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Dual Trigger for Elective Fertility Preservation

Phase 4
Completed
Conditions
Infertility
Interventions
Drug: Ovulation triggering with GnRH-a+rhCG
Drug: Ovulation triggering with GnRH-a
Registration Number
NCT04992468
Lead Sponsor
Fundación Santiago Dexeus Font
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
136
Inclusion Criteria
  • Able and willing to sign the Patient Consent Form and adhere to study visitation schedule
  • antral follicle count (AFC) <20
  • Anti-Mullerian hormone (AMH) ≤3ng/ml (AMH result of up to one year will be valid)
  • Age >=18 and ≤40 years
  • BMI >18 and <30 kg/m2
Exclusion Criteria
  • Medically indicated fertility preservation
  • AFC ≥ 20
  • Polycystic ovarian syndrome (PCOS) according to the Rotterdam criteria
  • FSH ≥ 20
  • History of untreated autoimmune, endocrine or metabolic disorders
  • Contraindication for hormonal treatment
  • Recent history of severe disease requiring regular treatment (clinically significant concurrent medical condition that could compromise subject safety or interfered with the trial assessment).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
GnRH-a+rhCGOvulation triggering with GnRH-a+rhCGOvulation triggering with GnRH-a+rhCG
GnRH-aOvulation triggering with GnRH-aOvulation triggering with GnRH-a
Primary Outcome Measures
NameTimeMethod
Number of mature oocytes (MIIs) retrieved7 -20 days from initiation of ovarian stimulation
Secondary Outcome Measures
NameTimeMethod
Number of oocytes retrieved7 -20 days from initiation of ovarian stimulation
Change in Estradiol valuesDay 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Change in LH valuesDay 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Change in FSH valuesDay 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl
Ovarian hyperstimulation syndrome (OHSS) (percent)Until 15 days after the end of ovarian stimulation
Change in Progesterone valuesDay 1 of ovarian stimulation, Day of HCG/HCG+Decapeptyl administration and Day after HCG/HCG+Decapeptyl

Trial Locations

Locations (1)

Hospital Universitario Quiron Dexeus

🇪🇸

Barcelona, Spain

Hospital Universitario Quiron Dexeus
🇪🇸Barcelona, Spain

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