The Role of Cetrotide Acetate in Prevention of Ovarian Hyperstimulation Syndrome (OHSS) in Oocyte Donors
Condition: Ovarian Hyperstimulation Syndrome
MeSH terms: Ovarian Hyperstimulation Syndrome; Syndrome
Study type: Interventional

Summary: 
      This pilot study aims to address whether the prophylactic use of Cetrorelix Acetate after a
      long gonadotropin-releasing hormone (GnRH) agonist protocol post-hCG (human chorionic
      gonadotropin) administration can significantly reduce the incidence of OHSS in oocyte donors.
    

Detailed description: 
      With varying complications, OHSS is an iatrogenic condition cause by ovarian stimulation.
      Classified as mild, moderate, or severe, mild OHSS is relatively common as it occurs in up to
      1/3 of women undergoing ovarian stimulation. Symptoms include abdominal ascites, nausea,
      vomiting, increased abdominal girth and weight gain, with increasing ranges for mild to
      moderate. Severe OHSS occurs in 1% and includes hemodynamic instability, thrombosis,
      pulmonary difficulties, oliguria, and rarely death. Therefore, strategies to prevent or
      severely decrease the incidence of OHSS are sorely needed.

      More aggressive ovarian stimulation increases the risk of OHSS, but it is not easy to predict
      who or who will not develop OHSS. Certain patient types, however, are considered to be at a
      higher risk than others, including oocyte donors. OHSS in oocyte donors manifests early, i.e.
      within days of oocyte retrieval, yet does not have the continued complication of pregnancy as
      observed in IVF patients. Therefore, as a in this vulnerable patient population, oocyte
      donors are ideal to study.

      GnRH antagonists been most recently used in high risk patients undergoing IVF. Aside the
      reduction of OHSS observed after the traditional utilization of the antagonist protocol,
      alternative uses have also suggested favorable outcomes. Two retrospective, cohort matched
      studies evaluated a Ganirelix Acetate substitution in women who were at high risk for
      developing OHSS (E2 > 2,000 pg/ml on cycle day 6 or a projected peak E2 > 5,000 pg/ml with >
      25 follicles on the day of HCG administration) after being down-regulated using GnRHa (or
      using a microdose flare protocol) and undergoing ovarian stimulation The GnRHa was stopped
      and only a low dose of hMG was continued when Ganirelix Acetate was started. The Ganirelix
      Acetate use resulted in an average drop of 41-49.5% in peak E2 levels. While those two
      studies were provocative, they were retrospective and not controlled. In the only prospective
      study evaluating the use of Ganirelix Acetate in the prevention of OHSS compared to coasting,
      the "historic" gold standard, Ganirelix Acetate resulted in a 36% drop in E2 level after one
      injection and a 59% drop in peak E2 after 3 days of use (46.8% required only one injection,
      38.3% required two, and only 14.9% required 3 injections) as opposed to a 9% increase in E2
      level 24 hours after coasting. The use of Ganirelix acetate resulted in significant decrease
      in OHSS risk (2.1-2.3% in the two retrospective studies, and 0% in the only prospective study
      vs 9-38% in prior publications) without affecting the pregnancy outcome. The mean number of
      Ganirelix Acetate injections was 1.74 + 0.91. Although, Ganirelix Acetate appears to be
      successful in lowering the OHSS risk previous to hCG administration as suggested by these
      studies, this pilot study questions the effect after the ovulation induction is administered.
      To date, no such study has asked this question.

      All donors will be evaluated daily with hormonal levels (FSH, LH, E2, P, CBC, and
      comprehensive metabolic profile (which includes liver function tests) for at least 3 days
      after the oocyte retrieval. Daily weights and abdominal circumference will also be measured.
      All oocyte donors will also present for one last visit one week after oocyte retrieval. The
      incidence of OHSS will be the main outcome measured.
    

Intervention name(s): Cetrotide acetate
Intervention type(s): Drug
Intervention description(s): cetrotide acetate is a GnRH antagonist. The dose is 3 mg once on the day of oocyte retrieval.
Intervention MeSH terms: Cetrorelix
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: ovarian hyperstimulation syndrome; cetrotide acetate; GnRH antagonist; oocyte donors