Clinical trial NCT02823080: Outcome of Cetrotide Therapy for Management of Women at High-risk of Ovarian Hyperstimulation Syndrome
Official title: Sequential E2 Levels Not Ovarian Maximal Diameter Estimates Were Correlated With Outcome of Cetrotide Therapy for Management of Women at High-risk of Ovarian Hyperstimulation Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Infertility
Lead sponsor: Benha University
Sponsor class: OTHER
First posted: 2016-07-06
Enrollment: 48
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate safety and efficacy of 3-day cetrotide therapy started on day of oocyte retrieval (Day-0) in women at high-risk for development of ovarian hyperstimulation syndrome (OHSS) after gonadotropin- releasing hormon agonist induction protocol.

Patients \& Methods: Forty-eight women fulfilling inclusion criteria underwent ultrasound scanning for maximal ovarian diameter (MOD) estimation and ascites grading. Patients underwent embryo freezing, but study group received 3-day Cetrotide sc injection (0.25 mg/day) started on Day-0. Serum E2, pain scores and MOD were checked daily. Hematocrit value (Ht%), total leucocytic count (TLC), gastrointestinal (GI) manifestations and ascites grading were re-evaluated on Day-3, 6 and 8

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. number of retrieved oocytes was ≥20
2. mean number of follicles with a diameter of \>16 mm was ≥18
3. serum E2 concentrations of ≥3500 pg/ml
4. ovarian diameter on the day of ovum retrieval of \>10 cm
5. presentation of evident symptoms of OHSS on the day of aspiration .

Exclusion Criteria:

1- Absence of one or more of the items of the inclusion criteria.

Primary outcomes:
measure: Daily Serum E2 Levels
timeFrame: 8 days
measure: Daily Maximal Ovarian Diameter
timeFrame: 8 days
Secondary outcomes:
measure: Daily Numerical Pain Visual Analogue Scale Score
timeFrame: 8 days.
measure: Daily Hematocrits Value
timeFrame: 0-8 days.
measure: Ultrasound Detected Severity Grades of Ascites From Days 0-8
timeFrame: 0-8 days
measure: Daily Total Leucocytic Count
timeFrame: 0 -8days.
Other outcomes:
measure: Resolution of Gastrointestinal Manifestations Determined Prior to Start of Therapy
timeFrame: 0-6 days
Locations:
city: Benha
country: Egypt
facility: Benha university hospitalا
state: El qalubia
Study officials:
affiliation: Benha University
name: khalid M salama, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Scott J, Huskisson EC. Graphic representation of pain. Pain. 1976 Jun;2(2):175-84. No abstract available.
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citation: Albano C, Smitz J, Camus M, Riethmuller-Winzen H, Van Steirteghem A, Devroey P. Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation. Fertil Steril. 1997 May;67(5):917-22. doi: 10.1016/s0015-0282(97)81407-0.
citation: Navot D, Bergh PA, Laufer N. Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil Steril. 1992 Aug;58(2):249-61. doi: 10.1016/s0015-0282(16)55188-7.
citation: Salama KM, Abo Ragab HM, El Sherbiny MF, Morsi AA, Souidan II. Sequential E2 levels not ovarian maximal diameter estimates were correlated with outcome of cetrotide therapy for management of women at high-risk of ovarian hyperstimulation syndrome: a randomized controlled study. BMC Womens Health. 2017 Nov 13;17(1):108. doi: 10.1186/s12905-017-0466-z.