Mahmoud Salama

Female fertility loss and preservation: threats and opportunities

BACKGROUND Ovarian aging and cytotoxic treatments are the most common causes for fertility loss in women. With increasing numbers of young female survivors following cytotoxic cancer treatments, the issue of fertility preservation has assumed greater importance. METHODS We review the literature on the causes of female fertility loss as well as the recent advances in fertility preservation options and strategies that might be of interest to oncologists. Currently, several methods and techniques exist for fertility preservation of female patients with cancer including embryo freezing, ovarian protection techniques, oocyte cryopreservation, ovarian tissue cryopreservation followed by autotransplantation, and recently in vitro culture of ovarian tissue, follicles, and oocytes. Each method or technique has advantages and disadvantages related to current success rate, required delay in cancer treatment, sperm requirement, and risk of reintroducing cancer cells. RESULTS To date, embryo freezing is the only established method successfully and widely used for fertility preservation of female patients with cancer. The other methods are promising but still considered experimental. CONCLUSION Patient awareness, physician knowledge, early counseling, costs management, international registry, interdisciplinary networks, and research development are necessary to improve the current care in the field of female fertility preservation.

New advances in ovarian autotransplantation to restore fertility in cancer patients

Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results.

Updates in preserving reproductive potential of prepubertal girls with cancer: Systematic review

INTRODUCTION With increasing numbers of adult female survivors of childhood cancers due to advances in early diagnosis and treatment, the issue of preserving the reproductive potential of prepubertal girls undergoing gonadotoxic treatments has gained greater attention. METHODS According to PRISMA guidelines, a systematic review of the literature was performed for all relevant full-text articles published in PubMed in English throughout the past 15 years to explore the significant updates in preserving the reproductive potential of prepubertal girls with cancer. RESULTS The two established fertility preservation options, embryo freezing and egg freezing, cannot be offered routinely to prepubertal girls as these options necessitate prior ovarian stimulation and subsequent mature oocytes retrieval that are contraindicated or infeasible before puberty. Therefore, the most suitable fertility preservation options to prepubertal girls are (1) ovarian tissue freezing and autotransplantation, (2) in vitro maturation, and (3) ovarian protection techniques. In this review, we discuss in detail those options as well as their success rates, advantages, disadvantages and future directions. We also suggest a new integrated strategy to preserve the reproductive potential of prepubertal girls with cancer. CONCLUSION Although experimental, ovarian tissue slow freezing and orthotopic autotransplantation may be the most feasible option to preserve the reproductive potential of prepubertal girls with cancer. However, this technique has two major and serious disadvantages: (1) the risk of reintroducing malignant cells, and (2) the relatively short lifespan of ovarian tissue transplants. Several medical and ethical considerations should be taken into account before applying this technique to prepubertal girls with cancer.

Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe

Purpose Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health–funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements.Purpose Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health–funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements.

Anticancer treatments and female fertility: clinical concerns and role of oncologists in oncofertility practice

ABSTRACT Introduction: Anticancer treatments such as aggressive chemotherapy and radiotherapy have deleterious gonadotoxic side effects and are considered the most common causes of pathological and iatrogenic fertility loss in women. Areas covered: In order to preserve fertility of young women and girls with cancer, several established, experimental, and debatable options can be offered in the emerging field of oncofertility. This article reviews the effects of anticancer treatments on female fertility and discusses the current challenges and future directions of fertility preservation options that can be offered to the female patients with cancer. Expert commentary: Although promising, several medical, economic, social and legal barriers face oncofertility practice around the globe especially in underserved areas. To overcome such barriers, more effective solutions should be provided to spread awareness and enhance communication between patients, oncologists and gynecologists. Early referral by oncologists before initiation of chemotherapy and radiotherapy is an important key factor for success in female fertility preservation strategies.

Survey of Third-Party Parenting Options Associated With Fertility Preservation Available to Patients With Cancer Around the Globe

Purpose In the accompanying article, “Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe,” we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions. Methods We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed. Results We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms. Conclusion Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients.Purpose In the accompanying article, “Analysis of Fertility Preservation Options Available to Patients With Cancer Around the Globe,” we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions. Methods We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed. Results We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms. Conclusion Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients.

Advances in fertility preservation of female patients with hematological malignancies

ABSTRACT Introduction: The most common forms of hematological malignancies that occur in female reproductive years are lymphoma and leukemia. Areas covered: Several aggressive gonadotoxic regimens such as alkylating chemotherapy and total body irradiation are used frequently in treatment of lymphoma and leukemia leading to subsequent iatrogenic premature ovarian failure and fertility loss. In such cases, female fertility preservation options should be offered in advance. Expert commentary: In order to preserve fertility of young women and girls with lymphoma and leukemia, several established, experimental, and debatable options can be offered before starting chemotherapy and radiotherapy. However, each of those female fertility preservation options has both advantages and disadvantages and may not be suitable for all patients. That is why a fertility preservation strategy should be individualized and tailored distinctively for each patient in order to be effective. Artificial human ovary is a novel experimental in vitro technology to produce mature oocytes that could be the safest option to preserve and restore fertility of young women and girls with hematological malignancies especially when other fertility preservation options are not feasible or contraindicated. Further research and studies are needed to improve the results of artificial human ovary and establish it in clinical practice.

Transplante de tecido ovariano criopreservado e restauração do metabolismo ósseo em ratas castradas

OBJECTIVES to evaluate estradiol levels and autotransplantation heated ovarian tissue effects, after vitrification, on rats bone metabolism previously oophorectomized bilaterally. METHODS experimental study with 27 rats aged 11 to 12 weeks and weighing 200g to 300g, submitted to bilateral oophorectomy and ovarian tissue cryopreservation for subsequent reimplantation. Animals were divided into two groups, A and B, with 8 and 19 rats, respectively. Autotransplantation occurred in two periods according to castration time: after one week, in group A, and after one month in group B. Serum estradiol measurements and ovary and tibia histological analysis were performed before and after oophorectomy period (early or late) and one month after reimplantation. RESULTS in groups A and B, tibia median cortical thickness was 0.463±0.14mm (mean±SD) at the baseline, 0.360±0.14mm after oophorectomy and 0.445±0.17mm one month after reimplantation p<0.005). Trabecular means were 0.050±0.08mm (mean±SD) at baseline, 0.022±0.08mm after oophorectomy and 0.049±0.032mm one month after replantation (p<0.005). There was no statistical difference in estradiol variation between the two study groups (p=0.819). CONCLUSION cryopreserved ovarian tissue transplantation restored bone parameters, and these results suggest that ovarian reimplantation in women may have the same beneficial effects on bone metabolism.

Building Oncofertility Core Competency in Developing Countries: Experience From Egypt, Tunisia, Brazil, Peru, and Panama

Purpose Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care. Materials and Methods To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed. Results Common barriers were identified by each country, including financial barriers (lack of insurance coverage and high out-of-pocket costs for patients), lack of awareness among providers and patients, cultural and religious constraints, and lack of funding to help to support oncofertility programs. Conclusion Despite barriers to care, many opportunities exist to grow the field of oncofertility in these five developing countries. It is important to continue to engage stakeholders in developing countries and use powerful networks in the United States and other developed countries to aid in the acceptance of oncofertility on a global level.Purpose Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care. Materials and Methods To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed. Results Common barriers were identified by each country, including financial barriers (lack of insurance coverage and high out-of-pocket costs for patients), lack of awareness among providers and patients, cultural and religious constraints, and lack of funding to help to support oncofertility programs. Conclusion Despite barriers to care, many opportunities exist to grow the field of oncofertility in these five developing countries. It is important to continue to engage stakeholders in developing countries and use powerful networks in the United States and other developed countries to aid in the acceptance of oncofertility on a global level.

Updates in preserving reproductive potential of pre-pubertal girls with cancer

W increasing numbers of adult female survivors of childhood cancers due to advances in early diagnosis and treatment, the issue of preserving the reproductive potential of prepubertal girls undergoing gonadotoxic treatments has gained greater attention. Unfortunately, the two established fertility preservation options, embryo freezing and egg freezing, cannot be offered routinely to prepubertal girls as these options necessitate prior ovarian stimulation and subsequent mature oocytes retrieval that are contraindicated or infeasible before puberty. Therefore, the most suitable fertility preservation options to prepubertal girls are (1) ovarian tissue freezing and autotransplantation, (2) in vitro maturation, and (3) ovarian protection techniques. In this presentation, those fertility preservation options as well as their success rates, advantages, disadvantages and future directions will be discussed in detail. Also a new integrated strategy to preserve the reproductive potential of prepubertal girls with cancer will be highlighted. Although experimental, ovarian tissue slow freezing and orthotopic autotransplantation may be the most feasible option to preserve the reproductive potential of prepubertal girls with cancer. However, this technique has two major and serious disadvantages: (1) the risk of reintroducing malignant cells and (2) the relatively short lifespan of ovarian tissue transplants. Several medical and ethical considerations should be taken into account before applying this technique to prepubertal girls with cancer.