Fertility Preservation In Women Research Articles

Preservation of Fertility in Women Undergoing Reduced-Intensity Conditioning Allogeneic Transplantation With a Fludarabine-Based Regime

Preservation of Fertility in Women Undergoing Reduced-Intensity Conditioning Allogeneic Transplantation With a Fludarabine-Based Regime

Characterization of the gonadotropin releasing hormone response in the ovary

Gonadotropin releasing hormone agonists (GnRHa) are increasingly used for fertility preservation in women undergoing gonadotoxic chemotherapy. However, the mechanisms of action for these compounds have not yet been elucidated. In this study, we aimed to determine whether GnRHa have a direct effect on ovarian granulosa/cumulus cells.

Fertility preservation with IVF OR IVM for women with hematological malignancy – experiences and expectations

Women with hematological malignancy are often referred for fertility preservation before commencing potentially gonadotoxic chemotherapy.Treatment is individualized according to age, ovarian reserve, and urgency of chemotherapy. In vitro fertilization (IVF), and more recently, in vitro maturation (IVM), offer the potential to cryopreserve embryos or oocytes.This study compares IVF and IVM techniques for fertility preservation in women with hematological malignancy. Retrospective cohort study,single tertiary center. Women underwent fertility preservation with IVF or IVM for hematological malignancy, during 2003-2011. Age,antral follicle count (AFC), oocytes retrieved (total and MII), MII oocytes after maturation, and number of embryos or oocytes for cryopreservation were compared for each treatment arm. 66 women with hematological malignancy underwent treatment with either IVF (38) or IVM (28) for oocyte and/or embryo cryopreservation. 37 women had Hodgkin's lymphoma (20 IVF, 17 IVM), 19 non-hodgkin's lymphoma (11 IVF/8 IVM), 5 AML(2 IVF/3 IVM), 3 myelodyslastic syndrome (all IVF) and 2 aplastic anemia (both IVF). Age (27.2vs 25.7) and AFC (16.3 vs 20.2) were similar. Women who underwent IVF had significantly more MII oocytes collected compared with those who underwent IVM (8.4 vs. 2.1, P<0.05). However, there was no significant difference in oocytes collected (10.6 vs 11.6), total MII oocytes (8.9 vs 8.4), embryos fertilized (6.7 vs 6.75), or number of embryos (5.9 vs 6.25) or oocytes (8.6 vs 8.25) for cryopreservation. Fertility preservation treatment for women with hematological malignancy should be tailored for ovarian reserve, prognosis, and cancer treatment protocol and timing. Whilst IVM with oocyte or embryo cryopreservation for malignancy is still investigational, it may offer an alternative to IVF for fertility preservation. Larger studies, as well as data regarding pregnancy outcomes, are needed to provide support and evidence for this treatment option.

DNA Double Strand Breaks but Not Interstrand Crosslinks Prevent Progress through Meiosis in Fully Grown Mouse Oocytes

There is some interest in how mammalian oocytes respond to different types of DNA damage because of the increasing expectation of fertility preservation in women undergoing chemotherapy. Double strand breaks (DSBs) induced by ionizing radiation and agents such as neocarzinostatin (NCS), and interstrand crosslinks (ICLs) induced by alkylating agents such as mitomycin C (MMC), are toxic DNA lesions that need to be repaired for cell survival. Here we examined the effects of NCS and MMC treatment on oocytes collected from antral follicles in mice, because potentially such oocytes are readily collected from ovaries and do not need to be in vitro grown to achieve meiotic competency. We found that oocytes were sensitive to NCS, such that this ionizing radiation mimetic blocked meiosis I and caused fragmented DNA. In contrast, MMC had no impact on the completion of either meiosis I or II, even at extremely high doses. However, oocytes treated with MMC did show γ-H2AX foci and following their in vitro maturation and parthenogenetic activation the development of the subsequent embryos was severely compromised. Addition of MMC to 1-cell embryos caused a similarly poor level of development, demonstrating oocytes have eventual sensitivity to this ICL-inducing agent but this does not occur during their meiotic division. In oocytes, the association of Fanconi Anemia protein, FANCD2, with sites of ICL lesions was not apparent until entry into the embryonic cell cycle. In conclusion, meiotic maturation of oocytes is sensitive to DSBs but not ICLs. The ability of oocytes to tolerate severe ICL damage and yet complete meiosis, means that this type of DNA lesion goes unrepaired in oocytes but impacts on subsequent embryo quality.

