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Mild OHSS often resolves on its own, however, moderate OHSS may include treatments such as:
Mild OHSS often resolves on its own, however, moderate OHSS may include treatments such as<ref name="WikiOHSS" />:


*Anti-nausea medication and prescription painkillers
*Anti-nausea medication and prescription painkillers
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Severe OHSS requires hospital care for monitoring levels and aggressive treatment such as intravenous fluids. Some medications may be given such as:
Severe OHSS requires hospital care for monitoring levels and aggressive treatment such as intravenous fluids. Some medications may be given such as<ref name="WikiOHSS" />:


*Cabergoline lessens OHSS symptoms
*Cabergoline lessens OHSS symptoms
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*Anticoagulant medications decrease the risk of blood clots in your legs
*Anticoagulant medications decrease the risk of blood clots in your legs


- If at risk OHSS, alternates include using a GnRH antagonist instead of hCG however its effects on pregnancy rates are questionable (see OHSS Wiki).
If at risk OHSS, alternates include using a GnRH agonist instead of hCG however its effects on pregnancy rates are questionable. Using a GnRH agonist to replace the use of hCG for final oocyte stimulation will see a 6% decrease in delivery rate.  


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Revision as of 12:33, 5 October 2015

2015 Student Projects 
2015 Projects: Three Person Embryos | Ovarian Hyper-stimulation Syndrome | Polycystic Ovarian Syndrome | Male Infertility | Oncofertility | Preimplantation Genetic Diagnosis | Students
2015 Group Project Topic - Assisted Reproductive Technology
This page is an undergraduate science embryology student and may contain inaccuracies in either description or acknowledgements.

Ovarian Hyper-stimulation Syndrome (OHSS)

Ovarian Hyper stimulation Syndrome (OHSS) is an iatrogenic complication of assisted reproduction technology, in which women take medications to stimulate oocyte growth. It is generally identified by cystic enlargements of the ovaries a fluid shift from the intravascular to the third space due to the increased capillary permeability and ovarian neoangiogenesis [1]. It is an occurrence which is dependent on the administration of the Human Chorionic Gonadotropin (hCG). This wikipage aims to provide clear information on the epidemiology, causatives of OHSS, symptoms as well as treatment and prevention methods.

Epidemiology

Ovarian Hyper-Stimulation Syndrome (OHSS) rarely occurs sporadically, and if it does, it is usually the result of an underlying genetic problem. The majority of OHSS is due to the ovaries being stimulated to mature and release an abundance of oocytes, in response to hormones Human Chorionic Gonadotropin (hCG) and Follicle Stimulating hormone (FSH), during IVF. Rarely, Clomifene Citrate therapy can cause OHSS.[2]

Severe OHSS only affects 0.5-5% of women undergoing Ovarian Hyper-stimulation, but despite its small prevalence, it is a potentially fatal outcome of a non-vital procedure and remains a prevalent problem for fertility specialists.[3] Age has been cited as a factor affecting those with OHSS, with younger women more at risk. Additionally, women with allergies were seen to have a higher incidence of OHSS. It is important to note that at this point in time, there is no positive correlation between gonadotropin dose and OHSS.

Causative Agents

Being done by user Z3374116

<pubmed>19573285</pubmed>

<pubmed>26190539</pubmed>

Symptoms

OHSS is classified based on a criteria from mild, moderate and severe:

Mild Symptoms- abdominal bloating, minimal weight gain, nausea, diarrhoea and a feeling of fullness.

Moderate Symptoms- Substantial weight gain (on average 2 or more pounds a day), increased abdominal girth, darkend urine and excessive thirst in addition to the mild symptoms.

Severe Symptoms- In addition to the symptoms associated with Mild and Moderate OHSS, in severe OHSS, you see shortness of breath, calf and chest pains and pleural effusion [2].

