Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial

Behringer, Karolin; Thielen, Indra; Mueller, Horst; Goergen, Helen; Eibl, Angelika Diana; Rosenbrock, Johannes; Halbsguth, Teresa; Eichenauer, Dennis A.; Fuchs, Michael; Reiners, Katrin S.; Renno, Joerg H.; Ven, Katrin van der; Kuehr, Marietta; Wolff, Michael von; Diehl, Volker; Engert, Andreas; Borchmann, Peter

doi:10.1093/annonc/mdr575

Cited by 93 publications

(79 citation statements)

References 30 publications

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“…Relevant to this highly debatable issue, Behringer et al [12] also found that the use of GnRHa during chemotherapy has significantly increased the probability to become pregnant (OR 5 12.87; p 5 .001). Similarly, Del Mastro et al [11] and the authors of several other recent meta-analyses of RCTs [1] concluded that the significant reduction (p 5 .013) in POF rate, associated with GnRHa, provides convincing evidence in support of the efficacy of this preventive strategy.…”

Section: Discussionmentioning

confidence: 99%

“…The quality of evidence for recommending such strategies may be considered low, according to Fleisher et al [17], because it is based on nonrandomized, case-control, or observational studies. On the contrary, the role of GnRHa therapy in preserving ovarian function has been assessed both in randomized trials and in nonrandomized, case-control studies [1,3,5,8,9,[11][12][13][14][15].…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

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

2015

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“…Однако при использовании программ с меньшими суммарными дозами алкили-рующих препаратов (2 цикла ВЕАСОРР-эск + 2 цикла ABVD) эффект защиты яичников возможен. Число беременностей оказалось выше в группе женщин, которым проводилась защита яичников во время хи-миотерапии [25]. Аналогичные результаты получены Ю.В.…”

Section: клиническая онкогематологияunclassified

First-Line Therapy for Patients with Advanced Hodgkin’s Lymphoma: Efficacy and Toxicity of Intensive ЕАСОРР-14 Program (NN Blokhin National Medical Cancer Research Center Data)

Демина¹,

Леонтьева²,

Tumyan³

et al. 2017

Клиническая онкогематология

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Aim. To assess the efficacy and toxicity of intensive 6 courses EACOPP-14 treatment with or without radiotherapy (RT) for advanced stages of Hodgkin's lymphoma (HL). Materials & Methods. From November 2009 to February 2015, 95 patients with advanced stages of HL (IIX-IIE, III-IV) aged between 17 and 50 years (median 29 years) were selected for the participation in the protocol ЛХМосква1-3. The study population consisted of 46.3 % men and 53.7 % women. The results of the treatment were assessed in 91 patients who have received more than 2 courses of EACOPP-14. The follow up period was at least 3 months after the receiving the therapy. Consolidation RT with a total dose of 30 Gy for residual tumor lesions and/or initially large tumors was performed after the chemotherapy. Results. Complete remission was achieved in 82 (90.1 %) patients, partial remission in 2 (2.2 %), and the progression was observed in 7 (7.7 %) patients. The overall 4-year survival rate was 90.8 %, the progression-free survival was 88.2 %. The toxicity of the ЕАСОРР-14 program was slightly lower than that of 8 courses of ВЕАСОРРesc, and was comparable to the toxicity of other modifications of intensified ВЕАСОРР scheme. Hematological toxicity grade 3 and 4 was most commonly observed: leukopenia was observed after 64.9 % of courses, anemia - after 24 % of courses, thrombocytopenia - after 3.8 % of courses. The rate of infections did not singificantly differ and accounted for 24 %. The most frequent non-infectious complications were mucositis (21.1 %) and polyneuropathy (11.7 %). Complications resulted in the change of treatment in only 3 (3.01 %) of patients. The exclusion of bleomycine from the ЕАСОРР-14 program reduced the frequency of RT complications. Grade 3 pulmonitis developed in 4.5 % of cases, while radiation-induce pulmonary fibrosis verified by CT developed in 15.2 % of cases. The ЕАСОРР-14 6 courses program showed its high efficacy both with and without RT, high tolerance and the possibility of full administration for the majority of patients with the various stages of HL. Conclusion. Current research showed the efficacy of treatment without RT for patients with advanced stages of HL with negative PET results and small (< 2.5 cm) residual tumors after intensive ЕАСОРР-14 program. This approach allowed to avoid a number of late treatment complications.

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“…Consistent with previous observations that AYA women in their 30s are more likely than younger women to develop chemotherapy-associated premature ovarian failure, AMH recovery following chemotherapy is more likely in younger, compared to older AYAs with a history of Hodgkin's lymphoma. 65 …”

Section: Measuring Ovarian Reserve: Anti-mullerian Hormonementioning

confidence: 99%

Innovative fertility preservation strategies and programs for young adults with cancer

Johnson¹

2016

COAYA

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Preservation of fertility is a key issue for young adults newly diagnosed with cancer. Up to 90% of cancer patients under the age of 45 are at risk for fertility impairment following cancer therapy. Cancer patients who are not offered fertility preservation (FP) and those who become infertile following therapy may experience long-term psychosocial distress. This review summarizes the numerous effective strategies for preserving fertility, including sperm banking, electroejaculation, and testicular sperm extraction in males and cryopreservation of embryos or oocytes in females. This paper also highlights novel methods currently in development, such as gonadal tissue cryopreservation and in vitro maturation of gametes. In women, anti-Mullerian hormone is emerging as an accurate marker of ovarian reserve, and the use of gonadotropin releasing hormone analogs to protect fertility is increasingly well validated. Although national guidelines mandate FP counseling and referral prior to the start of cancer therapy for patients with reproductive potential, only a minority of young cancer patients in the USA currently take steps to preserve fertility prior to the start of therapy. Some cancer centers across the USA are developing institutional strategies to support FP, resulting in increased utilization of fertility services by newly diagnosed cancer patients.

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Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial

Abstract: Hormonal levels after 2+2 indicate a reduced ovarian reserve. However, 2+2 in combination with GnRH analogues does not compromise fertility within the evaluated observation time.

Cited by 93 publications

References 30 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

First-Line Therapy for Patients with Advanced Hodgkin’s Lymphoma: Efficacy and Toxicity of Intensive ЕАСОРР-14 Program (NN Blokhin National Medical Cancer Research Center Data)

Innovative fertility preservation strategies and programs for young adults with cancer

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