InfertilityPhase 3FlushingNCT02641808
Does Follicular Flushing Improve the Outcome in Monofollicular IVF Therapy?
A Phase 3 study testing follicular flushing and no follicular flushing in people with Infertility, run by Insel Gruppe AG, University Hospital Bern.
Trial summary
Follicular aspiration as well as follicular flushing are standardized techniques and have been practiced in polyfollicular IVF (in vitro fertilization) therapy for years. Monofollicular IVF therapy is a standard technique as well. Read more about this study
- Who is it for?
- Ages 18 to 42 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility
- What is being tested?
- follicular flushing and no follicular flushing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2016to 17 Jul 2020
- Phase
- Phase 3
- 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 42 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Indication for in vitro Fertilisation
- Desire of natural cycle IVF and ICSI fertilisation
- Regular menstrual cycle, both ovaries can be reached for follicule aspiration
- 18-42 years
- size of the follicle ≥16mm
- max. 2 previous embryo transfers
Who cannot join
- <18 and >42 years
- Preterm ovulation
- >= 3 previous embryo transfers
About this study
Follicular aspiration as well as follicular flushing are standardized techniques and have been practiced in polyfollicular IVF (in vitro fertilization) therapy for years. Monofollicular IVF therapy is a standard technique as well. IVF can be done in natural cycles or with a minimal stimulation with clomifen citrate to achieve a monofollicular response. Our study aims to compare follicular aspiration and follicular flushing in monofollicular stimulation. First the investigators want to answer the question whether flushing is beneficial for the oocyte yield. In case of a positive result the investigators want to establish a recommendation about the optimal number of flushings taking into account the duration of the procedure and the pain during manipulation.
Read the detailed description
There is an increase in mono- and oligofollicular IVF therapies worldwide. With the increase in oligo- and monofollicular IVF techniques, a re-evaluation of the aspiration techniques is necessary. The lower the number of mature follicules, the higher the need to obtain the oocyte. The number of embryos obtained is dependent on the number of oocytes retrieved (Wood 2000).
Von Wolff et al. showed (2013) that, three flushings almost doubled not only the number of aspirated oocytes but also the transfer rate in monofollicular IVF. Oocytes, collected by flushing, were as mature and fertilizable as those aspirated without flushing. Mendez Lozano et al. performed an aspiration without flushing in 79 women and with triple flushing in 47 women. They were stimulated with HMG (human menopausal gonadotropin) and controlled with GnRH (Gonadotropin releasing hormone) antagonists in a semi natural cycle IVF. The percentage of patients with a good embryo was 28.8% in the group without flushing and 37.8% in the group with flushing; however, the difference was not significant. Women with an indication for an IVF therapy and the wish of natural cycle IVF are randomized to the intervention (flushing) or control arm (no flushing). In natural cycle IVF, there is no gonadotropin stimulation. Clomifen citrate (25mg e.g. Serophene®, Merck Serono, from the 6th day of cycle) or singles doses of GnRH-antagonists (e.g. Orgalutran®, MSD, Merck Sharp \& Dohme AG) are only given to avoid premature ovulation. Once maturity of the follicle is achieved (follicle size ≥16mm), 5000IU urinary human chorionic gonadotropin (uHCG) is used to trigger ovulation. Oocyte pickup (OPU) is performed 36.5 (36-37) hours after ovulation induction. No anesthesia is used for this procedure. For the aspiration 19 gauge single lumen needles are used. After the aspiration the needle is removed and flushed. Depending on randomisation the follicle is not flushed (group A) or flushed adapted to follicule size (16mm 2ml, 18mm 3ml, and 20mm 4ml etc.) up to five times with (e.g.flushing media with heparin (SynVitro® Flush, Origio, Berlin, Germany). In case more than 1 follicle develops, only the largest follicle is analysed. The flushings are collected each in a separate collecting tube (group B). The analysis of the collected oocytes is performed in the IVF lab. The aspirated fluid is analyzed in the IVF lab by the independent biologist. Pain is monitored by VAS (visual analogue scale) score and time of intervention is measured. In the IVF lab the oocytes are fertilised by ICSI (intracytoplasmatic sperm injection) and the embryo transferred 2-3 days later.
