InfertilityNCT01668056
Synchronization of Ovarian Stimulation for in Vitro Fertilization With Follicular Wave Emergence
A study testing Ovulation induction with choriogonadotropin alfa and Aspiration of the dominant follicle in people with Infertility, run by University of Sao Paulo General Hospital at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Ovulation induction with choriogonadotropin alfa and Aspiration of the dominant follicle
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBrazil
- Study dates
- Jan 2012to Dec 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Paulo HM Bianchi, MD contact
Brazil1 site, 1 recruiting
- Recruiting
University of Sao Paulo General Hospital
São Paulo, São Paulo
Paulo HM Bianchi, MD, paulobianchi35@gmail.com
Paulo HM Bianchi, MD
About this study
Official title: The Role of Controlling Follicular Wave Emergence to Synchronize Ovarian Stimulation for in Vitro Fertilization
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).
- Conditions
- Infertility
- Being tested
- Ovulation induction with choriogonadotropin alfa, Aspiration of the dominant follicle, Control
- Keywords
- in vitro fertilization, ovarian stimulation, follicular waves, luteal phase
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ovulation induction with choriogonadotropin alfaDrug
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.
Aspiration of the dominant follicleProcedure or surgery
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.
ControlOther
Conventional flexible GnRH antagonist protocol of ovarian stimulation for in vitro fertilization, with gonadotropin star at the third day of a natural menstrual cycle.
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | 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. Receives: Other: Control |
| Ovulation induction | Experimental | 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. Receives: Drug: Ovulation induction with choriogonadotropin alfa |
| Dominant follicle aspiration | Experimental | 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. Receives: Procedure: Aspiration of the dominant follicle |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: One year
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
Measured: One year
Secondary outcomes (5)
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.
Measured: One year
Number of mature oocytes retrieved
Evaluate the number of metaphase II oocytes retrieved in each of the three groups
Measured: One year
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)
Measured: One year
Fertilization rate
Number of embryos formed in relation with the number of oocytes inseminated
Measured: One year
Pregnancy rate
Positive beta hCG determination on blood 10 days after embryo transfer
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2012 (estimated)
- Study startJan 2012
- Primary completionDec 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edmund c Baracat, PhD, Study chair, University of Sao Paulo Medical SchoolPaulo C Serafini, PhD, Study director, University of Sao Paulo Medical SchoolPaulo HM Bianchi, MD, Principal investigator, University of Sao Paulo Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01668056
- Sponsor's protocol ID
- 1099/09
- Status last verified
- Sep 2013
- First submitted
- 6 Aug 2012
- Last updated
- 10 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 12849812Baerwald 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.
PubMed 12748128Baerwald 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.
PubMed 22068695Adams 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.
PubMed 22626769de 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.
PubMed 20439948Bianchi 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.
PubMed 25701140
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Controlling Follicular Wave Emergence to Synchronize Ovarian Stimulation for in Vitro Fertilization
- ClinicalTrials.gov ID
- NCT01668056
- Acronym / sponsor ID
- 1099/09
- Conditions
- Infertility
- Keywords
- in vitro fertilization, ovarian stimulation, follicular waves, luteal phase
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 17 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Other: ControlPatients 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. |
| Ovulation induction | Experimental | Drug: Ovulation induction with choriogonadotropin alfaPatients 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. |
| Dominant follicle aspiration | Experimental | Procedure: Aspiration of the dominant folliclePatients 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ovulation induction with choriogonadotropin alfaAdministration 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. | Drug | Ovulation induction |
| Aspiration of the dominant follicleAspiration 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. | Procedure or surgery | Dominant follicle aspiration |
| ControlConventional flexible GnRH antagonist protocol of ovarian stimulation for in vitro fertilization, with gonadotropin star at the third day of a natural menstrual cycle. | Other | Control |
Primary outcome
Emergence of an ovarian follicular wave after dominant follicle aspiration or hCG administration
Time frame: 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
Time frame: 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
5 secondary outcomes
Estradiol and progesterone levels during ovarian stimulation
Time frame: One year
Number of mature oocytes retrieved
Time frame: One year
Total dose of gonadotrophins used
Time frame: One year
Fertilization rate
Time frame: One year
Pregnancy rate
Time frame: One year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2013.
- Background: PubMed 12849812Baerwald 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.
- Background: PubMed 12748128Baerwald 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.
- Background: PubMed 22068695Baerwald 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.
- Background: PubMed 22626769Adams 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.
- Background: PubMed 20439948de 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.
- Derived from this study: PubMed 25701140Bianchi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paulo HM Bianchi, MD contact
Edmund c Baracat, PhD study chair
University of Sao Paulo Medical School
Paulo C Serafini, PhD study director
University of Sao Paulo Medical School
Paulo HM Bianchi, MD principal investigator
University of Sao Paulo Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ovulation induction with choriogonadotropin alfa and Aspiration of the dominant follicle in people with Infertility, run by University of Sao Paulo General Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Paulo HM Bianchi, MD (paulobianchi35@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Emergence of an ovarian follicular wave after dominant follicle aspiration or hCG administration (time frame: One year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01668056, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2013.