OHSS is an uncommon but serious side effect of assisted reproduction techniques. Learn why it occurs, what its symptoms are, and how it can be treated.

If you are about to embark on assisted reproductive therapy to stimulate ovarian follicle development and ovulation, awareness of potential side effects is important. Ovarian hyperstimulation syndrome (OHSS) is an uncommon side effect of these therapies, but it can be serious and even life-threatening if left untreated. Here, we explain what OHSS is, the causes, symptoms and treatment options.

What is OHSS?

OHSS is generally an uncommon condition characterized by ovarian enlargement, high concentration of sex steroids, such as estrogen (or a form of estrogen known as estradiol) and progesterone, and fluid buildup leaked from the blood vessels within and surrounding the ovary. OHSS predominantly occurs in response to hormonal treatment or fertility drugs given during assisted reproductive techniques (ART), such as in vivo or in vitro fertilisation (IVF), ovulation induction therapy or controlled ovarian stimulation.

What causes OHSS to occur?

Controlled ovarian stimulation involves using fertility medication to encourage the growth and maturation of multiple ovarian follicles to induce a successful ovulation or follicle extraction for egg (oocyte) harvesting.

There are different forms of drugs that are given, but most are injectable gonadotropins, which act on the pituitary gland in the brain, causing it to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones directly stimulate the ovarian follicle to grow and mature.

In addition to the gonadotropins, women may be given gonadotropin-releasing hormone (GnRH) agonists or antagonists, which control the premature release of LH from the pituitary gland and prevents early ovulation. The last step involves administering human chorionic gonadotropin (hCG) in a single dose after controlled ovarian stimulation, which mimics LH surge and encourages ovulation.

It is believed that the problem with OHSS occurs due to exposure to hCG, which causes the follicles to release substances that increase vascular permeability (the ability of blood vessels to allow fluid and molecules to pass through their walls). This increase in vascular permeability results in fluid leaking from the blood vessels into the surrounding cavity and tissue; specifically, the ovaries begin to swell due to the fluid buildup. The changes in fluid dynamics can affect the electrolytes (sodium, potassium) and proteins in the blood and can have knock-on effects on various bodily functions and cause a multitude of symptoms (see below section).

How frequently does it occur?

As the use of ART has increased in recent decades, so has the occurrence of OHSS, and techniques to detect it; thus, reporting of OHSS has risen in recent years. Studies suggest that moderate to severe OHSS occurs in between 1 and 5 percent of stimulated cycles, but it is difficult to give a precise number as a clinical diagnosis is lacking. Incidence for mild OHSS is difficult because it may go undetected and resolve itself.

Signs and symptoms of OHSS

OHSS is categorized into three severity categories—mild, moderate, and severe—and is either described as early or late depending on time to symptom onset after initiating hormone therapy. Symptoms for each severity category are as follows:

Mild OHSS:

  • Abdominal bloating and feeling full
  • Nausea
  • Diarrhea
  • Slight weight gain
  • Enlarged ovaries

Moderate OHSS (in addition to mild symptoms, you may experience the following):

  • Increased waistline
  • Vomiting
  • Diarrhea
  • Dark urine
  • Lack of urination
  • Feeling thirsty
  • Pain or discomfort in the region of the ovaries

Severe OHSS (includes the features of mild and moderate, plus):

  • Low blood pressure
  • Excessive and rapid weight gain (>1 kg in 24 hours)
  • A feeling of fullness but above the waistline, in the chest and upper body
  • Shortness of breath
  • Chest pains
  • Darker urine or a complete lack of urination
  • Low and severe abdominal pains
  • Venous thrombosis
  • Electrolyte imbalances (specifically, sodium and potassium)

Complications

Although cases are often mild to moderate and can resolve by themselves within 1 to 2 weeks (but persist longer if pregnancy occurs), severe OHSS can lead to complications, such as:

  • Ovarian torsion – due to swelling of the ovary and twisting from its usual position
  • Electrolyte imbalances
  • Rupture of ovarian cyst
  • Fluid buildup on the chest and in the abdomen
  • Breathing difficulties
  • Blood clots
  • Kidney disease
  • In extremely rare cases, death can occur
  • Increased risk of adverse pregnancy outcomes and low birthweight

Risk factors

Some women may be at an increased risk of developing OHSS. The following have been associated with an increased risk of OHSS:

How is OHSS diagnosed?

