Outcome of Cetrotide Therapy for Management of Women at High-risk of Ovarian Hyperstimulation Syndrome

The current study is conducted at Assisted Reproduction Unit at Almana general Hospital, kingdom of saudi arabia.and other private centers in Egypt. The study protocol was approved by the Local Ethical Committee. The study aimed to include women suspected to be at high risk for development of OHSS during agonist ovarian stimulation protocol.The study includes only women of couples singed written consent to participate in the study, to undergo embryo freezing and to postpone for transfer of cryopreserved embryo.

All patients are clinically evaluated for the presence of abdominal pain and if present will be graduated using a numerical pain visual analogue scale (VAS) with 0 means no pain and 10 means severe intolerable pain. Patients are evaluated for the presence of nausea and/or vomiting and sense of abdominal distension. Symptoms are scored using verbal analogue scale as nil, mild, moderate, and severe symptom. Blood samples are obtained under complete aseptic condition for estimation of serum E2 level and determination of hematocrit value (Ht%) and total leucocytic count (TLC).

Then, all patients underwent ultrasound scanning for estimation of ovarian measurements that were represented as the maximal ovarian diameter (MOD) and for ascites grading if present. Ultrasound scanning is performed using a 5 megahertz vaginal probe , otherwise a 3.5 megahertz, 2.6 megahertz or 5megahertz abdominal probe is used if visualization using a vaginal probe is compromised. Ascites is graded according to the quantity of fluid accumulation in the peritoneal cavity with the patient in the anti-Trendelenburg position.

Women fulfilling inclusion criteria were randomely allocated,using sealed envelops, into two equal groups. Group with embryo freezing alone (Control group) or while the other group additionally receives cetrotide subcutaneous injection in a daily dose of 0.25 mg started on day of oocyte retrieval for 3 days (Study group). Symptomatic treatment for associated symptoms as analgesics, antiemetics and antispasmodics are also prescribed. Patients are categorized according to classification grading of OHSS.

Class Clinical features Biochemical features

Mild - Abdominal distension/ discomfort

• Mild nausea/vomiting
• Diarrhea
• Ovarian size usually < 8 cm No clinically important laboratory findings

Moderate - Mild features plus

• US evidence of ascites - Elevated Ht (>41%)
• Elevated TLC >15,000/ ml
• Hypoproteinemia

Severe - Mild \& Moderate features plus

• Clinically detected ascites
• Severe abdominal pain
• Intractable nausea
• Rapid weight gain (>1 kg/24 hr)
• Pleural effusion
• Severe dyspnea
• Oliguria/anuria
• Low blood/central venous pressures
• Syncope
• Venous thrombosis
• Hemoconcentration (Ht >55%)
• TLC >25,000/ ml
• Serum creatinine >1.6 mg/dl
• creatinine clearance <50 ml/min
• Hyponatremia (Na+<135milliequivalent per litre)
• Hypokalemia (K+ < 5 milliequivalent per litre)
• Elevated liver enzymes

Critical - Severe features plus

• Anuria/ Acute renal failure
• Arrhythmia
• Pericardial effusion
• Massive hydrothorax
• Thrombo-embolism
• Arterial thrombosis
• (ARDS)Adult respiratory distress syndrome
• Sepsis - Worsening of biochemical findings seen with severe OHSS

US: Ultrasound; Ht%:Ht; Hematocrit value; TLC: Total leucocytic count: ARDS; adult respiratory distress syndrome.

All patients are managed as outpatients unless management of severe symptoms necessitated hospital admission. Pain scores, serum E2 levels and MOD are evaluated daily. Patients are evaluated for associated symptoms previously determined during clinical evaluation, ascites grading and TLC and Ht value were evaluated at 3 and 6 days and on end of the trial on the 8th day after oocyte retrieval.