Infertility
Conditions
Keywords
in vitro fertilization, ovarian stimulation, follicular waves, luteal phase
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).
Interventions
DRUGOvulation 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.
PROCEDUREAspiration 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.
OTHERControl
Conventional flexible GnRH antagonist protocol of ovarian stimulation for in vitro fertilization, with gonadotropin star at the third day of a natural menstrual cycle.
Sponsors
University of Sao Paulo General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Emergence of an ovarian follicular wave after dominant follicle aspiration or hCG administration | One year | 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 | One year | 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
| Measure | Time frame | Description |
|---|---|---|
| Total dose of gonadotrophins used | One year | 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) |
| Estradiol and progesterone levels during ovarian stimulation | One year | 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. |
| Pregnancy rate | One year | Positive beta hCG determination on blood 10 days after embryo transfer |
| Fertilization rate | One year | Number of embryos formed in relation with the number of oocytes inseminated |
| Number of mature oocytes retrieved | One year | Evaluate the number of metaphase II oocytes retrieved in each of the three groups |
Countries
Brazil
Contacts
Primary ContactPaulo HM Bianchi, MD
Outcome results
None listed