Utility of Gonadotropin-Releasing Hormone Agonists for Fertility Preservation: Lack of Biologic Basis and the Need to Prioritize Proven Methods

Fertility Preservation Using GnRH Agonists: Rationale, Possible Mechanisms, and Explanation of Controversy

“…130 Although no randomized trials assessed the role of ovarian or oocyte cryopreservation strategies for fertility preservation, many investigators, but not recent ASCO recommendations, 130 refer to cryopreservation of ovarian tissue as an established method of fertility preservation. More recently, an argument was raised 119,120,131 whereby none of the studies favoring GnRHa effect for fertility preservation was blinded or placebo controlled; therefore, they are unacceptable. On the other hand, these authors 119,120,131 claim that the successful reports on ovarian cryopreservation should lead to accepting this method as an unequivocally established method for fertility preservation.…”

“…Another argument brought up by opponents of GnRHa use is that since 8% of prepubertal children exposed to gonadotoxic chemotherapy may suffer POF/POI by age 40, there is no logic for creating a prepubertal milieu in young women in parallel to chemotherapy. 118-140 Several studies in the last decade 136-139 found that survivors of childhood cancer have about 8% risk of suffering POF/POI before age 40. This hazard risk is in keeping with the published results whereby women of reproductive age treated with adjuvant GnRHa along chemotherapy experienced POF in the range of 8% to 13% (simulating prepubertal exposure), whereas control survivors who received chemotherapy without the agonist had a 30% to 60% risk of POF.…”

“…More recently, an argument was raised 119,120,131 whereby none of the studies favoring GnRHa effect for fertility preservation was blinded or placebo controlled; therefore, they are unacceptable. On the other hand, these authors 119,120,131 claim that the successful reports on ovarian cryopreservation should lead to accepting this method as an unequivocally established method for fertility preservation. However, none of the reports on cryopreservation of embryos, ova, or ovarian tissue were “blinded or placebo controlled” nor RCT.…”

Utility of gonadotropin-releasing hormone agonists for fertility preservation in women receiving chemotherapy: pros and cons

“…Why apply a double standard? (44,45,92,93) Demeestere et al (98) did not find a difference in the POF rate between the GnRH-a and control groups after 1 year, but at the 2-year follow-up (31), the ''.restored ovarian function CON: GnRH-a should not be used for fertility preservation in women receiving chemotherapy (continued)…”

“…The disagreement between the supporters of GnRH-a cotreatment and opponents has turned occasionally inflamed (44,45,(92)(93)(94)(95)(96)(97) A raised argument claimed that none of the ''GnRH-a PRO'' studies were blinded or placebo controlled, and therefore were unacceptable (93). On the other hand, these authors (93) asserted that ovarian cryopreservation should be unequivocally established. How many of the ovarian tissue cryopreservation studies were ''blinded or placebo controlled'' or RCTs?…”