Does Follicular Flushing Improve the Outcome in Monofollicular IVF Therapy?
Condition: Infertility
MeSH terms: Infertility; Flushing
Study type: Interventional
Phase: Phase 3

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. 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.
    

Intervention name(s): follicular flushing; no follicular flushing
Intervention type(s): Other; Other
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment