Ovarian hyperstimulation syndrome is a condition where a woman receiving fertility drugs (usually gonadotropins) over-responds by developing a large number of ovarian follicles which upon administration of hCG triggers a series of systemic events that can place the woman at risk.

Moderately severe ovarian hyperstimulation is quite common. Here, the hyperstimulated ovaries are enlarged and there will usually be a moderate amount of free fluid in the abdominal cavity (ascites) and/or in the chest cavity (pleural effusion). There will usually NOT be vomiting, diarrhea, diminished urine flow severe abdominal pain or shortness of breath in cases of moderate OHS.

Severe ovarian hyperstimulation syndrome (OHSS) presents with the symptoms and signs of OHS but they are usually much more severe. The abdomen becomes very distended with fluid, often to the point of causing severe pain and shortness of breath due to ovarian enlargement and gross ascites that splints the diaphragm and cause labored breathing. The increased intra-abdominal pressure also commonly exerts pressure on the upper gastro-intestinal tract causing part of the stomach to slide through the diaphragmatic opening by which the esophagus passes. This creates a ” functional hiatal hernia” causing gastric reflux, pain and vomiting. In addition, the marked ovarian enlargement can stimulate the vagus nerve leading to marked slowing of the heart rate (bradycardia), sweating, diarrhea, and vomiting.

Women with OHSS require a full hematologic, biochemical and physical evaluation and depending on severity of the condition, may need to be admitted to hospital for close observation and management.

Draining excessive intra-abdominal fluid (paracentesis): In cases of severe ascites that causes undue pain and difficulty in breathing, paracentesis ( transvaginal or transabdominal drainage of the fluid) usually affords immediate symptomatic relief because it alleviates growing intra-abdominal pressure. This helps reduce compression of major blood vessels allowing for improved liver, kidney and intestinal function. Paracentesis can be repeated every few days (as needed) until the condition resolves.

Predicting OHSS: OHSS is a condition that rarely occurs in normally ovulating or older (>39Y) women. It is most commonly seen in women with polycystic ovarian syndrome (PCOS) and women who for other reasons do not ovulate spontatneously. An experienced IVF physician will always have a high index of suspicion in such cases and be on guard , especially in cases where early on in the course of undergoing controlled ovarian hyperstimulation (COH) with gonadotropins, the woman develops >25 ovarian follicles of 14mm-16mm (in mean diameter) in association with a blood estradiol (E2) level of above 2,5000pg/ml prior to the “hCG trigger. He/she will also know that as when in such cases the blood E2 level rises to above 4,000pg/ml, the risk of OHSS escalates dramatically and that when at the time of the hCG trigger it reaches above 6,000pg/ml, the likelihood of OHSS developing will be greater than 80%.

OHSS is a self-limiting condition: The development of OHSS is linked to the effect of hCG and thus does not occur until the “hCG trigger” is administered. In fact, there is no risk until hCG is administered. If a woman who develops OHSS does not conceive, the hCG hormone clears her ncirculation within 10-14 days of hCG administration, whereupon the condition spontaneously resolves… sometimes overnight. If, on the other hand, the woman conceives, then the severity of OHSS with its incumbent risks usually increases exponentially, commensurate with rising hCG production by the developing root system (placenta) of the conceptus. The good news is that even if this should happen the condition will self-resolve by 7-8 weeks into the pregnancy.

The challenge of treatment is to try and avoid over administration of gonadotropins to susceptible women and, in the event of inadvertent overstimulation , to institute measures that will minimize the risk after the “hCG trigger”. To achieve this requires that all women with 25 or more ovarian follicles be critically reassessed for OHSS, risk-factors prior to receiving the “hCG trigger.”

Once pregnancy occurs there is no turning back as OHSS will then have to run its own natural course. Thus, if the warning signs of potential OHSS developing were missed and the hCG trigger was inadvetently administered, the egg retrieval should be conducted but the fresh embryo transfer (ET) should be deferred until day 5 or 6 post-fertilization in order to allow for time to assess how the condition evolves before deciding and whether it would be safe proceed to a fresh embryo transfer.If she is deemed to be at risk of developing OHSS her embryos should rather be cryo-stored (frozen) and the embryo transfer deferred to a subsequent hormone-prepared cycle.

Avoiding OHSS through Prolonged Coasting (PC). PC, is a procedure introduced by us in 1991. It involves abruptly stopping gonadotropin therapy while continuing to administer the GnRH agonist (e.g Lupron) and then deferring the “hCG trigger” until the woman is out of risk (as evidenced by a drop in plasma estradiol level below 2,500pg/ml). A word of caution…. Unless PC is initiated at precisely the right time, it will result in poor quality eggs and embryos. It should be initiated as soon as at least 2 follicles have attained a mean diameter of 18-22mm and 50% of the remaining follicles have reached 14-16mm . T start the process of PC any earlier or any later, while still protecting the woman from OHSS, would almost certainly result in compromised eggs and embryos…with ultimate failure of the IVF cycle. Simply stated, the precise timing of initiating the PC process is critical.

In most cases, after initiating PC, the blood E2 level will continue to rise for a period od of time ranging from 1-5 days while the follicles will continue to grow . Thereupon, follicle growth will cease and the blood E2 levels will start to decline. Only once the E2 concentration drops below 2,500pg/ml should the “hCG trigger” be administered. Proper implementation of PC will almost always prevent OHSS without seriously compromizing egg/embryo quality.

Since we first reported on the benefits of PC in the early 90’s, this approach has gained widespread international acceptance as the method of choice by which OHSS can be without cancelling the IVF cycle altogether.

The fact that OHSS is relatively infrequent is somewhat reassuring. However,this also presents somewhat of a a problem, Because many IVF physicians are unfamiliar in dealing with the full blown condition and are so fearful of its consequences that when confronted with even moderately severe OHS, and even the possibility that the conditionmight evolve into OHSS they either cancel the IVF cycle altogether or administer the “hCG trigger” prematurely in the hope of stopping the process in its tracks. In such cases, the eggs retrieved will almost always be “immature” and be of such poor quality as to yield “incompetent” embryos that are incapable of propagating a pregnancy.

When correctly implemented, “prolonged coasting (PC)” prevents OHSS, protects egg /embryo quality, removes the need to cancel the IVF cycle and thus avoids canceled dreams.