Ovarian hyperstimulation syndrome
| Classification according to ICD-10 | |
|---|---|
| N98.1 | Hyperstimulation of the ovaries |
| ICD-10 online (WHO version 2019) | |
The term ovarian hyperstimulation syndrome (OHSS) is understood to be a clinical picture that can occur in rare cases during ovulation induction during artificial insemination . The clinical picture varies greatly depending on the severity: while around 30% of all women who undergo in vitro fertilization (IVF) experience a mild form of OHSS, the severe form of OHSS (sOHSS) only affects 0, 5–5% of all IVF patients. The syndrome is caused by the external supply of hormones ( gonadotropins ), which stimulate the ovarian follicles or are supposed to induce ovulation .
classification
There are several ways to classify the OHSS. The variants that are most widespread among experts are described here.
Golan classification
The classification according to Golan divides the OHSS into three different degrees of severity, which are based on the symptoms
| Degree | Symptoms |
|---|---|
| Mild |
|
| Moderate |
|
| Heavy |
|
The classification according to Navot is mainly used to distinguish the severe form of OHSS (sOHSS) from the life-threatening
| parameter | heavy OHSS | life threatening OHSS |
|---|---|---|
| Diameter of the ovaries | variably enlarged | variably enlarged |
| Ascites | massive, with / without hydrothorax | Tension ascites, with / without hydrothorax |
| Hematocrit | 45-55% | > 55% |
| Total leukocyte count | 15,000 / mm³-35,000 / mm³ | > 35000 / mm³ |
| Creatinine | 90-140 mmol / l | > 140 mmol / l |
| Creatinine clearance | > 50 ml / min | <50 ml / min |
| Oliguria (urine <500 ml / d) | possibly available | available |
| Liver dysfunction | available | available |
| Anasarka | available | available |
| Kidney failure | No | Yes |
| thromboembolic events | No | Yes |
| acute respiratory distress syndrome (ARDS) | No | Yes |
Classification according to Rizk and Aboulghar
This classification differs from the earlier schemes in some respects. The mild form of OHSS was omitted, as it occurs in many patients during the stimulation phase and does not require any special therapy. The sOHSS is divided into three different types (A, B and C).
| shape | Symptoms |
|---|---|
| moderate shape | Malaise and mild pain, nausea, feeling of flatulence , ultrasound detection of ascites and enlarged ovaries, normal blood counts |
| severe form |
Shortness of breath, oliguria , nausea, vomiting, diarrhea, abdominal pain, clinical evidence of ascites, noticeable tension in the abdomen and hydrothorax, ultrasound shows enlarged ovaries and marked ascites, normal biochemical profile
Grade A plus massive tension ascites, markedly enlarged ovaries, severe dyspnea and oliguria, increased hematocrit , increased serum creatinine and liver dysfunction
Complications such as ARDS, kidney failure or venous thrombosis |
Risk factors
Various studies have shown a connection between the occurrence of OHSS and age. Most women are affected before the age of 35. As a possible explanation for the fact applies that the ovaries of young women have a higher density of gonadotropin - receptors , and accordingly stronger to a force acting from the outside administration of gonadotropins react. Another explanation for the increased occurrence of OHSS in young women is the fact that this group, in contrast to older women, still has a larger number of fertile ovarian follicles, which represent a good ovarian reserve.
It is under discussion whether a low body weight ( body mass index less than 20) is also a risk factor. So if you add additional hormones from the outside, as is the case with an IVF cycle , women with lower body weight have great ovarian potential, as there are many follicles in their ovaries that have never burst and then possibly on the Overreacting hormone administration, i.e. developing OHSS.
The presence of polycystic ovarian syndrome (PCO) also increases the likelihood of developing OHSS. Polycystic ovaries are diagnosed in up to 63% of women with severe OHSS.
