Safety Of Fertility Preservation Research Articles

Fertility Preservation and Assisted Reproduction in Patients With Breast Cancer Interrupting Adjuvant Endocrine Therapy to Attempt Pregnancy.

We investigated time to pregnancy, efficacy and safety of fertility preservation, and assisted reproductive technologies (ARTs) in women with early hormone receptor-positive breast cancer (BC) desiring future pregnancy. POSITIVE is an international, single-arm, prospective trial, in which 518 women temporarily interrupted adjuvant endocrine therapy to attempt pregnancy. We evaluated menstruation recovery and factors associated with time to pregnancy and investigated if ART use was associated with achieving pregnancy. The cumulative incidence of BC-free interval (BCFI) events was estimated according to the use of ovarian stimulation at diagnosis. The median follow-up was 41 months. Two hundred seventy-three patients (53%) reported amenorrhea at enrollment, of whom 94% resumed menses within 12 months. Among 497 patients evaluable for pregnancy, 368 (74%) reported at least one pregnancy. Young age was the main factor associated with shorter time to pregnancy with cumulative incidences of pregnancy by 1 year of 63.5%, 54.3%, and 37.7% for patients age <35, 35-39, and 40-42 years, respectively. One hundred and seventy-nine patients (36%) had embryo/oocyte cryopreservation at diagnosis, of whom 68 reported embryo transfer after enrollment. Cryopreserved embryo transfer was the only ART associated with higher chance of pregnancy (odds ratio, 2.41 [95% CI, 1.75 to 4.95]). The cumulative incidence of BCFI events at 3 years was similar for women who underwent ovarian stimulation for cryopreservation at diagnosis, 9.7% (95% CI, 6.0 to 15.4), compared with those who did not, 8.7% (95% CI, 6.0 to 12.5). In POSITIVE, fertility preservation using ovarian stimulation was not associated with short-term detrimental impact on cancer prognosis. Pregnancy rates were highest among those who underwent embryo/oocyte cryopreservation followed by embryo transfer.

Less is more in endometrial cancer (SLN, conservative treatment, radical hysterectomy, molecular classification).

The management of endometrial cancer has known many evolutions within the last decades. In this review, we aim to summarize recent evolutions (mainly toward less aggressive management) that have occurred in the management of endometrial cancer. Enhanced by molecular classification, the determination of lymph node status, in young women, in case of cervical invasion, the treatment is evolving toward a less aggressive strategy. The predictive value and the safety of sentinel lymph node biopsy explain why most societies propose to abandon systematic pelvic and para aortic lymphadenectomy. For young women, the safety of fertility preservation is now well established and efficient protocols have been validated. In stage II endometrial cancer (stromal cervical invasion), radical hysterectomy appears excessive. The Cancer Genome Atlas classification increases prognostic evaluation in association with the traditional pathological classification and permits to tailor adjuvant treatment more accurately.

Spermatogonial Stem Cell-Based Therapies: Taking Preclinical Research to the Next Level.

Fertility preservation via biobanking of testicular tissue retrieved from testicular biopsies is now generally recommended for boys who need to undergo gonadotoxic treatment prior to the onset of puberty, as a source of spermatogonial stem cells (SSCs). SSCs have the potential of forming spermatids and may be used for therapeutic fertility approaches later in life. Although in the past 30 years many milestones have been reached to work towards SSC-based fertility restoration therapies, including transplantation of SSCs, grafting of testicular tissue and various in vitro and ex vivo spermatogenesis approaches, unfortunately, all these fertility therapies are still in a preclinical phase and not yet available for patients who have become infertile because of their treatment during childhood. Therefore, it is now time to take the preclinical research towards SSC-based therapy to the next level to resolve major issues that impede clinical implementation. This review gives an outline of the state of the art of the effectiveness and safety of fertility preservation and SSC-based therapies and addresses the hurdles that need to be taken for optimal progression towards actual clinical implementation of safe and effective SSC-based fertility treatments in the near future.

Barriers to fertility preservation (FP) in a prospective pan-Canadian study of young women with breast cancer (YWBC).

