Fertility preservation for women with breast cancer: a multicentre randomized controlled trial on various ovarian stimulation protocols.
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ABSTRACT:
SUBMITTER: Balkenende EME
PROVIDER: S-EPMC9340107 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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Fertility preservation for women with breast cancer: a multicentre randomized controlled trial on various ovarian stimulation protocols.
Balkenende Eva M E EME Dahhan Taghride T Beerendonk Catharina C M CCM Fleischer Kathrin K Stoop Dominic D Bos Annelies M E AME Lambalk Cornelis B CB Schats Roel R Smeenk Jesper M J JMJ Louwé Leonie A LA Cantineau Astrid E P AEP de Bruin Jan Peter JP Linn Sabine C SC van der Veen Fulco F van Wely Madelon M Goddijn Mariëtte M
Human reproduction (Oxford, England) 20220701 8
<h4>Study question</h4>Does ovarian stimulation with the addition of tamoxifen or letrozole affect the number of cumulus-oocyte complexes (COCs) retrieved compared to standard ovarian stimulation in women with breast cancer who undergo fertility preservation?<h4>Summary answer</h4>Alternative ovarian stimulation protocols with tamoxifen or letrozole did not affect the number of COCs retrieved at follicle aspiration in women with breast cancer.<h4>What is known already</h4>Alternative ovarian sti ...[more]
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Project description:Study questionHow efficacious and safe are the current approaches to controlled ovarian stimulation (COS) aimed at fertility preservation (FP) in women with breast cancer (BC)?Summary answerIn women with BC undergoing COS aiming at egg/embryo cryopreservation, letrozole-based protocols and those randomly started were equally effective compared with conventional COS, and the overall survival was similar between the women that proceeded to FP and those who did not.What is known alreadyCryopreservation of oocytes and embryos is an established method for FP in women with BC. Recent improvements to COS protocols include concomitant use of letrozole, random-cycle start day of stimulation and the use of GnRHa for the egg maturation trigger. To date, limited sample size of the available studies has not allowed investigation of differences in the efficacy of the different approaches to COS for FP in this patient population.Study design, size, durationA prospective multicenter study with national coverage including 610 women with BC counseled between 1 January 1995 and 30 June 2017 at six Swedish FP regional programs.Participants/materials, setting, methodsAfter counseling, 401 women elected to undergo COS. Treatments differed in the use or not of concomitant letrozole, a conventional or random-cycle day COS initiation and the use of hCG versus GnRHa trigger for oocyte maturation. Numbers of cryopreserved oocytes and embryos were defined as primary outcome. Pregnancy attempts, reproductive outcomes and long-term survival, investigated by the linking of individuals of the cohort to the total population register of the Swedish Tax Agency (up to 25 November 2018), were evaluated.Main results and the role of chanceUsing letrozole or not resulted in similar numbers of oocytes and embryos cryopreserved (meanoocytes = 9.7 versus 10 and meanembryos 4.0 versus 5.3, respectively), similar to COS with random versus conventional start (meanoocytes 9.0 versus 10.6 and meanembryos 4.8 versus 4.8). In COS with letrozole, a GnRHa trigger was associated with a higher number of oocytes retrieved (P < 0.05) and embryos cryopreserved (P < 0.005), compared with conventional hCG trigger. Of 99 women who returned to fertility clinics after cancer treatment, 32 proceeded to thawing of oocytes or embryos and 10 of them had live births. The all-cause survival between the women that underwent COS and those who did not was similar and did not differ between the two groups.Limitations, reasons for cautionData on tumor characteristics and estrogen receptor (ER) status were not known for all women at the time of FP counseling and planning of COS, thus protocols with letrozole have been used for both estrogen-sensitive and non-estrogen-sensitive BC. For the same reason, subsequent adjustment for ERs in the BC or tumor characteristics as potential confounders were not performed as these parameters were not available and did not influence the provision of FP through COS.Wider implications of the findingsThe results of our study support the premise that recently introduced potential improvements to COS protocols for FP in women with BC are efficacious and safe.Study funding/competing interest(s)This study was supported by research grants from the Swedish Cancer Society, the Stockholm County Council, the Percy Falk Stiftelsen, Radiumhemmets Forskningsfonder, The Swedish Breast Cancer Association and Karolinska Institutet to K.A.R.W. J.B. reports grants from Amgen, AstraZeneca, Pfizer, Roche, Sanofi-Aventis and Merck, outside the submitted work, and payment from UpToDate to Asklepios Medicine HB for a chapter on BC prediction and prognostication. All the other authors have no competing interests to report.
| S-EPMC7192532 | biostudies-literature
Project description:PurposeWe have previously reported an approach to ovarian stimulation for the purpose of fertility preservation (FP) in women with breast cancer via embryo freezing with the concurrent use of letrozole. The aim of this study was to provide the pregnancy and FP outcomes when embryos generated with the same protocol are used.Patients and methodsIn all, 131 women with stage ≤ 3 breast cancer underwent ovarian stimulation and received concurrent letrozole 5 mg per day before receiving adjuvant chemotherapy and cryopreserving embryos.ResultsThirty-three of the 131 women underwent 40 attempts to transfer embryos to their own uterus (n = 18) or via the use of a gestational carrier (n = 22) at a mean age of 41.5 ± 4.3 years with a median 5.25 years after embryo cryopreservation. The overall live birth rate per embryo transfer was similar to the US national mean among infertile women of a similar age undergoing in vitro fertilization-embryo transfer (45.0 v 38.2; P = .2). Seven (38.8%) of the 18 pregnancies were twins with no higher-order pregnancies being encountered. No fetal anomalies or malformations were reported in 25 children after a mean follow-up of 40.4 ± 26.4 months. Seventeen of the 33 women attempting pregnancy had at least one child, translating into an FP rate of 51.5% per attempting woman.ConclusionEmbryo cryopreservation after ovarian stimulation with the letrozole and follicle-stimulating hormone protocol preserves fertility in women with breast cancer and results in pregnancy rates comparable to those expected in a noncancer population undergoing in vitro fertilization.
| S-EPMC4507464 | biostudies-literature
Project description:BackgroundIn women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this setting, allowing to prevent delay in the initiation of cancer treatments. However, there is still the need to optimize the regimen of ovarian stimulation, to make treatments more patient-friendly and to reduce costs.MethodsThis retrospective study compares two periods (2019 and 2020), corresponding to two different ovarian stimulation regimens. In 2019, women were treated with corifollitropin, recombinant FSH and GnRH antagonists. Ovulation was triggered with GnRH agonists. In 2020, the policy changed, and women were treated with a progestin-primed ovarian stimulation (PPOS) protocol with human menopausal gonadotropin (hMG) and dual trigger (GnRH agonist and low dose hCG) Continuous data are reported as median [Interquartile Range]. To overcome expected changes in baseline characteristics of the women, the primary outcome was the ratio between the number of mature oocytes retrieved and serum anti-mullerian hormone (AMH) in ng/ml.ResultsOverall, 124 women were selected, 46 in 2019 and 78 in 2020. The ratio between the number of mature oocytes retrieved and serum AMH in the first and second period was 4.0 [2.3-7.1] and 4.0 [2.7-6.8], respectively (p = 0.80). The number of scans was 3 [3-4] and 3 [2-3], respectively (p<0.001). The total costs of the drugs used for ovarian stimulation were 940 € [774-1,096 €] and 520 € [434-564 €], respectively (p<0.001).ConclusionsRandom start PPOS with hMG and dual trigger represents an easy and affordable ovarian stimulation protocol for fertility preservation in women with cancer, showing similar efficacy and being more friendly and economical.
