Ovarian hyperstimulation syndrome

The term of the ovarian hyperstimulation syndrome ( OHSS) is defined as a disease that can occur in rare cases in ovulation induction in the course of in vitro fertilization. The clinical picture is very different depending on the severity: while around 30 % of all women undergoing in vitro fertilization ( IVF) undergo a mild form of OHSS occurs is the severe form of OHSS ( sOHSS ) only 0, 5-5 % of all IVF patients. The syndrome is caused by the extrinsic supply of hormones ( gonadotropins ), which stimulate the ovarian follicles, or to bring about ovulation.

Classification

There are several ways to classify the OHSS. Here those variants are presented, which are common in the art at the furthest.

Classification according to Golan

The classification according to Golan divides the OHSS in three different degrees of severity, which orients itself to the symptomatology

• Grade 1:

• Grade 2:

• Grade 3:

• Grade 4:

• Grade 5:

Classification by Navot

The division by Navot is mainly used to delineate the severe form of OHSS ( sOHSS ) of the life-threatening

Classification according to Rizk and Aboulghar

This classification differs from the previous schemes in some aspects. Thus, the mild form of OHSS was omitted because it occurs in many patients during the stimulation phase and requires no special treatment. When sOHSS (A, B and C) is divided into three different types.

• A:

Dyspnea, oliguria, nausea, vomiting, diarrhea, abdominal pain, clinical evidence of ascites, noticeable tension of the abdomen and hydrothorax, ultrasound shows enlarged ovaries and significant ascites, normal biochemical profile

• B:

Grade A plus massive Spannungsaszites, very greatly enlarged ovaries, severe dyspnea, and oliguria, elevated hematocrit, serum creatinine is ascended and liver dysfunction

• C:

Complications such as ARDS, kidney failure, or venous thrombosis

Risk Factors

A correlation between the occurrence of OHSS and age has been shown in various studies. It affects mostly women before the age of 35. As a possible explanation for this is true, the fact that the ovaries of young women have a higher density of gonadotropin receptors and therefore more responsive to a force acting from outside the administration of gonadotropins. Another explanation for the increased incidence of OHSS in young women provides the fact that this group, in contrast to older women, even over a greater number of ovarian follicles capable of fertilization have to be a good ovarian reserve.

It is under discussion whether a low body weight ( body mass index less than 20 ) is also considered a risk factor. Thus, one from the outside additional hormones, as is the case in an IVF cycle, women with low body weight have a large ovarian potential because many follicles are present in their ovaries who never jumped and possibly the hormone administration over-reacting, so develop OHSS.

The presence of polycystic ovary syndrome (PCO) likewise has a negative effect on the occurrence of OHSS. With up to 63 % of affected of severe OHSS women polycystic ovaries can be diagnosed.

In addition, OHSS occurs far more often in women who have the following clinical or sonographic parameters:

• Rapidly rising estradiol levels
• Large and numerous follicles
• HCG stimulation in the luteal phase
• In IVF treatment been incurred pregnancy
• Stimulation protocols using GnRH agonists

Pathophysiology

The pathophysiology of the syndrome is largely unknown. The clinical implications are, however, mainly attributed to the increased capillary permeability. This causes a shift of intravascular fluid into the extracellular space (ECR ). The decrease in intravascular volume leads to an increase of albumin in the blood and related increased blood viscosity (hematocrit > 45 % at sOHSS, > 55% of life-threatening OHSS). It results from an increased risk of thrombosis as well as decreased blood flow to the kidneys, which may lead to a decrease in urine production and, ultimately, kidney failure.

The increase in the ECR enriched proteins just there oncotic pressure, it forms ascites, possibly also a effusion in the pleura or the pericardium, an imbalance of electrolytes and in the most serious cases, a hydrothorax. As already mentioned above, it may also occur Spannungsaszites that accompanies usually with kidney failure in cases of life-threatening OHSS.

The possible involvement of the ovarian renin -angiotensin system in the pathophysiology of OHSS is also often the subject of discussion and is explained as follows: In the theca cells of the ovarian prorenin and renin is synthesized free. HMG and hCG lead to renin activity in the follicular fluid and stimulate the ovarian Proreninproduktion. In the follicular fluid of women undergoing controlled ovarian hyperstimulation, is also still find the angiotensin -converting enzyme (ACE ), angiotensin I and angiotensin II The latter has the ability to regulate the vascular wall permeability. Studies have shown a correlation between the concentration of free renin in the serum and the severity of OHSS. Furthermore, a reduction of OHSS symptoms by an ACE - blockade has been shown in a model of rabbit; Nevertheless, it can be explained with the locking action of the ovarian renin -angiotensin system, not all the pathophysiology of hyperstimulation syndrome.

Also, cytokines, prostaglandins, histamine, and the vascular endothelial growth factor ( VEGF) have been investigated for their potential role as mediators in the development of OHSS. The most important role in the pathophysiology of OHSS was attributed by all studied regulators of the VEGF in several studies. VEGF is not only correlated with the occurrence of OHSS, but even directly with the degree of disease. He has the ability to increase the permeability of endothelial cells, resulting in a fluid shift from the intravascular space results in the ECR.

Prevention

The ovarian hyperstimulation syndrome occurs after ovulation or puncture and is not causal but to treat only a symptom- oriented. The ability to prevent OHSS is therefore given only in the stimulation phase. Thus, it is important to recognize in particular the risk factors in order to possibly put preventive measures. In high-risk patients should be started with low doses of hMG and only minor increases in doses.

If an estradiol value above 3000 pg / ml measured, you can try by so-called Coasting to save the cycle before the demolition, the follicles should have already reached a diameter of 15 to 18 mm. When coasting, the stimulation is suspended and waiting under a continuing down-regulation until the estradiol level drops below 3000 pg / ml.

Therapy

Mild forms of OHSS can usually be treated on an outpatient basis:

Moderate up to life-threatening form of OHSS need to be hospitalized: