Infertility treatment has become increasingly popular in recent years. As a result of new advances in this field, the success rate and safety of assisted ovulation is improving daily. The most common ways to treat infertility in women are injections of hormones to promote ovulation and assisted reproductive techniques like in vitro fertilisation (IVF) and intrauterine insemination.
There is no treatment without any risk. Like any other medical treatment, you may experience some side effects during infertility treatment. One such potentially life-threatening complication is ovarian hyperstimulation syndrome (OHSS).
You must be aware of the symptoms of OHSS if you are planning to seek medical treatments for infertility. Also, discuss your concerns with the doctor to reduce the risk of OHSS for safe and successful therapy.
What is ovarian hyperstimulation syndrome?
OHSS is a medical condition characterised by cystic enlargement of the ovaries. It occurs due to the complication of assisted reproductive technology (ART) and other fertility treatments done with human chorionic gonadotropin (hCG) or related medication.1,2
An exaggerated response by ovarian follicles to the gonadotropin leads to fluid leaking from blood vessels to the surrounding space. It can extend to the thoracic and peritoneal areas and affect organs such as the lungs, liver, and kidneys. A severe form of OHSS can be fatal and need immediate intervention.1,2
Causes of ovarian hyperstimulation syndrome
The exact cause of OHSS is unknown, but it is a known complication of assisted conception and medication. Exposure to hCG or similar hormones, like follicle-stimulating hormone (FSH), is thought to be the primary cause of OHSS.
Controlled ovarian stimulation (COS) produces numerous ovarian follicles and eggs that improve the chances of a successful pregnancy. However, some ovarian follicles express abnormal and exaggerated responses during assisted ovarian stimulation leading to OHSS.1,2 Such responses lead to overproduction of vascular endothelial growth factors, and inflammatory factors. These factors in turn cause ovarian follicle rupture, increase vascular permeability and leakage of fluid into the surrounding area. This massive body fluid shifts into the surrounding cavities causing oedema, ascites, hydrothorax and hydropericardium.1,2,3
Signs and symptoms of ovarian hyperstimulation syndrome
Clinical presentations of OHSS can vary, progressing from mild to severe. Mild to moderate symptoms may remain unnoticed or require outpatient management, whereas severe OHSS may be fatal.
- Abdominal pain
- Bloating of abdomen
- A rapid increase in weight
- Poor appetite
- Difficulty in breathing
- Pleural effusion - fluid built up in the layers of tissue that line the chest cavity and lungs
- Reduced urine output
- Haemorrhage from rupture of the ovary
- Thromboembolism and blood clots in internal organs
Management and treatment for ovarian hyperstimulation syndrome
There are different approaches to managing OHSS depending on the results from physical examinations, imaging and laboratory investigation, and the degree of ovarian hyperstimulation.
Mild OHSS: It is self-limiting and requires supportive care. It can progress to moderate or severe OHSS. Therefore, constant monitoring for at least 2 weeks is advised.1,5
Moderate OHSS: It also needs regular monitoring and supportive care comprising bed rest and adequate hydration. The doctor will recommend laboratory tests to check the hormone and electrolyte status and ultrasound imaging to determine ovarian cyst size.1,5
Severe OHSS: Women with OHSS are hospitalised and treated according to the severity of the symptoms and to reduce the complications associated with OHSS. It includes: 1,5,6
- Intravenous fluid for correction of body fluid and electrolyte replacement
- Anticoagulant therapy for patients with a risk of thromboembolism
- Relieving of ascites and effusion by paracentesis
- Pharmacological treatment for vomiting and pain
- Antibiotic treatment for patients undergoing catheterisations, venipunctures, or body fluid tapping
- Surgical treatment for ruptured ovarian cyst, ovarian torsion, or ectopic pregnancy
- Termination of pregnancy in critical circumstances
Critical OHSS: Features symptoms indicative of hepato-renal and multiorgan failure; requires admission to the intensive care unit.1,5
In the UK, fertility clinics must follow the guidelines set out by the Human Fertilisation and Embryology Authority (HFEA). Any untoward incidents, severe or critical where hospitalisation is required, must be informed within 24 hours to the HFEA.5
The symptoms of OHSS are non-specific and can mimic other medical conditions. Therefore, diagnosis of OHSS requires a multidisciplinary approach, and it includes: 5,6
- Medical history - a detailed history of infertility and risk factors for OHSS
- Physical examination - features suggestive of OHSS, such as ascites, pleural effusion and dehydration, can be identified during a clinical examination
- Imaging - chest X-ray and ultrasound of abdomen and pelvic region
- Biochemical test- serum electrolyte and liver function test
- Complete blood count and coagulation profile
- Hormone levels - there are raised serum hCG and estradiol in OHSS
Identifying the risk factors can help you and your doctor prepare for any likelihood of developing OHSS during induction of ovulation. Risk factors can be primary or secondary.
Primary risk factors
These are pre-existing risk factors. 2,3,6
- Age younger than 30 years
- Women with polycystic ovarian syndrome
- Low body weight women having fertility treatment
- Previous history of OHSS
- High level of serum anti-mullerian hormones in the blood
Secondary risk factors
These are the factors that occur because of the response of the ovary to induction:2
- Numerous oocytes retrieval on the same day after induction
- A sudden rise of estradiol during controlled ovarian stimulation
Progression of the disease may lead to various life-threatening complications. 2,3,6
- Respiratory difficulty
- Torsion of ovary
- Multiorgan failures, such as liver and kidney failure
How can I prevent ovarian hyperstimulation syndrome?
