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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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 groups in NCT02641808
Study groupRoleWhat they receive
follicular flushing groupExperimentalMonofollicular 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 groupActive comparatorMonofollicular 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.

  1. Proportion of mature oocytes retrieved

    Measured: day of intervention

Secondary outcomes (7)
  1. Number of flushings necessary to retrieve the oocyte (intervention arm only)

    Measured: day of intervention

  2. Fertilisation rate

    Measured: one day after intervention

  3. Embryo quality (BLEFCO and ASEBIR score) on day 2 after fertilisation

    Measured: two days after intervention

  4. Transfer rate

    Measured: 2-3 days after intervention

  5. Pregnancy rate

    Measured: up to 9 months after the intervention

  6. Pain during intervention measured on a VAS scale

    Measured: day of intervention

  7. 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.

  1. First posted29 Dec 2015 (estimated)
  2. Study start1 Aug 2016
  3. Primary completion17 Jul 2020
  4. Study completion17 Jul 2020

Resources

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)
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

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.

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