Ovarian Cysts and IVF

“Functional ovarian cysts” are literally nothing more than ovarian follicles that become enlarged, dilated and distended with fluid. They acquire special relevance when detected in women about to undergo controlled ovarian hyperstimulation (COH) with gonadotropins where they can literally, “throw a wrench in the works,” causing a slight delay, postponement or even a cancellation of the cycle of treatment.

Ovarian cysts may be either "functional cysts” or "cystic tumors". Functional cysts grow in response to a sustained elevation in blood levels of luteinizing hormone (LH) and/or follicle stimulating hormone (FSH), whether produced by their own pituitary glands or administered to them. By definition, tumors (in contrast with “functional” ovarian cysts) are capable of independent growth, thus cystic ovarian tumors do not respond to gonadotropin stimulation. It is this that distinguishes them from “functional” ovarian cysts. It follows that “functional” ovarian cysts may develop as a result of non-physiological, sustained pituitary gonadotropin stimulation or as a result of prolonged administration of gonadotropins (e.g. Folistim, Gonal F, Puregon, Bravelle, Menopur or Repronex).

Aside from causing menstrual dysfunction such as a delay in the onset of bleeding, irregular cycles, and mild lower abdominal discomfort, unruptured “functional” cysts are usually relatively non-problematic. In some cases, such functional cysts undergo rapid distention (often as a result of a minor degree of bleeding inside the cyst itself) and the woman will experience a sharp or aching pain on one side of her lower abdomen and/or deep seated pain during intercourse. They may even rupture, causing the sudden onset of severe lower abdominal pain, which may simulate an attack of acute appendicitis or even a ruptured ectopic (tubal) pregnancy. While very unpleasant, a ruptured “functional” cyst hardly ever produces a degree of internal bleeding that warrants surgical intervention. The pain, which is made worse on movement, almost always subsides progressively over a period of four to five days.

Whenever an ovarian cyst is detected (usually by ultrasound examination), the first consideration should be to determine whether it is a “functional” cyst or a cystic ovarian tumor. The reason is that tumors are subject to a variety of complications such as twisting (torsion), hemorrhage, infection and even malignant change, all of which will require surgical intervention.

Gonadotropin releasing hormone agonists (GnRHa) such as Lupron, Buserelin, Nafarelin and Synarel, administered daily, starting a few days prior to menstruation, all elicit an initial and rapid, out-pouring (“surge”) of pituitary LH and FSH release. This “surge” lasts for a day or two. Then, as the pituitary reservoir of FSH and LH becomes depleted, the blood FSH and LH levels fall rapidly, reaching near undetectable concentrations within a day or two. At the same time, the declining FSH results in a drop in blood estradiol (E2) concentration, leading to a withdrawal bleed (menstruation).

The progressive exhaustion of pituitary FSH/LH along with the decline in blood E2 is referred to as “down-regulation.” The continued daily administration of GnRHa or its replacement with a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) results in blood LH concentrations being sustained at a very low level throughout the ensuing cycle of controlled ovarian hyperstimulation (COH) with gonadotropins, thereby optimizing follicular maturation and promoting E2 induced endometrial proliferation.

Regardless of whether down-regulation with GnRHa is initiated while the woman is taking birth control pills (BCPs) or by starting treatment on day 20-23 (the mid luteal phase) of a natural cycle, the initial FSH/LH “surge” sometimes so accelerates follicular growth that it leads to the development of one or more “functional” ovarian cysts. These cysts release E2 and cause the blood E2 often to remain elevated (>70pg/ml). Depending on the extent of this effect, it sometimes leads to a delay in the onset of menstruation and thus also in the initiation of ovarian stimulation with gonadotropins. While in most cases, further continuation of GnRHa therapy (with sustained suppression of FSH/LH) would ultimately (within a week or two) lead to absorption and disappearance of functional cysts followed by menstruation, delaying COH can have drawbacks. This is because prolonged uninterrupted GnRHa therapy can blunt subsequent ovarian follicular response to gonadotropins. Thus, it is not good policy to continue GnRHa administration for much longer than 14 days prior to initiating COH.

Failure of menstruation to commence within 4-7 days of initiating treatment with GnRHa suggests a potential underlying “functional”ovarian cyst and calls for an ultrasound examination to make the diagnosis. Once diagnosed, there are two therapeutic options, depending upon the number and size of cysts detected.: 1) wait to see whether the cyst will absorb spontaneously within a few days or, 2) immediately resort to needle aspiration of the cyst(s) under local anesthesia. My preference is to perform needle aspiration, sooner rather than later in such cases. Menstruation will usually follow a successful aspiration within 2-4 days. Upon menstruation, a blood E2 level is measured. Provided it is less than 70pg/ml, COH can be initiated.

“Functional” ovarian cysts do not present a serious health hazard. Almost without exception, they will spontaneously resolve within 4 to 6 weeks, while “cystic tumors” will not. Accordingly, the persistence of any ovarian cyst for longer than 6 weeks should raise suspicion that you are dealing with a tumor rather than with a “functional” cyst. Since ovarian tumors can be malignant (or might later undergo malignant change), all ovarian cysts that persist for longer than 6 weeks (whether in non-pregnant or pregnant women), should be treated by surgical removal, followed by pathological analysis.