136 Background: Despite ASCO recommendations that oncologists routinely offer FP to young cancer patients prior to treatment, studies show that only a minority of YWBC are given this option. We sought to determine whether an intervention, including educational materials and regular reminders to breast surgeons, would improve FP referral. The current report examines the rates of FP discussion, referral, uptake and reasons for declining, according to participants’ self-reported pre-diagnosis fertility plans. Methods: Consecutive women ≤ age 40 newly diagnosed with breast cancer at 30 Canadian sites were offered enrolment in a national study of YWBC. At 3 months each participant was surveyed regarding her pre-diagnosis (dx) fertility plans and post-dx oncofertility management. Results: Of the 712 recruits (09/15 to 08/18) with invasive disease (mean age 36), 46%, 15% and 29% had 0, 1 or 2 children respectively and 77% were in a stable relationship. Among the 480 women who completed the fertility survey, 392 (82%) indicated they had a pre-treatment fertility discussion initiated by a health care provider (HCP) - in 232 cases (48%) the surgeon/nurse and in 130 cases (27%) the medical oncologist/ nurse. Only 14 (16%) of the 88 women not approached by a HCP initiated such a discussion. Rates of FP discussion, referral and uptake are shown below. Among the 38 women who definitely wanted (more) children prior to dx and were offered FP but declined the consult or procedure, the commonest reasons were cost (n = 9) and fear that treatment delay (n = 8) or FP (n = 4) could cause recurrence. Conclusions: Post-intervention FP discussion rates were higher than previously reported. Yet 26% of patients who had definitely/probably not completed their family were not referred for a FP consult. Cost remains a significant FP barrier. Studies are needed to confirm the long-term safety of FP for ER+ patients. [Table: see text]

Current Multidisciplinary Approach to Fertility Preservation for Breast Cancer Patients.

Adverse effects on fertility are a significant problem for premenopausal breast cancer patients. Since April 2009, we have been referring young patients for fertility counseling provided by a multidisciplinary team. Here we evaluated the efficacy and safety of our current fertility preservation approach. We retrospectively analyzed the cases of 277 patients < 45 years old at diagnosis, which was made between 2009 and 2016. Seventy-two (26%) patients received fertility counseling. Seventeen (6%) of the 277 patients decided to preserve their fertility before starting adjuvant systemic therapy. Six (35%) patients underwent oocyte cryopreservation, and 11 (65%) married patients opted for embryo cryopreservation. There were no pregnancies among the patients undergoing oocyte cryopreservation, whereas 3 (27%) of the patients who opted for embryo cryopreservation became pregnant. Two (12%) patients stopped endocrine therapy after 2 years in an effort to become pregnant, but their breast cancers recurred. Though the problem of fertility loss for breast cancer patients is important and we should assess the infertility risk for all patients, we should also consider the prognosis. In June 2016, we launched a prospective multicenter cohort study to evaluate the efficacy and safety of fertility preservation in greater detail.

Safety of fertility preservation in breast cancer patients in a register-based matched cohort study

PurposeTo determine if women with breast cancer that undergo fertility preservation (FP), with or without hormonal stimulation, present with an increased risk of breast cancer recurrence.MethodsA matched cohort study on women with breast cancer attempting to ensure FP in Stockholm from 1999 to 2013 [exposed women (n = 188), age-matched unexposed controls (n = 378)] was designed using the Stockholm regional data from the Swedish National Breast Cancer Quality Register. Breast cancer relapse rates [incidence rate ratio (IRR)] and 95% confidence interval (CI) were estimated using Cox regression and adjusted for potential confounding factors. Completeness of the registry at the time of the study was close to 99%.ResultsMost women attempted FP by hormonal stimulation treatment (n = 148, 79%) with the objective of freezing their eggs or embryos. A smaller group elected FP methods without hormone stimulation (n = 40, 21%). Women who received hormone stimulation did not present with a higher relapse rate than unexposed control women in a model adjusted for age and calendar period of diagnosis (IRR 0.59, 95% CI 0.34–1.04). The results remained virtually unchanged after adjustment for tumor size, estrogen receptor status, affected lymph nodes, and chemotherapy treatment (IRR 0.66, 95% CI 0.37–1.17).ConclusionEvidence was not found that fertility preservation, with or without hormonal stimulation, was associated with an increased risk of breast cancer recurrence. The high coverage rate of this population-based study supports the safe practice of fertility preservation in young women with breast cancer.