Fertility Preservation in Women Undergoing Treatment for Breast Cancer in the U.K.: A Questionnaire Study

Fertility preservation is an important survivorship issue for women treated for breast cancer. The aim of this work was to examine the referral practices of health care professionals who treat women with breast cancer in the United Kingdom, and to investigate their understanding and knowledge of the fertility preservation options available. An invitation to participate in a confidential, online questionnaire was e-mailed to surgeons, oncologists, and clinical nurse specialists who manage patients with breast cancer in the United Kingdom. n = 306 respondents. Factors which influenced whether fertility preservation options were discussed with a patient included the following: patient's age (78%), final tumor/nodes/metastasis status (37.9%); concern that fertility preservation would delay chemotherapy (37.3%); whether the patient had children (33.5%) or a partner (24.7%); estrogen receptor expression (22.6%), lack of knowledge regarding the available options (20.9%); and concern that fertility preservation would compromise the success of cancer treatment (19.8%). Twenty-seven percent did not know whether fertility preservation was available for their patients on the National Health Service. Nearly half (49.4%) of respondents said that gonadotropin-releasing hormone agonists were used for fertility preservation outside the setting of a clinical trial. Knowledge regarding the available options varied according to different members of the multidisciplinary team, with consultant oncologists better informed than consultant surgeons or clinical nurse specialists (p < .05). Many health care professionals have incomplete knowledge regarding the local arrangements for fertility preservation for patients with breast cancer. This may result in patients receiving inadequate or conflicting information regarding fertility preservation.

Ethical issues in infertility treatment

Two currently contentious domains in infertility treatment are discussed: assisted reproduction for same-sex couples and fertility preservation for women with cancer. Despite an increasing recognition of the rights of same-sex couples, in many countries they are still not eligible for assisted reproductive technology. The main justification for excluding same-sex couples from treatment is that the welfare of the future children would be compromised. Empirical evidence, however, shows that this is not the case. Another group of non-infertile women seeking assistance from reproductive medicine are women with cancer who are at risk of impaired or lost fertility as a result of their illness or cancer treatment. In this field, the future holds many promising options. Several of these, however, are currently in an experimental phase, which elicits ethical concerns about participant recruitment and research participation of children.

Fertility Preservation in Women With Malignant Tumors and Gonadotoxic Treatments

Because of improved survival rates and recent advances in reproductive medicine, fertility preservation methods in women of reproductive age with malignant or autoimmune diseases have risen in importance. Selective literature review based on the authors' clinical and scientific experience. Fertility-preserving techniques are recommended for all girls and women up to age 40 who are at high risk of ovarian failure. As these techniques are complex, special expertise in counseling and treatment is needed; in the German-speaking countries, such expertise is available in centers belonging to the FertiPROTEKT network (www.fertiprotekt.eu). Most of these techniques carry a very low risk and can be performed in two weeks or less. Success rates depend on the patient's age, the experience of the center, and the particular technique used. The highest attainable likelihood of pregnancy after the use of a combination of cryopreservation techniques is estimated at 40% to 50%. Fertility preservation is generally not covered by health insurance; its cost ranges from several hundred to several thousand euros. Girls and women up to age 40 who are about to undergo gonadotoxic treatment should be counseled about the availability of fertility-preserving techniques and, if appropriate, should be treated with such techniques in a specialized center.

Fertility preservation in women undergoing treatment for breast cancer in the UK: A questionnaire study

Background: Fertility preservation is an important survivorship issue for women treated for breast cancer. Patients should be informed of the risk of infertility and offered referral to discuss fertility preservation options before systemic treatment commences. The aim of this work was to examine the referral practices of healthcare professionals who treat women with breast cancer in the UK.