- Conditions
- Infertility
- Being tested
- follicular flushing, no follicular flushing
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
follicular flushingOther
Depending on randomisation the follicle is not flushed (group A) or flushed adapted to follicule size (16mm 2ml, 18mm 3ml, and 20mm 4ml etc.) up to five times with (e.g.flushing media with heparin (SynVitro® Flush, Origio, Berlin, Germany). The flushings are collected each in a separate collecting tube (group B). The analysis of the collected oocytes is performed in the IVF lab.
no follicular flushingOther
| Study group | Role | What they receive |
|---|---|---|
| follicular flushing group | Experimental | Monofollicular IVF therapy with follicular flushing up to five times after aspiration of the follicule at the time to the oocyte pick-up Receives: Other: follicular flushing |
| aspiration group | Active comparator | Monofollicular IVF therapy with aspiration only at the time of the oozyte pick-up Receives: Other: no follicular flushing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of mature oocytes retrieved
Measured: day of intervention
Secondary outcomes (7)
Number of flushings necessary to retrieve the oocyte (intervention arm only)
Measured: day of intervention
Fertilisation rate
Measured: one day after intervention
Embryo quality (BLEFCO and ASEBIR score) on day 2 after fertilisation
Measured: two days after intervention
Transfer rate
Measured: 2-3 days after intervention
Pregnancy rate
Measured: up to 9 months after the intervention
Pain during intervention measured on a VAS scale
Measured: day of intervention
Time used for intervention
Measured: day of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study start1 Aug 2016
- Primary completion17 Jul 2020
- Study completion17 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bern
- Responsible party
- Principal investigator, Alexandra Kohl Schwartz, Insel Gruppe AG, University Hospital Bern
- Investigators
- Alexandra S Kohl Schwartz, MD, Principal investigator, Reproductive Endocrinologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02641808
- Sponsor's protocol ID
- 2015-00150
- Other IDs
- 2015
- Acronym
- Flushing
- Status last verified
- Jul 2020
- First submitted
- 12 Dec 2015
- Last updated
- 20 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Kohl Schwartz AS, Calzaferri I, Roumet M, Limacher A, Fink A, Wueest A, Weidlinger S, Mitter VR, Leeners B, Von Wolff M. Follicular flushing leads to higher oocyte yield in monofollicular IVF: a randomized controlled trial. Hum Reprod. 2020 Oct 1;35(10):2253-2261. doi: 10.1093/humrep/deaa165.
PubMed 32856073
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Follicular Flushing Improve the Outcome in Monofollicular IVF Therapy?
- ClinicalTrials.gov ID
- NCT02641808
- Acronym / sponsor ID
- Flushing / 2015-00150
- Conditions
- Infertility
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- University of Bern
- Study start
- 1 Aug 2016 (actual)
- Primary completion
- 17 Jul 2020 (actual)
- Study completion
- 17 Jul 2020 (actual)
- First posted
- 29 Dec 2015 (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.
Follicular aspiration as well as follicular flushing are standardized techniques and have been practiced in polyfollicular IVF (in vitro fertilization) therapy for years. Monofollicular IVF therapy is a standard technique as well. IVF can be done in natural cycles or with a minimal stimulation with clomifen citrate to achieve a monofollicular response. Our study aims to compare follicular aspiration and follicular flushing in monofollicular stimulation. First the investigators want to answer the question whether flushing is beneficial for the oocyte yield. In case of a positive result the investigators want to establish a recommendation about the optimal number of flushings taking into account the duration of the procedure and the pain during manipulation.
Detailed description
There is an increase in mono- and oligofollicular IVF therapies worldwide. With the increase in oligo- and monofollicular IVF techniques, a re-evaluation of the aspiration techniques is necessary. The lower the number of mature follicules, the higher the need to obtain the oocyte. The number of embryos obtained is dependent on the number of oocytes retrieved (Wood 2000).
