GnRH Antagonist Pre-treatment in the Early Follicular Phase for Resolution of a Baseline Functional Ovarian Cyst - A Proof-of-concept Pilot Study

Reports on the effect of a baseline ovarian cyst on IVF cycle cancellation and outcome are scare and inconsistent. A cystic structure of the ovary may be functional or non-functional. Functional ovarian cysts are usually created by disruption of normal ovulation with the accumulation of intrafollicular fluid. Hormonal dysfunction prior to ovulation results in expansion of the follicular antrum with serous fluid. These cysts may be more frequent using Progesterone only contraceptives, Levonogetstrel-containing intrauterine device and following controlled ovarian stimulation during fertility treatments . Most functional cysts regress spontaneously within the first few days of menstruation or within the first 1-2 cycles and up to 6 months.

An ovarian cystic structure, even if hormonally inactive, may interfere with ovarian function during ovulation induction. These cysts may have a mechanical effect by reducing the space for growing follicles or by impairing ovarian blood supply. This may result in a lower number of oocytes and poor embryo quality, or utilization of higher doses of gonadotropins(GT) to reach the same oocyte yield.

Several studies have investigated the outcome of GnRH antagonist supplementation at the beginning of the menstrual cycle prior to GT stimulation mainly for the purpose of synchronization of antral follicles preventing a premature follicular recruitment. The delayed start protocol which combines estradiol priming followed by GnRH antagonist for 7 days at the beginning of menses prior to GT administration to further synchronize antral follicles improved ovarian response in poor responders and reduced cycle cancellation rate with no significant effect on pregnancy rates. A preliminary study investigated the effect of three day administration of GnRH antagonist at the beginning of the follicular phase prior to GT stimulation in normal responders regardless of baseline hormonal levels and found a trend towards increase in clinical pregnancy rate, and similar profiles of early embryo development, compared to standard fixed GnRH antagonist protocol.

Patients receiving an antagonist protocol usually start their stimulation on day 2-3 of menses. A baseline US and hormonal blood test are performed to determine adequacy of cycle start.

Patients presenting with a simple ovarian cyst larger then 25-30 mm in our unit, even in the presence of normal baseline estradiol levels are deferred to start their treatment in the following menstrual cycle as these structures may negatively affect treatment outcome. It is possible that these cystic structures, most being remnants of previous cycle, would have resolved spontaneously within a few days, but since GT treatment is to be started on the 2-3 day of the cycle to prevent leading follicle recruitment, we cannot wait to find out whether cyst has resolved and are inclined to postpone treatment to the following menstrual cycle.