Preservation Of Ovarian Function Research Articles

The role of LHRH agonists in ovarian function preservation in premenopausal women undergoing chemotherapy for early stage breast cancer: A systematic review and meta-analysis.

1050 Background: The risks of chemotherapy-induced ovarian dysfunction and fertility impairment remain a clinical challenge in the management of premenopausal women diagnosed with early breast canc...

Anti-Müllerian hormone and assessment of ovarian reserve after ovarian toxic treatment: a systematic narrative review.

Since serum anti-Müllerian hormone (AMH) levels enable quantitative evaluation of ovarian damage, we conducted a computer-based search, using key words, of all articles published in English through the PubMed database from inception until September 2013 to summarize available studies evaluating ovarian reserve after ovarian toxic interventions to discuss the usefulness of serum AMH levels. We found that most of the studies demonstrated a decline in serum AMH levels when compared to control or pretreatment levels, with levels dependent on the type of treatment modality. Measurement of serum AMH levels enables quantitative evaluation of ovarian damage caused by ovarian toxic interventions, such as chemotherapy and radiotherapy, instead of qualitative evaluation using menstrual condition or basal follicle-stimulating hormone levels. Serum AMH levels are becoming indispensable to assess the ovarian reserve of patients who desire preservation of ovarian function for fertility and endogenous sex steroid hormones.

Preservation of Ovarian Function after Hematopoietic Cell Transplantation (HCT): More Possible Than We Thought?

s / Biol Blood Marrow Transplant 21 (2015) S171eS184 S178 and level of supportive care given was significantly higher in patients with icterus than without (P 1⁄4 0.224) and P1⁄4 0.0081) respectively. Total days for disease resolution in patients with icterus was 32 days compared to 16 days for those without (p1⁄40.022). Nine of the patients with icterus received specific treatment compared to only one in the anicteric group. Seven cases were diagnosed with VOD by the Seattle criteria at a median of day +15 post HSCT, but treatment was delayed by 1-11 days for lack of hyperbilirubinemia, 2 of these never developed hyperbilirubinemia; 4 of 7 cases died. Overall 2 with anicteric and 12 cases with icteric VOD died. Discussion: The Baltimore criteria appear to bemore stringent and cases with anicteric VOD do not meet these diagnostic criteria. This retrospective study describes the features of anicteric VOD at a single center. Even if the patients met the Seattle criteria, treatment was delayed for lack of hyperbilirubinemia or flow reversal on hepatic ultrasound, neither of which are required criteria. Patients with anicteric VOD had a better outcome than those with hyperbilirubinemia, but our study shows that there can be significant morbidity and even mortality associated with anicteric VOD. There seems to be a poor understanding and awareness of anicteric VOD as a diagnosis.Earlierdisease recognitioncould lead tomorepromptand aggressive treatment leading to improved outcomes.

Dexrazoxane abrogates acute doxorubicin toxicity in marmoset ovary.

Preservation of ovarian function following chemotherapy for nonovarian cancers is a formidable challenge. For prepubescent girls, the only option to prevent chemotherapy damage to the ovary is ovarian tissue cryopreservation, an experimental procedure requiring invasive surgeries to harvest and reimplant tissue, which carries the risk of cancer reintroduction. Drugs that block the primary mechanism of chemotherapy insult, such as dexrazoxane (Dexra) in the context of anthracycline chemotherapy, provide a novel approach for ovarian protection and have the potential to overcome current limitations to oncofertility treatment. Dexra is a catalytic topoisomerase 2 inhibitor that protects the mouse ovary from acute doxorubicin (DXR) chemotherapy toxicity in vitro by preventing DXR-induced DNA damage and subsequent gammaH2AX activation. To translate acute DXR ovarian insult and Dexra protection from mouse to nonhuman primate, freshly obtained marmoset ovarian tissue was cultured in vitro and treated with vehicle or 20 μM Dexra 1 h prior to 50 nM DXR. Cultured ovarian tissue was harvested at 2, 4, or 24 h post-DXR treatment. Dexra prevented DXR-induced DNA double-strand breaks as quantified by the neutral comet assay. DXR treatment for 24 h increased gammaH2AX phosphorylation, specifically increasing the number of foci-positive granulosa cells in antral follicles, while Dexra pretreatment inhibited DXR-induced gammaH2AX phosphorylation foci formation. Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1 phosphorylation and caspase-9 activation as assayed by Western blots of ovarian tissue lysates. The combined findings suggest Dexra prevents primary DXR-induced DNA damage, the subsequent cellular response to DNA damage, and may diminish early apoptotic signaling in marmoset ovarian tissue. This study provides initial translation of Dexra protection against acute ovarian DXR toxicity from mice to marmoset monkey tissue.

