Ovarian hyperstimulation following the sole administration of agonistic analogues of gonadotrophin releasing hormone

Abstract

Ovarian hyperstimulation following the sole administration of gonadotrophin-releasing hormone agonists (GnRHa) is exceedingly rare. We hereby report on two infertile patients undergoing in-vitro fertilization-embryo transfer who developed ovarian hyperstimulation under such circumstances. In both patients, GnRHa were administered using the 'long protocol' regimen. The first patient developed ovarian hyperstimulation on two occasions, with mid-luteal depot administration of triptorelin and with early follicular triptorelin, administered as daily subcutaneous injections. In both cycles, within 2 weeks of triptorelin therapy, massive ovarian multifollicular enlargement occurred, concomitant with high serum oestradiol concentrations, which resolved spontaneously following expectant management. The second patient developed ovarian hyperstimulation following daily injections of leuprolide acetate starting at the mid-luteal phase. The final stage of ovulation was triggered by human chorionic gonadotrophin (HCG) and 11 oocytes were retrieved. In-vitro fertilization resulted in embryo formation, but failed to result in pregnancy. The same phenomenon recurred in a subsequent cycle despite preventive pretreatment with an oral contraceptive. A negative GnRH test, performed just before HCG administration, suggested than an ongoing 'flare-up effect' was unlikely to cause ovarian stimulation. Ovarian hyperstimulation can occur following the sole administration of GnRHa irrespective of the preparation used and the administration protocol. Although spontaneous resolution is the rule, once this condition has developed, HCG administration and oocyte retrieval are feasible. This rare entity probably represents an exaggerated form of ovarian cyst formation following GnRHa administration, the underlying pathophysiology of which remains unresolved.

Clinical and endocrine response to the withdrawal of gonadotropin-releasing hormone agonists during prolonged coasting

“…The GnRH receptors are present in various ovarian compartments including the granulosa, theca, interstitium, and corpus luteum (CL) (20). A significant literature based on data from experimental animals as well as clinical observations suggest that GnRHa may have stimulatory effects on the ovary including oocyte maturation (7), ovulation in hypophysectomized animals (7), steroidogenesis, follicular luteinization, and prostaglandin accumulation in experimental animals (7,10,21,22), steroidogenesis (23)(24)(25), ovarian hyperstimulation (26)(27)(28)(29), and cyst formation in women (30). These effects appear dependent on the agonist dose as well as the stage of follicular maturation (9-13).…”

Follicular development, acquisition of mature oocytes, and pregnancy after 2 weeks of leuprolide acetate administration during the midluteal phase

“…Four oocytes were retrieved out of which one fertilized and cleaved but eventually arrested. The authors suggested that this rare entity probably represented an exaggerated form of ovarian cyst formation after GnRH-a administration; nevertheless they admitted that they were unable to provide an explanation for the underlying pathophysiology (12).…”

Follicular growth and development under continuous gonadotropin-releasing hormone antagonist administration

“…Such follicles have been shown to harbor fertilizable oocytes, and while their growth is maintained, the pituitary appears to be suppressed, as evidenced by the GnRH test (4). A pregnancy resulting in a live birth has been described after oocyte retrieval in a patient with GnRH agonist-related ''cysts'' (5).…”