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Zhang M, Feng J, Ma W, Qiu L, Wang D, Yang Z. Current status of fertility preservation procedures in gynecologic oncology: from a Chinese perspective. J Assist Reprod Genet 2025; 42:635-645. [PMID: 39812764 PMCID: PMC11871211 DOI: 10.1007/s10815-024-03341-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 11/26/2024] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND The "Healthy China" initiative, along with advancements in technology for cancer diagnosis and treatment, has significantly enhanced outcomes for patients with gynecologic tumors. The trends of late marriage and delayed childbirth have led to an increasing number of women diagnosed with gynecologic cancers who are seeking fertility preservation in China. This issue is critical yet often overlooked in clinical practice. This review aims to synthesize the existing research on fertility preservation within the field of gynecologic oncology, emphasizing both clinical explorations and expert guidelines. METHODS We conducted a comprehensive literature review on fertility preservation in the context of gynecologic tumors, examining treatment approaches, commonly employed tumor management technologies, and specific techniques for preserving fertility. RESULTS This extensive review highlights the importance of integrating fertility preservation strategies into treatment plans for gynecologic tumors. It explores various methods to safeguard fertility during chemotherapy, radiation therapy, and surgical interventions. For patients with early-stage cervical cancer, surgical options are available; however, these may result in obstetric complications. Neoadjuvant chemotherapy is currently under investigation as an alternative approach. Endometrial cancer can be managed through hysteroscopic resection combined with hormonal therapy. The feasibility of fertility preservation in ovarian cancer varies based on tumor type and patient age. In cases of vulvar and vaginal cancers, partial excision may be considered following a thorough evaluation. Chemotherapy for gestational trophoblastic tumors has proven effective and typically preserves fertility despite potential decreases in AMH levels. CONCLUSION This review provides a comprehensive and current synthesis of the latest evidence and clinical practice guidelines regarding fertility preservation in gynecologic cancers. Its aim is to assist clinicians and researchers in addressing the urgent and increasing demand for effective fertility preservation strategies for their patients.
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Affiliation(s)
- Manlin Zhang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jing Feng
- Department of Gynaecology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning Province, Shenyang, 110001, The People's Republic of China
| | - Wenxin Ma
- Department of Gynaecology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning Province, Shenyang, 110001, The People's Republic of China
| | - Lin Qiu
- Department of Gynaecology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning Province, Shenyang, 110001, The People's Republic of China
| | - Danbo Wang
- Department of Gynaecology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning Province, Shenyang, 110001, The People's Republic of China
| | - Zhuo Yang
- Department of Gynaecology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning Province, Shenyang, 110001, The People's Republic of China.
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Boutas I, Kontogeorgi A, Koufopoulos N, Dimas DT, Sitara K, Kalantaridou SN, Dimitrakakis C. Breast Cancer and Fertility Preservation in Young Female Patients: A Systematic Review of the Literature. Clin Pract 2023; 13:1413-1426. [PMID: 37987428 PMCID: PMC10660549 DOI: 10.3390/clinpract13060127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/20/2023] [Accepted: 11/08/2023] [Indexed: 11/22/2023] Open
Abstract
INTRODUCTION Breast cancer affects almost 1.5 million women worldwide below the age of 45 years each year. Many of these women will be advised to undergo adjuvant chemotherapy to minimize the risk of death or recurrence of the tumor. For these patients, chemotherapy is a known cause of infertility, as it can damage primordial follicles, which can lead to early menopause or premature ovarian insufficiency. This systematic review aims to synthesize the current evidence of the most suitable treatments for fertility preservation. METHODOLOGY This review was performed following the PRISMA guidelines. The authors conducted an extensive search from the last 15 years. Relevant studies were pursued in PubMed, Embase, and the Cochrane Library up until 31 July 2023. A total of seven eligible studies were identified. RESULTS From the reviewed literature, ovarian suppression with gonadotropin-releasing hormone agonists showed promising results in preserving fertility for breast cancer patients undergoing chemotherapy. Additionally, oocyte and embryo cryopreservation demonstrated successful outcomes, with embryo cryopreservation being the most effective option. Notably, the slow-freezing and vitrification methods were both effective in preserving embryos, with vitrification showing superior results in clinical-assisted reproductive technologies. Ovarian tissue cryopreservation emerged as a viable option for prepubertal girls and those unable to undergo conventional ovarian stimulation. The potential of in vitro maturation (IVM) as an alternative method presents a promising avenue for future fertility preservation research. DISCUSSION The most suitable treatments for fertility preservation in young patients is the temporary suppression with luteinizing hormone-releasing analogs, while the patient undergoes chemotherapy and cryopreservation. For cryopreservation, the physicians might deem it necessary to either cryopreserve ovarian tissue taken from the patient before any treatment or cryopreserve embryos/oocytes. Cryopreservation of oocytes and/or embryos is the most effective solution for fertility preservation in women of reproductive age, who have a sufficient ovarian reserve and are diagnosed with breast cancer, regardless of the histological type of the tumor. Because approximately 50% of young breast cancer patients are interested in becoming pregnant right after completion of therapy, the evolution and development of fertility preservation techniques promise to be very exciting.
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Affiliation(s)
- Ioannis Boutas
- Breast Unit, Rea Maternity Hospital, P. Faliro, 17564 Athens, Greece
| | - Adamantia Kontogeorgi
- Third Department of Obstetrics and Gynecology, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, 12462 Chaidari, Greece; (A.K.); (S.N.K.)
| | - Nektarios Koufopoulos
- Second Pathology Department, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, 12462 Chaidari, Greece;
| | - Dionysios T. Dimas
- Breast Unit, Athens Medical Center, Psychiko Clinic, 11525 Athens, Greece;
| | - Kyparissia Sitara
- Department of Internal Medicine, “Elpis” General Hospital, 11522 Athens, Greece;
| | - Sophia N. Kalantaridou
- Third Department of Obstetrics and Gynecology, Attikon University Hospital, National and Kapodistrian University of Athens, Rimini 1, 12462 Chaidari, Greece; (A.K.); (S.N.K.)
| | - Constantine Dimitrakakis
- First Department of Obstetrics and Gynecology, Alexandra University Hospital, National and Kapodistrian University of Athens, Lourou 4-2, 11528 Athens, Greece;
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Marchante M, Ramirez-Martin N, Buigues A, Martinez J, Pellicer N, Pellicer A, Herraiz S. Deciphering reproductive aging in women using a NOD/SCID mouse model for distinct physiological ovarian phenotypes. Aging (Albany NY) 2023; 15:10856-10874. [PMID: 37847151 PMCID: PMC10637815 DOI: 10.18632/aging.205086] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 09/08/2023] [Indexed: 10/18/2023]
Abstract
Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. Thus, we aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life. NOD/SCID mice of different ages (8-, 28-, and 36-40-week-old) were employed to mimic ovarian phenotypes of young, Advanced Maternal Age (AMA), and old women (~18-20-, ~36-38-, and >45-years-old, respectively). Mice were stimulated, mated, and sacrificed to recover oocytes and embryos. Then, ovarian reserve, follicular growth, ovarian stroma, mitochondrial dysfunction, and proteomic profiles were assessed. Age-matched C57BL/6 mice were employed to cross-validate the reproductive outcomes. The quantity and quality of oocytes were decreased in AMA and Old mice. These age-related effects associated spindle and chromosome abnormalities, along with decreased developmental competence to blastocyst stage. Old mice had less follicles, impaired follicle activation and growth, an ovarian stroma inconducive to growth, and increased mitochondrial dysfunctions. Proteomic analysis corroborated these histological findings. Based on that, NOD/SCID mice can be used to model different ovarian aging phenotypes and potentially test human anti-aging treatments.
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Affiliation(s)
- María Marchante
- IVIRMA Global Research Alliance, IVI Foundation, Valencia 46026, Spain
- Department of Pediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia 46010, Spain
| | - Noelia Ramirez-Martin
- IVIRMA Global Research Alliance, IVI Foundation, Valencia 46026, Spain
- Reproductive Medicine Research Group, Instituto Investigación Sanitaria La Fe (IIS La Fe), Valencia 46026, Spain
| | - Anna Buigues
- IVIRMA Global Research Alliance, IVI Foundation, Valencia 46026, Spain
- Reproductive Medicine Research Group, Instituto Investigación Sanitaria La Fe (IIS La Fe), Valencia 46026, Spain
| | - Jessica Martinez
- IVIRMA Global Research Alliance, IVI Foundation, Valencia 46026, Spain
- Reproductive Medicine Research Group, Instituto Investigación Sanitaria La Fe (IIS La Fe), Valencia 46026, Spain
| | - Nuria Pellicer
- IVIRMA Global Research Alliance, IVI Foundation, Valencia 46026, Spain
- IVIRMA Valencia, Valencia 46015, Spain
| | - Antonio Pellicer
- IVIRMA Global Research Alliance, IVI Foundation, Valencia 46026, Spain
- Reproductive Medicine Research Group, Instituto Investigación Sanitaria La Fe (IIS La Fe), Valencia 46026, Spain
- IVIRMA Rome, Rome 00197, Italy
| | - Sonia Herraiz
- IVIRMA Global Research Alliance, IVI Foundation, Valencia 46026, Spain
- Reproductive Medicine Research Group, Instituto Investigación Sanitaria La Fe (IIS La Fe), Valencia 46026, Spain
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Ip PNP, Mak JSM, Law TSM, Ng K, Chung JPW. A reappraisal of ovarian stimulation strategies used in assisted reproductive technology. HUM FERTIL 2023; 26:824-844. [PMID: 37980170 DOI: 10.1080/14647273.2023.2261627] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 07/10/2023] [Indexed: 11/20/2023]
Abstract
Ovarian stimulation is a fundamental step in assisted reproductive technology (ART) with the intention of inducing ovarian follicle development prior to timed intercourse or intra-uterine insemination and facilitating the retrieval of multiple oocytes during a single in vitro fertilization (IVF) cycle. The basis of ovarian stimulation includes the administration of exogenous gonadotropins, with or without pre-treatment with oral hormonal therapy. Gonadotropin-releasing hormone agonist or antagonist is given in addition to the gonadotropins to prevent a premature rise of endogenous luteinizing hormone that would in turn lead to premature ovulation. With the advancement in technology, various stimulation protocols have been devised to cater for different patient needs. However, ovarian hyperstimulation syndrome and its serious complications may occur following ovarian stimulation. It is also evident that suboptimal ovarian stimulation strategies may have a negative impact on oogenesis, embryo quality, endometrial receptivity, and reproductive outcomes over recent years. This review describes the various forms of pre-treatment for ovarian stimulation and stimulation protocols, and aims to provide clinicians with the latest available evidence.
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Affiliation(s)
- Patricia N P Ip
- Assisted Reproductive Technology, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jennifer S M Mak
- Assisted Reproductive Technology, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Tracy S M Law
- Assisted Reproductive Technology, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Karen Ng
- Assisted Reproductive Technology, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jacqueline P W Chung
- Assisted Reproductive Technology, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
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Ronsini C, Solazzo MC, Molitierno R, De Franciscis P, Pasanisi F, Cobellis L, Colacurci N. Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: Can One Still Effectively Become a Mother? A Systematic Review of Fertility Outcomes. Ann Surg Oncol 2023; 30:5587-5596. [PMID: 37261562 PMCID: PMC10409841 DOI: 10.1245/s10434-023-13542-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 04/09/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC); however, there is currently no standard of care for women with ECC ≥ 2 cm who wish to preserve their fertility. The current orientation of the scientific community comprises upfront surgical techniques and neoadjuvant chemotherapy (NACT) followed by minor surgery such us conization. However these approaches are not standardized. This systematic review aimed to collect the evidence in the literature regarding the obstetric outcomes of the different techniques for applying FSTs in ECC ≥ 2 cm. METHODS A systematic review was performed in September 2022 using the Pubmed and Scopus databases, from the date of the first publication. We included all studies containing data regarding pregnancy, birth, and preterm rates. RESULTS Fifteen studies fulfilled the inclusion criteria, and 352 patients were analyzed regarding fertility outcomes. Surgery-based FST showed the pregnancy rate (22%), birth rate (11%), and preterm rate (10%). Papers regarding FST using the NACT approach showed a pregnancy rate of 44%, with a birth rate of 45% in patients who managed to get pregnant. The preterm rate amounted to 44%, and pregnancy rates and birth rates were significantly different between the two groups (p < 0.001). CONCLUSION Fertility preservation in patients with ECC > 2 cm is challenging. The endpoint for evaluating the best treatment should include oncological and fertility outcomes together. From this prospective, NACT followed by less radical surgery could be a reasonable compromise.
