Gonadotropin-Releasing Hormone Agonist Cotreatment During Chemotherapy May Increase Pregnancy Rate in Survivors

Abstract

Background. The use of gonadotropin‐releasing hormone analogs (GnRHas) for fertility preservation is not unequivocally accepted. It is controversial whether GnRHa can increase the pregnancy rate in survivors. Patients and Methods. This is a retrospective cohort study. Every patient referred for fertility preservation was offered cryopreservation of embryos, ova, and ovarian tissue and GnRHa. The patients were consecutively included. The primary outcome was spontaneous pregnancies. The secondary outcome was cyclic ovarian function (COF) versus premature ovarian failure (POF). These outcomes were assessed 2 years or more after chemotherapy. Results. We compared 286 patients who received gonadotropin‐releasing hormone agonist (GnRHa) with chemotherapy with 188 patients who were treated with chemotherapy alone. Ovarian function could be determined in 217 patients. Overall, 87% (127 of 146) of the patients in the GnRHa group retained COF and 13% (19 of 146) suffered POF, whereas in the control group, 49% (35 of 71) experienced COF and 51% (36 of 71) suffered POF (p = .0001). The odds ratio (OR) for preserving COF was 6.87 for the patients who received GnRHa (95% confidence interval [CI] 3.4–13.4). Overall 60% (112 of 188) of the survivors conceived: 69.3% (84 of 122) of the patients in the GnRHa group compared with 42.4% (28 of 66) in the control group (p = .006). In the GnRHa group, 123 healthy newborns were delivered, versus 40 in the controls. Spontaneous pregnancies occurred in 65.6% (80 of 122) of the survivors in the GnRHa group versus 37.9% (25 of 66) in the control group (p = .0004, OR 3.12, 95% CI 1.7–5.8). Conclusion. Adding GnRHa to chemotherapy significantly increases the OR for spontaneous conception, in addition to COF. It is suggested that GnRHa cotreatment should be added before and during gonadotoxic chemotherapy. Implications for Practice: The use of gonadotropin‐releasing hormone analogs (GnRHa) for fertility preservation is not unequivocally accepted and is even controversial. This study compared 286 patients who received GnRHa with chemotherapy with 188 patients who were treated with chemotherapy alone. Ovarian function could be determined in 217 patients. The odds ratio for preserving cyclic ovarian function was 6.87 for the patients who received GnRHa. Furthermore, the total and spontaneous pregnancy rate was significantly higher for those who received the agonist (p = .006). Adding GnRHa to chemotherapy significantly increased the odds ratio for spontaneous conception, in addition to preserving regular ovarian function. It is suggested that GnRHa cotreatment should be administered to young women in conjunction with gonadotoxic chemotherapy.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

“…122 Some studies, including randomized trials, have evaluated the role of menstrual suppression with gonadotropin-releasing hormone (GnRH; also known as LH-releasing hormone [LHRH]) agonists to preserve ovarian function during chemotherapy. [123][124][125][126][127][128][129][130][131] Some meta-analyses have shown that GnRH agonist may be beneficial for fertility preservation. [132][133][134] However, the impact of these meta-analyses are limited by flaws such as only examining women with breast cancer and only including trials that were not adequately powered and did not use blinding and/ or a placebo condition.…”

Temporary Ovarian Suppression With Gonadotropin-Releasing Hormone Agonist During Chemotherapy for Fertility Preservation: Toward the End of the Debate?

“…In the chemotherapy plus GnRHa arm of the POEMS-SWOG S0230 study, 25 patients declared attempting pregnancy, and 22 (88%) achieved pregnancy [9]. In the study by Blumenfeld et al, 69.7% of patients conceived after chemotherapy [1]. These findings confirm the importance of maintaining fertility of young cancer patients who are candidates to receive gonadotoxic therapies.…”

“…A total of 85 patients (69.7%) conceived in the GnRHa group compared with 28 (42.4%) in the control group (p 5 .0003), resulting in 124 and 40 newborns (p , .01), respectively [1]. Spontaneous pregnancies occurred in 80 women (65.6%) in the GnRHa group and 25 (37.9%) in the control group (OR: 3.12; p 5 .0004) [1].…”

“…In this retrospective cohort study, the fertility outcomes (i.e., cyclic ovarian function recovery and pregnancies after chemotherapy) of 286 patients who received GnRHa during cytotoxic therapy were compared with those of 188 women who underwent chemotherapy alone [1]. Among evaluable patients, more patients in the GnRHa group resumed cyclic ovarian function after chemotherapy than patients receiving chemotherapy alone (87% vs 49%; odds ratio [OR]: 6.87; p 5 .0001) [1]. A total of 85 patients (69.7%) conceived in the GnRHa group compared with 28 (42.4%) in the control group (p 5 .0003), resulting in 124 and 40 newborns (p , .01), respectively [1].…”

Is Menstruation or the Serum Hormone Level a Useful Predictor for Live Birth after Gonadotropin-Releasing Hormone Agonist during Chemotherapy in Young Breast Cancer Patients

“…GnRH agonist treatment is simple and inexpensive compared with other methods, and has been used for the purpose of fertility preservation over the last decade. Although clinical data regarding the efficacy of concomitant GnRH agonist treatment are conflicting [10,11] and some clinical guidelines consider this method to be experimental [3,9], growing evidence and several guidelines indicate that it is now a reliable method to provide protection against POF [12][13][14][15][16].…”