Which patients pursue fertility preservation treatments? A multicenter analysis of the predictors of fertility preservation in women with breast cancer

To evaluate predictors of undergoing fertility preservation treatment (FPT) in women with breast cancer. Secondary analysis of a clinical database. Three academic fertility preservation centers. One hundred eight patients with breast cancer undergoing FPT and 77 patients with breast cancer not undergoing FPT from 2005 to 2010. None. Patients' demographic and medical information. Women who had FPT were older, wealthier, and had lower cancer stage compared with women who did not have FPT. The rate of the administration of neoadjuvant chemotherapy (NAC) was significantly lower in women who underwent FPT. After adjusting for age, body mass index (BMI), income, cancer stage, and center, a negative correlation persisted between NAC and FPT (odds ratio 0.091, 95% confidence interval 0.009-0.904). When we stratified the women by center, women at center 1 had a significantly lower FPT rate, lower parity, higher BMI, more advanced cancer stage, and lower income compared with centers 2 and 3. The rates of NAC were significantly higher in center 1. Although age, BMI, income, cancer stage, center, and NAC seem to be associated with undergoing FPT, NAC is the only modifiable variable. Because NAC restricts the time available for FPT, oncologists may consider offering adjuvant chemotherapy, except in cases in which NAC clearly improves survival, in women who are interested in FPT.

Fertility preservation in women with ovarian endometriosis

Endometriosis is one of the most frequently encountered benign diseases in gynecology. Complete resolution of endometriosis is not yet possible, but therapy has essentially three main objectives: (1) to preserve and improve fertility, (2) to reduce pain, and (3) to delay recurrence for as long as possible. The aim of this paper is to focus on fertility preservation in women with severe endometriosis. In moderate and severe endometriosis, a medico-surgical approach remains the gold standard, but more and more papers are reporting a low ovarian reserve after laparoscopic cystectomy for endometriomas. Indeed, very frequently, normal ovarian tissue is excised together with the endometrioma wall. Ovarian surgery in endometriosis patients should therefore be performed by experienced surgeons in order to both preserve and improve fertility. Preservation of ovarian tissue should be considered in all patients at serious risk of future fertility impairment, particularly before any treatment likely to result in ovarian endometriosis recurrence and/or premature ovarian failure.

Fertility Preservation in Women After the Cancer

Thanks to the recent advances in cancer care, more and more young women can survive but suffer from infertility as a result of cancer treatment that had to be submitted. There are a variety of methods to preserve fertility, as chemoprotection, ovariopexy, and some assisted reproductive technologies, although some of these are promising but still highly experimental techniques. Cryopreservation of embryos for example is already established, while the oocyte banking is still considered an experimental practice. Many experiments have been conducted around the world on the cryopreservation of ovarian tissue and maturation of ovarian follicles, in an attempt to demonstrate its potential use in fertility preservation. Although in recent years there has been major improvements in the preservation of ovarian tissue, there are still many unresolved technical issues related to these procedures. In this chapter we examine the recent evidence of the pathophysiology of chemotherapy / radiotherapy-induced gonadal toxicity, and recent data regarding the indications and results of the techniques used to preserve fertility in women with cancer.

Fertility preservation in women with ovarian endometriosis

Fertility preservation in women with ovarian endometriosis

Which patients pursue fertility preservation treatments? A multicenter analysis of the predictors of fertility preservation in women with breast cancer

Which patients pursue fertility preservation treatments? A multicenter analysis of the predictors of fertility preservation in women with breast cancer

Fertility preservation in women with cancer

Fertility preservation (FP) is an effort to retain the fertility of cancer patients, and as an emerging discipline, it plays a central role in cancer care. Because of improvement in diagnostic and therapeutic strategies, an increasingly large number of patients are surviving with cancer. FP specialists should make an effort to spread the significance of FP among reproductive women with cancer and provide appropriate education both for associated physicians and for cancer patients who wish to preserve their fertility. Physicians who take part in the initial diagnosis and management of cancer should consider the importance of early referral of young cancer patients to FP specialists and take care of those patients by providing timely information and appropriate counseling. Individualized treatment strategies should be delivered depending on the patient's situation with appropriate team approach.

P5-23-04: Gonadotrophin-Releasing Hormone Analogues for Ovarian Function Preservation in Women with Premenopausal Breast Cancer Undergoing Adjuvant Chemotherapy: A Systematic Review and Meta-Analysis.