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Affiliation(s)
- Carlo Ronsini
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - M C Solazzo
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - R Molitierno
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - P De Franciscis
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - F Pasanisi
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - L Cobellis
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - N Colacurci
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
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6
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Yang X, Yang L. Current understanding of the genomic abnormities in premature ovarian failure: chance for early diagnosis and management. Front Med (Lausanne) 2023; 10:1194865. [PMID: 37332766 PMCID: PMC10274511 DOI: 10.3389/fmed.2023.1194865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/17/2023] [Indexed: 06/20/2023] Open
Abstract
Premature ovarian failure (POF) is an insidious cause of female infertility and a devastating condition for women. POF also has a strong familial and heterogeneous genetic background. Management of POF is complicated by the variable etiology and presentation, which are generally characterized by abnormal hormone levels, gene instability and ovarian dysgenesis. To date, abnormal regulation associated with POF has been found in a small number of genes, including autosomal and sex chromosomal genes in folliculogenesis, granulosa cells, and oocytes. Due to the complex genomic contributions, ascertaining the exact causative mechanisms has been challenging in POF, and many pathogenic genomic characteristics have yet to be elucidated. However, emerging research has provided new insights into genomic variation in POF as well as novel etiological factors, pathogenic mechanisms and therapeutic intervention approaches. Meanwhile, scattered studies of transcriptional regulation revealed that ovarian cell function also depends on specific biomarker gene expression, which can influence protein activities, thus causing POF. In this review, we summarized the latest research and issues related to the genomic basis for POF and focused on insights gained from their biological effects and pathogenic mechanisms in POF. The present integrated studies of genomic variants, gene expression and related protein abnormalities were structured to establish the role of etiological genes associated with POF. In addition, we describe the design of some ongoing clinical trials that may suggest safe, feasible and effective approaches to improve the diagnosis and therapy of POF, such as Filgrastim, goserelin, resveratrol, natural plant antitoxin, Kuntai capsule et al. Understanding the candidate genomic characteristics in POF is beneficial for the early diagnosis of POF and provides appropriate methods for prevention and drug treatment. Additional efforts to clarify the POF genetic background are necessary and are beneficial for researchers and clinicians regarding genetic counseling and clinical practice. Taken together, recent genomic explorations have shown great potential to elucidate POF management in women and are stepping from the bench to the bedside.
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Affiliation(s)
- Xu Yang
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lin Yang
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China
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7
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Suzuki R, Horage-Okutsu Y, Kawahara T, Nakamura K, Shiraishi E, Iwahata H, Suzuki-Takahashi Y, Sugishita Y, Takae S, Suzuki N. The effect of aromatase inhibitor on controlled ovarian stimulation for oocyte cryopreservation in adolescent and young cancer patients. J Obstet Gynaecol Res 2023; 49:973-979. [PMID: 36606606 DOI: 10.1111/jog.15535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/19/2022] [Indexed: 01/07/2023]
Abstract
AIM To determine the impact of aromatase inhibitor (AI) use in oocyte cryopreservation among Japanese adolescent and young adult (AYA) cancer patients for fertility preservation, we evaluated the oocyte cryopreservation outcomes following AI therapy in combination with the follicular phase start (FPS) and random start (RS) protocols. METHODS This retrospective study included 81 cycles of controlled ovarian stimulation (COS) among 73 AYA patients with cancer who underwent oocyte cryopreservation to maintain fertility. The outcome measures were the total number of matured oocytes that were retrieved and cryopreserved, as well as their maturation rates. The AI (+) and AI (-) groups were compared using the RS and FPS protocols. RESULTS Our results showed that the combined use of AI and COS decreases serum E2 levels and maintains the number of retrieved and cryopreserved mature oocytes. We also confirmed the efficacy of the RS protocol, which was found to have comparable outcomes to that of the FPS protocol in both AI (+) and AI (-) groups. CONCLUSION The combined use of AI and COS is beneficial for oocyte cryopreservation in patients with estrogen-sensitive cancer, regardless of the menstrual cycle phase of COS initiation.
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Affiliation(s)
- Reiko Suzuki
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
| | - Yuki Horage-Okutsu
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
| | - Tai Kawahara
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
| | - Kentaro Nakamura
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
| | - Eriko Shiraishi
- Department of Obstetrics and Gynecology, The Jikei University school of medicine, Tokyo, Japan
| | - Hideyuki Iwahata
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
| | - Yuki Suzuki-Takahashi
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
| | - Yodo Sugishita
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
| | - Seido Takae
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
| | - Nao Suzuki
- Department of Obstetrics and Gynecology, Saint Marianna University School of Medicine, Kawasaki, Japan
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Investigation of the female infertility risk associated with anti-cancer therapy. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2023:10.1007/s12094-023-03087-8. [PMID: 36689055 DOI: 10.1007/s12094-023-03087-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 01/11/2023] [Indexed: 01/24/2023]
Abstract
Female infertility is a significant health issue worldwide with a rising incidence. Anti-cancer therapy is one of the most important reasons for increasing infertility. Although anti-cancer treatment increases the rate of survival, it decreases the quality of life through its side effects. The most substantial side effects are sexual dysfunction and infertility. Breast cancer is the most common cancer. The first-line treatment of breast cancer is chemotherapy by alkylating agents like cyclophosphamide, which leads to infertility. For instance, persistent chemotherapy-induced amenorrhea among breast cancer patients could affect almost half of the patients that undergo such therapy. However, some agents or therapeutic methods can ameliorate these intoxicating effects. Chemotherapy plus gonadotropin-releasing hormone agonist, in breast cancer patients, can not only improve overall survival but also reduce ovarian toxicity. Age plays an essential role in chemotherapy-induced amenorrhea. Chemotherapy at a younger age can reduce the risk of infertility. Gynecological cancers including uterine and ovarian cancer, which have high mortality rates, are the most related cancers to infertility. Surgery is the primary treatment of gynecological cancers. Studies demonstrated that fertility-sparing surgery is a better option than radical surgery. In addition, neoadjuvant chemotherapy is mostly a better option than primary cytoreductive surgery in terms of survival and fertility. Immune checkpoint inhibitors (ICIs) have recently played a major role in treating various cancer types. However, ICIs are associated with hypophysitis, which affects ovaries and can lead to infertility. There are some options for ovarian preservation such as embryo cryopreservation, oocyte cryopreservation, ovarian transposition, ovarian tissue cryopreservation, and ovarian suppression by GnRH agonists. Anti-müllerian hormone level can be utilized to monitor the ovarian reserve. Moreover, to avoid fertility loss, approaches such as using transplantation of human placenta mesenchymal stem cells, administrating anti-inflammatory agents and hormone therapy are under investigation.
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Marklund A, Lekberg T, Hedayati E, Liljegren A, Bergh J, Lundberg FE, Rodriguez-Wallberg KA. Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis. JAMA Oncol 2022; 8:1438-1446. [PMID: 36006625 PMCID: PMC9412846 DOI: 10.1001/jamaoncol.2022.3677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Question Is fertility preservation at time of breast cancer diagnosis associated with any increased risk of disease-specific relapse or mortality? Findings In this population-based Swedish nationwide cohort study that included 1275 women with breast cancer, fertility preservation at time of breast cancer diagnosis was not statistically significantly associated with any increased risk of disease-specific mortality or relapse. Meaning Findings of this study support the safety of fertility preservation in women with breast cancer, which is highly relevant for reproductive counseling of women with breast cancer diagnosed at a young age. Importance Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis. Objective To investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis. Design, Setting, and Participants This Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022. Main Outcomes and Measures Relapse and disease-specific mortality after a diagnosis of BC. Results The final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference). Conclusions and Relevance In this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.
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Affiliation(s)
- Anna Marklund
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Solna, Sweden.,Division of Gynecology and Reproduction, Department of Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Tobias Lekberg
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Solna, Sweden.,Breast Cancer Theme Center, Karolinska University Hospital and Karolinska Comprehensive Cancer Centre, Stockholm, Sweden
| | - Elham Hedayati
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Solna, Sweden.,Breast Cancer Theme Center, Karolinska University Hospital and Karolinska Comprehensive Cancer Centre, Stockholm, Sweden
| | - Annelie Liljegren
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Solna, Sweden.,Department of Internal Medicine, Southern Hospital, Stockholm, Sweden
| | - Jonas Bergh
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Solna, Sweden.,Breast Cancer Theme Center, Karolinska University Hospital and Karolinska Comprehensive Cancer Centre, Stockholm, Sweden
| | - Frida E Lundberg
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Solna, Sweden.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden
| | - Kenny A Rodriguez-Wallberg
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Solna, Sweden.,Division of Gynecology and Reproduction, Department of Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.,Laboratory of Translational Fertility Preservation, BioClinicum, Stockholm, Sweden
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10
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Clinical outcome of embryo cryopreservation in Japanese breast cancer patients: pregnancy rates after transfer of thawed embryos. J Assist Reprod Genet 2022; 39:1769-1777. [PMID: 35980490 PMCID: PMC9428083 DOI: 10.1007/s10815-022-02575-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 07/11/2022] [Indexed: 01/19/2023] Open
Abstract
PURPOSE To examine pregnancy outcomes after cryopreserved embryo transfer (ET) in breast cancer patients and to investigate the effect of controlled ovarian hyperstimulation (COH) as well as that of aromatase inhibitor (AI) administration and of the random start (RS) ovarian stimulation method. METHODS This retrospective study covered 126 patients who underwent embryo cryopreservation between 2010 and 2019. Thirty-one patients underwent frozen embryo transfer (FET), and we examined resulting pregnancy rates (PRs) and live birth rates (LBRs) in those who did and did not undergo COH and in relation to the AI and RS methods. RESULTS PR and LBR per patient were higher among patients who underwent COH than among those who did not. PR per ET did not differ from that documented for non-cancer infertility patients, after adjustment for age. The PR and LBR did not differ between use and non-use of AI (27.8% vs 35.2%). In addition, there was no significant difference in the PR or LBR between RS and conventional start ovarian stimulation (33.3% vs 30.8%). No prenatal fetal abnormalities were observed in 8 cases (including 5 AI cases and 2 RS cases). CONCLUSIONS This study showed that the outcome of FET after FP was equivalent to that seen in non-cancer patients. Further, neither use of AI nor the RS method influenced LBR. COH including use of AI and the RS method are useful in FP for collecting and freezing many embryos within a short period and for increasing the per patient LBR after cancer treatment.
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11
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Balkenende EME, Dahhan T, Beerendonk CCM, Fleischer K, Stoop D, Bos AME, Lambalk CB, Schats R, Smeenk JMJ, Louwé LA, Cantineau AEP, Bruin JPD, Linn SC, van der Veen F, van Wely M, Goddijn M. Fertility preservation for women with breast cancer: a multicentre randomized controlled trial on various ovarian stimulation protocols. Hum Reprod 2022; 37:1786-1794. [PMID: 35776109 PMCID: PMC9340107 DOI: 10.1093/humrep/deac145] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 04/01/2022] [Indexed: 12/24/2022] Open
Abstract
STUDY QUESTION 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? SUMMARY ANSWER Alternative ovarian stimulation protocols with tamoxifen or letrozole did not affect the number of COCs retrieved at follicle aspiration in women with breast cancer. WHAT IS KNOWN ALREADY Alternative ovarian stimulation protocols have been introduced for women with breast cancer who opt for fertility preservation by means of banking of oocytes or embryos. How these ovarian stimulation protocols compare to standard ovarian stimulation in terms of COC yield is unknown. STUDY DESIGN, SIZE, DURATION This multicentre, open-label randomized controlled superiority trial was carried out in 10 hospitals in the Netherlands and 1 hospital in Belgium between January 2014 and December 2018. We randomly assigned women with breast cancer, aged 18–43 years, who opted for banking of oocytes or embryos to one of three study arms; ovarian stimulation plus tamoxifen, ovarian stimulation plus letrozole or standard ovarian stimulation. Standard ovarian stimulation included GnRH antagonist, recombinant FSH and GnRH agonist trigger. Randomization was performed with a web-based system in a 1:1:1 ratio, stratified for oral contraception usage at start of ovarian stimulation, positive estrogen receptor (ER) status and positive lymph nodes. Patients and caregivers were not blinded to the assigned treatment. The primary outcome was number of COCs retrieved at follicle aspiration. PARTICIPANTS/MATERIALS, SETTING, METHODS During the study period, 162 women were randomly assigned to one of three interventions. Fifty-four underwent ovarian stimulation plus tamoxifen, 53 ovarian stimulation plus letrozole and 55 standard ovarian stimulation. Analysis was according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE No differences among groups were observed in the mean (±SD) number of COCs retrieved: 12.5 (10.4) after ovarian stimulation plus tamoxifen, 14.2 (9.4) after ovarian stimulation plus letrozole and 13.6 (11.6) after standard ovarian stimulation (mean difference −1.13, 95% CI −5.70 to 3.43 for tamoxifen versus standard ovarian stimulation and 0.58, 95% CI −4.03 to 5.20 for letrozole versus standard ovarian stimulation). After adjusting for oral contraception usage at the start of ovarian stimulation, positive ER status and positive lymph nodes, the mean difference was −1.11 (95% CI −5.58 to 3.35) after ovarian stimulation plus tamoxifen versus standard ovarian stimulation and 0.30 (95% CI −4.19 to 4.78) after ovarian stimulation plus letrozole versus standard ovarian stimulation. There were also no differences in the number of oocytes or embryos banked. There was one serious adverse event after standard ovarian stimulation: one woman was admitted to the hospital because of ovarian hyperstimulation syndrome. LIMITATIONS, REASONS FOR CAUTION The available literature on which we based our hypothesis, power analysis and sample size calculation was scarce and studies were of low quality. Our study did not have sufficient power to perform subgroup analysis on follicular, luteal or random start of ovarian stimulation. WIDER IMPLICATIONS OF THE FINDINGS Our study showed that adding tamoxifen or letrozole to a standard ovarian stimulation protocol in women with breast cancer does not impact the effectiveness of fertility preservation and paves the way for high-quality long-term follow-up on breast cancer treatment outcomes and women’s future pregnancy outcomes. Our study also highlights the need for high-quality studies for all women opting for fertility preservation, as alternative ovarian stimulation protocols have been introduced to clinical practice without proper evidence. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by a grant (2011.WO23.C129) of ‘Stichting Pink Ribbon’, a breast cancer fundraising charity organization in the Netherlands. M.G., C.B.L. and R.S. declared that the Center for Reproductive Medicine, Amsterdam UMC (location VUMC) has received unconditional research and educational grants from Guerbet, Merck and Ferring, not related to the presented work. C.B.L. declared a speakers fee for Inmed and Yingming. S.C.L. reports grants and non-financial support from Agendia, grants, non-financial support and other from AstraZeneca, grants from Eurocept-pharmaceuticals, grants and non-financial support from Genentech/Roche and Novartis, grants from Pfizer, grants and non-financial support from Tesaro and Immunomedics, other from Cergentis, IBM, Bayer, and Daiichi-Sankyo, outside the submitted work; In addition, S.C.L. has a patent UN23A01/P-EP pending that is unrelated to the present work. J.M.J.S. reported payments and travel grants from Merck and Ferring. C.C.M.B. reports her role as unpaid president of the National guideline committee on Fertility Preservation in women with cancer. K.F. received unrestricted grants from Merck Serono, Good Life and Ferring not related to present work. K.F. declared paid lectures for Ferring. D.S. declared former employment from Merck Sharp & Dohme (MSD). K.F. declared paid lectures for Ferring. D.S. reports grants from MSD, Gedeon Richter and Ferring paid to his institution; consulting fee payments from MSD and Merck Serono paid to his institution; speaker honoraria from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono paid to his institution. D.S. has also received travel and meeting support from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono. No payments are related to present work. TRIAL REGISTRATION NUMBER NTR4108. TRIAL REGISTRATION DATE 6 August 2013. DATE OF FIRST PATIENT’S ENROLMENT 30 January 2014.
