‘An ounce of prevention is worth a pound of cure’: the case for and against GnRH-agonist for fertility preservation

Blumenfeld, Zeev; Katz, Guy; Evron, Ayelet

doi:10.1093/annonc/mdu036

Cited by 54 publications

(108 citation statements)

References 55 publications

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“…The OR for preserving COF was 6.87 for the patients who received GnRHa in addition to chemotherapy (95% CI 3.4-13.4) and 3.12 (95% CI 1.7-5.8) (p , .001) for spontaneously conceiving versus those who were treated with chemotherapy without the GnRHa. Although, 25 studies (over 10 prospective RCTs) have shown a significant decrease in POF rate in survivors of chemotherapy and GnRHa, and there are nine publications not supporting GnRHa use [1].The ASCO [5], the ASRM [6], and the ESMO [7] do not support GnRHa as a proven method for fertility preservation and consider it experimental. One of the main arguments against considering the GnRHa cotreatment as an established method for fertility preservation is that preserving COF and regular menses in survivors is only a surrogate marker not equivalent to fertility, that is, pregnancies [10].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the late effects of cancer treatment have recently gained a worldwide interest [1][2][3][4], and the protection against iatrogenic infertility caused by chemotherapy assumes a high priority. Resumption of menses may not be an accurate marker of fertility, because infertility and diminished ovarian reserve are observed in women who resume normal menstrual cycles after treatment with chemotherapy [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…Several options have been put forward for preserving female fertility: ovarian transposition, cryopreservation of embryos, unfertilized oocytes, and/or ovarian tissue, and administration of GnRHa in an attempt to decrease the gonadotoxic effects of chemotherapy by simulating a prepubertal hormonal milieu [1][2][3][4][5][6]. Unfortunately, none of the suggested methods is ideal, and none guarantees future fertility in survivors.…”

Section: Introductionmentioning

confidence: 99%

“…The in vitro maturation of primordial follicles to fertilizable metaphase-II oocytes is a future endeavor with enormous potential, but it requires overcoming many technological obstacles and is not clinically available yet. We have recently summarized the case for and against gonadotropinreleasing hormone agonist (GnRHa) for fertility preservation [1,3,4]. Indeed, GnRHa has been used by many groups of clinicians for minimizing the gonadotoxic effects of chemotherapy, with the rationale and philosophy that preventing premature ovarian failure (POF) in survivors is preferable to treating it, following the dictum: "an ounce of prevention is worth a pound of cure" [1].…”

Section: Introductionmentioning

confidence: 99%

“…To date, 25 studies (15 retrospective and 10 prospective, randomized controlled trials [RCTs]) have reported on 2,145 patients treated with GnRHa in parallel to chemotherapy, showing a significant decrease in POF rate in survivors versus nine studies reporting on 593 patients, not supporting GnRHa use [1]. However, the American Society of Clinical Oncology (ASCO), the American Society for Reproductive Medicine (ASRM), and the European Society for Medical Oncology (ESMO) concluded that GnRHa is not considered a proven effective method of fertility preservation [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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

2015

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2015

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Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms

Stone

Schiffer

2017

Holland‐Frei Cancer Medicine

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Overview Acute myeloid leukemia (AML) is the most common variant of acute leukemia occurring in adults, comprising approximately 80% of acute leukemia cases diagnosed in individuals of age >20 years. Remarkable advances in transfusion medicine, treatment of infections, development of potent antiemetics, improved chemotherapeutic approaches, and increased use of safer allogeneic transplantation have led to an improved outcome at least in younger patients. Moreover, a more sophisticated understanding of pathophysiology, particularly in the area of genomics, may soon lead to less toxic, patient‐specific, and more effective therapies. At present, approximately 80% of younger (age <60 years) adults and 30%–50% of all older patients achieve complete remission (CR) defined as a morphologically normal bone marrow with reasonable neutrophil and platelet counts and no evidence of extramedullary disease. Varying with patient age and other biologic factors, 10–70% of these complete responders can be expected to achieve long‐term survival with the likelihood that most of these individuals are cured of their disease. However, AML is largely an intrinsically chemoresistant disease, the outcome in older adults has changed little, and the chemotherapeutic approach has remained stagnant.

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Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms

Stone¹,

Schiffer²,

DeAngelo³

2022

Holland‐Frei Cancer Medicine

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Overview Acute myeloid leukemia (AML) is a heterogeneous disease characterized by unbridled proliferation of myeloid stem cells resulting in bone marrow failure and death without effective therapy. The median age of AML is approximately 70; predisposing factors include inherited mutations, exposure to industrial solvents, ionizing radiation, or certain chemotherapy given for other malignancies or conditions. The disease results from the accumulation of mutations in pathways that promote cellular proliferation or impairing differentiation. Prognosis is based on a combination of host and disease factors, especially diagnostic cytogenetics and genomics. In younger fit patients, therapy consists of myelosuppressive induction chemotherapy to minimize disease burden and allow restoration of normal hematopoiesis. Postremission chemotherapy with additional myelo‐intense chemotherapy and/or allogeneic stem cell transplant is required to potentiate cure. In older and less fit patients (perhaps those with adverse prognosis) the current standard is repetitive cycles of a hypomethylating agent or low‐dose cytarabine plus the BCL‐2 inhibitor, venetoclax. The application of molecularly targeted therapies at both diagnosis and relapse may change the natural history of the disease, the management of which requires a comprehensive integration of disparate fields including social work, nutrition, pharmacy, blood bank, and medical oncology.

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‘An ounce of prevention is worth a pound of cure’: the case for and against GnRH-agonist for fertility preservation

Cited by 54 publications

References 55 publications

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

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

Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms

Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms

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