GnRH analogs do not protect ovaries from chemotherapy-induced ultrastructural injury in Hodgkin’s lymphoma patients

Nitzschke, Markus; Raddatz, Juliane; Bohlmann, Michael K.; Stute, Petra; Strowitzki, Thomas; Wolff, Michael von

doi:10.1007/s00404-009-1308-5

Cited by 40 publications

(27 citation statements)

References 23 publications

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“…Although several investigators have demonstrated that GnRH-a may inhibit chemotherapy-induced ovarian follicular depletion in rats and rhesus monkeys, some investigators still consider it to be an equivocal and controversial issue in humans [14,[39][40][41][42][43][44]. The only prospective randomized study with histological counting of follicles [38] has shown that in rhesus monkeys, GnRH-a protected the ovary against cyclophosphamide-induced damage by significantly decreasing the number of primordial and primary follicles lost during the chemotherapeutic insult.…”

Section: Discussion: the Arguments 'For And Against' Gnrh-a Co-treatmentmentioning

confidence: 94%

“…However, there are also seven studies claiming that GnRH-a is not helpful for the preservation of ovarian function [9,14,[39][40][41][42][43][44], which were brought up by the opponents to this treatment as an evidence against its use as a co-treatment. Waxman et al found in 1987 that four out of eight female patients treated with Buserelin GnRH-a in parallel to chemotherapy suffered POF (50%) versus six of the nine patients in the control group (66.7%) [40].…”

Section: Discussion: the Arguments 'For And Against' Gnrh-a Co-treatmentmentioning

confidence: 95%

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Preservation of ovarian function and fertility despite gonadotoxic chemotherapy

Blumenfeld

2012

Expert Review of Endocrinology & Metabolism

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Meta-analysis of GnRH-a for preservation of ovarian function showing that not only ovarian function but also pregnancies benefit from this co-treatment. 26 Ben-Aharon I, Gafter-Gvili A, Leibovici L, Stemmer SM. Pharmacological interventions for fertility preservation during chemotherapy: a systematic review Blumenfeld Expert Review of Endocrinology & Metabolism Downloaded from informahealthcare.com by University of Queensland on 02/03/15 For personal use only. 78 Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N. Engl.

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Section: Discussion: the Arguments 'For And Against' Gnrh-a Co-treatmentmentioning

confidence: 94%

Section: Discussion: the Arguments 'For And Against' Gnrh-a Co-treatmentmentioning

confidence: 95%

Preservation of ovarian function and fertility despite gonadotoxic chemotherapy

Blumenfeld

2012

Expert Review of Endocrinology & Metabolism

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“…47,48 Two other studies (the most recent was conducted by the German group) that randomized oral contraceptives and GnRH in patients treated with escalated BEACOPP were unable to find evidence of any efficacy of GnRH which did not improve the hormone assays. 49,50 Analogs of LHRH are, therefore, not recommended in the absence of studies demonstrating their effectiveness. For women who experience premature menopause, hormone replacement therapy may reduce the risks of estrogen deficiency, such as osteoporosis.…”

Section: Different Fertility Preservation Methodsmentioning

confidence: 99%

Management of fertility in patients treated for Hodgkin's lymphoma

Harel¹,

Fermé²,

Poirot³

2011

Haematologica

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“…An argument against GnRHa use [18] claims that prepubertal children, whose hypogonadotropic milieu is simulated by the GnRHa, receiving high-dose chemotherapy given before hematopoietic stem cell transplantation still suffer from ovarian failure. Remérand et al [19] have described four spontaneous pregnancies and successful deliveries in a patient after prepubertal high-dose busulfan and cyclophosphamide conditioning and bone marrow transplantation (BMT), demonstrating that successful pregnancies may occur in patients undergoing prepubertal BMT.…”

Section: Discussionmentioning

confidence: 99%

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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GnRH analogs do not protect ovaries from chemotherapy-induced ultrastructural injury in Hodgkin’s lymphoma patients

Abstract: The results of this study demonstrate ultrastructural ovarian damage in Hodgkin's lymphoma patients irrespective of GnRHa co-treatment. These findings do not support previous studies, showing GnRHa to protect ovarian function.

Cited by 40 publications

References 23 publications

Preservation of ovarian function and fertility despite gonadotoxic chemotherapy

Preservation of ovarian function and fertility despite gonadotoxic chemotherapy

Management of fertility in patients treated for Hodgkin's lymphoma

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

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