Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists

Hickman, Lisa C.; Llarena, Natalia C.; Valentine, Lindsey N.; Liu, Xiaobo; Falcone, Tommaso

doi:10.1007/s10815-018-1128-2

Cited by 44 publications

(32 citation statements)

References 54 publications

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“…Several meta-analyses have been conducted to summarize the results from the available randomized trials performed to investigate the clinical efficacy of temporary ovarian suppression with GnRHa during chemotherapy in premenopausal cancer patients (Table 6) [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120]. The oldest meta-analyses included also prospective non-randomized studies, some were restricted to a single tumor type (i.e.…”

Section: Meta-analyses Of Randomized Trialsmentioning

confidence: 99%

Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application

Lambertini

Horicks

Mastro

et al. 2019

Cancer Treatment Reviews

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Survivorship issues are an area of crucial importance to be addressed as early as possible by all health care providers dealing with cancer patients. In women diagnosed during their reproductive years, the possible occurrence of chemotherapy-induced premature ovarian insufficiency (POI) is of particular concern being associated with important menopause-related symptoms, psychosocial issues as well as infertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy has been studied to reduce the gonadotoxic impact of chemotherapy thus diminishing the chance of developing POI. Despite more than 30 years of research in both preclinical and clinical settings, the performance of this strategy has remained highly debated until recently. In particular, the potential mechanisms of action for the protective effects of GnRHa during chemotherapy are still not clearly identified. Nevertheless, important novel research efforts in the field have better elucidated the role of this option that is now endorsed for clinical use by several guidelines. This manuscript aims at providing an extensive overview of the literature on the use of temporary ovarian suppression with GnRHa during chemotherapy in cancer patients by addressing its biological rationale, the available preclinical and clinical evidence as well as the still existing grey zones in this field that future research efforts should address.

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Section: Meta-analyses Of Randomized Trialsmentioning

confidence: 99%

Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application

Lambertini

Horicks

Mastro

et al. 2019

Cancer Treatment Reviews

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“…Timing of cancer treatment, the specific regimen, cancer typology, presence or absence of a partner, patient's age, body mass index and ovarian reserve status are the main factors for clinicians to record in order to establish the most suitable fertility preservation method (12). A reproductive plan need to implemented and one option not exclude another one: Gn-RH analog can be considered in breast cancer patients, but without excluding oocyte and/or ovarian tissue preservation (13, 14). The Italian law regulating assisted reproduction does not permit the cryopreservation of embryos for infertile couples (15) and although this banning was abolished by the Constitutional Court in 2009 (16), its use in fertility preservation is still unclear in our country.…”

Section: Introductionmentioning

confidence: 99%

Oocyte Cryopreservation in Oncological Patients: Eighteen Years Experience of a Tertiary Care Referral Center

et al. 2019

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Objective: The aim of the present study is to report our experience on elective women fertility preservation before cancer treatment.Study Design: This is a single-center retrospective observational study, including all patients who underwent elective fertility preservation before oncological treatment between January 2001 and March 2019 at our Institute.Results: Of a total of 568 women who received fertility counseling, 244 (42.9%) underwent 252 oocyte retrieval cycles after controlled ovarian stimulation for cryopreservation. The majority of patients were diagnosed with breast cancer (59.9%), followed by women affected by Hodgkin's and non-Hodgkin's lymphoma (27.4%). A minority comprised patients diagnosed with other malignancies that affected soft tissues (2.8%), ovary borderline type (2.4%), digestive system (1.6%), leukemia (1.6%), uterine cervix (1.2%). The remaining 3.1% were affected by other cancer types. The mean age of the cohort was 31.3 ± 6.4 years and the mean oocyte retrieval was 13.5± 8.4. Of 11 women who returned to attempt a pregnancy, three performed two thawed cycles. We obtained four pregnancies from 24 embryo transfers (Pregnancy Rate 36.4% for couple): two miscarriages and two live births. Overall, 95.7% of oocytes are still in storage.Conclusions: A close collaboration between Cancer and Fertility Center in a tertiary care hospital is essential to provide a good health service in oncological patients. Offering fertility preservation is no longer considered optional and must be included in every therapeutic program for women who receive an oncological diagnosis in their reproductive age. Oocyte cryopreservation appears to be a good opportunity for fertility preservation. Our results, although they are obtained in a small sample, are encouraging, even if only 4.5% of patients returned to use their gametes.

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“…The lack of a standardized definition of chemotherapy-associated POI has been identified in several MAs as a limitation to the interpretation of findings in the literature regarding GnRHa. All MAs covered in this review analyzed the amenorrhea rate or resumption of menses as the primary outcome and the rate of spontaneous pregnancy as the secondary outcome, except for two studies [ 88 , 89 ]. Three studies assessed the results of the primary endpoint without setting a specific time point [ 90 - 92 ], one study analyzed the primary outcome 2 years after completion of treatment [ 88 ], and the remaining studies included analyses of the primary outcome at 1 year after the end of chemotherapy [ 89 , 93 - 96 ].…”

Section: Lack Of a Standardized Definition Of Poi After Chemotherapymentioning

confidence: 99%

“…All MAs covered in this review analyzed the amenorrhea rate or resumption of menses as the primary outcome and the rate of spontaneous pregnancy as the secondary outcome, except for two studies [ 88 , 89 ]. Three studies assessed the results of the primary endpoint without setting a specific time point [ 90 - 92 ], one study analyzed the primary outcome 2 years after completion of treatment [ 88 ], and the remaining studies included analyses of the primary outcome at 1 year after the end of chemotherapy [ 89 , 93 - 96 ]. The rate of amenorrhea 1 year after the end of chemotherapy is a commonly adopted primary endpoint in several RCTs [ 79 , 80 , 82 , 86 , 87 ] because menopause is clinically defined as the absence of menstruation for a year, and resumption of menses is a clinically relevant and reproducible outcome [ 93 ].…”

Section: Lack Of a Standardized Definition Of Poi After Chemotherapymentioning

confidence: 99%

The role of gonadotropin-releasing hormone agonists in female fertility preservation

Lee¹,

Choi²

2021

Clin Exp Reprod Med

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Advances in anticancer treatments have resulted in increasing survival rates among cancer patients. Accordingly, the quality of life after treatment, particularly the preservation of fertility, has gradually emerged as an essential consideration. Cryopreservation of embryos or unfertilized oocytes has been considered as the standard method of fertility preservation among young women facing gonadotoxic chemotherapy. Other methods, including ovarian suppression and ovarian tissue cryopreservation, have been considered experimental. Recent large-scale randomized controlled trials have demonstrated that temporary ovarian suppression using gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy is beneficial for preventing chemotherapy-induced premature ovarian insufficiency in breast cancer patients. It should also be emphasized that GnRHa use during chemotherapy does not replace established fertility preservation methods. All young women facing gonadotoxic chemotherapy should be counseled about and offered various options for fertility preservation, including both GnRHa use and cryopreservation of embryos, oocytes, and/or ovarian tissue.

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Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists

Abstract: GnRHa may have a protective effect against the development of POF after gonadotoxic chemotherapy; however, the duration of benefit is unclear and requires further study.

Cited by 44 publications

References 54 publications

Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application

Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application

Oocyte Cryopreservation in Oncological Patients: Eighteen Years Experience of a Tertiary Care Referral Center

The role of gonadotropin-releasing hormone agonists in female fertility preservation

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