Ovarian function in female survivors after multimodal Ewing sarcoma therapy.

With advances in cancer care, more young women with Ewing sarcoma (ES) survive after treatment. Thus, we sought to analyze the ovarian function in prepubertal, pubertal and postpubertal females and young women receiving multimodal therapy for ES, and to identify patients at risk of infertility on whom fertility preservation would be indicated. Twenty-seven female survivors of ES were included in this retrospective multiinstitutional study. Patients were classified into four groups according to the treatment received: chemotherapy (CHT) without pelvic radiation (pRT), chemotherapy and pRT, CHT and autologous hematopoietic cell stem rescue (aHSCT) without pRT, and CHT + pRT + aHSCT. The ovarian function and fertility outcomes were analyzed. At a median follow-up of 5.7 years from diagnosis, and at median age at follow-up of 16.3 years, 67% of the survivors had premature ovarian insufficiency, including all patients receiving pelvic RT and 87.5% of patients who underwent aHSCT, independent of chemoprotection. Thirty-seven percent of patients had a clinical syndrome of premature menopause. The relative risk (RR) of premature ovarian insufficiency of a survivor was 3.9 (p 0.03) for pRT, and 2.4 (p 0.07) for aHSCT. On multivariate analysis, radiation therapy was a significant predictor of higher risk of premature ovarian insufficiency over chemotherapy alone. A large proportion of women receiving multimodal therapy for ES develop premature ovarian insufficiency. Patients and guardians should be informed about the reproductive potential and strategies for preservation of ovarian function should be considered individually. Pediatr Blood Cancer 2015;62:341-345. © 2014 Wiley Periodicals, Inc.

GnrH-agonist co-treatment during chemotherapy for the preservation of ovarian function: a meta-analysis

GnrH-agonist co-treatment during chemotherapy for the preservation of ovarian function: a meta-analysis

Ovarian function preservation with GnRH agonist in young breast cancer patients: Does it impede the effect of adjuvant chemotherapy?

BackgroundConcurrent endocrine therapy with chemotherapy had a concern of potential antagonism. However, gonadotropin-releasing hormone (GnRH) agonist has been used concurrently with chemotherapy to prevent premature ovarian failure for young breast cancer patients. The aim of this study was to determine the impact of concurrent use of GnRH agonists on relapse-free and overall survival, and to establish the oncologic safety of ovarian protection with GnRH agonists. MethodsPremenopausal women aged between 20 and 40 years who received adjuvant chemotherapy for breast cancer from January 2002 to April 2012 were classified into two groups; One treated with GnRH agonists for ovarian protection during chemotherapy, and the other without ovarian protection. A propensity score matching strategy was used to create matched sets of two groups with age, pathologic stage, hormone receptor, and Her2 status. ResultsA total of 101 patients treated with concurrent GnRH agonist during chemotherapy were compared with 335 propensity score matched patients. Among them, 81.2% were younger than 35 years and 58.4% were hormone responsive. Survival analysis using stratified Cox regression showed that women treated with concurrent GnRH agonists had better recurrence-free survival (adjusted Hazard ratio 0.21, p = 0.009; unadjusted Hazard ratio 0.33, p = 0.034). ConclusionsOvarian protection using GnRH agonists can be safely considered for young women with breast cancer in terms of oncologic outcomes. Further studies are needed to assess the long-term outcomes of concurrent GnRH agonist use with chemotherapy.

