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

Infertility Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02823080
• Other study ID #: Benha U
• Secondary ID: kmsalama
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: June 21, 2016
• Last updated: June 30, 2016
• Start date: October 2014
• Est. completion date: October 2016

Study information

• Verified date: June 2016
• Source: Benha University
• Contact: khalid M salama, MD
• Phone: 01225861026
• Email: dr.khalid_sleem[@]yahoo.com
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Higher Education
• Study type: Interventional

Clinical Trial 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

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 allowed to choose between embryo freezing alone (Control group) or to additionally receive 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: October 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 35 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Ovarian Hyperstimulation Syndrome

Intervention

Drug:
• Cetrorelix
study group received 3-day Cetrorelix Acetate 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 control (24 patients) did not receive Cetrorelix Acetate. Grading were re-evaluated on Day-3, 6 and 8.

Locations

Country	Name	City	State
Egypt	Benha university hospital?	Benha	El qalubia

Sponsors (1)

Lead Sponsor	Collaborator
Benha University

Country where clinical trial is conducted

Egypt, 

References & Publications (4)

Albano C, Smitz J, Camus M, Riethmüller-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. — View Citation

Lainas TG, Sfontouris IA, Zorzovilis IZ, Petsas GK, Lainas GT, Kolibianakis EM. Management of severe early ovarian hyperstimulation syndrome by re-initiation of GnRH antagonist. Reprod Biomed Online. 2007 Oct;15(4):408-12. — View 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. Review. Erratum in: Fertil Steril 1993 Jun;59(6):1334. — View Citation

Scott J, Huskisson EC. Graphic representation of pain. Pain. 1976 Jun;2(2):175-84. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	resolution of gastrointestinal manifestations determined prior to start of therapy	-severity grades of gastrointestinal manifestations determined at Day -3 and Day -6.	3-6 days	Yes
Primary	regression of elevated blood E2 levels	Serum E2 levels (Serum E2 level in picograms/ml) were evaluated daily.	8 days	Yes
Primary	change of maximal ovarian diameter (MOD)	MOD (maximal ovarian diameter in mm) were evaluated daily.	8 days	Yes
Secondary	resolution of pain determined prior to start of therapy	-pain VAS score determined daily up to Day 8.	8 days.	Yes
Secondary	diminution of laboratory manifestations determined prior to start of therapy	Ht value(%)	8 -14days.	Yes
Secondary	resolution of US manifestations determined prior to start of therapy	-US detected severity grades of ascites determined at Day -3 and Day -8.	3-8 days	Yes
Secondary	laboratory findings	TLC(x 1ooo cells/ml)	8 -14days.	Yes

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