaluate with periodic transvaginal ultrasound scan the size (mm), number and growth rate (mm/day) of ovarian follicles in each of the three groups	One year	No
Secondary	Estradiol and progesterone levels during ovarian stimulation	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.	One year	No
Secondary	Number of mature oocytes retrieved	Evaluate the number of metaphase II oocytes retrieved in each of the three groups	One year	No
Secondary	Total dose of gonadotrophins used	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)	One year	No
Secondary	Fertilization rate	Number of embryos formed in relation with the number of oocytes inseminated	One year	No
Secondary	Pregnancy rate	Positive beta hCG determination on blood 10 days after embryo transfer	One year	No