Abstract Background: Breast cancer, the most common female malignancy, is also the most frequent tumor in women of reproductive age. Young women with breast cancer usually present adverse prognostic features and higher rates of recurrence when compared with their older counterparts. Adjuvant chemotherapy is usually recommended for this group of patients and premature ovarian failure (POF) is a potential complication. Material and Methods: We conducted a systematic search in MEDLINE, EMBASE, Cochrane Systematic Reviews databases and ***ClinicalTrials.gov from their inception until June 2011. The search was conducted to include published peer-reviewed studies on the issue of fertility preservation in women with breast cancer undergoing adjuvant chemotherapy. The search terms were tailored individually for each database to include the following Medical Subject Headings (MeSH) and text words: gonadotropin releasing hormone, breast neoplasms, drug therapy, premature ovarian failure and fertility. No language restriction was applied. We also searched for additional studies by reviewing the reference lists of retrieved articles, and studies presented in abstract form were also located in this manner. The main outcomes were return of spontaneous menstruation, ovulation and pregnancy rate. Results: We found 8 RCTs that met the inclusion criteria. Data were extracted from 3 RCTs. Data were only available for resumption of ovulation. There were no data available for markers of ovarian function, rate of ovulation and pregnancy. The rate of women with spontaneous menstruation demonstrated a statistically significant difference in favor of the use of GnRH-a (OR 3.11;95% CI, 2.04-472). Discussion: Use of GnRH concomitant to adjuvant chemotherapy in premenopausal breast cancer women aiming to reduce rates of POF has been subject of controversy during the last decade. Evidence from recently presented RCTs suggests there is a benefit of GnRH for ovarian function protection in this setting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-23-04.

Ovarian aging

In the past few decades, women have been intentionally delaying pregnancy and ovarian aging has become one of the most detrimental factors of pregnancy achievement. This review will discuss contemporary methods of ovarian aging assessment and present an overview of current management strategies. Antimullerian hormone (AMH) and antral follicle count (AFC) seem to be the most reliable predictors of ovarian aging appraisal. Nevertheless, they have not been shown to predict pregnancy achievement in assisted reproduction. Heritability has a high impact on ovarian aging. Employing several genetic approaches, it is now being widely investigated, but the task is far from being accomplished. Although multivariate models have not been proven to be superior to AFC, new data support the notion that chronological age and genetic markers inclusion may increase their reliability. Several strategies have been suggested to treat ovarian aging in assisted reproductive technology (ART) settings. None of the stimulation protocol manipulations have been found to be advantageous and individualization of treatment is still recommended. Ovarian priming by different androgen preparations has been shown to be promising but more randomized controlled trials are needed to support these findings. Except for oocyte donation other ART strategies have not shown a convincing benefit for ovarian aging. The new development of oocyte vitrification may well introduce opportunities for fertility preservation to women at risk of ovarian aging. Proper assessment and detection of ovarian aging, employing current or developing predictors of ovarian reserve, especially genetic tests, may enable health providers to recommend, at appropriate biological time, early pregnancy achievement or fertility preservation in women at risk.

Fertility in Female Patients After Allogeneic Stem Cell Transplantation Following Reduced-Intensity Conditioning (RIC allo-SCT)

