Dados do Trabalho

Title

Severe ovarian hyperstimulation syndrome associated with long-acting GnRH agonist after oocyte retrieval in oncofertility patient: a case report

Objective

To report a case of severe ovarian hyperstimulation syndrome (OHSS) in oncofertility patient receiving chemoprotective long-acting GnRH agonist (GnRHa_dep) after controlled ovarian hyperstimulation (COH).

Methods

Medical record and literature review about OHSS in oncofertility patients.

Results

A 28 year-old woman with luminal breast cancer presents to medical consult for fertility preservation. Random start COH for egg retrieval was indicated. Basal antral follicle count was 32 and there was a 15mm follicle at the time COH was started (D1). The adopted protocol was follitropin delta (72mg), combined to urofollitropin (450UI). Clomifene citrate and letrozole were associated for ovulation inhibition and to minimize impact on cancer cells. Ovulation was detected on D6. In D9 double triggering was performed with 2500 UI human gonadotrofin (hCG) and 0,1mg triptorrelin subcutaneously. Thirty-three oocytes were aspirated, and 24 were frozen in M2 stage. The patient presented abdominal distension, light pain, reduced appetite, nausea and constipation from the day after the procedure. Support measures and telemonitoring were thoroughly adopted. Five days after follicle aspiration there was worsening of the symptoms. From sixth day on there was a slow but steady improvement, as menstrual flow began. On the eigth day post oocyte retrieval (OR) she was feeling significantly better, when chemotherapy was iniciated. GnRHa_dep (10,8mg goserelin) was prescribed by the oncologist for fertility preservation despite recent OR. Forty-eight hours after GnRHa_dep there was major worsening of OHSS, with detection of dyspnea, resurgence of ascites, tachycardia (124 bpm), vomiting and dehydration. Pacient was hospitalized for intensification of hydration, analgesia, profhylatic heparinization. Significant ascites and small pleural effusion were observed and 3 liters of serosanguineous peritoneal fluid were aspirated by ultrasound guided paracentesis. Total lenght of hospitalization was 10 days. OHSS is a major complication associated with assisted reproductive technology (ART) and occurs in approximately 1–5% of treatment cycles. It is characterized by ovarian enlargement, ascites, hemoconcentration, hypercoagulability, and electrolyte imbalances. The cause of OHSS is believed to be massive luteinization of granulosa cells induced by hCG with production of vascular endotelial growth factor (VEGF) which increases vascular permeability. The gold standard strategy for fertility preservation in female cancer patients is oocytes or embryo cryopreservation. GnRHa_dep is also supposed to exert a chemoprotective effect on the ovaries and long acting formulations have come into common usage as co-treatment during chemotherapy. Short after GnRHa_dep is given, there is a gonadotropin “flare” phase resulting in a rise in FSH, LH, and estradiol, which usually lasts for 7–14 days. It is believied that sustained gonadotropin elevation during the flare phase of GnRHa_dep may mimic the effect of hCG and contribute to severe OHSS cases as the one reported here. In a previous study, the authors demonstrated that the function of human corpus luteum can be rescued and function normally after seven days of deprivation from gonadotrophin stimulation in patients with hypogonadotropic hypogonadism. Therefore, we may assume that the risk of rescuing corpus luteum (and potentially causing OHSS) with GnRHa_dep injection remains at least until the seventh-eighth day after OR. Candidates to hormonal chemoprevention might not receive GnRHa injection for this period (or even more) to avoid corpus luteum rescuing. Severe OHSS may be especially catastrophic for patients undergoing chemotherapy as this can result in delays in initiating cancer treatment as well as place the patient at risk for significant complications.

Conclusion

Risk of severe OHSS may be increased when a GnRHa_dep is used for chemoprotection following oocyte retrieval. The timing for GnRHa_dep administration should be established between oncologist and gynecologist in order to avoid risks.

Keywords

severe ovarian hyperstimulation syndrome – oncofertility - long-acting GnRH agonist