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Affiliation(s)
- Eva M E Balkenende
- Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Taghride Dahhan
- Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Catharina C M Beerendonk
- Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Kathrin Fleischer
- Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Dominic Stoop
- Center for Reproductive Medicine, UZ Brussel, Free University of Brussels, Brussels, Belgium.,Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium
| | - Annelies M E Bos
- Department of Reproductive Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Cornelis B Lambalk
- Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Roel Schats
- Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Jesper M J Smeenk
- Department of Obstetrics and Gynaecology, St Elisabeth Hospital, Tilburg, The Netherlands
| | - Leonie A Louwé
- Department of Gynaecology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Astrid E P Cantineau
- Center for Reproductive Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jan Peter de Bruin
- Department of Obstetrics and Gynecology, Jeroen Bosch Hospital, Den Bosch, The Netherlands
| | - Sabine C Linn
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Fulco van der Veen
- Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Madelon van Wely
- Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Mariëtte Goddijn
- Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands
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12
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Oliveira RD, Maya BG, Nogueira MBS, Conceição GS, Bianco B, Barbosa CP. Fertility preservation in breast cancer with oral progestin: is it an option? A pilot study. EINSTEIN-SAO PAULO 2021; 19:eAO5859. [PMID: 34431852 PMCID: PMC8354590 DOI: 10.31744/einstein_journal/2021ao5859] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 11/30/2020] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE To compare the effectiveness of oral progestins and injectable gonadotropin-releasing hormone antagonist medication in cancer fertility preservation in patients with breast cancer. METHODS A cross-sectional study with 40 breast cancer patients submitted to cancer fertility preservation, who were divided into two groups according to histochemical analysis of progesterone receptors to define luteinizing hormone block: if positive, use of gonadotropin-releasing hormone antagonist, if negative, use of oral progestins. The mean age, medication days, antral follicle count, number of oocytes in metaphase II and the occurrence of ovarian hyperstimulation syndrome were compared. RESULTS A total of 20 patients both in the group using gonadotropin-releasing hormone antagonist, and in the group with oral progestins, respectively, had a mean age of 33.9 (32-35.8) and 33.8 (32-35.6) years; days of medications of 11 (9.7-12.3) and 12.8 (11.6-13.9), p=0.037; antral follicle count of 9 (7.11-12) and 8.5 (6-11.9), p=0.370; metaphase II oocyte number of 4 (2.1-9.8) and 7.5 (3.1-10), p=0.348; and ovarian hyperstimulation syndrome of 2 (10%) and 5 (25%) cases, p=0.212. CONCLUSION The use of oral progestins, in spite of requiring longer treatment time, is effective in relation to the protocol with gonadotropin-releasing hormone antagonist, and offers greater comfort at a lower cost in breast cancer patients with negative progesterone receptors, submitted to cancer fertility preservation.
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Affiliation(s)
- Renato de Oliveira
- Sexual, Reproductive Health, and Population Genetics, Department of Community Health, Centro Universitário FMABC, Santo André, SP, Brazil
| | - Bárbara Gomes Maya
- Sexual, Reproductive Health, and Population Genetics, Department of Community Health, Centro Universitário FMABC, Santo André, SP, Brazil
| | - Mariana Bittencourt Silva Nogueira
- Sexual, Reproductive Health, and Population Genetics, Department of Community Health, Centro Universitário FMABC, Santo André, SP, Brazil
| | - Gabriel Seixas Conceição
- Sexual, Reproductive Health, and Population Genetics, Department of Community Health, Centro Universitário FMABC, Santo André, SP, Brazil
| | - Bianca Bianco
- Sexual, Reproductive Health, and Population Genetics, Department of Community Health, Centro Universitário FMABC, Santo André, SP, Brazil
| | - Caio Parente Barbosa
- Sexual, Reproductive Health, and Population Genetics, Department of Community Health, Centro Universitário FMABC, Santo André, SP, Brazil
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13
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Sahin G, Goker ENT, Gokmen E, Yeniay L, Acet F, Zekioglu O, Tavmergen E. Controlled ovarian stimulation outcomes of fertility preservation procedures in newly diagnosed breast cancer patients: a retrospective study from a single-tertiary-IVF centre. J OBSTET GYNAECOL 2021; 42:518-523. [PMID: 34382483 DOI: 10.1080/01443615.2021.1931067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The aim of this study was to evaluate the effectiveness of controlled ovarian stimulation (COS) using the letrozole-supplemented stimulation protocol in breast cancer (BC) patients prior to their cancer treatment. Sixty-one BC patients (Stages 0-3) who were referred to a university IVF unit for fertility preservation (FP) and underwent embryo and/or oocyte cryopreservation between 2008 - 2020 were included in this retrospective study. Time intervals between breast surgery and initial fertility consultation (IFC)/completion of FP procedures were evaluated. COS outcomes were assessed and compared between the early follicular phase (EFP) and the random-start (RS) protocols. The patients' mean age was 33.3 ± 4.9 years. The mean time interval between breast surgery and IFC was 20.6 ± 11 (day, mean ± SD) and from IFC to completion of FP procedure was 14.7 ± 5.3. Overall, 9.1 ± 5.9 mature oocytes were obtained, with a peak serum oestradiol level of 388 ± 358 pg/mL. The number of oocytes obtained (11.5 ± 9.3 vs. 10.9 ± 6.9, p = .9) and maturation rates (84.3 ± 17.5% vs. 89.2 ± 11.7, p = .5) were not statistically different between the EPF and RS protocols. The study results support that oocyte or embryo freezing can be performed effectively in a limited time period with letrozole-supplemented COS protocols before the initiation of oncological treatments in breast cancer patients.Impact statementWhat is already known on this subject? Currently, embryo and oocyte freezing are considered the most established fertility preservation (FP) methods for newly diagnosed cancer patients.What do the results of this study add? This study reports the COS outcomes of newly diagnosed breast cancer patients for FP over a period of twelve years from a single IVF unit. The results support that a considerable number of oocytes can be harvested with letrozole-supplemented COS protocol, which appears to be an effective protocol for BC patients.What are the implications of these findings for clinical practice and/or further research? There is a need for additional studies evaluating long-term follow-up of patients with their pregnancy outcomes.
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Affiliation(s)
- Gulnaz Sahin
- Ege University, Family Planning and Infertility Research and Practice Center, Izmir, Turkey
| | - Ege Nazan Tavmergen Goker
- Ege University, Family Planning and Infertility Research and Practice Center, Izmir, Turkey.,Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Erhan Gokmen
- Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Levent Yeniay
- Department of General Surgery, Ege University, Faculty of Medicine, Izmir, Turkey
| | - Ferruh Acet
- Ege University, Family Planning and Infertility Research and Practice Center, Izmir, Turkey.,Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Osman Zekioglu
- Department of Pathology, Ege University, Faculty of Medicine, Izmir, Turkey
| | - Erol Tavmergen
- Ege University, Family Planning and Infertility Research and Practice Center, Izmir, Turkey.,Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey
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14
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Greer AC, Lanes A, Poorvu PD, Kennedy P, Thomas AM, Partridge AH, Ginsburg ES. The impact of fertility preservation on the timing of breast cancer treatment, recurrence, and survival. Cancer 2021; 127:3872-3880. [PMID: 34161610 DOI: 10.1002/cncr.33601] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 02/10/2021] [Accepted: 03/03/2021] [Indexed: 11/08/2022]
Abstract
BACKGROUND Many young women with breast cancer undergo fertility preservation (FP) before cancer treatment. This study examined the impact of FP on breast cancer outcomes. METHODS The authors performed a retrospective cohort study of 272 women aged 20 to 45 years with newly diagnosed stage 0 to III breast cancer who underwent an FP consultation between 2005 and 2017. Among these women, 123 (45.2%) underwent FP (fertility preservation-positive [FP+]). The remaining 149 women did not undergo FP (fertility preservation-negative [FP-]). RESULTS The characteristics at enrollment were similar with the exception of ethnicity (FP+, 87.8% White; FP-, 67.8% White; P = .002) and BRCA status (FP+, 27.7% BRCA+; FP-, 15.5% BRCA+; P = .021). The median follow-up was approximately 4 years. Women who underwent FP had longer times to first treatment (FP+, 37 days; FP-, 31 days; adjusted hazard ratio [aHR], 0.74; confidence interval [CI], 0.56-0.99) and neoadjuvant chemotherapy (FP+, 36 days; FP-, 26 days; aHR, 0.41; CI, 0.24-0.68) and from surgery to adjuvant chemotherapy (FP+, 41 days; FP-, 33 days; aHR, 0.58; CI, 0.38-0.90). Adjusted 3- and 5-year invasive disease-free survival (IDFS) rates were comparable between the 2 groups (3-year IDFS: FP+, 85.4%; FP-, 79.4%; P = .411; 5-year IDFS: FP+, 73.7%; FP-, 67.1%; P = .288). Similarly, no difference in overall survival (OS) was observed between the 2 groups (3-year OS: FP+, 95.5%; FP-, 93.5%; P = .854; 5-year OS: FP+, 84.2%; FP-, 81.4%; P = .700). CONCLUSIONS FP after a breast cancer diagnosis delays the time to treatment by a small amount, but this delay does not lead to inferior IDFS or OS.
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Affiliation(s)
- Anna C Greer
- Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Andrea Lanes
- Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Philip D Poorvu
- Harvard Medical School, Boston, Massachusetts.,Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.,Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Patricia Kennedy
- Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Ann M Thomas
- Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Ann H Partridge
- Harvard Medical School, Boston, Massachusetts.,Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.,Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Elizabeth S Ginsburg
- Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts.,Harvard Medical School, Boston, Massachusetts
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15
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Predictors and outcomes in breast cancer patients who did or did not pursue fertility preservation. Breast Cancer Res Treat 2021; 186:429-437. [PMID: 33392838 DOI: 10.1007/s10549-020-06031-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 11/18/2020] [Indexed: 12/17/2022]
Abstract
PURPOSE Breast cancer is the most common cancer in reproductive age women, and treatment can affect fertility; however, there is often concern regarding the safety of increased estradiol (E2) levels and potential delays in treatment with ovarian stimulation for fertility preservation (FP). The aim of this study was to compare recurrence and survival in breast cancer patients who pursued FP without concurrent letrozole to those who did not (non-FP). METHODS We reviewed charts of women with breast cancer who contacted the FP patient navigator (PN) at Northwestern University from 01/2005-01/2018. Oncology and fertility outcome data were collected. Data were analyzed by Chi-square test or regression, as appropriate. Kaplan-Meier curves were used to examine breast cancer recurrence and survival. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows. RESULTS 332 patients were included, of which 157 (47.3%) underwent FP. Median days to treatment after consulting the PN was 35 in the FP group and 21 in non-FP (p < 0.05). Cancer recurrence was noted in 7 (4.7%) FP patients and 13 (7.9%) non-FP patients (NS), and mortality in 5 (3.2%) FP patients and 7 (4.2%) non-FP patients (NS). Within the FP group, no significant differences were found in recurrence or mortality based on ER status, age, BMI, peak E2 level or total gonadotropin dose. Likelihood of pursuing FP was primarily a function of age and parity, and was not affected by breast cancer stage. To date, 21 have used cryopreserved specimens, and 13 (62%) had a live birth. CONCLUSIONS FP is safe and effective in breast cancer patients, regardless of receptor status; E2 elevations and the 2-week delay in treatment start are unlikely to be clinically significant. These findings are unique in that our institution does not use concomitant letrozole during stimulation to minimize E2 elevations in breast cancer patients.
