What is Ovarian Hyperstimulation Syndrome (OHSS)?

What is Ovarian Hyperstimulation Syndrome (OHSS)?

Ovarian Hyperstimulation Syndrome (OHSS) takes place when a women’s body over-responds to the hormone medications (notably injectable gonadotropins) used to stimulate egg development during a fertility treatment cycle.

OHSS is typically accompanied by fluid leaking into the abdominal cavity, bloating, swelling, nausea, and potentially more severe symptoms.

What Causes OHSS?

The underlying reason OHSS happens isn't entirely known or clear, but as mentioned, it is nearly always caused by excess hormones administered during a fertility treatment to cause improved or excess egg development (egg quality and quantity) and release (ovulation).

One hypothesis is that higher levels of human chorionic gonadotropin (hCG) play a role. hCG is a hormone that a woman's body naturally produces during pregnancy, but during fertility treatment, it can be used as a "trigger shot" to stimulate the final phase of egg maturation. Sometimes ovarian blood vessels abnormally react to the hCG and begin to leak fluid. This fluid can cause the ovaries to swell, and sometimes the fluid moves into the abdomen and other areas where it may cause pain or discomfort. This hypothesis is further supported by one of the main ways OHSS can be avoided (more on that later!).

When does OHSS Occur?

As mentioned, OHSS generally occurs during a fertility treatment that uses injectable medications. It is most common during an In Vitro Fertilization (IVF) or Egg Freezing cycle due to the higher doses that are used but can also happen with Intrauterine Insemination (IUI - AKA artificial insemination).

It typically happens within 2-6 days after an hCG injection is administered, which as mentioned is taken to stimulate the final maturation of an egg prior to the egg retrieval. If one becomes pregnant, the body begins to produce its own hCG and the OHSS can worsen.

OHSS can also occur with oral medications like clomiphene citrate (Clomid), though it is far less common.

Symptoms of OHSS

Symptoms of OHSS can range from extremely mild to so severe that they require treatment or even hospitalization. Symptoms usually appear within a week or two of using injectable medications to stimulate ovulation and include:

· Abdominal swelling or bloating, pain or discomfort

· Rapid weight gain — more than 3 pounds within 24 hours

· Shortness of breath or the inability to breathe deeply without discomfort

· Nausea, Vomiting, and Diarrhea

· Infrequent urination or dark-colored urine

· Tenderness around ovaries

Symptoms tend to become more pronounced with activity. Severe OHSS can be life-threatening, with rare cases of death reported. If you experience these symptoms, it is best to call your doctor immediately so he or she can monitor your symptoms and treat them early and aggressively.

Why are ovarian stimulation and trigger shots used if they cause OHSS?

When left to Mother Nature, most women who ovulate produce just one or two mature eggs each month as part of their regular menstrual cycle. But that is not the total number of eggs that start to develop each month. At the beginning of each menstrual cycle, dozens and even hundreds of eggs are driven by a hormone called Follicle Stimulating Hormone (FSH) to develop. But because FSH levels fall off fairly quickly, only eggs that have developed enough FSH receptors and blood vessels around them are able to survive the drop in FSH and continue to develop.

This one or occasionally two eggs are considered “dominant” and will be the egg or eggs that are ovulated. The remaining, smaller follicles do not mature and die off. Luteinizing Hormone (LH) from the brain triggers ovulation by causing the egg to mature and the follicle to rupture, releasing the egg from the ovary where it is pulled into the fallopian tube to await fertilization.

Why FSH is Used for Ovarian Stimulation?

More eggs mean a better chance of bringing home a baby. For women undergoing fertility treatment, particularly IVF, relying on a singular egg each month doesn't improve their odds of getting pregnant that much. Here’s why: during the IVF process, there is natural attrition at every stage along the way. While a woman has many follicles, not every follicle produces an egg each month. Not every egg retrieved is mature. Not every mature egg is successfully fertilized by sperm. Not every embryo (a fertilized egg) develops correctly in the lab. Not every embryo that develops properly and can be transferred results in a pregnancy, and unfortunately, not every pregnancy will ultimately result in a live birth. Because of this, starting with more eggs leads to a higher likelihood of a live birth happening. Stimulating the ovaries with high doses of FSH helps grow many eggs and is one of if not the most significant ways in which IVF works to beat infertility.

Numerous research studies [1] [2] have shown that a woman’s chance of a live birth rises significantly as the number of eggs retrieved goes up. But only until the number of eggs retrieved is somewhere around 15-20. This is the point of diminishing returns, meaning producing and retrieving more than 15-20 eggs doesn’t substantially raise the odds of a live birth and may actually increase the odds of serious complications like OHSS. So, most fertility doctors try to find a dosage that will produce this golden 15-20 eggs.

Why Trigger Shots Are Used?

During an IVF cycle, the high levels of FSH and the resulting number of mature eggs could naturally cause the body to ovulate and release those eggs, which if you're doing an IVF cycle, you absolutely do not want to happen (you want the eggs to grow, them be surgically removed by a doctor during the egg retrieval, grown in a lab, and transferred back into your uterus). In order to prevent ovulation, a specific category of fertility medications known as GnRH antagonists or simply antagonists are administered starting around six days of FSH use. GnRH antagonists prevent ovulation from happening. But, by introducing these antagonists, the eggs do naturally encounter the hormones that trigger their final maturation and thus need a third type of medication to "trigger" the final stage of maturation and ovulation. Of course, it is important that the eggs are removed before ovulation actually occurs - still, this final stage of maturation is critical, and that's why trigger shots are used.