Gonadotropin-releasing hormone agonists for the preservation of ovarian function among women with breast cancer who did not use tamoxifen after chemotherapy: a systematic review and meta-analysis

To determine whether concurrent use of GnRH agonists with chemotherapy preserves ovarian function in women with breast cancer who did not use tamoxifen. Systematic review and meta-analysis. University-based hospitals. Premenopausal women with breast cancer treated with chemotherapy who did not receive tamoxifen. Randomization to concurrent GnRH agonists with chemotherapy or chemotherapy alone. Odds ratio (OR) of resumption of menses 1 year or more after chemotherapy. Searches were conducted in PubMed, Scopus, Cochrane Trials Register, and the National Research Register through March 2014, and all randomized trials that reported resumption of menses 1 year or more after GnRH agonist with chemotherapy or chemotherapy alone among women with breast cancer who did not receive tamoxifen were included. Four studies were analyzed in the meta-analysis and included 252 patients (GnRH agonist with chemotherapy, n=131; chemotherapy alone, n=121). There was no significant difference in the rate of return of menses between the two groups (OR, 1.47; 95% confidence interval [0.60-3.62]). Heterogeneity among the trials was not significant (I2=16.6%). Concurrent GnRH agonists with chemotherapy may not preserve ovarian function in women with breast cancer. Furthermore, randomized data are limited regarding fertility after concurrent use of GnRH agonists with chemotherapy.

Outcomes of ovarian transposition in gynaecological cancers; a systematic review and meta-analysis.

BackgroundPelvic irradiation is essential for improving survival in women with pelvic malignancies despite inducing permanent ovarian damage. Ovarian transposition can be performed in premenopausal women in an attempt to preserve ovarian function. As uncertainty occurs over the proportion of women who are likely to benefit from the procedure, we performed a systematic review and meta-analysis of the proportion of women with ovarian function preservation, symptomatic or asymptomatic ovarian cysts and metastatic ovarian malignancy following ovarian transposition.MethodsMedline, Embase and The Cochrane Library databases were systematically searched for articles published from January 1980 to December 2013. We computed the summary proportions for ovarian function preservation, ovarian cyst formation and metastatic ovarian disease following ovarian transposition by random effects meta-analysis with meta-regression to explore for heterogeneity by type of radiotherapy.ResultsTwenty four articles reporting on 892 women undergoing ovarian transposition were included. In the surgery alone group, the proportion of women with preserved ovarian function was 90% (95% CI 92–99), 87% (95% CI 79–97) of women did not develop ovarian cysts and 100% (95% CI 90–111) did not suffer metastases to the transposed ovaries. In the brachytherapy (BR) ± surgery group, the proportion of women with preserved ovarian function was 94% (95% CI 79–111), 84% (95% CI 70–101) of women did not develop ovarian cysts and 100% (95% CI 85–118) did not suffer metastases to the transposed ovaries. In the external beam radiotherapy (EBRT) + surgery ± BR group, the proportion of women with preserved ovarian function was 65% (95% CI 56–74), 95% (95% CI 85–106) of women did not develop ovarian cysts and 100% (95% CI 90–112) did not suffer metastases to the transposed ovaries. Subgroup meta-analysis revealed transposition to the subcutaneous tissue being associated with higher ovarian cyst formation rate compared to the “traditional” transposition.ConclusionOvarian transposition is associated with significant preservation of ovarian function and negligible risk for metastases to the transposed ovaries despite common incidence of ovarian cysts.