| S-EPMC10047511 | biostudies-literature
Project description:BackgroundCurrent fertility preservation strategies for young breast cancer patients planning a future motherhood include the association of controlled ovarian stimulation with the aromatase inhibitor letrozole (let-COS) to harvest mature oocytes while maintaining low estradiol levels. Despite this is a widely adopted protocol, the safety of let-COS on breast cancer outcomes has been poorly investigated and its use remains off-label. We assessed the safety of let-COS in breast cancer patients using circulating tumor DNA (ctDNA) as a surrogate biomarker of disease recurrence.MethodsBROVALE is an interventional non-randomized prospective study designed to evaluate the efficacy and safety of let-COS for fertility preservation in early breast cancer patients before starting (neo)adjuvant chemotherapy. Letrozole was administered throughout the COS cycle, until ovulation triggering. Safety was a secondary endpoint. Data on oncological outcomes were collected during the follow-up as well as plasma and whole blood for evaluation of ctDNA levels at the time of enrollment (i.e. before starting let-COS) and oocyte retrieval (i.e. 48 hours after the last administration of letrozole). Targeted gene sequencing on the primary tumor samples was performed to identify specific mutations used for ctDNA analysis by digital PCR. DNA extracted from whole blood samples was used to discriminate between somatic and germline mutations.ResultsFrom April 2014 to May 2017, 29 young early breast cancer patients enrolled in the BROVALE study who had available tissue samples participated to the ctDNA substudy. Among them, 15 had at least one validated somatic mutation. ctDNA was undetectable neither before nor after let-COS in 9 of them. Six patients had detectable ctDNA in the plasma samples collected before Let-COS. No change in ctDNA level after let-COS was observed in 3 patients and the level decreased (fold-change ≤ 0.5) in two women. One patient experienced an increased (fold-change ≥ 2) in ctDNA level but without disease relapse 34 months after diagnosis.ConclusionsNo increase in ctDNA level was observed in 93% (14/15) of the patients receiving let-COS supporting its use as a safe strategy for young women with early breast cancer interested in fertility preservation before chemotherapy.
| S-EPMC8370091 | biostudies-literature
Project description:PurposeThe study aims to evaluate the risk factors and incidence of thromboembolic events among adult women with cancer who underwent controlled ovarian hyperstimulation (COH) for fertility preservation.MethodsRetrospective, descriptive cohort analysis of patient demographics, medical history, cancer type/treatment, laboratory values, thrombosis within 6 months of COH.Results4 of 127 study participants experienced a venous thromboembolic event within 6 months of COH. The median time between oocyte aspiration and the event was 0.25 years (range = 0.10-0.50). The average age at time of event was 25.3 years (SD = 5.3). Three of four thrombotic patients had ovarian cancer, one had breast cancer. All had received surgery and chemotherapy for treatment. All underwent an antagonist cycle ovarian stimulation protocol - none developed ovarian hyperstimulation syndrome. The average anti-mullerian hormone level at the time of hyperstimulation in the thrombosis group was 1.6 (SD = 1.3), compared to 3.6 in the non-thrombosis group. The average max estradiol level reached during ovarian stimulation was 1281.3 (SD = 665.3) in the thrombosis group and 1839.1 (SD = 1513.9) in the non-thrombosis group. Thromboembolic events were not directly associated with mortality.ConclusionsWithin this small descriptive study, the incidence of thromboembolic events in women with cancer undergoing COH for fertility preservation is high. Cancer may play a greater role than COH in thrombosis risk. Ovarian cancer patients who undergo ovarian stimulation may have an increased risk compared to other cancer types. These findings may inform future, prospective studies to determine the role of thromboprophylaxis.
| S-EPMC9790832 | biostudies-literature
Project description:Context and objectiveThere has been increased attention to the issue of fertility preservation (FP). We aimed to investigate the long-term safety of FP via controlled ovarian stimulation with letrozole supplementation (COSTLES) prior to breast cancer treatment.Design, setting, and participantsThis is a prospective, nonrandomized, controlled study conducted between the years 2002 and 2014. A total of 337 women diagnosed with stage 3 or less invasive breast cancer were enrolled during a FP consultation before chemotherapy. Of those, 120 elected to undergo COSTLES for FP prior to chemotherapy (FP group). The remaining 217 patients did not undergo any FP procedure and served as the controls.Main outcome measureThe primary end point was cancer recurrence defined as the detection of locoregional tumor (chest wall, regional nodal disease), distant metastases, or contralateral invasive breast cancer.ResultsThe baseline characteristics at enrollment were similar between the FP and control groups except for the less frequent lymph node involvement (P = .02) in the former. The mean follow-up after diagnosis was 5.0 years in the FP group and 6.9 years in the control group. In the FP group, the hazard ratio for recurrence after ovarian stimulation was 0.77 (95% confidence interval 0.28–2.13), and the survival was not compromised compared with controls (P = .61). Neither BRCA gene mutation status (P = .57) nor undergoing FP before or after breast surgery (P = .44) affected survival outcomes in the FP group. Likewise, none of the tumor characteristics including the estrogen receptor status affected the survival rates after the COSTLES.ConclusionsCOSTLES is unlikely to cause a substantially increased recurrence risk in breast cancer during the 5 years after diagnosis.