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16
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Diminished Ovarian Reserve Chemotherapy-Induced Mouse Model: A Tool for the Preclinical Assessment of New Therapies for Ovarian Damage. Reprod Sci 2020; 27:1609-1619. [PMID: 32430713 DOI: 10.1007/s43032-020-00191-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Twenty-one Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were allocated to 3 groups (n = 7/group): control, single dose of vehicle (Dimethyl Sulfoxide [DMSO]); DOR, single reduced chemotherapy dose; and POI, single standard chemotherapy dose. After 21 days, mice underwent ovarian hyperstimulation and mating. Part of the animals were harvested to analyze ovarian reserve, ovulation and fertilization rates, and morphology, apoptosis, and vascularization of the ovarian stroma. The remaining mice underwent multiple matings to assess pregnancy rates and litter sizes. The DOR and POI mice showed an impaired estrous cyclicity and a decrease in ovarian mass, number of follicles, Metaphase II (MII) oocytes, and embryos as well as in ovarian stroma vascularization. Mice in both models showed also an increase in the percentage of morphologically abnormal follicles, stromal degeneration, and apoptosis. Similar to that observed in DOR and POI patients, these impairments were less severe in DOR than in POI mice. None of the POI females were able to achieve a pregnancy. Meanwhile, DOR females achieved several consecutive pregnancies, although litter size was decreased when compared to controls. In conclusion, a mouse model which displayed most of the ovarian characteristics and fertility outcomes of women with DOR has been established using a single dose of chemotherapy.
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17
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Kim SW, Han SJ, Han JY, Kim H, Ku SY, Suh CS. Predictor for supraphysiologic serum estradiol elevation on hCG triggering day of controlled ovarian stimulation using letrozole and gonadotropins in women with estrogen-dependent cancers. PLoS One 2020; 15:e0240870. [PMID: 33085706 PMCID: PMC7577464 DOI: 10.1371/journal.pone.0240870] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 10/04/2020] [Indexed: 11/29/2022] Open
Abstract
The objective of this study was to evaluate predicting factors for supraphysiologic serum estradiol elevation during controlled ovarian stimulation (COS) with administration of letrozole and gonadotropins in patients with estrogen-dependent cancer. Use of aromatase inhibitors is recommended to prevent the potential effects of elevated serum estradiol levels and recurrence of tumor in patients with estrogen-dependent cancers during COS. Although previous studies reported that letrozole have shown an effective lowering of peak estrogen levels, a part of patients shows supraphysiologic levels of estrogen associated with ovarian stimulation despite the administration of letrozole. From January 2009 to December 2019, patients with estrogen-dependent cancer who underwent COS with antagonist protocol using a letrozole (5 mg/ day) to keep estrogen levels low were included in this study. Early monitoring serum estradiol was measured in all patients on the 4-6th day of stimulation. Subjects were classified into two groups according to the serum estradiol level on hCG triggering day, physiologic estradiol group (≤400 pg/mL) and supraphysiologic estradiol group (>400 pg/mL). A total of 96 COS cycles were retrospectively analyzed. Supraphysiologic level of serum estradiol was found in 21.9% of the patients. Mean age, AMH, duration of stimulation, total dose of gonadotropins administered were not different between the two groups. However, early monitoring serum estradiol level was significantly higher in the supraphysiologic estradiol group (67.1±47.9 vs. 115.6±78.1, p = 0.001) and was associated with the occurrence of supraphysiologic elevation of serum estradiol on hCG triggering day. Patients with early monitoring serum estradiol ≥84.5 pg/mL had an odds ratio of 5.376 [95% CI, 1.613–17.913] for supraphysiologic elevation of serum estradiol compared to those with early monitoring serum estradiol below 84.5 pg/mL. In conclusion, early monitoring serum estradiol is an independent predicting factor for supraphysiologic level of serum estradiol on hCG triggering day in the COS cycles using letrozole and gonadotropins.
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Affiliation(s)
- Sung Woo Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, South Korea
| | - Soo Jin Han
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, South Korea
| | - Ji Yeon Han
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, South Korea
| | - Hoon Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, South Korea
- Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, South Korea
| | - Seung-Yup Ku
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, South Korea
- Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, South Korea
- * E-mail:
| | - Chang Suk Suh
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, South Korea
- Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, South Korea
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18
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Amaadour L, El Mrabet FZ, Atreche L, El Rhazi K, Oualla K, Benbrahim Z, Arifi S, Mellas N. [Chemotherapy induced ovarian failure in breast cancer: Retrospective study of 100 cases]. Bull Cancer 2020; 107:854-860. [PMID: 32762944 DOI: 10.1016/j.bulcan.2020.05.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Revised: 05/17/2020] [Accepted: 05/27/2020] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Breast cancers affect about a quarter of women of reproductive age worldwide. Chemotherapy is frequently indicated due to the aggressive biomolecular cancer subtypes usually observed in the localized forms, which may compromise the fertility of these young patients. The aim of our study is to report the incidence of chemotherapy induced ovarian failure in premenopausal breast cancer patients after chemotherapy, and to identify related risk factors. METHODS It is a retrospective cross-sectional cohort study which included all premenopausal patients with early breast cancer treated at the department of medical oncology, Hassan II University Hospital of Fez, during a period of one year. Chemotherapy induced amenorrhea (CIA) and associated risk factors were studied. RESULTS The study included 100 patients. The mean age of the subjects was 36 years. The incidence of CIA was 82 %, 66.7 % regained menstruations. Risk factors associated with CIA were analyzed, only the patient age at diagnosis was found to be statistically significantly associated with CIA. CONCLUSION Our study found a high incidence of CIOF (Chemotherapy-induced ovarian failure) with a relatively low incidence of reversible amenorrhea. Only the patient age has been shown to be an independent factor, statistically significantly associated with ovarian failure after chemotherapy. Methods of fertility preservation should be considered in those patients to reduce the impact of chemotherapy on ovarian reserves.
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Affiliation(s)
| | | | - Loubna Atreche
- CHU Hassan II de Fès, service d'oncologie médicale, Maroc
| | | | - Karima Oualla
- CHU Hassan II de Fès, service d'oncologie médicale, Maroc
| | | | - Samia Arifi
- CHU Hassan II de Fès, service d'oncologie médicale, Maroc
| | - Nawfel Mellas
- CHU Hassan II de Fès, service d'oncologie médicale, Maroc
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19
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Bercaire LMN, Cavagna M, Donadio NF, Rocha AR, Portela R, Alves VR, Santos TBB, Cavagna F, Dzik A, Gebrim LH, Nahas EAP. The impact of letrozole administration on oocyte morphology in breast cancer patients undergoing fertility preservation. JBRA Assist Reprod 2020; 24:257-264. [PMID: 32293820 PMCID: PMC7365524 DOI: 10.5935/1518-0557.20200002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Objective: Patients submitted to oncological fertility preservation with letrozole and gonadotropins seem to present a higher rate of immature oocytes and lower fertilization rates in comparison to infertile patients submitted to IVF cycles with gonadotropins. The aim of this study was to evaluate the influence of letrozole on oocyte morphology in patients with breast cancer submitted to fertility preservation. Methods: Retrospective analysis performed at a public tertiary hospital in São Paulo, Brazil. The oocytes were retrieved from patients with breast cancer undergoing fertility preservation (n=69), and from infertile women undergoing in vitro fertilization (n=92). We evaluated 750 oocytes obtained from breast cancer patients submitted to ovarian stimulation with letrozole and gonadotropins, and 699 oocytes from patients without breast cancer submitted to ovarian stimulation for in vitro fertilization with gonadotropins only due to male factor infertility. The mature oocytes retrieved were analyzed for the presence of refractile bodies, ooplasm color and regularity, central granulation degree, cortical granules, zona pellucida staining and regularity, perivitelline space, presence of vacuoles or abnormal smooth-surfaced endoplasmic reticle and oocyte retraction. Results: There was a higher incidence of alterations in oocyte morphology in the letrozole group when compared to the control group: increased perivitelline space (p=0.007), irregular zona pellucida (p<0.001), refractile bodies (p<0.001), dark ooplasm (p<0.001), granular ooplasm (p<0.001), irregular ooplasm (p<0.001) and dense central granulation (p<0.001). Conclusion: Letrozole is a risk factor for worse oocyte morphology. However, the clinical impact of ovarian stimulation protocol with combined use of gonadotropins and letrozole for fertility preservation remains unclear in this setting. These data underline the importance of establishing the predictive potential of morphological dimorphisms of human oocytes in IVF outcomes.
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Affiliation(s)
- Ludmila M N Bercaire
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil.,Gynecology and Obstetrics Department, Botucatu Medical School, UNESP - Universidade Estadual de São Paulo, Botucatu, SP, Brazil
| | - Mario Cavagna
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Nilka F Donadio
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Andressa R Rocha
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Rafael Portela
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Vanessa R Alves
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Thamara B B Santos
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Felipe Cavagna
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Artur Dzik
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Luiz H Gebrim
- Human Reproduction Department. Women's Health Reference Center - Pérola Byington Hospital, São Paulo, SP, Brazil
| | - Eliana A P Nahas
- Gynecology and Obstetrics Department, Botucatu Medical School, UNESP - Universidade Estadual de São Paulo, Botucatu, SP, Brazil
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20
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Zhang H, Wang G, Cao M, Yin L, Xing Y, Wang J, Yang J, Zhang J. Level of Knowledge and Needs on Fertility Preservation in Reproductive-Aged Male Patients with Cancer. JOURNAL OF CANCER EDUCATION : THE OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER EDUCATION 2020; 35:321-326. [PMID: 30618008 PMCID: PMC7075821 DOI: 10.1007/s13187-018-1467-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
There is a growing concern about the fertility preservation (FP) for cancer patients of childbearing age. This study is the first in China to survey men with cancer, of reproductive age, regarding their knowledge of FP and their related needs. A 12-item cross-sectional survey was conducted of 332 male patients. The score for knowledge of FP was 3.5 ± 0.67, of a possible score of 8. Only 10.6% of the subjects had chosen to preserve fertility before treatments, but during therapy 68.7% wanted more information about FP. Younger patients were more likely have more knowledge concerning FP than older patients (odds ratio [OR] 0.86). The decision to make arrangements for FP before treatments was heavily influenced by being young and without children (OR, 0.78; OR, 0.11). Male cancer patients of reproductive age had limited knowledge of FP, and the majority was disinclined to make FP arrangements before therapy in China. Therefore, male cancer survivors should be well informed about FP soon after diagnosis and programs should be considered to improve the FP-related knowledge of male cancer survivors. We suggest that an assessment of patients' understanding of FP issues, before treatment, should be standard in clinical work.
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Affiliation(s)
- Hanfeng Zhang
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55, 4th Section of Renmin South Road, Chengdu, 610040 Sichuan Province People’s Republic of China
| | - Guorong Wang
- Department of Nursing, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55, 4th Section of Renmin South Road, Chengdu, 610040 Sichuan Province People’s Republic of China
| | - Maoqiu Cao
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55, 4th Section of Renmin South Road, Chengdu, 610040 Sichuan Province People’s Republic of China
| | - Li Yin
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55, 4th Section of Renmin South Road, Chengdu, 610040 Sichuan Province People’s Republic of China
| | - Yan Xing
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55, 4th Section of Renmin South Road, Chengdu, 610040 Sichuan Province People’s Republic of China
| | - Jing Wang
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55, 4th Section of Renmin South Road, Chengdu, 610040 Sichuan Province People’s Republic of China
| | - Jing Yang
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55, 4th Section of Renmin South Road, Chengdu, 610040 Sichuan Province People’s Republic of China
| | - Jian Zhang
- Department of Nursing, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55, 4th Section of Renmin South Road, Chengdu, 610040 Sichuan Province People’s Republic of China
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21
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Carvacrol and Thymol Modulate the Cross-Talk between TNF- α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:3173745. [PMID: 31531182 PMCID: PMC6721489 DOI: 10.1155/2019/3173745] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 07/01/2019] [Accepted: 07/18/2019] [Indexed: 02/08/2023]
Abstract
Premature ovarian failure (POF) is a common cause of infertility in premenopausal women who are unavoidably exposed to cytotoxic therapy. Radiotherapy is one of the most effective cytotoxic treatments. However, the radiosensitivity of ovarian tissues limits its therapeutic outcome and results in the depletion of the primordial follicle and loss of fertility. Therefore, the need for an effective radioprotective therapy is evident especially when none of the current clinically used modalities for radioprotection succeeds efficiently. The present study investigated the potential radioprotective effect of carvacrol (CAR) (80 mg) or thymol (80 mg) on gamma- (γ-) irradiation-induced ovarian damage as well as their role in the cross-talk between IGF-1 and TNF-α signaling and antioxidative activity. In immature female Wister rats, a single dose of whole-body irradiation (3.2 Gy, LD20) produced considerable ovarian damage, which was evident by histopathological findings and hormonal changes. Interestingly, pretreatment with CAR or thymol significantly enhanced the follicular development and restored the anti-Mullerian hormone (AMH), E2, and FSH levels. Both essential oils improved the irradiation-mediated oxidative stress and reduction in proliferating cell nuclear antigen (PCNA) expression. Moreover, irradiated rats exhibited an inverse relationship between IGF-1 and TNF-α levels two days post irradiation, which was further inverted by the pretreatment with CAR and thymol and ought to contribute in their radioprotective mechanisms. In conclusion, CAR and thymol showed a radioprotective effect and rescued the ovarian reserve mainly through counteracting oxidative stress and the dysregulated cross-talk between IGF-1 and TNF-α.