Doctors will monitor women undergoing controlled ovarian stimulation, especially in those with certain risk factors. To diagnose OHSS, the doctor will usually:

  • Physical examination: your doctor will ask you about any signs and symptoms (nausea, vomiting, diarrhea, pain, bloating etc.) you are experiencing, as well as take your waist measurements and weigh you. They will examine your lower abdomen for signs of swelling and tenderness.
  • Ultrasound imaging: your doctor will perform a transvaginal ultrasound to detect any fluid buildup in the ovaries and your abdomen. They will likely measure the size of the ovaries and, if visible, check the number and size of the ovarian follicles.
  • Blood test: your doctor will take a blood sample to measure the levels of various substances, such as electrolytes, proteins, hormones and blood cells. They will look for signs of hemoconcentration (increased blood concentration), hypoproteinemia (decreased blood protein levels), and hypercoagulability (increased blood clotting tendency). Kidney and liver function will also be checked.

Treatment

Treatment depends on the severity of OHSS and the duration of symptoms. Often, mild cases of OHSS resolve themselves once menstruation occurs. However, moderate to severe cases will need close monitoring and treatment, even more so if a pregnancy occurs. Treatment strategies involve:

  • Daily monitoring of your symptoms, waist measurements and weight
  • Regular blood tests to monitor improvements
  • Measuring the amount of urine passed daily
  • Draining the fluid (a form of paracentesis): this is often done under anaesthesia and involves a specialized needle being inserted into the abdomen or through the vagina to drain the fluid from the abdomen and ovaries. Ultrasound can be used to visualize the areas to be aspirated, limiting injury to the ovaries and surrounding tissue and organs.
  • For severe OHSS, you may be hospitalized to stabilize the condition, with hormones to suppress ovarian activity, anticoagulants to prevent blood clots, and surgery to treat ruptured ovary or torsion of the ovary.

Lifestyle and home remedies

If your symptoms are mild, your doctor may recommend the watch-and-wait method, in which you can monitor your weight, waist circumference and symptoms at home. It is important to let your doctor know you are experiencing these symptoms, so they can determine if they need to monitor and examine you.

Avoid strenuous activity, lifting and sex until the condition is resolved, as these could result in ovarian rupture or torsion.

Prevention

OHSS is one of the most serious complications of controlled ovarian stimulation, and knowing the signs and symptoms, as well as those women at risk of developing the syndrome, means that every attempt should be made to prevent the syndrome from occurring. If the condition does arise, its progression should be monitored, especially if it occurs along with pregnancy.

  • GnRH agonists: Several studies have looked at the type of stimulation protocol and its associated risks for OHSS. In general, using a different type of medication known as a gonadotropin-releasing hormone (GnRH) agonist instead of hCG in the final step to trigger the development of mature eggs, may reduce the risk of OHSS and should be considered in patients with risk factors for OHSS, such as women with PCOS.
  • Dopamine agonists: The increased vascular permeability seen in OHSS can trigger the release of various substances that can be toxic to the body and cause excessive inflammation. Studies have shown that dopamine agonists (e.g. cabergoline) can act on a set of receptors that are affected by these released substances and prevent OHSS from developing, specifically in non-pregnant high-risk women.
  • Aspirin: to improve the problems arising from the increase in vascular permeability, daily aspirin from the start of IVF to oocyte retrieval or menstruation has been suggested to reduce the incidence of severe OHSS.
  • Metformin: specifically for women undergoing ovarian stimulation who have PCOS, metformin has been shown to decrease the risk of developing severe OHSS.

Takeaway

Although OHSS is uncommon, it can be serious if it does arise. If you are going through ART and have taken medication to stimulate the ovaries, then it is good to be aware of OHSS. If you start developing any of the symptoms mentioned, it is important to speak with your doctor to stop the therapy or change medication. Your doctor will advise you on the best approach for your situation.

Our compassionate team at Cada Fertility can advise you on this topic and guide you personally through your fertility treatment. Contact us to for a free consultation today.