Clinical trial NCT01668056: Synchronization of Ovarian Stimulation for in Vitro Fertilization With Follicular Wave Emergence
Official title: The Role of Controlling Follicular Wave Emergence to Synchronize Ovarian Stimulation for in Vitro Fertilization
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infertility
Keywords: in vitro fertilization
ovarian stimulation
follicular waves
luteal phase
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2012-08-17
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility 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)

Primary outcomes:
measure: Emergence of an ovarian follicular wave after dominant follicle aspiration or hCG administration
timeFrame: One year
measure: Follicular growth pattern on ultrasound scan
timeFrame: One year
Secondary outcomes:
measure: Estradiol and progesterone levels during ovarian stimulation
timeFrame: One year
measure: Number of mature oocytes retrieved
timeFrame: One year
measure: Total dose of gonadotrophins used
timeFrame: One year
measure: Fertilization rate
timeFrame: One year
measure: Pregnancy rate
timeFrame: One year
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: University of Sao Paulo General Hospital
Study officials:
affiliation: University of Sao Paulo Medical School
name: Edmund c Baracat, PhD
role: STUDY_CHAIR
affiliation: University of Sao Paulo Medical School
name: Paulo C Serafini, PhD
role: STUDY_DIRECTOR
affiliation: University of Sao Paulo Medical School
name: Paulo HM Bianchi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1016/s0015-0282(03)00544-2.
citation: Baerwald AR, Adams GP, Pierson RA. Characterization of ovarian follicular wave dynamics in women. Biol Reprod. 2003 Sep;69(3):1023-31. doi: 10.1095/biolreprod.103.017772. Epub 2003 May 14.
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.
citation: 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.
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.
citation: Bianchi PH, Viera LM, Gouveia GR, Rocha AM, Baruselli PS, Baracat EC, Serafini PC. Study of two strategies to induce follicular wave emergence for assisted reproductive treatments (ART)-a preliminary trial. J Assist Reprod Genet. 2015 Apr;32(4):543-9. doi: 10.1007/s10815-015-0432-3. Epub 2015 Feb 21.