Gonadotrophin Releasing Hormone Analogues for Ovarian Function Preservation in Young Females Undergoing Chemotherapy

Chemotherapy has significantly improved the prognosis of cancer patients with various malignancies. However, female patients, especially those whoich are premenopausal, suffer from significant chemotherapy induced ovarian function impairment, which decreases their quality of life. Many new techniques for ovarian preservation have been established in recent years. Although the use of gonadotrophin releasing hormone analogues (GnRHa) for this purpose is not a new concept, its effectiveness in protection of ovarian function is still debatable. This article deals with studies and metaanalyses which have been undertaken in the past, demonstrating the impact of GnRHa in ovarian function preservation, and whether their use can be implemented in routine practice.

Gonadotropin-Releasing Hormone for Preservation of Ovarian Function during Chemotherapy in Lymphoma Patients of Reproductive Age: A Summary Based on 434 Patients

BackgroundGonadotropin-releasing hormone agonists (GnRHa) might play a role in preserving ovarian function in lymphoma patients by inhibiting chemotherapy-induced ovarian follicular damage. However, studies of its clinical efficacy have reported conflicting results.MethodWe conducted a meta-analysis to determine the effect of the preservation of ovarian function by administering GnRHa in young patients with lymphoma undergoing chemotherapy. Seven studies were identified that met inclusion criteria and comprised 434 patients assigned to GnRHa combined chemotherapy or chemotherapy alone.ResultsThe incidence of women with premature ovarian failure (POF) demonstrated a statistically significant difference in favor of the use of GnRHa (OR=0.32, 95% CI 0.13-0.77). In addition, the final level of FSH in the GnRH group was significantly lower than control group. (MD= -11.73, 95% CI,-22.25- -1.20), and the final level of AMH in the GnRH group was significantly higher than control group (MD=0.80; 95% CI, 0.61–0.98). However, there was no statistically significant difference between treatment and the control groups in the incidence of a spontaneous pregnancy (OR=1.11; 95% CI, 0.55–2.26).ConclusionThis meta-analysis suggests that GnRHa may be effective in protecting ovarian function during chemotherapy in lymphoma patients. More well-designed prospective studies are needed to carry out for further understanding of this topic.

Fertilité et cancer

Information about chemo and/or radiotherapy gonadotoxicity and about fertility preservation is essential. Sperm cryopreservation has to be systematically offered before gonadotoxic treatments. Efficiency of ovarian function preservation with GnRH agonists is still debated. A controlled ovarian stimulation is necessary before oocyte or embryo cryopreservation. It is only feasible if the treatment is not urgent and if the tumor is not hormone-sensitive. If the treatment is highly gonadotoxic, an ovarian tissue cryopreservation may be appropriate. It is the only fertility preservation technique feasible for prepubertal girls. It is now possible to preserve the fertility of prepubertal boys by cryopreservation of testicular tissue. It is essential to send patients and/or their parents to a specialized fertility preservation center.

Systematic review and meta-analysis of GnRH agonist for preservation of ovarian function in women with hormone receptor negative breast cancer after chemotherapy

Randomized trials of GnRH agonist (GnRHa) with chemotherapy (CHEM) to preserve ovarian function in premenopausal women with breast cancer (BC) reported conflicting results. Several trials included women on Tamoxifen for treatment of hormone receptor (HR) positive BC, which may confound the results as Tamofixen is associated with amenorrhea. We performed a systematic review and meta-analysis analyzing the rate of return of menses in women after CHEM for HR negative BC with or without GnRHa.

Effect of leuprolide acetate on ovarian function after cyclophosphamide–doxorubicin-based chemotherapy in premenopausal patients with breast cancer: results from a phase II randomized trial

