Comparative Study Between Calcium Gluconate With Diosmin, Cabergoline and Cabergoline With Diosmin

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

Eligibility Criteria:
Inclusion Criteria:

* High risk patient for OHSS is defined as previous history of OHSS or \> 24 antral follicles of the ovaries on base line ultrasound (polycystic ovary)
* During ovarian stimulation-increased number of small follicles (8-12 mm)
* High AMH
* Rapidly rising serum E2
* High serum E2 at hCG trigger (\>3000 pg/ ml) or presence of \> 20 follicles on the day of retrieval, by ultrasound examination or \>20 oocytes retrieved

Exclusion Criteria:

* patients with endocrine disorder e.g diabetes mellitus, Cushing's disease, and congenital adrenal hyperplasia,
* Patients with hypertension,
* Patients systemic disease e.g asthma, collagen vascular disease, hypercholesterolemia and sickle cell anemia.