Von Wolff et al. showed (2013) that, three flushings almost doubled not only the number of aspirated oocytes but also the transfer rate in monofollicular IVF. Oocytes, collected by flushing, were as mature and fertilizable as those aspirated without flushing. Mendez Lozano et al. performed an aspiration without flushing in 79 women and with triple flushing in 47 women. They were stimulated with HMG (human menopausal gonadotropin) and controlled with GnRH (Gonadotropin releasing hormone) antagonists in a semi natural cycle IVF. The percentage of patients with a good embryo was 28.8% in the group without flushing and 37.8% in the group with flushing; however, the difference was not significant. Women with an indication for an IVF therapy and the wish of natural cycle IVF are randomized to the intervention (flushing) or control arm (no flushing). In natural cycle IVF, there is no gonadotropin stimulation. Clomifen citrate (25mg e.g. Serophene®, Merck Serono, from the 6th day of cycle) or singles doses of GnRH-antagonists (e.g. Orgalutran®, MSD, Merck Sharp \& Dohme AG) are only given to avoid premature ovulation. Once maturity of the follicle is achieved (follicle size ≥16mm), 5000IU urinary human chorionic gonadotropin (uHCG) is used to trigger ovulation. Oocyte pickup (OPU) is performed 36.5 (36-37) hours after ovulation induction. No anesthesia is used for this procedure. For the aspiration 19 gauge single lumen needles are used. After the aspiration the needle is removed and flushed. Depending on randomisation the follicle is not flushed (group A) or flushed adapted to follicule size (16mm 2ml, 18mm 3ml, and 20mm 4ml etc.) up to five times with (e.g.flushing media with heparin (SynVitro® Flush, Origio, Berlin, Germany). In case more than 1 follicle develops, only the largest follicle is analysed. The flushings are collected each in a separate collecting tube (group B). The analysis of the collected oocytes is performed in the IVF lab. The aspirated fluid is analyzed in the IVF lab by the independent biologist. Pain is monitored by VAS (visual analogue scale) score and time of intervention is measured. In the IVF lab the oocytes are fertilised by ICSI (intracytoplasmatic sperm injection) and the embryo transferred 2-3 days later.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| follicular flushing group | Experimental | Other: follicular flushingMonofollicular IVF therapy with follicular flushing up to five times after aspiration of the follicule at the time to the oocyte pick-up |
| aspiration group | Active comparator | Other: no follicular flushingMonofollicular IVF therapy with aspiration only at the time of the oozyte pick-up |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Indication for in vitro Fertilisation
- Desire of natural cycle IVF and ICSI fertilisation
- Regular menstrual cycle, both ovaries can be reached for follicule aspiration
- 18-42 years
- size of the follicle ≥16mm
Key exclusion criteria (3 listed)
- <18 and >42 years
- Preterm ovulation
- >= 3 previous embryo transfers
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 |
|---|---|---|
| follicular flushingDepending on randomisation the follicle is not flushed (group A) or flushed adapted to follicule size (16mm 2ml, 18mm 3ml, and 20mm 4ml etc.) up to five times with (e.g.flushing media with heparin (SynVitro® Flush, Origio, Berlin, Germany). The flushings are collected each in a separate collecting tube (group B). The analysis of the collected oocytes is performed in the IVF lab. | Other | follicular flushing group |
| no follicular flushing | Other | aspiration group |
Primary outcome
Proportion of mature oocytes retrieved
Time frame: day of intervention
7 secondary outcomes
Number of flushings necessary to retrieve the oocyte (intervention arm only)
Time frame: day of intervention
Fertilisation rate
Time frame: one day after intervention
Embryo quality (BLEFCO and ASEBIR score) on day 2 after fertilisation
Time frame: two days after intervention
Transfer rate
Time frame: 2-3 days after intervention
Pregnancy rate
Time frame: up to 9 months after the intervention
Pain during intervention measured on a VAS scale
Time frame: day of intervention
Time used for intervention
Time frame: day of intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2020.
- Derived from this study: PubMed 32856073Kohl Schwartz AS, Calzaferri I, Roumet M, Limacher A, Fink A, Wueest A, Weidlinger S, Mitter VR, Leeners B, Von Wolff M. Follicular flushing leads to higher oocyte yield in monofollicular IVF: a randomized controlled trial. Hum Reprod. 2020 Oct 1;35(10):2253-2261. doi: 10.1093/humrep/deaa165.
- Individual participant dataSharing planned: No
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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.
Alexandra S Kohl Schwartz, MD principal investigator
Reproductive Endocrinologist
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing follicular flushing and no follicular flushing in people with Infertility, run by Insel Gruppe AG, University Hospital Bern.
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 6 inclusion and 3 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: finished, as of the sponsor's last update on 20 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of mature oocytes retrieved (time frame: day of intervention). 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 NCT02641808, which also lists 1 linked publication.
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 20 Jul 2020; AzTrials last refreshed its copy on 7 Nov 2026.