No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial

Abstract

To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.

Gonadotropin‐releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta‐analysis

“…Five studies involved administration of triptorelin intramuscularly [23][24][25][26]35 , one used intranasal buserelin 27 , five used goserelin [28][29][30][31][32] , one administered diphereline 33 and one used leuprolide acetate 34 . In all included studies GnRHa administration was maintained throughout the chemotherapy treatment.…”

“…the rate of persistent amenorrhea) at the end of their follow-up. Four studies reported the frequency of POI, defined by persistent amenorrhea and elevated follicle-stimulating hormone (FSH) levels 28,31,34,35 . The duration of follow-up ranged from 6 months 33 to 7 years 25 .…”

“…The duration of follow-up ranged from 6 months 33 to 7 years 25 . As secondary outcome, nine studies reported the number of participants that became pregnant during the follow-up [23][24][25][26][27][29][30][31]35 . All reported pregnancies resulted from spontaneous (i.e.…”

“…Demeestere (2016) 35 Giuseppe (2007) 24 Waxman (1987) 27 Subtotal (95% CI) Lambertini (2015) 25 Leonard (2017) 30 Moore (2015) 31 Munster (2012) 26 Song (2013) 34 Sverrisdottir (2009) and receptor negative (RR, 0.62; 95% CI, 0.33-1.14) tumors. When all patients were subdivided according to chemotherapy regimen into high toxicity vs low/medium toxicity 6 , the benefit of GnRHa therapy in preventing POI appeared to be of greater magnitude among women treated with low/medium toxicity chemotherapy (RR, 0.49; 95% CI, 0.29-0.84) compared with women treated with highly toxic chemotherapy (RR, 0.66; 95% CI, 0.45-0.96; Figure 4).…”

“…Five studies had unclear risk of selection bias because the authors did not provide any information about the randomization process or the allocation concealment 24,27,29,33,34 . Four studies had a high proportion (more than 25%) of participants randomized but not included in the final analysis and were therefore rated as unclear risk of attrition bias [30][31][32]35 . One study had high risk of attrition bias because the two groups differed significantly in their follow-up lengths 24 .…”