Classifications of Ovarian Hyper-stimulation Syndrome [1]

Classification Symptoms
Mild Grade 1 - Abdominal distention and discomfort

Grade 2 - Abdominal distention, discomfort with nausea, vomiting and/or diarrhea and ovarian enlargement from 5~12cm

Moderate Grade 3 - All features of Mild OHSS with ultrasonographic evidence of ascites
Severe Grade 4 - All features of Moderate OHSS with the addition of clinical evidence of ascites and breathing difficulties present

Grade 5 - All of the above symptoms along with a change in the blood volume, increased blood viscosity due to coagulation and diminished renal function


PMID 24996451 [4]

PMID 23378404 [5]

Diagnosis

Whilst symptoms of OHSS can occur as soon as 24 hours post hCG administration, they are usually seen in women 7-10 days post administration. Initially women with OHSS will present with abdominal bloating, as a result of fluid in the peritoneal cavity and an increase in ovary size. When women present with severe OHSS they are often dehydrated, due to increased vascular permeability, and have hemoconcentration. The above results in a decrease in intravascular volume, leading to oligouria.

A thorough history of the patient is taken during which the clinician looks for evidence of ovarian stimulation, followed by ovulation. During this history taking, the clinician will inquire into any weight gain notices, urine output, and the woman's ability to maintain oral hydration. A key diagnostic tool for clinicians regarding women who are taking gonadotropins is to identify if they are at an increased risk of developing OHSS. Some risk factors include woman aged less than 30, women who have polycystic ovaries, woman with a previous history of OHSS and women who have greater than 20 oocytes retrieved.

After a history of the patient is taken, the next step is to perform a physical exam on the patient. Women who present with abdominal bloating will produce a shifting dullness upon abdominal percussion. Additionally the clinical will test the woman's vital signs, measure her abdominal girth, weight and will look for evidence of ascites or increase in calf size (usually unilateral).

If the clinician further suspects a women of having OHSS, an ultrasound can be done.The intraperitoneal fluid is best imaged via vaginal ultrasound due to the enlarged ovaries making it difficult to image the pelvis using transabdominal ultrasound. The clinician can also order laboratory testing to look for urine specific gravity and hemoconcentration with a hematocrit.

Once a clinician has deduced a women is suffering from OHSS, the severity of their condition needs to be established as either mild, moderate or severe. This is done by referring to the criteria under the sub-heading Symptoms. The subsequent course of treatment for the woman will be based upon this evaluation. [6]

Pathophysiology

The definition of Ovarian Stimulation is enlarged ovaries with many luteinized cysts, that can present with secondary complications. What distinguishes Ovarian Stimulations from OHSS is the presence of vascular hyper-permeability that results in fluids being redirected elsewhere in the body.

The key process to OHSS appears to be caused by Vascular Endothelial Growth Factor (VEGF), that is released along with other cytokines, estrogen and progesterone due to the ovary undergoing luteinization as a result of stimulation by hCG. VEGF increases vascular permeability and as a result the capillaries become more "leaky" to the fluids in them. These fluids can then escape the capillaries and accumulate in the pleural and abdominal cavities as ascites. The women then becomes hypovolemic and is at an increased risk of circulatory, renal and respiratory issues such as arterial thromboembolism due to the thickening of the blood. Note, the blood is thickened as fluid is leaving the capillaries, leaving behind red blood cells and other cellular components of the blood [2].

Complications

Ovarian torsion or rupture, renal insufficiency and thrombophlebitis can all complicate OHSS. If a pregnancy occurs, symptoms may persist longer than the usual 1 to 2 weeks and become more severe, however, even with severe OHSS, they do not extend past the first trimester [2].

1-2% of women who suffer from ovarian stimulation develop a severe form of OHSS. Complications from severe OHSS include:

  • Fluid collection in the abdomen
  • Electrolyte disturbances (sodium and potassium)
  • Kidney failure
  • Ovary twisting
  • Rupture of a cyst in an ovary
  • Breathing problems
  • Blood clots in large vessels (most commonly the legs)
  • Pregnancy loss from miscarriage or termination
  • Rarely, death

Treatment

Mild to Moderate OHSS

Mild OHSS often resolves on its own, however, moderate OHSS may include treatments such as[2]:

  • Anti-nausea medication and prescription painkillers
  • Regular physical examinations and ultrasounds
  • Daily weigh-ins and waist measurements
  • Measuring the amount of urine produced each day
  • Blood tests for monitoring dehydration and electrolyte imbalance
  • Maintaining a high balance of fluids
  • Draining excess abdominal fluid by inserting a needle in the abdominal cavity
  • Wearing support stockings which help prevent blood clots