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22
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Planned and unplanned pregnancies in breast cancer survivors. Breast 2019; 46:75-80. [DOI: 10.1016/j.breast.2019.05.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 04/07/2019] [Accepted: 05/02/2019] [Indexed: 01/21/2023] Open
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23
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Buonomo B, Brunello A, Noli S, Miglietta L, Del Mastro L, Lambertini M, Peccatori FA. Tamoxifen Exposure during Pregnancy: A Systematic Review and Three More Cases. Breast Care (Basel) 2019; 15:148-156. [PMID: 32398983 DOI: 10.1159/000501473] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 06/13/2019] [Indexed: 12/16/2022] Open
Abstract
Tamoxifen is frequently used as adjuvant treatment in premenopausal patients with hormone receptor-positive early breast cancer. According to guidelines, the use of nonhormonal barrier contraception is recommended during tamoxifen treatment and up to 3 months after its interruption prior to attempting conception. Nevertheless, when conception occurs inadvertently during tamoxifen treatment, the effects on the fetus and on the course of pregnancy are still not completely known. Here, we report 3 cases of young women who accidentally became pregnant while taking tamoxifen and perform a systematic review of the literature to provide more elements for better and clear multidisciplinary counselling of women facing this challenging situation.
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Affiliation(s)
- Barbara Buonomo
- Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.,Fertility and Procreation Unit, Division of Gynecologic Oncology, European Institute of Oncology IRCCS, Milan, Italy
| | - Antonella Brunello
- Medical Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV - IRCCS, Padua, Italy
| | - Stefania Noli
- Fertility and Procreation Unit, Division of Gynecologic Oncology, European Institute of Oncology IRCCS, Milan, Italy.,Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Loredana Miglietta
- U.O.C. Oncologia Medica 2, Department of Medical Oncology, Ospedale Policlinico San Martino, Genoa, Italy
| | - Lucia Del Mastro
- S.S. Sviluppo Terapie Innovative, Department of Medical Oncology, Ospedale Policlinico San Martino, Genoa, Italy.,Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, Genoa, Italy
| | - Matteo Lambertini
- Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, Genoa, Italy.,Clinica di Oncologia Medica, Department of Medical Oncology, Ospedale Policlinico San Martino - IST, Genoa, Italy
| | - Fedro Alessandro Peccatori
- Fertility and Procreation Unit, Division of Gynecologic Oncology, European Institute of Oncology IRCCS, Milan, Italy
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24
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Buigues A, Marchante M, Herraiz S, Pellicer A. Diminished Ovarian Reserve Chemotherapy-Induced Mouse Model: A Tool for the Preclinical Assessment of New Therapies for Ovarian Damage. Reprod Sci 2019:1933719119831784. [PMID: 30791852 DOI: 10.1177/1933719119831784] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Twenty-one Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were allocated to 3 groups (n = 7/group): control, single dose of vehicle (Dimethyl Sulfoxide [DMSO]); DOR, single reduced chemotherapy dose; and POI, single standard chemotherapy dose. After 21 days, mice underwent ovarian hyperstimulation and mating. Part of the animals were harvested to analyze ovarian reserve, ovulation and fertilization rates, and morphology, apoptosis, and vascularization of the ovarian stroma. The remaining mice underwent multiple matings to assess pregnancy rates and litter sizes. The DOR and POI mice showed an impaired estrous cyclicity and a decrease in ovarian mass, number of follicles, Metaphase II (MII) oocytes, and embryos as well as in ovarian stroma vascularization. Mice in both models showed also an increase in the percentage of morphologically abnormal follicles, stromal degeneration, and apoptosis. Similar to that observed in DOR and POI patients, these impairments were less severe in DOR than in POI mice. None of the POI females were able to achieve a pregnancy. Meanwhile, DOR females achieved several consecutive pregnancies, although litter size was decreased when compared to controls. In conclusion, a mouse model which displayed most of the ovarian characteristics and fertility outcomes of women with DOR has been established using a single dose of chemotherapy.
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Affiliation(s)
- Anna Buigues
- 1 IVI Foundation, Valencia Spain
- 2 Department of Pediatrics, Obstetrics and Gynecology, School of Medicine, Valencia University, Valencia, Spain
| | - Maria Marchante
- 1 IVI Foundation, Valencia Spain
- 2 Department of Pediatrics, Obstetrics and Gynecology, School of Medicine, Valencia University, Valencia, Spain
| | - Sonia Herraiz
- 1 IVI Foundation, Valencia Spain
- 3 Reproductive Medicine Research Group, IIS La Fe, Valencia, Spain
- 4 IVI-RMA Valencia, Valencia, Spain
| | - Antonio Pellicer
- 1 IVI Foundation, Valencia Spain
- 3 Reproductive Medicine Research Group, IIS La Fe, Valencia, Spain
- 5 IVI-RMA Rome, Rome, Italy
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25
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Garrido-Marín M, Argacha PM, Fernández L, Molfino F, Martínez-Soler F, Tortosa A, Gimenez-Bonafé P. Full-term pregnancy in breast cancer survivor with fertility preservation: A case report and review of literature. World J Clin Cases 2019; 7:58-68. [PMID: 30637253 PMCID: PMC6327133 DOI: 10.12998/wjcc.v7.i1.58] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 11/20/2018] [Accepted: 12/01/2018] [Indexed: 02/05/2023] Open
Abstract
A 43-year-old woman with an associated history of gynecological pathology and breast cancer with only one cryopreserved embryo wished to be a mother. Several factors that influenced the success of the pregnancy in this case were analyzed. Favorable factors included: triple positive breast cancer [positive hormone receptors and positive human epidermal growth factor receptor 2], which is more hormosensitive and chemosensitive; absence of metastasis; correct endometrium preparation; and the patient’s optimistic attitude and strict health habits. In contrast, the factors against success were: breast cancer; adjuvant breast cancer therapy gonadotoxicity; the age of the patient (> 40-year-old); endometriosis; ovarian cyst; hydrosalpinx; submucosal fibroids and the respective associated surgery done for the above-mentioned pathology (all resolved prior to the embryo transfer); and a low quantity of ovules (low ovarian reserve) after ovarian stimulation. This is a very special clinical case of a patient with theoretically low pregnancy success probability due to the consecutive accumulation of gynecological and oncological pathologies, who nonetheless became pregnant and delivered a full-term infant and was able to provide adequate breastfeeding.
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Affiliation(s)
- Marta Garrido-Marín
- Department of Physiological Sciences, Physiology Unit, Faculty of Medicine and Health Sciences, Bellvitge Campus, Universitat de Barcelona, IDIBELL, L’Hospitalet del Llobregat, Barcelona 08907, Spain
| | | | - Luís Fernández
- Servicio de Oncología Médica, Consorcio Corporación Sanitaria Parc Taulí, Barcelona, Sabadell 08208, Spain
| | | | - Fina Martínez-Soler
- Department of Basic Nursing, Faculty of Medicine and Health Sciences, Universitat de Barcelona, IDIBELL, L’Hospitalet del Llobregat, Barcelona 08907, Spain
| | - Avelina Tortosa
- Department of Basic Nursing, Faculty of Medicine and Health Sciences, Universitat de Barcelona, IDIBELL, L’Hospitalet del Llobregat, Barcelona 08907, Spain
| | - Pepita Gimenez-Bonafé
- Department of Physiological Sciences, Physiology Unit, Faculty of Medicine and Health Sciences, Bellvitge Campus, Universitat de Barcelona, IDIBELL, L’Hospitalet del Llobregat, Barcelona 08907, Spain
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26
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Cavagna F, Pontes A, Cavagna M, Dzik A, Donadio NF, Portela R, Nagai MT, Gebrim LH. Specific protocols of controlled ovarian stimulation for oocyte cryopreservation in breast cancer patients. ACTA ACUST UNITED AC 2018; 25:e527-e532. [PMID: 30607119 DOI: 10.3747/co.25.3889] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Background Fertility preservation is an important concern in breast cancer patients. In the present investigation, we set out to create a specific protocol of controlled ovarian stimulation (cos) for oocyte cryopreservation in breast cancer patients. Methods From November 2014 to December 2016, 109 patients were studied. The patients were assigned to a specific random-start ovarian stimulation protocol for oocyte cryopreservation. The endpoints were the numbers of oocytes retrieved and of mature oocytes cryopreserved, the total number of days of ovarian stimulation, the total dose of gonadotropin administered, and the estradiol level on the day of the trigger. Results Mean age in this cohort was 31.27 ± 4.23 years. The average duration of cos was 10.0 ± 1.39 days. The mean number of oocytes collected was 11.62 ± 7.96 and the mean number of vitrified oocytes was 9.60 ± 6.87. The mean estradiol concentration on triggering day was 706.30 ± 450.48 pg/mL, and the mean dose of gonadotropins administered was 2610.00 ± 716.51 IU. When comparing outcomes by phase of the cycle in which cos was commenced, we observed no significant differences in the numbers of oocytes collected and vitrified, the length of ovarian stimulation, and the estradiol level on trigger day. The total dose of follicle-stimulating hormone and human menopausal gonadotropin administered was statistically greater in the group starting cos in the luteal phase than in the group starting in the late follicular phase. Conclusions Our results suggest that using a specific protocol with random-start ovarian stimulation for oocyte cryopreservation in breast cancer patients is effective and could be offered to young women undergoing oncologic treatment.
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Affiliation(s)
- F Cavagna
- Women's Health Reference Center, Hospital Perola Byington, Sao Paulo, Brazil
| | - A Pontes
- Department of Gynecology and Obstetrics, Botucatu Medical School, University of the State of Sao Paulo, Botucatu, Brazil
| | - M Cavagna
- Women's Health Reference Center, Hospital Perola Byington, Sao Paulo, Brazil
| | - A Dzik
- Women's Health Reference Center, Hospital Perola Byington, Sao Paulo, Brazil
| | - N F Donadio
- Women's Health Reference Center, Hospital Perola Byington, Sao Paulo, Brazil
| | - R Portela
- Women's Health Reference Center, Hospital Perola Byington, Sao Paulo, Brazil
| | - M T Nagai
- Women's Health Reference Center, Hospital Perola Byington, Sao Paulo, Brazil
| | - L H Gebrim
- Women's Health Reference Center, Hospital Perola Byington, Sao Paulo, Brazil
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27
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Ortega I, García-Velasco JA, Pellicer A. Ovarian manipulation in ART: going beyond physiological standards to provide best clinical outcomes. J Assist Reprod Genet 2018; 35:1751-1762. [PMID: 30056596 DOI: 10.1007/s10815-018-1258-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 07/03/2018] [Indexed: 12/11/2022] Open
Abstract
Current knowledge on ovarian physiology has challenged the traditional concept of folliculogenesis, creating the basis for novel ovarian stimulation protocols in assisted reproduction technology. The purpose of this review was to evaluate the efficacy of novel clinical interventions that could aid clinicians in individualizing their protocols to patients' characteristics and personal situations. We conducted a literature review of the available evidence on new approaches for ovarian stimulation from both retrospective and prospective studies in the PubMed database. Here, we present some of the most important interventions, including follicle growth in the gonadotropin-independent and dependent stage, manipulation of estradiol production throughout ovarian stimulation, control of mid-cycle gonadotropin surges, and luteal phase support after different stimulation protocols and trigger agents. The latest research on IVF has moved physicians away from the classical physiology, allowing the development of new strategies to decouple organ functions from the female reproductive system and challenging the traditional concept of IVF.