Women Most at Risk for OHSS

While moderate to severe OHSS is possible with any IVF treatment and happens in approximately 0.3-5%[3] of cycles, it is more common in young women (under age 35), women with high AMH levels (signifying that woman has many eggs in reserve) and women with PCOS. Other risk factors include women who have a large number of follicles, low body weight, high or quickly increasing estrogen levels before an HCG trigger shot, or those who have experienced previous episodes of OHSS.

The Best Way to Prevent OHSS

To decrease your chances of developing OHSS, your doctor will need to create an individualized plan for your fertility medications. Fortunately, through close monitoring, appropriate dosing, and the proper choice of trigger medications, severe forms of hyperstimulation can be largely avoided. Expect to have frequent ultrasounds to check the development of follicles and blood tests to check your hormone levels. This will allow your doctor to adjust your dosage, add medications, or stop treatment, if necessary, to avoid OHSS.

Choose the Proper Dosage or Use Low Dose/Natural Cycle Stimulation

Using a dose of gonadotropin can help avoid complications from OHSS. An IVF cycle which uses less medications is commonly referred to as mini-IVF. Natural IVF is also a potential solution and uses no medications, but only allows for one embryo transfer and no additional frozen embryo transfers should the first transfer fail or the patient want more than one child. For this reason, it is generally not recommended.

Using a Different Trigger Medication: Lupron

Since Ovarian Hyperstimulation Syndrome often develops after an HCG trigger shot is administered, alternative trigger protocols have been developed. Notably, using Gn-RH agonists such as leuprolide (Lupron) as the trigger medication. Both hCG and Lupron effectively trigger egg maturation, which is necessary for IVF success, but Lupron is better tolerated, particularly by women at risk for OHSS. Following an antagonist protocol rather than an agonist protocol reduces the odds of hyperstimulation from 12 to 2.7% percent [3]. And using a Lupron/GnRH trigger rather than an hCG trigger reduces the odds to virtually nil [4] [5] [6].

Using Additional Medications

There are some additional medications or supplements that can help reduce the risk of OHSS without affecting the chances of pregnancy. Taking the drug metformin during stimulation may help women with PCOS prevent hyperstimulation. Also, the addition of at least 200 grams a day of oral protein in any form plus additional electrolytes like Ultima or Gatorade-type drinks combined with bed rest can help ensure ideal kidney function. Patients are usually advised to start these protocols if they have PCOS, have high estrogen, many antral follicles, a history of OHSS, or when they exhibit any symptoms of OHSS.

High-Protein Diet

Several studies[7] [8] looked at incorporating plasma expanders such as intravenous albumin. Administering oral protein works in much the same way, but is significantly cheaper, easier, more convenient, and and presents less risk. Another study[9] examined whether taking oral whey protein starting on the day of oocyte retrieval, in addition to conventional treatment, would help prevent OHSS. Although the number of subjects was small, researchers concluded that whey protein might be an excellent alternative for preventing OHSS in high-risk patients, especially severe forms.

Acupuncture

Eastern medicine offers a less invasive solution than western medicine. Acupuncture has the ability to move extra fluid, help with digestion, break blood stagnation, help your body get rid of the extra hormones that are causing OHSS, resolve stagnation in the pelvic area, and reduce the duration of OHSS symptoms.

In addition to adding protein and fluids, several acupuncture protocols incorporate "fluid moving" techniques to reduce pain and fluid retention. Drs. Magarelli and Cridennda have developed one such protocol. In their decades of multi-center experience, they have found that in most cases (over 95%), patients with OHSS who are managed with protein, fluids, and acupuncture can avoid hospitalization. A study[10] of female rats concluded that electroacupuncture might provide a simple and effective method for the prevention and treatment of OHSS.

Coasting the Use of Gonadotropins

If estrogen levels are high or you have a large number of developing follicles, your doctor may have you stop injectable medications and wait a few days before giving HCG, which triggers ovulation. Withholding gonadotrophins until the serum estradiol (E2) level decrease (otherwise known as “coasting”) is believed to help prevent OHHS. Because candidates for coasting are high responders and have numerous follicles, many oocytes are still obtained after coasting, often leaving a large number of embryos for cryopreservation.

Freezing Embryos for Future Frozen Embryo Transfer (FET)

A widely used strategy[11] to prevent severe OHSS is to freeze all embryos and perform a later Frozen Embryo Transfer (FET). However, this does not prevent the early form of OHSS and only helps lower the risk by eliminating the possibility of pregnancy and risking hCG levels.

The Bottom Line on OHSS

Ovarian Hyperstimulation Syndrome is arguably the single greatest risk during an IVF cycle. It can cause severe bloating, nausea, hospitalization, and in very rare cases, death. While it is in some ways a necessary evil that exists in response to aggressive fertility treatments like IVF, there are indeed many ways (like using a Lupron Trigger) that can virtually eliminate the risk or at least make that risk and potential side effects much more tolerable.

Medical Disclaimer:

The information provided in this blog is intended for general informational purposes only and should not be considered as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your healthcare provider or qualified medical professional with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this blog.