GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation

Abstract

Aromatase inhibitors can be utilized to minimize oestrogen exposure in breast cancer patients undergoing gonadotrophin stimulation. This retrospective-prospective study determined whether using a gonadotrophin-releasing hormone agonist (GnRHa) trigger instead of human chorionic gonadotrophin (HCG) would reduce oestrogen exposure and improve cycle outcomes in aromatase inhibitor cycles. Seventy-four breast cancer patients who desired fertility preservation, with normal ovarian reserve and <45 years of age received letrozole 5 mg/day plus recombinant FSH 150–300 IU/day for ovarian stimulation. Subjects either received HCG 5000–10,000 IU (n = 47) or leuprolide acetate 1 mg (GnRHa, n = 27) as trigger. Oestradiol measurements were repeated 4 days after the trigger and subjects were evaluated for ovarian hyperstimulation syndrome (OHSS). In the GnRHa group, oestradiol concentrations dropped significantly after the trigger than the HCG group (P = 0.013) and there was a lower incidence of OHSS. GnRHa trigger resulted in a higher number and percentage of mature oocytes and a higher number of cryopreserved embryos or oocytes compared with HCG. GnRHa trigger improves outcomes by increasing the yield of mature oocytes and embryos in aromatase inhibitor cycles and also decreases the post-trigger oestradiol exposure as well as OHSS risks in women with breast cancer.

Triggering final oocyte maturation with gonadotropin-releasing hormone agonist (GnRHa) versus human chorionic gonadotropin (hCG) in breast cancer patients undergoing fertility preservation: an extended experience

“…In our previously published pilot data of 74 breast cancer patients undergoing fertility preservation, we found reduced estrogen exposure and risk of OHSS when final oocyte maturation was triggered by GnRHa as compared to hCG [23].…”

“…Furthermore, there was a significant reduction in the rate of OHSS in the GnRHa group compared to the hCG group. Our current study builds on our pilot data and adds to the growing body of literature supporting the potential use of GnRHa triggers in certain high risk populations [23,25]. Although we do not have the sufficient data on pregnancy outcomes at the present time, our preliminary analysis does not suggest a difference in pregnancy rates between the two triggers.…”

“…Over time the protocol was transitioned to a GnRHa trigger with the aim of reducing OHSS risks and further reducing post-hCG rise in E2 levels; therefore, this is a comparison of the initial hCG trigger with the later GnRHa trigger [15,23]. All other aspects of the aromatase inhibitor-gonadotropin protocol remained the same (Fig.…”

Severe ovarian hyperstimulation syndrome after letrozole-gonadotropin stimulation: a case report

“…Although this patient developed severe OHSS despite treatment with letrozole, the clinical course of this patient may have been worse if she had not been on letrozole. In a study involving 74 patients receiving stimulation with letrozole and gonadotropins for FP, 11/74 (15%) developed mild-moderate OHSS [8], but none developed severe illness. High concentrations of E 2 alone are unlikely to cause OHSS unless hCG also is elevated [9].…”

IVF for fertility preservation in breast cancer patients—efficacy and safety issues

“…According to a suggested protocol [55], 5 mg of letrozole is started on the 2nd-3rd day of the cycle, followed by initiation of rFSH or hMG in variable doses. GnRH antagonist is used to avoid premature LH surge [56]. After oocyte retrieval, letrozole is continued until a proper decline in E2 levels is documented.…”