The Role of Cetrotide Acetate in Prevention of Ovarian Hyperstimulation Syndrome (OHSS) in Oocyte Donors

Ovarian Hyperstimulation Syndrome Clinical Trial

Official title:

The Role of Cetrotide Acetate in Prevention of Ovarian Hyperstimulation Syndrome in Oocyte Donors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00867659
• Other study ID #: VCRM2
• Status: Completed
• Phase: N/A
• First received: March 21, 2009
• Last updated: March 26, 2013
• Start date: March 2009
• Est. completion date: October 2011

Study information

• Verified date: March 2013
• Source: Virginia Center for Reproductive Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 32 Years

Eligibility

Inclusion Criteria:

• Prospective donors with BMIs between 19 and 28,

• Those with normal FSH levels and good antral follicle counts between 19-28 years of age, AND

• Donors would have passed all the required testing as mandated by VCRM and the FDA.

Exclusion Criteria:

• Oocyte donors exceeding a BMI of > 28,

• Those with any communicable diseases,

• Those with low antral follicle counts and small ovarian volumes,

• Those with elevated FSH levels,

• Those with positive sickle cell screen or cystic fibrosis screening,

• Smokers, OR

• Donors who are unable or unwilling to follow the research protocols.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Ovarian Hyperstimulation Syndrome
• Syndrome

Intervention

Drug:
• Cetrotide acetate
cetrotide acetate is a GnRH antagonist. The dose is 3 mg once on the day of oocyte retrieval.

Locations

Country	Name	City	State
United States	Virginia Center for Reproductive Medicine	Reston	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Virginia Center for Reproductive Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Volume of Ascites in the Abdomen is Indicative of the Severity of OHSS	evaluate by ultrasound examination, physical examination and blood work the incidence of ovarian hyperstimulation syndrome in oocyte donors receiving a single injection of 3 mg Cetrotide Acetate.	4 weeks	No
Primary	Ovarian Volumes as a Predictor of OHSS Severity	ultrasound measurements of both ovaries	30 days	No