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Affiliation(s)
- Israel Ortega
- IVI-Madrid, Madrid, Spain. .,Instituto de Investigación Sanitaria La Fé, Valencia, Spain.
| | - Juan A García-Velasco
- IVI-Madrid, Madrid, Spain.,Instituto de Investigación Sanitaria La Fé, Valencia, Spain.,Rey Juan Carlos University, Madrid, Spain.,IdiPAZ, Madrid, Spain
| | - Antonio Pellicer
- Instituto de Investigación Sanitaria La Fé, Valencia, Spain.,Rey Juan Carlos University, Madrid, Spain.,IdiPAZ, Madrid, Spain.,IVI-Roma, Rome, Italy
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28
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Nguyen QN, Zerafa N, Liew SH, Morgan FH, Strasser A, Scott CL, Findlay JK, Hickey M, Hutt KJ. Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility. Cell Death Dis 2018; 9:618. [PMID: 29795269 PMCID: PMC5966424 DOI: 10.1038/s41419-018-0633-7] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 04/15/2018] [Accepted: 04/26/2018] [Indexed: 12/14/2022]
Abstract
Female gametes are stored in the ovary in structures called primordial follicles, the supply of which is non-renewable. It is well established that DNA-damaging cancer treatments can deplete the ovarian reserve of primordial follicles, causing premature ovarian failure and infertility. The precise mechanisms underlying this chemotherapy-driven follicle loss are unclear, and this has limited the development of targeted ovarian-protective agents. To address this fundamental knowledge gap, we used gene deletion mouse models to examine the role of the DNA damage-induced pro-apoptotic protein, PUMA, and its transcriptional activator TAp63, in primordial follicle depletion caused by treatment with cyclophosphamide or cisplatin. Cyclophosphamide caused almost complete destruction of the primordial follicle pool in adult wild-type (WT) mice, and a significant destructive effect was also observed for cisplatin. In striking contrast, Puma-/- mice retained 100% of their primordial follicles following either genotoxic treatment. Furthermore, elimination of PUMA alone completely preserved fertility in cyclophosphamide-treated mice, indicating that oocytes rescued from DNA damage-induced death can repair themselves sufficiently to support reproductive function and offspring health. Primordial follicles were also protected in TAp63-/- mice following cisplatin treatment, but not cyclophosphamide, suggesting mechanistic differences in the induction of apoptosis and depletion of the ovarian reserve in response to these different chemotherapies. These studies identify PUMA as a crucial effector of apoptosis responsible for depletion of primordial follicles following exposure to cyclophosphamide or cisplatin, and this indicates that inhibition of PUMA may be an effective ovarian-protective strategy during cancer treatment in women.
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Affiliation(s)
- Quynh-Nhu Nguyen
- Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
| | - Nadeen Zerafa
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
| | - Seng H Liew
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
| | - F Hamish Morgan
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
| | - Andreas Strasser
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
| | - Clare L Scott
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
| | - Jock K Findlay
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Monash University, Clayton, VIC, Australia
| | - Martha Hickey
- Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia
- The Royal Womens Hospital, Parkville, VIC, 3052, Australia
| | - Karla J Hutt
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
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29
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Pregnancy Outcomes After a Breast Cancer Diagnosis: A Systematic Review and Meta-analysis. Clin Breast Cancer 2018; 18:e79-e88. [DOI: 10.1016/j.clbc.2017.06.016] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 04/13/2017] [Accepted: 06/30/2017] [Indexed: 11/24/2022]
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30
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Vaz-Luis I, Partridge AH. Exogenous reproductive hormone use in breast cancer survivors and previvors. Nat Rev Clin Oncol 2018; 15:249-261. [DOI: 10.1038/nrclinonc.2017.207] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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31
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A specific controlled ovarian stimulation (COS) protocol for fertility preservation in women with breast cancer undergoing neoadjuvant chemotherapy. Contemp Oncol (Pozn) 2017; 21:290-294. [PMID: 29416435 PMCID: PMC5799704 DOI: 10.5114/wo.2017.72395] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Accepted: 08/26/2017] [Indexed: 12/30/2022] Open
Abstract
Aim of the study The authors present a novel and specific controlled ovarian stimulation protocol for fertility preservation in women with estrogen-positive receptor breast cancer undergoing neoadjuvant chemotherapy. The protocol foresees random start ovarian stimulation and the use of letrozole associated to tamoxifen. Material and methods Forty breast cancer patients were included in the study. COS was performed either with recombinant FSH or hMG. Concomitantly with COS, letrozole in a dose of 5 mg and tamoxifen in a dose of 20 mg were given orally on a daily basis. The trigger was performed with 0.2 mg of triptorelin, in the presence of follicles ≥ 19 mm. Oocyte retrieval was scheduled 35-36 hours after triptorelin injection. Our main outcome measures were the number of oocytes collected and number of oocytes vitrified, the length of ovarian stimulation, total dose of gonadotropins administered, and levels of estradiol on the day of the trigger. Results The mean age of patients was 30.43 ±4.25 years. Nineteen women commenced COS in the luteal phase, eleven in the early follicular phase and ten in the late follicular phase. The mean number of collected oocytes was 11.78 ±9.12 and the mean number of vitrified oocytes was 9.72 ±7.36. The mean duration of COS was 10.03 ±1.33 days. The mean estradiol concentrations on the triggering day was 623.10 ±441.27, and the mean dose of gonadotropins administered was 2540 ±713.10. Conclusions The authors suggest that the protocol is efficient and may be a safe option for oocyte vitrification in these patients.
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Osmani AH, Haider G, Ali S, Ali F, Irfan M, Fatima DE. Knowledge and Perceptions about Cancer Treatment-associated Infertility among Young Patients at a Tertiary Care Hospital in Pakistan. Asian Pac J Cancer Prev 2017; 18:3261-3265. [PMID: 29286217 PMCID: PMC5980881 DOI: 10.22034/apjcp.2017.18.12.3261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Introduction: Infertility after cancer treatment can cause significant emotional stress and grief for cancer survivors. In this study we assessed knowledge and perceptions among young cancer patients regarding the topic of cancer and infertility related to different treatment options. Material and Methods: This cross-sectional study was conducted on young cancer patients in the Clinical Oncology Department, JPMC, Karachi, from January to August 2013. Patients were requested to fill in questionnaires. Comparisons between gender and age groups were performed using the Student’s t test and Pearson’s Chi-squared. Significance was concluded with a two tailed p-value less than 0.05. Results: The survey included 368 cancer patients, 194 males and 174 females. Ninety percent of respondents of either gender were not aware that cancer or cancer treatment can cause infertility, this being age dependent (P=0.06). However, on being made aware, 98% of males and 91% of females wanted their oncologist to discuss treatment-related infertility prior to initiating cancer treatment (P=0.005) and 92% and 78%, respectively, wanted to consider fertility preservation techniques prior to treatment (P<0.0001). Of age groups 15-30 years and 31-50 years, 91 % and 81% wanted to consider FP prior to cancer treatment (P =0.011). Among 226 married individuals, 89% males and 79% females underestimated that effects that infertility issues might have on their relationships with their spouses. Conclusions: We recommend physicians and oncology care givers to initiate discussion of the topic of cancer and treatment-related infertility with young cancer patients during their initial management planning.
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Affiliation(s)
- Asif Husain Osmani
- Department of Clinical Oncology, Jinnah Postgraduate Medical Centre, Karachi, Pakistan.
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Turan V, Bedoschi G, Emirdar V, Moy F, Oktay K. Ovarian Stimulation in Patients With Cancer: Impact of Letrozole and BRCA Mutations on Fertility Preservation Cycle Outcomes. Reprod Sci 2017; 25:26-32. [PMID: 28874104 DOI: 10.1177/1933719117728800] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Aromatase inhibitors (AI) have been introduced to reduce estrogen exposure in women with estrogen-sensitive cancer undergoing ovarian stimulation for oocyte/embryo cryopreservation. There have been questions regarding whether the addition of AI and the presence of BRCA mutations affect cycle outcomes. We sought to determine the impact of letrozole and BRCA mutations on fertility preservation (FP) cycle outcomes of patients undergoing ovarian stimulation with an antagonist protocol. METHODS The data were generated by the secondary analysis of a prospective database of all females diagnosed with cancer who underwent embryo or oocyte cryopreservation for FP. The final analysis included 145 patients stimulated with an antagonist protocol either using letrozole combined with recombinant follicle-stimulating hormone (rFSH; LF, n = 118) or rFSH alone (FA, n = 24). RESULTS The mean number of total (15.6 [7.9] vs 10.2 [7.8]; P = .004) and mature oocytes (10.4 [5.1] vs 7.8 [3.5]; P = .044) and embryos frozen (7.7 [5.3] vs 5.3 [2.7]; P = .043) were significantly higher after LF stimulation versus FA. In the LF group, women with BRCA mutations produced significantly fewer oocytes (11.0 [8.0] vs 16.4 [7.7], P = .015) and embryos (5.1 [4.4] vs 8.2 [4.7], P = .013), compared to those who were mutation negative. After adjusting for age, body mass index, baseline FSH level, and BRCA status, LF protocol still resulted in higher number of total oocytes (95% confidence interval [CI]: 1.9 to 3.6; P = .002) mature oocyte (95% CI: 0.3 to 1.4; P = .028), and embryo yield (95% CI: 0.7 to 1.4; P = .015). CONCLUSION In women with cancer undergoing FP, letrozole appears to enhance response to ovarian stimulation while the presence of BRCA mutations is associated with lower oocyte and embryo yield.
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Affiliation(s)
- Volkan Turan
- 1 Innovation Institute for Fertility and In Vitro Fertilization, New York, NY, USA.,2 Department of Obstetrics and Gynecology, GOP Hospital, Yeni Yuzyil University School of Medicine, Istanbul, Turkey
| | - Giuliano Bedoschi
- 1 Innovation Institute for Fertility and In Vitro Fertilization, New York, NY, USA.,3 Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Volkan Emirdar
- 1 Innovation Institute for Fertility and In Vitro Fertilization, New York, NY, USA
| | - Fred Moy
- 1 Innovation Institute for Fertility and In Vitro Fertilization, New York, NY, USA
| | - Kutluk Oktay
- 1 Innovation Institute for Fertility and In Vitro Fertilization, New York, NY, USA.,4 Laboratory of Molecular Reproduction and Fertility Preservation, Yale University School of Medicine, Department of Obstetrics and Gynecology and Reproductive Sciences, New Haven, CT, USA
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Dahhan T, Balkenende EME, Beerendonk CCM, Fleischer K, Stoop D, Bos AME, Lambalk CB, Schats R, van Golde RJT, Schipper I, Louwé LA, Cantineau AEP, Smeenk JMJ, de Bruin JP, Reddy N, Kopeika Y, van der Veen F, van Wely M, Linn SC, Goddijn M. Stimulation of the ovaries in women with breast cancer undergoing fertility preservation: Alternative versus standard stimulation protocols; the study protocol of the STIM-trial. Contemp Clin Trials 2017; 61:96-100. [PMID: 28710053 DOI: 10.1016/j.cct.2017.07.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 03/04/2017] [Accepted: 07/06/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND Chemotherapy for breast cancer may have a negative impact on reproductive function due to gonadotoxicity. Fertility preservation via banking of oocytes or embryos after ovarian stimulation with FSH can increase the likelihood of a future live birth. It has been hypothesized that elevated serum estrogen levels during ovarian stimulation may induce breast tumour growth. This has led to the use of alternative stimulation protocols with addition of tamoxifen or letrozole. The effectiveness of these stimulation protocols in terms of oocyte yield is unknown. METHODS/DESIGN Randomized open-label trial comparing ovarian stimulation plus tamoxifen and ovarian stimulation plus letrozole with standard ovarian stimulation in the course of fertility preservation. The study population consists of women with breast cancer who opt for banking of oocytes or embryos, aged 18-43years at randomisation. Primary outcome is the number of oocytes retrieved at follicle aspiration. Secondary outcomes are number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation. DISCUSSION Concerning the lack of evidence on which stimulation protocol should be used in women with breast cancer and the growing demand for fertility preservation, there is an urgent need to undertake this study. By performing this study, we will be able to closely monitor the effects of various stimulation protocols in women with breast cancer and pave the way for long term follow up on the safety of this procedure in terms of breast cancer prognosis. TRIAL REGISTRATION NTR4108.
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Affiliation(s)
- T Dahhan
- Center for Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - E M E Balkenende
- Center for Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands.
| | - C C M Beerendonk
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - K Fleischer
- Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - D Stoop
- Center for Reproductive Medicine, UZ Brussel, Free University of Brussels, Belgium
| | - A M E Bos
- Department of Reproductive Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - C B Lambalk
- Department of Reproductive Medicine, VU University Medical Center, Amsterdam, The Netherlands
| | - R Schats
- Department of Reproductive Medicine, VU University Medical Center, Amsterdam, The Netherlands
| | - R J T van Golde
- Department of Reproductive Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - I Schipper
- Department of Obstetrics and Gynaecology, St Elisabeth Hospital, Tilburg, The Netherlands
| | - L A Louwé
- Department of Gynaecology, Leiden University Medical Centre, Leiden, The Netherlands
| | - A E P Cantineau
- Department of Obstetrics and Gynaecology, University Medical Center Groningen, Groningen, The Netherlands
| | - J M J Smeenk
- Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - J P de Bruin
- Department of Obstetrics and Gynecology, Jeroen Bosch Hospital, Den Bosch, The Netherlands
| | - N Reddy
- Assisted Conception Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom
| | - Y Kopeika
- Assisted Conception Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom
| | - F van der Veen
- Center for Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - M van Wely
- Center for Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - S C Linn
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - M Goddijn
- Center for Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands
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Nishi K, Gunasekaran VP, Arunachalam J, Ganeshan M. Doxorubicin-induced female reproductive toxicity: an assessment of ovarian follicular apoptosis, cyclicity and reproductive tissue histology in Wistar rats. Drug Chem Toxicol 2017; 41:72-81. [DOI: 10.1080/01480545.2017.1307851] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Kumari Nishi
- Department of Biomedical Science, Bharathidasan University, Tiruchirappalli, Tamilnadu, India
| | | | - Jaganath Arunachalam
- Department of Biomedical Science, Bharathidasan University, Tiruchirappalli, Tamilnadu, India
| | - Mathan Ganeshan
- Department of Biomedical Science, Bharathidasan University, Tiruchirappalli, Tamilnadu, India
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Unexpected pregnancy during tamoxifen treatment: a case report and review of the literature. CASE REPORTS IN PERINATAL MEDICINE 2016. [DOI: 10.1515/crpm-2015-0077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
We report a patient who became pregnant while on tamoxifen treatment for breast cancer and who elected to continue her pregnancy. The normal child was delivered except for a right renal pelvicaliceal dilatation. The use of tamoxifen in pregnancy is complex, but is not necessarily associated with fetal harm. The relatively high frequency of severe congenital abnormalities indicates that it is prudent to stop tamoxifen before pregnancy.