Previous studies provided inconclusive evidence for the effectiveness of gonadotropin-releasing hormone analogue on ovarian function protection against chemotherapy-induced genotoxicity in premenopausal patients. This study was designed to examine the efficacy of leuprolide acetate on ovarian function preservation in patients with breast cancer. A total of 220 patients were recruited in this prospective clinical trial and were assigned randomly to receive cyclophosphamide-doxorubicin-based chemotherapy only or chemotherapy plus leuprolide acetate. Resumption of menses or premenopausal levels of both follicle-stimulating hormone (FSH) and estradiol (E2) within 12 months after the end of chemotherapy were considered as effective ovarian preservation. A total of 183 patients were considered evaluable (94 in chemotherapy-only group and 89 in chemotherapy plus leuprolide acetate group). At the end of follow-up, 27 patients in chemotherapy group and 15 in chemotherapy plus leuprolide acetate group resumed menses; seven patients in chemotherapy group and 14 in chemotherapy plus leuprolide acetate group restored premenopausal levels of FSH and E2. The median time to resume menses was 9.2 months for patients in chemotherapy plus leuprolide acetate group and was not reached in chemotherapy-only group. In addition, our results demonstrated that age and chemotherapy doses made no significant difference in the occurrence of premature menopause. The leuprolide acetate treatment simultaneously with cyclophosphamide-doxorubicin-based chemotherapy reduced the risk of developing premature menopause in premenopausal patients with breast cancer.

Ovarian transposition before pelvic irradiation: Indications and functional outcome

To investigate the indications and effectiveness of ovarian transposition before pelvic irradiation. This was a retrospective analysis of patients with malignancies who underwent ovarian transposition before pelvic irradiation. The collected data included age of patient, type and stage of cancer, details of irradiation treatment, and clinical and biochemical parameters of ovarian function during the period of follow-up. Fourteen adult and four pediatric patients with different types of cancers underwent ovarian transposition during the study period. The common tumor types for the adult patients were cervical cancer (n = 4), rectal cancer (n = 4) and medulloblastoma (n = 3), and for pediatric patients was medulloblastoma (n = 2). The mean age for adult patients was 31 years (range, 21-40) and for pediatric patients was 7 years (range, 4-10). Of the adult patients, 10 had adjuvant chemotherapy and four had neoadjuvant chemotherapy added to their radiotherapy program. All pediatric patients received adjuvant chemotherapy. Thirteen of 14 (92.85%) adult patients had normal serum level of follicle-stimulating hormone (FSH; ≤12 IU/L) and E2 (>50 pg/mL). Only one patient had premature menopause. All pediatric patients demonstrated a normal serum level of FSH (<12) and E2 for their age at 3 and 6 months after completion of their treatment. The mean follow-up was 42 months (range, 34-50). Ovarian transposition is an effective procedure for the preservation of ovarian function. Young patients with non-hormone-dependent pelvic tumors should be offered a laparoscopic ovarian transposition before the start of pelvic radiotherapy.

Gonadotropin-Releasing Hormone Analog Cotreatment for the Preservation of Ovarian Function during Gonadotoxic Chemotherapy for Breast Cancer: A Meta-Analysis

ObjectiveTo determine by meta-analysis whether gonadotropin-releasing hormone analog (GnRHa) cotreatment accompanying chemotherapy for breast cancer protects ovarian function.MethodsRandomized controlled trials (RCTs) comparing GnRH cotreatment with chemotherapy alone in premenopausal women were collected by electronic and manual searches of Pubmed, MEDLINE (OVID), CENTRAL (The Coehrane Central Register of Controlled Trials), CBM, CNKI, VIP and Wanfang data bases. All the data was analyzed by Stata 11.2.ResultsSeven studies with a total of 677 participants met the inclusion criteria. The outcome of meta-analysis implied that, compared with adjuvant chemotherapy alone, the number of patients with resumption of spontaneous menstruation was statistically greater in the GnRH cotreatment patients (OR 2.83; 95% CI, 1.52–5.25).ConclusionsEvidence from RCTs suggests a potential benefit of GnRH cotreatment with chemotherapy in premenopausal women, producing higher rates of spontaneous resumption of menses.

Preservation of Fertility in Female Cancer Patients Desiring Future Child Bearing; What is Available and What can be Offered.

