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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Fady I. Sharara, M.D, Virginia Center for Reproductive Medicine
ClinicalTrials.gov Identifier:
NCT00867659
First received: March 21, 2009
Last updated: March 26, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Ovarian Hyperstimulation Syndrome
Drug: Cetrotide acetate

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: The Role of Cetrotide Acetate in Prevention of Ovarian Hyperstimulation Syndrome in Oocyte Donors

Resource links provided by NLM:


Further study details as provided by Virginia Center for Reproductive Medicine:

Primary Outcome Measures:
  • Volume of Ascites in the Abdomen is Indicative of the Severity of OHSS [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Ovarian Volumes as a Predictor of OHSS Severity [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    ultrasound measurements of both ovaries


Enrollment: 20
Study Start Date: March 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetrotide acetate
oocyte donors will receive cetrotide acetate on the day of oocyte retrieval. The incidence of OHSS will be assessed.
Drug: Cetrotide acetate
cetrotide acetate is a GnRH antagonist. The dose is 3 mg once on the day of oocyte retrieval.

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.

  Eligibility

Ages Eligible for Study:   19 Years to 32 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00867659

Locations
United States, Virginia
Virginia Center for Reproductive Medicine
Reston, Virginia, United States, 20190
Sponsors and Collaborators
Virginia Center for Reproductive Medicine
Investigators
Principal Investigator: Fady I Sharara, M.D Virginia Center for Reproductive Medicine
  More Information

No publications provided

Responsible Party: Fady I. Sharara, M.D, Medical Director, Virginia Center for Reproductive Medicine
ClinicalTrials.gov Identifier: NCT00867659     History of Changes
Other Study ID Numbers: VCRM2
Study First Received: March 21, 2009
Results First Received: December 27, 2012
Last Updated: March 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Center for Reproductive Medicine:
ovarian hyperstimulation syndrome
cetrotide acetate
GnRH antagonist
oocyte donors

Additional relevant MeSH terms:
Ovarian Hyperstimulation Syndrome
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Cetrorelix
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 31, 2014