Abstract P4-11-05: Safety of fertility preservation indicated by a diagnosis of breast cancer: A Swedish registry-matched cohort study

Abstract Purpose The number of women that perform fertility preservation (FP) before initiating chemotherapy for treatment of breast cancer is increasing. Our purpose was to investigate the safety of performance of fertility preservation with and without hormonal stimulation in the incidence rate of breast cancer relapse. Patients and methods The study was designed as a matched cohort study. Women who had undergone FP at the Reproductive Medicine clinic of Karolinska University Hospital (N=187), irrespective of whether hormonal stimulation was required or not, were considered exposed. For all exposed women, two age-matched women who had not undergone fertility preservation were identified in the Regional Breast Cancer Registry Stockholm-Gotland and the Swedish National Quality Registry for Breast Cancer (N=319). The proportional hazards assumption was evaluated by applying the Grambsch-Therneau test on the Schoenfeld residuals obtained from each model, respectively. When interpreting the test results, a significance level of 5% was used to determine statistical significance. Results In the exposed cohort, a higher proportion of women underwent FP with hormonal stimulation aiming at freezing eggs or embryos (81%, N=142), whereas only 19% underwent freezing of ovarian tissue or attempted egg retrieval without hormonal stimulation (N=35). The mean follow up time was 6.3 years (range: 1.5-17.8 years), and median follow-up: 5.7 years. There was no evidence of non-proportional hazards with respect to the effects of fertility preservation on the risk of relapse in the whole FP cohort, irrespective if the women underwent hormonal stimulation or not for FP, or of receptor status or tumour size at diagnosis. A stratified Cox regression model that allowed separate baseline hazard functions for each level for the investigation of the effect of number of involved lymph nodes was performed. In this model, the effect of fertility preservation on the risk of relapse was virtually unchanged (IRR: 1.02, 95% CI:0.56-1.84). Conclusion Fertility preservation either using hormone stimulation or not is unlikely to cause substantially increase recurrence risk of breast cancer, and irrespective of the receptor status, tumorur size of lymph node compromise. The incidence of breast cancer relapse after hormonal or non-hormonal fertility preservation was not different from that of matched controls from the Regional Breast Cancer Registry in this large cohort study. Citation Format: Rodriguez-Wallberg KA, Eloranta S, Krawiec K, Lissmats A, Liljegren A. Safety of fertility preservation indicated by a diagnosis of breast cancer: A Swedish registry-matched cohort study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-05.

Safety of controlled ovarian stimulation with gonadotropins and letrozole in women with BRCA mutations

Safety of fertility preservation (FP) via controlled ovarian stimulation with letrozole supplementation (COSTLES) prior to breast cancer treatment has not been determined in BRCA mutation carriers. We sought to determine whether women with BRCA-mutation-positive (BRCA+) cancer were at higher risk for relapse after COSTLES.

Long-term safety of fertility preservation by ovarian stimulation and concurrent aromatase inhibitor treatment in women with breast cancer.

9521 Background: Cryopreservation of embryos and oocytes after ovarian stimulation (OS) is an established method of fertility preservation (FP). To minimize the elevation of serum estrogen levels, ...

Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropin in patients with breast cancer: a prospective controlled study with subgroup analysis

Breast cancer is the most common malignant neoplasm encountered in reproductive age women. Aromatase inhibitor protocols have been developed with a view to increase the safety margin of controlled ovarian stimulation (COS) for fertility preservation by oocyte or embryo cryopreservation before chemotherapy. The objective of this study was to investigate the safety of letrozole-gonadotropin COS protocol in breast cancer patients including various subgroup analysis (estrogen receptor (ER) positive vs.

Perception and needs of reproductive specialists with regard to fertility preservation of young breast cancer patients

Treatment-related infertility is one of the important quality-of-life issues in young breast cancer (YBC) patients. Although existing guidelines recommend supporting fertility preservation (FP) of YBC, the perceptions of reproductive specialists (RS) has not been evaluated. We investigated the perceptions and needs of RS with regard to FP of YBC patients. A cross-sectional survey was sent to 423 certified RS registered to the Japan Society for Reproductive Medicine to self-evaluate their perceptions and needs regarding FP in YBC patients. Two hundred RS (47 %) responded to the survey. 99 % responded that RS should be engaged in FP of YBC patients. 88 % responded that they would like to treat YBC patients, while 46 % responded that cancer treatment is more important than childbirth, even when the patient is recurrence-free 5 years after primary treatment. Respondents affiliated to private clinics were more likely to accept both fertilized and unfertilized egg preservation than those affiliated with academic or general hospitals. 70 % responded that they were anxious about treating breast cancer patients: concerns regarding a greater or unknown risk of recurrence (66 %), insufficient knowledge about breast cancer (47 %), and lack of a patient's spouse/partner (24 %) were identified as major barriers in supporting FP for YBC patients. RS recognize the need for FP in YBC patients and are willing to participate in their care. Affiliation of RS was related to a positive attitude to egg preservation. Various concerns regarding FP among RS indicate the need for evidence that supports the safety of FP, inter-disciplinary communication, and practice guidelines.