| S-EPMC4880171 | biostudies-literature
Project description:PurposeTo investigate whether the number of oocytes retrieved after controlled ovarian stimulation (COS) for fertility preservation (FP) can be predicted using serum anti-Müllerian hormone (AMH) levels in adolescent and young adult (AYA) women.MethodsThis is a retrospective cohort study in a large university-affiliated fertility center. AYA women aged 11 to 25 years received COS using gonadotropin-releasing hormone (GnRH) antagonist protocols for FP were enrolled. Those with canceled cycles or incomplete data were excluded. The primary outcome is to determine whether the number of oocytes retrieved can be predicted through serum AMH levels using multiple linear regression analysis.ResultsThe mean numbers of oocytes retrieved, mature oocytes retrieved, and oocytes cryopreserved were 10.3 ± 7.6, 6.9 ± 6.2, and 8.5 ± 6.8, respectively. Multiple stepwise linear regression analysis revealed that serum AMH level independently predicts COS outcomes, including the total number of oocytes retrieved (adjusted R2 = 0.222, P < 0.001), the number of mature oocytes retrieved (adjusted R2 = 0.102, P = 0.013), and the number of oocytes cryopreserved (adjusted R2 = 0.153, P = 0.003).ConclusionSerum AMH level was a significant predictor of the number of oocytes retrieved after COS for FP in AYA women, while antral follicle count and age were not significantly related.
| S-EPMC11920294 | biostudies-literature
Project description:Although breast cancer (BC) occurs more often in older women, it is the most commonly diagnosed malignancy in women of childbearing age. Owing to the overall advancement of modern medicine and the growing global trend of delaying childbirth until later age, we find ever more younger women diagnosed and treated for BC who have not yet completed their family. Therefore, fertility preservation has emerged as a very important quality of life issue for young BC survivors. This paper reviews currently available options for fertility preservation in young women with early-stage BC and highlights the importance of a multidisciplinary approach to fertility preservation as a very important quality of life issue for young BC survivors. Pregnancy after BC treatment is considered not to be associated with an increased risk of BC recurrence; therefore, it should not be discouraged for those women who want to achieve pregnancy after oncologic treatment. Currently, it is recommended to delay pregnancy for at least 2 years after BC diagnosis, when the risk of recurrence is highest. However, BC patients of reproductive age should be informed about the potential negative effects of oncologic therapy on fertility, as well as on the fertility preservation options available, and if interested in fertility preservation, they should be promptly referred to a reproductive specialist. Early referral to a reproductive specialist is an important factor that increases the likelihood of successful fertility preservation. Embryo and mature oocyte cryopreservation are currently the only established fertility preservation methods but they require ovarian stimulation (OS), which delays initiation of chemotherapy for at least 2 weeks. Controlled OS does not seem to increase the risk of BC recurrence. Other fertility preservation methods (ovarian tissue cryopreservation, cryopreservation of immature oocytes and ovarian suppression with gonadotropin-releasing hormone agonists) do not require OS but are still considered to be experimental techniques for fertility preservation.
| S-EPMC6629203 | biostudies-literature
Project description:PURPOSE:Women with early-stage breast cancer may still have a future child wish, while chemotherapy may impair fertility. To pursue on fertility preservation shortly after breast cancer diagnosis is complex. This review holds a critical reflection on all topics that need to be counseled to give them the opportunity to make a well-informed decision before starting any oncological treatment. METHODS:A comprehensive literature review was performed on papers published in English language on breast cancer in young women, risk of chemotherapy-induced infertility, fertility preservation techniques, impact of possible mutation carriership, and future pregnancy outcome. RESULTS:Below 40 years of age, the risk of permanent chemotherapy-induced ovarian function failure is approximately 20%, where taxanes do not significantly add to this risk. Overall, 23% of reported women who performed fertility preservation by cryopreserving oocytes or embryos returned for embryo transfer. Of these, 40% gave live birth. Both fertility preservation in women diagnosed with breast cancer and pregnancy after treatment seem safe with respect to breast cancer survival. Women who have a genetic predisposition for breast cancer like BRCA gene mutation should also be informed about the possibility of pre-implantation genetic diagnosis. CONCLUSIONS:Women with an early stage of breast cancer and a possible future child wish should be referred to an expertise center in breast cancer, fertility preservation, and genetics in this complex decision-making process, shortly after diagnosis.
| S-EPMC6910894 | biostudies-literature
Project description: Not available
| S-EPMC7458684 | biostudies-literature