In addition, OHSS is far more common in women who have the following clinical or sonographic parameters:
- High concentration of estradiol in the serum
- Rapidly rising levels of estradiol
- large and numerous follicles
- hCG stimulation in the luteal phase
- in the event of pregnancy resulting from IVF treatment
- , Stimulation protocols the GnRH agonist use
Pathophysiology
The pathophysiology of the syndrome is largely unknown. However, the clinical effects are mainly attributed to the increased capillary permeability. This causes a shift of the intravascular fluid into the extracellular space (ECR). The decrease in intravascular volume leads to an increase in albumin in the blood and the associated increased blood viscosity ( hematocrit > 45% in sOHSS,> 55% in life-threatening OHSS). This results in an increased risk of thrombosis and decreased blood flow to the kidneys, which can lead to a decrease in urine production and ultimately to kidney failure .
The proteins enriched in the EZR increase the oncotic pressure there, ascites, possibly also an effusion in the pleura or the pericardium , an imbalance of the electrolytes and, in particularly serious cases, a hydrothorax . As mentioned above, life-threatening OHSS can also lead to tension ascites, which is usually associated with kidney failure.
The possible involvement of the ovarian renin-angiotensin system in the pathophysiology of OHSS is also frequently the subject of discussion and is explained as follows: Prorenin and free renin are synthesized in the theca cells of the ovarian follicle . HMG and hCG induce renin activity in the follicular fluid and stimulate ovarian prorenin production. Angiotensin converting enzyme (ACE), angiotensin I and angiotensin II are also found in the follicular fluid of women undergoing controlled ovarian hyperstimulation . The latter has the ability to regulate the vessel wall permeability. Studies have shown a correlation between the concentration of free renin in serum and the severity of OHSS. Furthermore, in a rabbit model, an ACE blockade showed a reduction in OHSS symptoms; however, the mode of action of the ovarian renin-angiotensin system cannot conclusively explain the entire pathophysiology of hyperstimulation syndrome.
Also were cytokines , prostaglandins , histamine and the vascular endothelial growth factor (VEGF) been tested for their potential role as mediators in the development of OHSS. Of all the regulators examined, VEGF has already been assigned the most important role in the pathophysiology of OHSS in several studies. The VEGF correlates not only with the occurrence of OHSS, but even directly with the degree of the disease. It has the ability to increase the permeability of endothelial cells , which results in a shift of fluid from the intravascular space into the ECR.
Prevention
The ovarian hyperstimulation syndrome occurs after ovulation or puncture and should not be treated causally, but only symptom-oriented. The possibility of avoiding OHSS is therefore only given in the stimulation phase. It is therefore important to recognize the risk factors in order to be able to take preventive measures. In high-risk patients, low doses of hMG should be started and the doses should only be increased slightly.
If an estradiol value is measured above 3000 pg / ml, one can try to save the cycle from termination by so-called coasting, whereby the follicles should already have a diameter of 15 to 18 mm. During coasting, the stimulation is suspended and the downregulation is continued until the estradiol value falls below 3000 pg / ml.
therapy
Mild forms of OHSS can usually be treated on an outpatient basis:
- Blood draw and status
- Hydration (electrolyte drinks)
- Weight control
- no hCG as a lute support, but z. B. dydrogesterone or progesterone
- Transfer to the IVF clinic
Moderate to life-threatening form of OHSS must be treated as an inpatient:
- bed rest
- Weight control (possible ascites)
- Waist measurement
- daily fluid balance
- daily administration of low molecular weight heparin
- Medication for luteal phase support
- Infusion (daily)
- If the hematocrit is <40% furosemide
- For hematocrit> 41% furosemide
- With hematocrit> 46%: mannitol
- Puncture the abdominal cavity to drain the fluid
literature
- A. Golan, R. Ron-El, A. Herman, Z. Weinraub, Y. Soffer, E. Caspi: Ovarian hyperstimulation syndrome: an update syndrome. In: Obstet Gynecol Surv. 1989 Jun, 44 (6), pp. 430-440.
- D. Navot, PA Bergh, N. Laufer: Ovarian hyperstimulation syndrome in novel reproductive technologies: Prevention and treatment. In: Fertility and sterility. 1992 Aug, 58 (2), pp. 249-261.
- B. Rizk, M. Aboulghar: Classification, pathophysiology and management of ovarian hyperstimulation syndrome. In: P. Brinsden (Ed.): In-vitro fertilization and assisted reproduction . Parthenon Publishing, New York / London 1992, ISBN 1-85070-323-X .