Abstract P2-11-02: Perception and practice of reproductive specialists towards fertility preservation of young breast cancer patients

Abstract Background: The potential for infertility caused by treatment is one of the important quality-of-life issues in young breast cancer (YBC) patients. Insufficient communication and partnership between oncologists and reproductive specialists has been identified as a major barrier to meeting their needs. However, the perception of reproductive specialists towards fertility preservation (FP) of YBC has not been evaluated. Objective: To investigate the perception and needs of reproductive specialists towards FP of YBC patients. Methods: A cross-sectional survey was developed and sent to 423 certified reproductive specialists registered to the Japan Society for Reproductive Medicine to self-evaluate their perceptions and practices regarding FP in YBC patients. Results: Two hundred reproductive specialists (47%) responded to the survey. 99% responded that reproductive specialists should be engaged in FP of YBC patients. 46% responded that cancer treatment is more important than childbirth even if the patient was recurrence-free five years after primary treatment. 83% responded that they would like to treat YBC patients. Respondents affiliated with private clinics were more likely to accept both fertilized egg and unfertilized egg preservation than those affiliated with academic or general hospitals (p &amp;lt; 0.01). 58% responded that ovulation induction methods should be modified in YBC patients. The choice of ovulation induction methods varied both in non-cancer women and YBC patients, however, the frequency of the use of letrozole was significantly higher (p &amp;lt; 0.01) and that of LHRH-agonist short protocol was significantly less (p &amp;lt; 0.05) in the management of breast cancer patients than in the practice of non-cancer women. 70% of the reproductive specialists responded that they were anxious in treating YBC patients. Concerns for greater or unknown risk of disease recurrence (66%), insufficient knowledge about breast cancer (47%), and lack of patient's spouse/partner (24%) were identified as major barriers in supporting FP for YBC patients. Conclusion Reproductive specialists recognize the needs of FP in YBC patients and are willing to participate and support care for YBC. Affiliation of reproductive specialists was related to positive attitude towards to egg preservation. Various concerns regarding FP among reproductive specialists indicate the need for evidence that supports the safety of FP for YBC patients and guidelines that facilitate the practice and communication of oncologists and reproductive specialists. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-02.

The efficacy and safety of fertility preservation using ovarian stimulation and oocyte or embryo cryopreservation in female cancer patients

The efficacy and safety of fertility preservation using ovarian stimulation and oocyte or embryo cryopreservation in female cancer patients

Safety of Fertility Preservation by Ovarian Stimulation With Letrozole and Gonadotropins in Patients With Breast Cancer: A Prospective Controlled Study

Because of the accompanying increase in estrogen levels, safety of performing in vitro fertilization (IVF) in women with breast cancer is unknown. Our goal was to determine the effect of controlled ovarian stimulation (COS) using a combination of letrozole with standard fertility medications on disease-free survival in women undergoing embryo or oocyte cryopreservation before adjuvant chemotherapy. A total of 215 women with breast cancer were prospectively evaluated for fertility preservation before adjuvant chemotherapy. Of those, 79 elected to undergo COS with letrozole and gonadotropins for embryo or oocyte cryopreservation. The remaining 136 patients underwent no fertility-preserving procedure and served as controls. Study and control groups were similar at enrollment except for a trend for higher estrogen-receptor positivity in the COS group (P = .08). Time between surgery and chemotherapy was longer for IVF patients (45.08 v 33.46 days; P < .01). Peak estradiol levels ranged from 58.4 to 1,166 pg/mL (mean, 405.94 +/- 256.64 pg/mL or 1,486.76 +/- 942.13 pmol/L) in COS patients. The median follow-up after chemotherapy was 23.4 months (range, 7.5 to 63.6 months) in the COS group and 33.05 months (range, 4.5 to 63.6) in the control group. The hazard ratio for recurrence after IVF was 0.56 (95% CI, 0.17 to 1.9), and the survival was not compromised compared with controls (P = .36). Ovarian stimulation with gonadotropins and letrozole for the purpose of fertility preservation is unlikely to cause substantially increased recurrence risk. Further research, including longer-term follow-up is needed to confirm these findings.