The best way to prevent OHSS is to avoid IVF or any other assisted fertilisation technique. Unfortunately, there is always a chance to develop OHSS in assisted fertility. However, there are some steps that you can take to reduce the risk of OHSS, for example:2,3
- Following medication as prescribed by the doctor
- Discussing individualised treatment plan
Depending on your medical history and hormone level, your physician can assess if you are at risk for OHSS and recommend the following infertility treatment plan. 2,5,7
- Targeting uni follicular ovulation
- Considering alternatives to gonadotropins for inducing ovulation
- Reducing the duration of gonadotropin exposure
- Dopamine antagonist to inhibit the secretion of vascular endothelial growth factors
- Coasting- Withdrawing of gonadotropins when oestrogen level is at peak or when a large number of developed follicles are present to prevent triggering of OHSS
- Embryo cryopreservation- It can help restart the IVF process after normalising the body’s response to gonadotropins
How common is ovarian hyperstimulation syndrome?
- The incidence of OHSS is unknown as mild to moderate symptoms remain unnoticed and are not reported.5
- About 3%–6% of assisted technique cycles result in moderate OHSS.1
- Around 0.1-3% of women undergoing ovulation induction can progress to severe OHSS.1
- There is a possibility of severe OHSS in as many as 20% of high-risk cases.7
- Over the past two decades, clinically severe OHSS requiring ICU admission rates have decreased in the UK.8
When should I see a doctor?
Contact your doctor if you are taking treatment for infertility or experience features suggestive of OHSS during the course of treatment. You can ask these queries related to OHSS:
- Is this condition life-threatening?
- What are the chances of having OHSS during fertility treatment in your case?
- What are the available treatment options in the event of a reaction to current medication?
- Are there any benefits of freezing embryos for future fertility?
Ovarian hyperstimulation syndrome is a side effect of infertility treatment.Symptoms of this condition do not appear until it has progressed to a moderate or severe level. Diagnosis of OHSS requires a comprehensive approach that includes a medical history, clinical examination, and a battery of diagnostic testing. It is critical to tailor therapy duration and type based on individual risk factors. Severe OHSS can result in problems such as thrombosis, breathing difficulties, or death. Consultation with a doctor for a customised treatment plan is strongly advised to reduce the risk of OHSS in women. Because of increased awareness of OHSS and quick therapy, the incidence of OHSS has decreased in recent years.
In a woman seeking assisted ovulation for infertility, total prevention of OHSS is not attainable.
- Kumar P, Sait SF, Sharma A, Kumar M. Ovarian hyperstimulation syndrome. J Hum Reprod Sci [Internet]. 2011 [cited 2023 Jul 7];4(2):70–5. Available from: https://pubmed.ncbi.nlm.nih.gov/22065820/
- Smith V, Osianlis T, Vollenhoven B. Prevention of ovarian hyperstimulation syndrome: A review. Obstet Gynecol Int [Internet]. 2015 [cited 2023 Jul 7];2015:514159. Available from: https://pubmed.ncbi.nlm.nih.gov/26074966/
- Sun B, Ma Y, Li L, Hu L, Wang F, Zhang Y, et al. Factors associated with ovarian hyperstimulation syndrome (OHSS) severity in women with polycystic ovary syndrome undergoing IVF/ICSI. Front Endocrinol (Lausanne) [Internet]. 2020 [cited 2023 Jul 7];11:615957. Available from: https://pubmed.ncbi.nlm.nih.gov/33542709/
- Wittels KA, Mayes KD, Eyre A. Ovarian hyperstimulation syndrome: A simulation case for emergency medicine residents. MedEdPORTAL [Internet]. 2022 [cited 2023 Jul 7];18:11271. Available from: http://dx.doi.org/10.15766/mep_2374-8265.11271
- The Management of Ovarian Hyperstimulation Syndrome. Org.uk. [cited 2023 Jul 7]. Available from: https://www.rcog.org.uk/media/or1jqxbf/gtg_5_ohss.pdf
- Namavar Jahromi B MD, Parsanezhad ME MD, Shomali Z MD, Bakhshai P MD, Alborzi M MD, Moin Vaziri N MD PhD, et al. Ovarian hyperstimulation syndrome: A narrative review of its pathophysiology, risk factors, prevention, classification, and management. Iran J Med Sci [Internet]. 2018 [cited 2023 Jul 7];43(3):248–60. Available from: https://pubmed.ncbi.nlm.nih.gov/29892142/
- Nastri CO, Teixeira DM, Moroni RM, Leitão VMS, Martins WP. Ovarian hyperstimulation syndrome: pathophysiology, staging, prediction and prevention: Pathophysiology, staging, prediction and prevention of OHSS. Ultrasound Obstet Gynecol [Internet]. 2015;45(4):377–93. Available from: http://dx.doi.org/10.1002/uog.14684
- Abbara A, Patel B, Parekh I, Garg A, Jayasena CN, Comninos AN, et al. Ovarian Hyperstimulation Syndrome (OHSS) requiring Intensive Care Unit (ICU) admission between 1996-2020 in England, Wales, and Northern Ireland. Front Endocrinol (Lausanne) [Internet]. 2022;13. Available from: http://dx.doi.org/10.3389/fendo.2022.1060173