2015 Group Project 2

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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

<pubmed>12498425</pubmed>

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.[OHSS Wiki]

Causative Agents

--Z3374116 (talk) 23:39, 27 August 2015 (AEST) I've begun collating and writing information on word for now regarding this Subheading


<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 [OHSS Wiki]

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 [2]

PMID 23378404 [3]

Diagnosis

[1]Initially women with OHSS will present with abdominal bloating, as a result of fluid in the peritoneal cavity and an increase in ovary size. Whilst symptoms can occur as soon as 24 hours post hCG administration, they are usually seen in women 7-10 days post administration. 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 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. 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. [4]

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 [OHSS Wiki].

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 [OHSS Wiki].

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)

Blood clots in large vessels (most commonly the legs)

Kidney failure

Ovary twisting

Rupture of a cyst in an ovary

Breathing problems

Pregnancy loss from miscarriage or termination

Rarely, death

Treatment

Mild to Moderate OHSS Mild OHSS resolves on its own, However Moderate OHSS may include treatments such as:

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:

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 antagonist instead of hCG however its effects on pregnancy rates are questionable (see OHSS Wiki).

Prevention

<pubmed>26246873</pubmed>

--Z3372824 (talk) 09:09, 28 August 2015 (AEST) So this is quite a rough draft as im trying to get the ideas down. I'm thinking of changing the format of some subsections to bullet points. The risk factor section can arguably have a subheading of its own, but it is crucial in informing the subsequent prevention strategy to be undertaken.


The three key pathways by which the incidence of OHSS has been curtailed involve 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: Preexisting factors likely to exacerbate the ovarian stimulation response. 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 markers (AMH) are a newly developed predictive tool with a sensitivity of 90.5% and specificity of 81.3%. Ultrasonographic markers including antral follicle count PMID 26074966

Secondary:


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: a) Reduce hCG dose

b) Coasting

c) Cryopreservation of Embryos

d) Cancel Cycle

e) Use alternative Agents

PMID 20416867

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. <pubmed>24996451</pubmed>
  3. <pubmed>23378404</pubmed>
  4. <pubmed>22416285</pubmed>