Management of Ovarian Hyperstimulation Syndrome as a State of Defective Mineralocorticoid Response

Pathophysiology and Nature of Ovarian Hyperstimulation Syndrome (OHSS) as a Clinical Entity Could be Fully Explained and Effectively Managed as a State of Defective Mineralocorticoid Response

lines of evidence that support nature of ovarian hyperstimulation syndrome (OHSS) as "defective mineralocorticoid response" are cited, our hypothesis is tested clinically in both prophylaxis against and treatment of OHSS.

Study Overview

• Status: Completed
• Conditions: Ovarian Hyperstimulation Syndrome
• Intervention / Treatment: Drug: Bromocriptine; Drug: Fludrocortisone 0.1 Milligrams (mg)

Detailed Description

several studies state significant correlation between OHSS and activation of Renin-angiotensin-aldosterone system (RAAS), degree of activation of RAAS correlates with severity of OHSS. In OHSS there is a cascade of events that mainly involves capillary leak with resultant fluid shift and electrolytes imbalance, these consequences are more pronounced - according to our hypothesis - due to inadequate mineralocorticoid response/activity in susceptible individuals in the settings of high progesterone levels with its antimineralocorticoid property, OHSS can be interpreted as a (mineralocorticoid deficiency crisis) and may effectively be treated as being so, so we conducted this study to test the hypothesis in both treatment and prevention of OHSS.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Maadi
    • Cairo, Maadi, Egypt, 11728
      • Ganin Fertility Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria: patients undergoing ICSI who were considered at risk of developing OHSS:

• polycystic ovaries and/or previous history of OHSS, AMH > 40 pmol/L but patients were finally included in the study if serum E2 levels reached >3000 pg/ml on day of hCG trigger or at any stage of folliculometry
• age: 18-40

Exclusion Criteria:

• retrieval of less than 20 oocytes
• age less than 18 or above 40

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control group; patients at high risk for OHSS who are receiving conventional treatment either as a prophylaxis (in the form of bromocriptine) or as a management in case of developing OHSS (as continual bromocriptine and fluid monitoring and or paracentesis and or tube thoracostomy)	Drug: Bromocriptine; 2.5 mg prescribed Vaginally twice daily
Experimental: treatment group; patient who has developed OHSS while on conventional lines of management (as continual bromocriptine and fluid monitoring and or paracentesis and or tube thoracostomy) patients in this group, fludrocortisone was added to conventional lines of management.	Drug: Bromocriptine; 2.5 mg prescribed Vaginally twice daily; Drug: Fludrocortisone 0.1 Milligrams (mg); 0.2-0.6 mg/day of fludrocortisone is prescribed
Experimental: prevention group; patients at high risk for OHSS who are receiving fludrocortisone as a prophylaxis	Drug: Fludrocortisone 0.1 Milligrams (mg); 0.2-0.6 mg/day of fludrocortisone is prescribed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of recovery	Time needed for full clinical recovery	10 days
prevention of OHSS occurrence	percentage of cases that has developed OHSS in both control and prevention groups	21 days

Collaborators and Investigators

• Sponsor: Ganin Fertility Center
• Investigators: Principal Investigator: Muhammad S Zeafan, MBBCH, Ganin Fertility Center; Principal Investigator: khaled M Elqusi, BSc, Ganin Fertility Center; Principal Investigator: Hossam Elattar, MBBCH, Ganin Fertility Center; Study Director: Hosam Zaki, MSc, FRCOG, Ganin Fertility Center

Publications and helpful links

General Publications

• Navot D, Margalioth EJ, Laufer N, Birkenfeld A, Relou A, Rosler A, Schenker JG. Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome. Fertil Steril. 1987 Jul;48(1):57-61. doi: 10.1016/s0015-0282(16)59290-5.
• Delbaere A, Bergmann PJ, Englert Y. Features of the Renin-angiotensin system in ascites and pleural effusion during severe ovarian hyperstimulation syndrome. J Assist Reprod Genet. 1997 May;14(5):241-4. doi: 10.1007/BF02765823.
• Gomez-Sanchez E, Gomez-Sanchez CE. The multifaceted mineralocorticoid receptor. Compr Physiol. 2014 Jul;4(3):965-94. doi: 10.1002/cphy.c130044.
• Dunne FP, Barry DG, Ferriss JB, Grealy G, Murphy D. Changes in blood pressure during the normal menstrual cycle. Clin Sci (Lond). 1991 Oct;81(4):515-8. doi: 10.1042/cs0810515.
• Ujioka T, Matsuura K, Kawano T, Okamura H. Role of progesterone in capillary permeability in hyperstimulated rats. Hum Reprod. 1997 Aug;12(8):1629-34. doi: 10.1093/humrep/12.8.1629.
• Lainas T, Petsas G, Stavropoulou G, Alexopoulou E, Iliadis G, Minaretzis D. Administration of methylprednisolone to prevent severe ovarian hyperstimulation syndrome in patients undergoing in vitro fertilization. Fertil Steril. 2002 Sep;78(3):529-33. doi: 10.1016/s0015-0282(02)03290-9.
• Kim MK, Won HJ, Shim SH, Cha DH, Yoon TK. Spontaneous ovarian hyperstimulation syndrome following a thawed embryo transfer cycle. Clin Exp Reprod Med. 2014 Sep;41(3):140-5. doi: 10.5653/cerm.2014.41.3.140. Epub 2014 Sep 30.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): February 25, 2020
• Study Completion (Actual): February 29, 2020

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): April 17, 2020
• Last Update Submitted That Met QC Criteria: April 16, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: aldosterone; OHSS; Mineralocorticoid
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Syndrome; Ovarian Hyperstimulation Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Dopamine Agonists; Dopamine Agents; Hormone Antagonists; Antiparkinson Agents; Anti-Dyskinesia Agents; Fludrocortisone; Bromocriptine
• Other Study ID Numbers: MSM-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No