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Dyer KE, Quinn GP. Cancer and fertility preservation in Puerto Rico: a qualitative study of healthcare provider perceptions. Support Care Cancer 2016; 24:3353-60. [PMID: 26980331 PMCID: PMC5044868 DOI: 10.1007/s00520-016-3166-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 03/07/2016] [Indexed: 11/27/2022]
Abstract
PURPOSE This study aims to examine healthcare provider perceptions of cancer-related infertility and fertility preservation (FP) in an underserved population and to highlight cognitive and structural barriers to use. METHODS In-depth, semi-structured interviews were conducted with a sample of 16 healthcare providers participating in a larger ethnographic study on cancer survivorship and cancer-related infertility in Puerto Rico, an unincorporated US territory. Interviews were conducted in-person, audio-recorded, transcribed verbatim, and coded using the constant comparative method. RESULTS Providers identified several barriers to FP in Puerto Rico: high cost in relation to income levels, lack of insurance coverage, gaps in provider knowledge of fertility clinics and financial assistance, lower prioritization of quality-of-life needs leading to inconsistent physician disclosure of fertility risks, geographical location of fertility clinics, and logistical challenges to maintaining FP offerings. Two factors act as facilitators: a high value placed on patient-provider communication and relationships and the formation of local alliances between the oncology and reproductive medicine fields, potentially leading to increased cross-specialty communication and referral. CONCLUSIONS Infertility is a continuing source of distress for cancer patients and survivors, and barriers to FP vary cross-culturally. In Puerto Rico, context-specific factors indicate potential areas of intervention. Greater awareness of fertility risks and options can be fostered through physician training in conjunction with organizational measures targeting cost barriers.
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Affiliation(s)
- Karen E Dyer
- Department of Anthropology, University of South Florida, Tampa, FL, USA.
- Department of Health Behavior and Policy, School of Medicine, Virginia Commonwealth University, P.O. Box 980149, Richmond, VA, 23298, USA.
| | - Gwendolyn P Quinn
- Health Outcomes and Behavior Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Morsani College of Medicine, University of South Florida, Tampa, FL, USA
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Li XS, Lv Q, Du ZG, Chen J. Prediction of ovarian function in premenopausal breast cancer patients with amenorrhoea after chemotherapy: a simple clinical score. SPRINGERPLUS 2016; 5:1052. [PMID: 27462500 PMCID: PMC4940309 DOI: 10.1186/s40064-016-2671-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Accepted: 06/25/2016] [Indexed: 02/05/2023]
Abstract
We evaluated a non-invasive method for predicting the ovarian function of premenopausal breast cancer patients with amenorrhoea after chemotherapy. A total of 34 patients had ovarian function, whereas 56 had no ovarian function. Logistic regression analysis indicated that age (P = 0.034; hazards ratio [HR], 0.29; confidence interval [CI], 0.091–0.910), follicle-stimulating hormone (P = 0.032; HR 0.97; CI 0.944–0.997) and oestradiol (P = 0.047; HR 1.01; CI 1.000–1.015) were independent influencing factors that determine ovarian function. The ovarian function score (OFS) (P < 0.001; HR 48.00; CI 10.174–226.452) was obtained through a comprehensive analysis of these three variables, and it could more effectively predict ovarian function. According to receiver operating characteristic curve analysis, the OFS had the highest values compared with the other three variables (sensitivity, 94.6 %; specificity, 79.3 %). The OFS is simple and easy to use; thus, it is expected to become a new method for determining drug-induced amenorrhoea in women with breast cancer. Ovarian function likely still exists if the OFS is ≤1.
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Affiliation(s)
- Xiao Shi Li
- Department of Thyroid and Breast Surgery, West China Hospital of Sichuan University, Guo xue Lane 37, Chengdu, China
| | - Qing Lv
- Department of Thyroid and Breast Surgery, West China Hospital of Sichuan University, Guo xue Lane 37, Chengdu, China
| | - Zheng Gui Du
- Department of Thyroid and Breast Surgery, West China Hospital of Sichuan University, Guo xue Lane 37, Chengdu, China
| | - Jie Chen
- Department of Thyroid and Breast Surgery, West China Hospital of Sichuan University, Guo xue Lane 37, Chengdu, China
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Conlon N, Howard J, Catalano J, Gallagher M, Tan LK, Corben AD. Breast Carcinoma in Young Women: No Evidence of Increasing Rates of Metastatic Breast Carcinoma in a Single Tertiary Center Review. Breast J 2016; 22:287-92. [PMID: 26923423 PMCID: PMC5558606 DOI: 10.1111/tbj.12575] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Breast carcinoma in young women aged less than 40 years attracts a high level of mainstream media coverage, and there is a gap between societal perceptions of the disease as a growing problem and epidemiological trends. Several population studies have reported that the overall incidence of breast carcinoma in young women is stable, while one recent article suggested that the relative proportion of breast carcinoma in young women that is metastatic at diagnosis is growing. We sought to establish whether these trends were apparent at our institution. In this study, the clinical database at a breast carcinoma tertiary center was reviewed in terms of clinicopathologic data on patient age, diagnosis, clinical and pathologic stage, hormone receptor status, and HER-2 overexpression status for the period 2000-2011. Over the study period, young patients represented a decreasing proportion of all breast carcinoma cases (10.8% [2000-2003] to 8.7% [2008-2011]; p < 0.0001) treated at our institution. Young patients were more likely than patients aged 40 years or older to present with metastatic (M1) disease (5.4% versus 4.4%; p = 0.009), to be triple negative (21.6% versus 13%; p < 0.001), or to be HER-2 positive (24.3% versus 14.8%; p < 0.01). Young patients with HER-2-positive cancers were significantly more likely to present with metastatic disease (8.3% versus 4.8%; p = 0.004). This study showed no demonstrable increase in the relative proportion of breast cancer occurring in patients aged <40 years over the 12-year period 2000-2011 and no increase in the proportion of young patients presenting with metastatic disease.
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Affiliation(s)
- Niamh Conlon
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jane Howard
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jeffrey Catalano
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Meighan Gallagher
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Lee K Tan
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Adriana D Corben
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
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Valdelièvre C, Sonigo C, Comtet M, Simon C, Eskenazi S, Grynberg M. [Impact of gonadotropins in women suffering from cancer]. Bull Cancer 2016; 103:282-8. [PMID: 26917466 DOI: 10.1016/j.bulcan.2016.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 03/23/2015] [Indexed: 12/21/2022]
Abstract
The role of gonadotropins in the genesis of malignant diseases, in particular gynecologic cancers, is still controversial. The production of ovarian steroids, as a consequence of FSH and LH actions, may constitute a bias to draw reliable conclusions. Over the past decades, the use of exogenous gonadotropins has markedly increased in cancer patients, candidates for fertility preservation, and in survivors facing infertility as a consequence of gonadotoxic treatments. In gynecologic cancers, high serum estradiol levels may be problematic and can therefore be overcome by specific protocols of ovarian stimulation. However, exogenous gonadotropin administration in cancer patients should systematically be included in a multidisciplinary approach. The present article discusses the possible role of gonadotropins as tumorigenic factors and the use of exogenous gonadotropins in females suffering from cancer.
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Affiliation(s)
- Constance Valdelièvre
- Hôpital Jean-Verdier, service de médecine de la reproduction, avenue du 14-Juillet, 93140 Bondy, France
| | - Charlotte Sonigo
- Hôpital Jean-Verdier, service de médecine de la reproduction, avenue du 14-Juillet, 93140 Bondy, France; Université Paris XIII, 93000 Bobigny, France
| | - Marjorie Comtet
- Hôpital Jean-Verdier, service de médecine de la reproduction, avenue du 14-Juillet, 93140 Bondy, France
| | - Cynthia Simon
- Hôpital Jean-Verdier, service de médecine de la reproduction, avenue du 14-Juillet, 93140 Bondy, France
| | - Sarah Eskenazi
- Hôpital Jean-Verdier, service de médecine de la reproduction, avenue du 14-Juillet, 93140 Bondy, France
| | - Michaël Grynberg
- Hôpital Jean-Verdier, service de médecine de la reproduction, avenue du 14-Juillet, 93140 Bondy, France; Université Paris XIII, 93000 Bobigny, France; Université Paris-Diderot, unité Inserm U1133, 75013 Paris, France.
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D'Avila ÂM, Biolchi V, Capp E, Corleta HVE. Age, anti-müllerian hormone, antral follicles count to predict amenorrhea or oligomenorrhea after chemotherapy with cyclophosphamide. J Ovarian Res 2015; 8:82. [PMID: 26667243 PMCID: PMC4678664 DOI: 10.1186/s13048-015-0209-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 12/09/2015] [Indexed: 11/14/2022] Open
Abstract
Background A cohort study was performed to identify ovarian reserve markers (ORM) that predicts amenorrhea or oligomenorrhea 6 months after cyclophosphamide CTX in women with breast cancer. Methods 52 eumenorrheic patients with breast cancer were enrolled. FSH, anti-Müllerian hormone (AMH), antral follicles count (AFC) were measured before and 6 months after CTX. A logistic regression for independent samples and determination of the ROC curve were performed. Results The age of 32 years presented 96 % of sensitivity and 39 % of specificity to predict amenorrhea or oligomenorrhea with ROC area under the curve (AUC) of 0.77. ovarian reserve marker (ORM) with power to predict amenorrhea or oligomenorrhea in women after CTX were AMH <3.32 ng/mL (sensitivity of 85 %, specificity of 75 % and AUC 0.87), AFC <13 follicles (sensitivity 81 %, specificity 62 %, AUC 0.81). AMH cutoff to predict amenorrhea was 1.87 ng/mL (sensitivity 82 %, specificity 83 %, AUC 0.84) and AFC cutoff was 9 follicles (sensitivity 71 %, specificity 78 %, AUC 0.73). Conclusions ≥32-years-old women, AMH <3.32 ng/mL and AFC <13 follicles determined significantly higher risk of amenorrhea or oligomenorrhea after CTX with cyclophosphamide. The ORM age (≥32 years) analyzed together with AMH or AFC increases sensitivity and specificity in predicting amenorrhea or oligomenorrhea.
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Affiliation(s)
- Ângela Marcon D'Avila
- Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul School of Medicine, Bento Gonçalves, RS, Brazil.
| | - Vanderlei Biolchi
- Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Lajeado, RS, Brazil.
| | - Edison Capp
- Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul School of Medicine, Bento Gonçalves, RS, Brazil. .,Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Lajeado, RS, Brazil. .,Department of Obstetrics and Gynecology, Hospital de Clínicas de Porto Alegre, Sul School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. .,Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital Heidelberg, Heidelberg, Germany. .,Serviço de Ginecologia e Obstetrícia - Hospital de Clínicas de Porto Alegre Rua Ramiro Barcelos, 2350/11° andar, Porto Alegre, CEP 90035-903, RS, Brazil.
| | - Helena von Eye Corleta
- Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul School of Medicine, Bento Gonçalves, RS, Brazil. .,Department of Obstetrics and Gynecology, Hospital de Clínicas de Porto Alegre, Sul School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. .,GENERAR, Porto Alegre, RS, Brazil.
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Growth Hormone Ameliorates the Radiotherapy-Induced Ovarian Follicular Loss in Rats: Impact on Oxidative Stress, Apoptosis and IGF-1/IGF-1R Axis. PLoS One 2015; 10:e0140055. [PMID: 26465611 PMCID: PMC4605641 DOI: 10.1371/journal.pone.0140055] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 09/21/2015] [Indexed: 01/25/2023] Open
Abstract
Radiotherapy is one of the standard cytotoxic therapies for cancer. However, it has a profound impact on ovarian function leading to premature ovarian failure and infertility. Since none of the currently available methods for fertility preservation guarantees future fertility, the need for an effective radioprotective agent is highly intensified. The present study investigated the mechanisms of the potential radioprotective effect of growth hormone (GH) on γ irradiation-induced ovarian failure and the impact of the insulin like growth factor 1 (IGF-1) in the underlying protection. Immature female Sprague-Dawley rats were either exposed to single whole body irradiation (3.2 Gy) and/or treated with GH (1 mg/kg s.c). Experimental γ-irradiation produced an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (PCNA), oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1R axis expression was assessed using real-time PCR and immunolocalization techniques. Furthermore, after full maturity, fertility assessment was performed. GH significantly enhanced follicular development and restored anti-Mullerian hormone serum level as compared with the irradiated group. In addition, GH significantly ameliorated the deleterious effects of irradiation on oxidative status, PCNA and apoptosis. Interestingly, GH was shown to enhance the ovarian IGF-1 at transcription and translation levels, a property that contributes significantly to its radioprotective effect. Finally, GH regained the fertility that was lost following irradiation. In conclusion, GH showed a radioprotective effect and rescued the ovarian reserve through increasing local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.