Severe OHSS

Severe OHSS requires hospital care for monitoring levels and aggressive treatment such as intravenous fluids. Some medications may be given such as[2]:

  • Cabergoline lessens OHSS symptoms
  • Gn-RH antagonist suppresses ovarian activity

If there are serious complications then additional treatments are required:

  • Surgery for a ruptured ovarian cyst
  • Intensive care for the liver or lung complications
  • Anticoagulant medications decrease the risk of blood clots in your legs

If at risk OHSS, alternates include using a GnRH agonist instead of hCG however its effects on pregnancy rates are questionable. Using a GnRH agonist to replace the use of hCG for final oocyte stimulation will see a 6% decrease in delivery rate.

Prevention

<pubmed>26246873</pubmed>

There are three key avenues through which the incidence of OHSS may be prevented. These include identifying risk factors to predict OHSS development, modifying treatment regimes on the basis of the identified risk factors and intervention to prevent progression to OHSS once the patient has undergone Controlled Ovarian Stimulation.

1) Risk factors

Primary risk factors include preexisting factors likely to exacerbate the ovarian stimulation response. They include young age, low body weight, history of elevated response to gonadotropins, Polycystic Ovary Syndrome (PCOS), isolated PCOS characteristic or a previous history of OHSS. Anti-Mullerian Hormone (AMH) markers are a valuable predictive tool to identify women with a high pretreatment basal AMH concentration and thus risk of OHSS, with a 90.5% sensitivity and 81.3% specificity. PMID 26074966

Secondary risk factors involve the monitoring of ovarian response parameters for a rapidly rising E2 level, large number of developing follicles on the day hCG is administered and a large number of oocytes retrieved, once COS has been initiated. These factors in combination, act as a predictive tool to assess severe OHSS development, with a 83% sensitivity and 84% specificity.


2) Prevention

Primary: a) Gonadotropins: reduce duration, reduce dose, avoid GnRH Agonists PMID 23873146

b) Use Metformin Therapy

c) Target Unifollicular Ovulation

d) Avoid hCG

e) In Vitro Maturation

Secondary Prevention aims to prevent progression to OHSS once COS has been initiated and the patient has been found to mount an exaggerated response.

a) Reduce hCG dose

b) Coasting: This first-line secondary preventative strategy consists of the withdrawal of gonadotrophins when a critical number of follicles and/or E2 concentration is reached. hCG is administered once the E2 concentration reduces to a safe level, before the process of oocyte retrieval commences. This preventative strategy is conducted for a period of less than 3 days.

c) Cryopreservation of Embryos: After oocyte retrieval, the embryos are cryopreserved and transferred in an unstimulated IVF cycle where the patient's response to hCG is normalised. This procedure has been found to produce better pregnancy rates with a 32% increase, than fresh embryo transfer.

d) Cancel Cycle: Conducted as a last resort strategy whereby hCG is withheld. This strategy carries the risk of significant psychological distress and financial loss for the patient.

e) Use alternative Agents

PMID 20416867

Genetics


Animal Models

Glossary

Ascites- An accumulation of fluid in the peritoneal cavity with resultant abdominal swelling

Cabergoline - A dopamine receptor agonist used to treat hormone imbalance.

GnRH antagonist - Gonadotropin Releasing Hormone - A class of compounds that are similar in terms of the structure of natural Gonadotropin Releasing Hormone but has a antagonistic effect.

hCG- Human Chorionic Gonadotropin

Hemoconcentration- An increase in the concentration of circulating red blood cells in response to a decrease in blood plasma volume

Hypovolemic- A decrease in circulating blood volume

Intravenous fluids - Is the infusion of liquid substances directly into a vein.

IVF- In-vitro Fertilization

OHSS= Ovarian Hyper-stimulation Syndrome

Oliguria- Decreased urine output/small amounts of urine produced

References

  1. 1.0 1.1 <pubmed>22065820</pubmed>
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Wikipaedia, [ https://en.wikipedia.org/wiki/Ovarian_hyperstimulation_syndrome ], 'Ovarian Hyperstimulation Syndrome?'
  3. 12498425</pubmed>
  4. <pubmed>24996451</pubmed>
  5. <pubmed>23378404</pubmed>
  6. <pubmed>22416285</pubmed>