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Ovarian hyperstimulation syndrome is a potentially fatal iatrogenic condition. This syndrome is characterized by a sudden increase of the vascular permeability which results in the development of a massive extravascular exudate in the peritoneal cavity, pleural, pericardium causing ascites, pleural and pericardial effusion.
Severe forms are also accompanied by electrolyte disturbances and cardiopulmonary, hepatic, renal, and hemoconcentration associated with increased thromboembolic risk.
This syndrome is avoidable by the judicious use of gonadotropins and careful monitoring of stimulation regimens.
Ovarian hyperstimulation syndrome is a potentially fatal iatrogenic condition.
The major step to prevent hyperstimulation syndrome is to determine high risk patients as presence of polycystic ovarian syndrome, younger women with greater ovarian responsiveness, use of super active GnRH agonists, development of multiple immature and intermediate follicle during treatment, exposure to LH/hCG and previous history of hyperstimulation syndrome.
In addition, many different preventive modalities have been attempted such as decreasing the dose of FSH, using minimal or mild stimulating protocol as GnRH antagonists, use of insulin sensitizing agent as metformin, reduction the use of all follicles, decreasing the dose of hCG and administration of drugs which decrease capillary permeability as cabergoline, calcium gluconate, albumin, letrozole, hydroxyethyl starch and glucocorticoids.
Several different drugs have been used for prevention of hyperstimulation syndromes.
These include albumin, hydroxyethyl starch, aspirin, calcium, cabergoline, letrozole, and glucocorticoids. However, there is insufficient evidence about the benefits of these drugs in preventing hyperstimulation syndrome. Dopamine agonists (cabergoline) and calcium gluconate infusion are the most widely used preventive drugs.
Although these drugs have comparable effectiveness in preventing hyperstimulation syndrome with fewer maternal side effects, calcium maybe associated with arrhythmia
Recently attention has been focused on the use of Diosmin as a potent venotonic agent that decrease vascular permeability by reducing the release of inflammatory mediator such as prostaglandin E2 and thromboxane.
A study found that the combined use of diosmin and cabergoline in high-risk women undergoing ART was competent in avoiding hyperstimulation syndrome than using cabergoline alone. Moreover, this combination does not affect pregnancy rate, miscarriage nor multiple pregnancy
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Active Comparator | About 60 women patients,in which took IV infusion of calcium gluconate (Calcionate 10ml of 10% calcium gluconate, Memphis) in 200ml saline within 30 minutes of ovum pickup and contained for the next 3 days in addition to diosmin 2 tablets (500mg) t.d.s for 2 weeks. |
|
| Group B | Active Comparator | About 60 women patients,in which took cabergoline (Dostinex 0.5 mg, Pfizer, Montreal, Canada) orally daily for 8 days after hCG triggering. |
|
| Group C | Active Comparator | About 60 women patients,in which took diosmin , 2 tablets (500mg) t.d.s for 2 weeks in addition to cabergoline 1 tablet 0.5 mg/day orally for 8 days starting at the day of hCG injection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Calcium Gluconate | Drug | to compare the effectiveness of calcium gluconate, cabergoline and diosmin in preventing ovarian hyperstimulation syndrome in high-risk patient undergoing ICSI procedure. |
| Measure | Description | Time Frame |
|---|---|---|
| the incidence rate of moderate to severe OHSS. | OHSS is mainly characterized by abdominal distension, nausea, vomiting, diarrhea, hydrothorax, blood clotting disorders, and abnormal kidney function. Secondary outcomes included the clinical pregnancy rate, miscarriage rate, and live birth rate. | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hatem Sarhan, Professor | Professor of Pharmaceutics, Faculty of Pharmacy, Minia University. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Minia University, Faculty of Pharmacy | Minya | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41221041 | Derived | Abdallah AM, Hussien AK, Alarfaj SJ, Elmasry TA, Kamal M, Sarhan H, Mosbeh MH, Sadek EM. Comparative study between calcium gluconate with diosmin, cabergoline, and cabergoline with diosmin in prevention of ovarian hyperstimulation syndrome in high-risk women undergoing intracytoplasmic sperm injection (ICSI) procedures. Front Pharmacol. 2025 Oct 27;16:1655866. doi: 10.3389/fphar.2025.1655866. eCollection 2025. |
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| ID | Term |
|---|---|
| D016471 | Ovarian Hyperstimulation Syndrome |
| ID | Term |
|---|---|
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D002125 | Calcium Gluconate |
| D000077465 | Cabergoline |
| D004145 | Diosmin |
| ID | Term |
|---|---|
| D005942 | Gluconates |
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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|
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D009930 |
| Organic Chemicals |
| D006880 | Hydroxy Acids |
| D002241 | Carbohydrates |
| D004873 | Ergolines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047309 | Flavones |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006574 | Heterocyclic Compounds, 2-Ring |