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Incidence of chemotherapy-induced ovarian failure in premenopausal women undergoing chemotherapy for breast cancer. World J Surg 2015; 38:2288-96. [PMID: 24700093 DOI: 10.1007/s00268-014-2542-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Breast cancer is increasingly reported in young premenopausal women in Asia. Adjuvant chemotherapy improves survival; however, it has a unique consequence of ovarian failure in premenopausal patients. OBJECTIVE This study's aim was to find the incidence of chemotherapy-induced ovarian failure (CIOF) and reversible amenorrhea in premenopausal non-metastatic breast cancer patients. METHOD This mixed retrospective and prospective study follows premenopausal breast cancer patients receiving chemotherapy between 2008 and 2012. Patients in the prospective arm were followed up with menstrual history and serum ovarian hormones (follicle-stimulating hormone [FSH] and estradiol) until 1 year post-chemotherapy, and patients in the retrospective arm were contacted for their menstrual history. RESULTS The mean age of the 102 subjects was 43.3 years. Of the patients, 93.1 and 77.9 % were amenorrheic at completion of chemotherapy and at 12 months post-chemotherapy, respectively. Of those who developed amenorrhea, 24.6 % regained menstruation, on average after 7.86 (range 1-15) months post-chemotherapy. Age was the only statistically significant risk factor. CIOF and reversible amenorrhea was 57 and 50 % at <35 years, 95 and 31.6 % at 35-45 years, and 97.9 and 14.9 % at >50 years, respectively. The 33 prospective patients' estradiol and FSH levels seem to correlate well with onset of amenorrhea, with a falling estradiol and rising FSH trend. Tamoxifen use was associated with elevated estradiol levels 1 year post-chemotherapy. CONCLUSION This study found a high incidence of CIOF, with a relatively low rate of reversible amenorrhea. Premenopausal patients should be counselled prior to treatment and education and support provided.
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Oktay K, Turan V, Bedoschi G, Pacheco FS, Moy F. Fertility Preservation Success Subsequent to Concurrent Aromatase Inhibitor Treatment and Ovarian Stimulation in Women With Breast Cancer. J Clin Oncol 2015; 33:2424-9. [PMID: 26101247 DOI: 10.1200/jco.2014.59.3723] [Citation(s) in RCA: 130] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
PURPOSE We 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 METHODS In 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. RESULTS Thirty-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. CONCLUSION Embryo 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.
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Affiliation(s)
- Kutluk Oktay
- Kutluk Oktay, Volkan Turan, Giuliano Bedoschi, and Fernanda S. Pacheco, New York Medical College, Valhalla, and Innovation Institute for Fertility Preservation and In Vitro Fertilization, New York; and Fred Moy, New York Medical College, Valhalla, NY.
| | - Volkan Turan
- Kutluk Oktay, Volkan Turan, Giuliano Bedoschi, and Fernanda S. Pacheco, New York Medical College, Valhalla, and Innovation Institute for Fertility Preservation and In Vitro Fertilization, New York; and Fred Moy, New York Medical College, Valhalla, NY
| | - Giuliano Bedoschi
- Kutluk Oktay, Volkan Turan, Giuliano Bedoschi, and Fernanda S. Pacheco, New York Medical College, Valhalla, and Innovation Institute for Fertility Preservation and In Vitro Fertilization, New York; and Fred Moy, New York Medical College, Valhalla, NY
| | - Fernanda S Pacheco
- Kutluk Oktay, Volkan Turan, Giuliano Bedoschi, and Fernanda S. Pacheco, New York Medical College, Valhalla, and Innovation Institute for Fertility Preservation and In Vitro Fertilization, New York; and Fred Moy, New York Medical College, Valhalla, NY
| | - Fred Moy
- Kutluk Oktay, Volkan Turan, Giuliano Bedoschi, and Fernanda S. Pacheco, New York Medical College, Valhalla, and Innovation Institute for Fertility Preservation and In Vitro Fertilization, New York; and Fred Moy, New York Medical College, Valhalla, NY
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Margulies AL, Selleret L, Zilberman S, Nagarra IT, Chopier J, Gligorov J, Berveiller P, Ballester M, Darai E, Chabbert-Buffet N. [Pregnancy after cancer: for whom and when?]. Bull Cancer 2015; 102:463-9. [PMID: 25917345 DOI: 10.1016/j.bulcan.2015.03.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2014] [Accepted: 03/04/2015] [Indexed: 11/18/2022]
Abstract
Planning a pregnancy for patients with a history of cancer, including breast cancer, is a clinical situation that becomes more and more common. Several specific items are to be discussed: decrease of fertility after cancer treatment, fertility preservation options, impact of pregnancy on cancer recurrence risk and appropriate interval between cancer and pregnancy. Programming pregnancy after cancer is doable in a multidisciplinary setting, and begins at cancer diagnosis to anticipate the various specific pitfalls. Favor adequate oncologic care remains the leading rule.
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Affiliation(s)
- Anne Laure Margulies
- AP-HP, hôpital Bichat, département de gynécologie obstétrique médecine de la reproduction, 75018 Paris, France
| | - Lise Selleret
- AP-HP, université Pierre-et-Marie-Curie Paris 6, hôpital Tenon, département de gynécologie obstétrique médecine de la reproduction, 75020 Paris, France; Réseau INCA cancers associés à La grossesse (CALG), 75020 Paris, France
| | - Sonia Zilberman
- AP-HP, université Pierre-et-Marie-Curie Paris 6, hôpital Tenon, département de gynécologie obstétrique médecine de la reproduction, 75020 Paris, France; Réseau INCA cancers associés à La grossesse (CALG), 75020 Paris, France
| | | | | | - Joseph Gligorov
- Hôpital Tenon, service d'oncologie médicale, 75020 Paris, France
| | - Paul Berveiller
- Réseau INCA cancers associés à La grossesse (CALG), 75020 Paris, France; AP-HP, hôpital Trousseau, département de gynécologie obstétrique, 75012 Paris, France
| | - Marcos Ballester
- AP-HP, université Pierre-et-Marie-Curie Paris 6, hôpital Tenon, département de gynécologie obstétrique médecine de la reproduction, 75020 Paris, France; Réseau INCA cancers associés à La grossesse (CALG), 75020 Paris, France; Université Pierre-et-Marie-Curie Paris 6, UMRS-938, 75005 Paris, France
| | - Emile Darai
- AP-HP, université Pierre-et-Marie-Curie Paris 6, hôpital Tenon, département de gynécologie obstétrique médecine de la reproduction, 75020 Paris, France; Réseau INCA cancers associés à La grossesse (CALG), 75020 Paris, France; Université Pierre-et-Marie-Curie Paris 6, UMRS-938, 75005 Paris, France
| | - Nathalie Chabbert-Buffet
- AP-HP, université Pierre-et-Marie-Curie Paris 6, hôpital Tenon, département de gynécologie obstétrique médecine de la reproduction, 75020 Paris, France; Réseau INCA cancers associés à La grossesse (CALG), 75020 Paris, France; Université Pierre-et-Marie-Curie Paris 6, UMRS-938, 75005 Paris, France.
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Muñoz E, González N, Muñoz L, Aguilar J, Velasco JAG. Ovarian stimulation in patients with breast cancer. Ecancermedicalscience 2015; 9:504. [PMID: 25729417 PMCID: PMC4335970 DOI: 10.3332/ecancer.2015.504] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Indexed: 12/21/2022] Open
Abstract
Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer-free interval or mortality rates in these women.
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Affiliation(s)
- Elkin Muñoz
- IVI Vigo, Plaza Francisco Fernández del Riego, 7, Vigo 36203, Pontevedra, Spain
| | - Naira González
- IVI Vigo, Plaza Francisco Fernández del Riego, 7, Vigo 36203, Pontevedra, Spain
| | - Luis Muñoz
- Fundación Universitaria de Ciencias de la Salud, Bogotá, Cundinamarca 11001000, Colombia
| | - Jesús Aguilar
- IVI Vigo, Plaza Francisco Fernández del Riego, 7, Vigo 36203, Pontevedra, Spain
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Abstract
Preservation of fertility is an important issue in the management of young cancer patients. Though embryo cryostorage is a well-established procedure, it can only be availed by couples. Recent studies have indicated increasing success rates with mature and immature oocyte cryopreservation. Cryostorage induces injuries on the human oocytes which can be minimized by slow freezing and vitrification. Selection of candiidates is crucial so that the most suitable technique can be offered without any delay in initiation of cancer therapy. Factors affecting suitability are age of patient, assessment of ovarian reserve, hormonal status and type and stage of neoplastic disease. Encouraging results have been obtained with oocyte in vitro maturation (IVM) followed by vitrification for cryostorage. Data on the use of vitrified eggs in routine in vitro fertilization (IVF) show that pregnancy rates can be comparable to those achieved with fresh oocytes.
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Affiliation(s)
- Sharmila Dudani
- Department of Pathology, Army College of Medical Sciences, Delhi Cantonment, New Delhi, India
| | - Apurva Gupta
- Department of Gynaecology, Paras Spring Meadows Hospital, East of Kailash, New Delhi, India
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Coyne K, Purdy M, O'Leary K, Yaklic JL, Lindheim SR, Appiah LA. Challenges and considerations in optimizing ovarian stimulation protocols in oncofertility patients. Front Public Health 2014; 2:246. [PMID: 25538933 PMCID: PMC4256952 DOI: 10.3389/fpubh.2014.00246] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 11/06/2014] [Indexed: 01/31/2023] Open
Abstract
The scope of cancer treatment in women of childbearing age has changed in the last decade. Fertility preservation is no longer an afterthought but central to multi-disciplinary cancer treatment planning and should be addressed due to the cytotoxic effects of cancer therapy. However, oncology patients present as a unique treatment challenge as the physician must balance the urgency of fertility preservation with the risks of delaying cancer therapy. Controlled ovarian stimulation (COS) is routinely applied in assisted reproductive technology but can be contraindicated in women with estrogen-receptor-positive tumors. This paper reviews some of the challenges to consider when using COS and newer stimulation protocols to minimize risks and optimize outcomes in oncofertility patients.
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Affiliation(s)
- Kathryn Coyne
- Department of Obstetrics and Gynecology, Boonshoft School of Medicine, Wright State University , Dayton, OH , USA
| | - MacKenzie Purdy
- Department of Obstetrics and Gynecology, University of Kentucky College of Medicine , Lexington, KY , USA
| | | | - Jerome L Yaklic
- Department of Obstetrics and Gynecology, Boonshoft School of Medicine, Wright State University , Dayton, OH , USA
| | - Steven R Lindheim
- Department of Obstetrics and Gynecology, Boonshoft School of Medicine, Wright State University , Dayton, OH , USA
| | - Leslie A Appiah
- Department of Obstetrics and Gynecology, University of Kentucky College of Medicine , Lexington, KY , USA
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Martinez M, Rabadan S, Domingo J, Cobo A, Pellicer A, Garcia-Velasco JA. Obstetric outcome after oocyte vitrification and warming for fertility preservation in women with cancer. Reprod Biomed Online 2014; 29:722-8. [DOI: 10.1016/j.rbmo.2014.09.002] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Revised: 08/28/2014] [Accepted: 09/03/2014] [Indexed: 11/24/2022]
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Moffat R, Güth U. Preserving fertility in patients undergoing treatment for breast cancer: current perspectives. BREAST CANCER-TARGETS AND THERAPY 2014; 6:93-101. [PMID: 25114587 PMCID: PMC4108258 DOI: 10.2147/bctt.s47234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Invasive breast cancer (BC) is the most frequent cancer of young women. Considering the trend toward postponing childbearing until the later reproductive years, the number of childless women at diagnosis of BC will continue to increase. The American Society of Clinical Oncology and the American Society for Reproductive Medicine have recommended that the impact of cancer treatments on fertility should be addressed with all cancer patients of reproductive age and that options for fertility preservation, such as cryopreservation of embryos and oocytes, ovarian tissue, in vitro maturation of immature oocytes, and ovarian suppression with gonadotropin-releasing hormone analogs, should be discussed routinely. To optimally counsel patients on how to best weigh the risks and benefits of fertility preservation, both the health care provider and the patient must know about the options, their risks, and their likelihood of success. The aim of this review is to summarize current knowledge on fertility preservation options for young BC patients, surrogates of ovarian function, psychosocial aspects of infertility after cancer treatment, women’s attitudes towards childbearing after cancer treatment, and health care providers’ attitudes towards fertility preservation.
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Affiliation(s)
- Rebecca Moffat
- Women's Hospital, Clinic for Gynecologic Endocrinology and Reproductive Medicine, University Hospital Basel, Basel, Switzerland
| | - Uwe Güth
- Department of Gynecology and Obstetrics, Breast Center, SenoSuisse, Cantonal Hospital Winterthur, Winterthur, Switzerland
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