The aim of this review is to present an overview of available methods for preservation of ovarian function and fertility in female cancer patients who desire to maintain their child-bearing capacity for future pregnancies. A Medline search was conducted. Published articles from American and European studies from 1976 to present were reviewed. The effect of cancer treatment on the ovary, as well as different methods of fertility preservation and their reproductive outcomes are presented. Pregnancy rates vary according to the type of primary malignancy, stage of disease, method of fertility preservation (for example, hormonal therapy, cryopreservation, fertility-sparing surgery), and other confounding factors such as the patient’s age, reproductive capacity, status of partnership, and genetic disposition. The highest rates of successful pregnancy were observed with embryo cryopreservation. Today, higher cure rates and longer survival are a result of earlier cancer diagnosis and treatment. In conjunction with the advances in assisted reproduction, the preservation of ovarian function and fertility is a major part of multidisciplinary care that should be offered to any young female patient with cancer. Fertility preservation in young cancer patients raises a number of ethical issues particularly regarding standard versus experimental therapies, and long-term financial cost.

The Role of Robotics in Ovarian Transposition

CONFLICT OF INTEREST: NONE DECLAREDThe preservation of ovarian function in young patients after radical hysterectomy has an important role at the post-oncologic management and preserves life quality. Ovarian transposition is a technique in order to avoid irreversible damage to the ovaries caused by irradiation. The principal surgical ways in the transposition of the ovaries is both through laparotomy and laparoscopy. Recently, the application of the robotic technology on this method seems to be promising. We performed a literature search with terms related to robotic surgery and ovarian transposition in Pubmed and Scopus. Two articles were identified dealing with this technique. Robotic assisted ovarian transposition is presented and the possible advantages and disadvantages of such a technique are discussed.

Laparoscopic ovarian transposition before pelvic radiation in rectal cancer patient: safety and feasibility.

BackgroundInfertility due to pelvic radiation for advanced rectal cancer treatment is a major concern particularly in young patients. Pre-radiation laparoscopic ovarian transposition may offer preservation of ovarian function during the treatment however its use is limited.AimThe study investigates the safety, feasibility and effectiveness of pre-radiation laparoscopic ovarian transposition and its effect on ovarian function in the treatment o locally advanced rectal cancer.MethodsCharts review of all young female patients diagnosed with locally advanced rectal cancer, underwent laparoscopic ovarian transposition, then received preoperative radiotherapy at king Faisal Specialist Hospital and Research Centre between 2003–2007.ResultsDuring the period studied three single patients age between 21–27 years underwent pre-radiation laparoscopic ovarian transposition for advanced rectal cancer. All required pretreatment laparoscopic diversion stoma due to rectal stricture secondary to tumor that was performed at the same time. One patient died of metastatic disease during treatment. The ovarian hormonal levels (FSH and LH) were normal in two patients. One has had normal menstrual period and other had amenorrhoea after 4 months follow-up however her ovarian hormonal level were within normal limits.ConclusionsLaparoscopic ovarian transposition before pelvic radiation in advanced rectal cancer treatment is an effective and feasible way of preservation of ovarian function in young patients at risk of radiotherapy induced ovarian failure. However, this procedure is still under used and it is advisable to discuss and propose it to suitable patients.

Preservation of ovarian function and fertility despite gonadotoxic chemotherapy

The author aims to review the various strategies and avenues for fertility preservation despite gonadotoxic chemotherapy in young women. The recent increase in the survival of young patients has increased the worldwide attempts toward fertility preservation. The currently utilized methods are sperm cryopreservation and banking in male patients, and cryopreservation of embryos, unfertilized oocytes and ovarian tissue, as well as administration of gonadotropin-releasing hormone agonists (GnRH-a) before and during the gonadotoxic chemotherapy in young female patients. For those patients in whom pelvic irradiation is planned, ovariopexy is suggested. Since none of the suggested methods are ideal and none guarantees future fertility, a combination of several methods may optimize patients’ chance of fertility preservation. GnRH-a co-treatment may reduce ovarian damage significantly in female patients treated with gonadotoxic chemotherapy. GnRH-a should be considered for women of reproductive age receiving gonadotoxic chemotherapy in addition to assisted reproduction and cryopreservation of embryos, oocytes and ovarian tissue.