Dual Trigger for Elective Fertility Preservation
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 4

Summary: 
      The widespread availability of efficient contraception as well as women's increased education
      has led to childbearing postponement. Combined with the increased recognition of the concept
      of "ovarian aging", this has opened the Pandora´s box of EOC, which is currently considered a
      safe and cost-efficient approach among assisted reproduction techniques.

      Previous studies have shown that two main factors determine the CLBR after EOC: 1) patient's
      age at the time of oocyte banking, and 2) the number of oocytes retrieved. Therefore,
      measures aiming at increasing the oocyte yield, specially the number of mature oocytes
      retrieved, will maximize the success of this technique.

      In the last few years, the dual trigger for final oocyte maturation has emerged has an
      approach that seems to improve both oocyte yield and quality when compared to the hCG trigger
      alone. Nowadays, the standard of care in EOC patients is final oocyte maturation with a
      single bolus of GnRH-a. Understanding the impact of the dual trigger on the number of MII
      oocytes retrieved in patients undergoing EOC will improve the treatment protocols and allow
      for a better patient counselling.
    

Detailed description: 
      Elective oocyte cryopreservation (EOC) has been gaining increasing importance in the last few
      years, driven by the widespread information regarding the concept of 'age-related fertility
      decline', as well as the availability of efficient contraception and women's increasing
      educational and professional aspirations. Considering the similar clinical outcomes regarding
      live birth rate after vitrified-warmed and fresh oocytes and the proven cost-effectiveness of
      this approach, oocyte banking is now considered an efficient technique in assisted
      reproduction.

      Previous studies have shown that both patient's age and the number of oocytes retrieved have
      a significant impact on the cumulative live birth rate (CLBR) in patients undergoing EOC,
      highlighting the importance of maximizing oocyte yield in these patients.

      In all these former reports, final follicular maturation was triggered by one bolus of human
      chorionic gonadotropin (hCG) or, following recent trends in clinical practice, by a single
      bolus of Gonadotropin Releasing Hormone agonist (GnRH-a).

      More recently, the concomitant administration of both GnRH-a and a bolus of HCG prior to
      oocyte retrieval (dual trigger) has been proposed as a new strategy for final follicular
      maturation, aiming to improve oocyte and embryo quality . When compared to HCG trigger, the
      dual trigger adds the more physiologic follicular stimulating hormone (FSH) and luteinizing
      hormone (LH) peak provided by GnRH-a. With this approach, several studies have reported an
      increase in the number of MII oocytes retrieved, as well as in the number of good quality
      embryos and improved pregnancy outcomes in different subpopulations of infertile patients.

      Nowadays, the standard of care in patients undergoing a freeze-all approach, either for
      oocyte or embryo cryopreservation, is final follicular maturation with GnRH-a due to its more
      physiologic and shorter surge of both LH and FSH, terminating 24h after its onset, and
      reducing the risk of ovarian hyperstimulation syndrome (OHSS). So far, no study has compared
      the dual trigger approach to the use of a single bolus of GnRH-a. By adding HCG activity and,
      therefore, generating higher intracellular cyclic adenosine monophosphate (cAMP)
      accumulation, an amplification of the steroidogenic response of the pre-ovulatory follicle
      might be achieved with the dual trigger when compared to the GnRH-a trigger alone.

      Therefore, the investigators set out to perform this randomized controlled trial aiming to
      compare, for the first time, the dual trigger and the GnRH-a trigger regarding the number of
      MII oocytes retrieved in patients undergoing EOC.
    

Intervention name(s): Ovulation triggering with GnRH-a+rhCG; Ovulation triggering with GnRH-a
Intervention type(s): Drug; Drug
Intervention description(s): recombinant follicle stimulating hormone (rFSH) 225-300 IU (Gonal-F®/Puregon®/ Ovaleap®/Rekovelle®) Micronized progesterone 200mg (Utrogestan®) Ovulation trigger: Triptorelin 0.2 mg (Decapeptyl®) + Recombinant human chorionic gonadotropin (rhCG) 250μg (Ovitrelle®); rFSH 225-300 IU (Gonal-F®/Puregon®/Ovaleap®/ Rekovelle®) Micronized progesterone 200mg (Utrogestan®) Ovulation trigger: Triptorelin 0.2 mg (Decapeptyl®)
Intervention MeSH terms: Prolactin Release-Inhibiting Factors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment