Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility. Cancer is a major public health problem around the world and is the second leading cause of death in the USA [1]. In 2016, approximately 844,000 new cases of cancer will be diagnosed in women in the USA [1]. In recent years, the remarkable screening, diagnostic and therapeutic advances in oncology practice improved the prognosis for many cancer patients, adding years to their anticipated survival. In fact, all these measures have resulted in a 23% drop in the cancer death rates from 1991 to 2012 [1].Currently, about 5% of cancers affects women younger than 50 years [1]. As young patients with these once-fatal malignancies become long-term survivors, many must face the potentially devastating complications of the treatment. Young survivors will likely face compromised fertility that is now recognized as among the most prevalent long-term side effects of cancer therapy. The prospect of partial or total infertility can significantly add to anxiety and emotional strain during disease management, and may also compromise quality of life [2]. To offset these risks, women can be offered several options for fertility preservation, including conservative cancer management, and cryopreservation of oocyte, embryo or ovarian tissue. Embryo and oocyte cryopreservation are considered established fertility preservation techniques and have been widely applied across the world [3,4]. On the other hand, ovarian tissue cryopreservation is still considered an experimental technique, despite advances in recent years [5].Studies exploring the mechanisms behind the actions of the different chemotherapy agents are providing greater information as to the specific effects of each agent on the different cell types of the ovary. The effects of antineoplastic agents on the ovaries are clinically inferred from a variety This article will review all the mechanism and clinical impact of chemotherapy on ovarian reserve. Ovarian agingThe ovary has a finite endowment of primordial follicles that is established during the second half of intrauterine life, followed by a steady decline until menopause. Each primordial follicle consists of an immature oocyte surrounded by a single layer of granulosa cells. The primordial follicles constit...

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.

This article reviews the existing fertility preservation options for females diagnosed with Turner syndrome and provides practical guidelines for the practitioner. Turner syndrome is the most common sex chromosome abnormality in females, occurring in approximately one in 2500 live births. Women with Turner syndrome are at extremely high risk for primary ovarian insufficiency (POI) and infertility. Although about 70–80% have no spontaneous pubertal development and 90% experience primary amenorrhea, the remainder may possess a small residual of ovarian follicles at birth or early childhood. The present challenge is to identify these women as early in life as is possible, so as to allow them to benefit from a variety of existing fertility preservation options. To maximize the benefits of fertility preservation, all women with Turner syndrome should be evaluated by an expert as soon as possible in childhood as the vast majority will have their ovarian reserve depleted before adulthood. Cryopreservation of mature oocytes and embryos is a proven fertility preservation approach, while cryopreservation of ovarian tissue is a promising technique with a growing number of live births, but remain investigational. Oocyte cryopreservation has been performed in children with Turner syndrome as young as 13 and ovarian tissue cryopreservation in prepubertal children affected. However, current efficacy of these approaches is unknown in this cohort.. For those who have already lost their ovarian reserve, oocyte or embryo donation and adoption are strategies that allow fulfillment of desire for parenting. For those with Turner syndrome related cardiac contraindications to pregnancy, utilization of gestational surrogacy allows the possibility of biological parenting by using their own oocytes. Alternatively, gestational surrogacy can serve to carry pregnancy resulting from the use of donor oocytes or embryos, if needed.

Intracytoplasmic sperm injection (ICSI) has become the most commonly used method of fertilization in assisted reproductive technology. The primary reasons for its popularity stem from its effectiveness, the standardization of the procedure, which means that it can easily be incorporated into the routine practice of fertility centres worldwide, and the fact that it can be used to treat virtually all forms of infertility. ICSI is the clear method of choice for overcoming untreatable severe male factor infertility, but its (over)use in other male and non-male factor infertility scenarios is not evidence-based. Despite all efforts to increase ICSI efficacy and safety through the application of advanced sperm retrieval and cryopreservation techniques, as well as methods for selecting sperm with better chromatin integrity, the overall pregnancy rates from infertile men remain suboptimal. Treating the underlying male infertility factor before ICSI seems to be a promising way to improve ICSI outcomes, but data remain limited. Information regarding the health of ICSI offspring has accumulated over the past 25 years, and there are reasons for concern as risks of congenital malformations, epigenetic disorders, chromosomal abnormalities, subfertility, cancer, delayed psychological and neurological development, and impaired cardiometabolic profile have been observed to be greater in infants born as a result of ICSI than in naturally conceived children. However, as subfertility probably influences the risk estimates, it remains to be determined to what extent the observed adverse outcomes are related to parental factors or associated with ICSI.

Women with impaired ovarian reserve or poor ovarian response (POR) to exogenous gonadotropin stimulation present a challenge for reproductive specialists. The primary reasons relate to the still limited knowledge about the POR pathophysiology and the lack of practical solutions for the management of these conditions. Indeed, clinical trials using the current standards to define POR failed to show evidence in favor of a particular treatment modality. Furthermore, critical factors for reproductive success, such as the age-dependent embryo aneuploidy rates and the intrinsic ovarian resistance to gonadotropin stimulation, are not taken into consideration by the current POR criteria. As a result, the accepted definitions for POR have been criticized for their inadequacy concerning the proper patient characterization and for not providing clinicians a guide for therapeutic management. A novel system to classify infertility patients with “expected” or “unexpected” inappropriate ovarian response to exogenous gonadotropins—the POSEIDON criteria—was developed to provide a more nuanced picture of POR and to guide physicians in the management of such patients. The new standards are provoking as they challenge the current terminology of POR in favor of the newly defined concept of “low prognosis.” This article provides readers a critical appraisal of the existing criteria that standardize the definition of POR and explains the primary reasons for the development of the POSEIDON criteria.

Background Ovarian tissue cryopreservation is an experimental fertility preservation method and the transplantation techniques are still evolving. Objective We attempted to improve the technique with the utility of a human decellularized extracellular tissue matrix scaffold, robot-assisted minimally invasive surgery and peri-operative pharmacological support. Study design We prospectively studied 2 subjects with Hemophagocytic Lymphohistiocytosis (P-A) and Non-Hodgkin Lymphoma (P-B) who underwent ovarian tissue cryopreservation at the age of 23, before receiving preconditioning chemotherapy for hematopoietic stem cell transplantation. Both experienced ovarian failure post-chemotherapy and we transplanted ovarian cortical tissues to the contralateral menopausal ovary 7 and 12 years later, using a human extra cellular tissue matrix scaffold and robotic-assistance. The extra cellular tissue matrix scaffold-tissue compatibility was shown in pre-clinical studies. Patients also received estrogen supplementation and baby aspirin preoperatively to aid in the revascularization process. Results Ovarian follicle development was observed approximately ten (P-A) and eight (P-B) weeks after ovarian tissue transplantation. Following eight and seven cycles of in vitro fertilization, nine and ten day-3 embryos were cryopreserved (P-A and P-B, respectively). While the baseline FSH (range: 3.6–15.4 mIU/mL) levels near-normalized by seven months and remained steady post ovarian transplantation in P-A, P-B showed improved but elevated FSH levels throughout (range: 21–31 mIU/mL). Highest follicle yield was achieved 14 (8 follicles; P-A) and 11 months (6 follicles; P-B) post intervention. P-A experienced a chemical pregnancy after the third frozen embryo transfer attempt. She then conceived following her first fresh in vitro fertiliza tion-embryo transfer and the pregnancy is currently ongoing. P-B conceived after the first frozen embryo transfer attempt and delivered a healthy boy at term. Conclusions We reported the first pregnancies after the minimally-invasive transplantation of previously cryopreserved ovarian tissue with an extra-cellular tissue matrix scaffold. This approach seems to be associated with steady ovarian function after a follow up of up to 2 years.

Objective To investigate the safety and feasibility of performing two consecutive ovarian stimulation cycles with the use of letrozole protocol for fertility preservation in breast cancer patients. Design Retrospective cohort study. Setting Academic fertility preservation center. Patient(s) Seventy-eight women ≤ 45 years, diagnosed with stage ≤ 3 breast cancer, who desired fertility preservation Intervention(s) Two consecutive (2C) vs. single (1C) ovarian stimulation cycle with the Letrozole-FSH protocol. Main Outcome Measurement(s) Embryo or oocyte cryopreservation outcomes, time interval from surgery to chemotherapy (CT), and breast cancer recurrence rates. Results Sixty-one patients underwent 1C while 17 had 2C. The mean total number of oocytes harvested (16.1 ± 13.2 vs. 9.1 ± 5.2) and embryos generated (6.4 ± 2.9 vs. 3.7 ± 3.1) were significantly higher in patients in 2C vs. 1C. The time interval from surgery to CT was similar between the 2C and 1C groups (63.7 ± 7.7 vs. 58.0 ± 12.1 days). After a mean follow up of 58.5 ± 13.6 months, recurrence rates were similar between 2C (0/17) and 1C (2/49) patients. Conclusion It appears to be safe and feasible to perform two consecutive ovarian stimulation cycles to increase the oocyte/embryo yield for fertility preservation.

The ovaries are susceptible to damage following treatment with gonadotoxic chemotherapy, pelvic radiotherapy, and/or ovarian surgery. Gonadotoxic treatments have also been used in patients with various nonmalignant systemic diseases. Any women of reproductive age with a sufficiently high risk of developing future ovarian failure due to those medical interventions may benefit from embryo cryopreservation though the tools of assessment of such a risk are still not very precise. Furthermore, the risk assessment can be influenced by many other factors such as the delay expected after chemotherapy and the number of children desired in the future. Embryo cryopreservation is an established and most successful method of fertility preservation when there is sufficient time available to perform ovarian stimulation. This publication will review the current state, approach, and indications of embryo cryopreservation for fertility preservation.