Abstract 3057 ObjectiveThere is only limited data available on women's fertility for younger patients treated by reduced intensity conditioning allogeneic stem cell transplantation (RIC allo-SCT). This issue is important as RIC allo-SCT is a potential curative treatment and as women's fertility preservation methods had improved with now several births after ovarian cryoconservation for example. Materials and MethodsWe evaluate fertility among female patients younger than 35 years old receiving RIC allo-SCT for hematological malignancy or aplastic anemia. This is a single center retrospective study. Informations on therapies before RIC allo-SCT were collected including disease characteristics, previous therapy (chemo, radiotherapy, autologous SCT), and allogeneic transplantation modalities. Data on fertility evaluation after RIC allo-SCT included clinical and biological criteria (see below). Any proposed option of fertility preservation was analyzed as well as any information about potential loss of fertility and/or ovarian failure received by patients before RIC allo-SCT. ResultsNinety-six patients under the age of 35 underwent RIC allo-SCT between January 2000 and January 2010. Fifty patients are alive at last follow-up, 23 of them are female patients. Twenty-two patients were available for the study. Mean age at last follow-up is 32 (22–46), mean age at diagnosis is 27 (17–35). Median follow-up after RIC allo-SCT is 47 months. Diagnoses were: Hodgkin’s lymphoma (36, 4%), Acute myeloid leukemia (22, 7%), aplastic anaemia (13, 6%), Acute lymphoblastic leukemia (9%), multiple myelome (9%), non-Hodgkin’s lymphoma (4, 5%), Chronic lymphocytic leukemia (4, 5%). The median number of previous treatment regimen before allo was × (1 line (36.9%), 2 (41%), 3 (9%)). One patient received sub-diaphragmatic radiotherapy at dose of 36Gy and three patients received RIC allo-SCT without prior chemotherapy (AA cases). ASCT followed BEAM or high-dose Melphalan conditioning in 45, 4% of patients. RIC allo-SCT was realized after the following conditioning regimens: cyclophosphamide-ATG (13, 6%), fludarabine-busulfan-ATG (45, 4%), TBI 2Gy +/− Fludarabine + /- Cyclophosphamide (40, 9%). Before RIC allo-SCT 86, 3% of patients had regular menses and 50, 9% had previous pregnancies (1–3). After RIC allo-SCT, amenorrea affects 68% of patients, 87% of whom have menopausal symptoms. All three AA patients have regular cycles and became pregnant after RIC allo-SCT whereas none of the patient treated for hematological malignancy became pregnant. Biological hormonal evaluation showed impaired ovarian function for 82% of the patients with elevated LH and FSH values and low Oestradiol and Anti Mullerian Hormon values. On a more general aspect, Only six (27, 2%) patients declared to have been correctly informed before RIC allo-SCT on potential deleterious effects on fertility by anticancer treatment; five (22, 7%) patients declared to have been partially informed and 11 (50%) not informed at all, respectively. Fertility preservation was proposed to five patients before RIC allo-SCT: 2 refused, 2 had in vitro fecundation and 1 had ovarian cryopreservation. ConclusionThis is the first study specifically focusing on fertility after RIC allo-SCT among young female patients. Results show a high rate of ovarian failure, evaluated by both clinical and biological criteria. The significant difference here between AA and malignant diseases suggests that a potential deleterious role was played by previous anticancer treatments including HD chemotherapy followed by auto SCT rather than by RIC allo-SCT itself. Disclosures:No relevant conflicts of interest to declare.

Ovarian response to stimulation for fertility preservation in women with malignant disease: a systematic review and meta-analysis

To evaluate the current available data regarding ovarian performance of patients diagnosed with malignant disease undergoing controlled ovarian hyperstimulation (COH) for fertility preservation, before radio/chemotherapy, compared with age-matched, healthy patients undergoing COH for invitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). Meta-analysis of the data available from a systematic review of the literature. Academic centers of infertility and IVF. Patients with malignant disease, before radio/chemotherapy, undergoing COH for fertility preservation within comparative studies with healthy, age-matched controls. None. Peak estradiol levels on day of human chorionic gonadotropin administration, number of oocytes retrieved, fertilization rate, incidence of low ovarian response, and cycle cancellation. Only seven retrospective, case-controlled studies were found to match our objective. Overall, the results of the meta-analysis indicate that the number of retrieved oocytes rate was statistically significantly lower compared with age-matched healthy IVF patients. The incidence of poor ovarian performance and risk of cycle cancellation as well as the calculated number of two pronuclei zygotes achieved among patients with cancer were comparable with their age-matched controls. Women with malignant disease should expect a lower number of oocytes retrieved after COH for fertility preservation, compared with healthy, age-matched patients. Presently, there is paucity of evidence to assess the effect of a specific malignant disease on ovarian response to COH before IVF for fertility preservation. Multicentric studies should be conducted to resolve these important issues.

Fertility preservation in girls and young women

There is increasing interest and experience in the options available to preserve fertility in those about to undergo potentially gonadotoxic chemotherapy or radiation therapy, usually related to treatment for cancer. Recent years have seen the development of methods for prepubertal girls, female adolescents and adult women, although these remain less established than sperm cryopreservation for men. At present, the options for prepubertal boys remain experimental. Embryo cryopreservation following ovarian stimulation and IVF is a routine procedure technically and its success in the management of infertility is established. However, there are no data on uptake or success rates in the context of fertility preservation in women with cancer. Oocyte cryopreservation is technically challenging and requires ovarian stimulation, thus potentially resulting in a delay in cancer treatment. Oocyte vitrification offers increased success rates in comparison with slow freezing; however, this approach is also limited by the number of oocytes that can be obtained. The third possibility, ovarian tissue cryopreservation, can be performed without significant delay and is the only option for prepubertal girls. Worldwide, a small number of children have been born following reimplantation of frozen/thawed ovarian tissue. It is clear that fertility preservation is important for some girls and young women facing treatments that will compromise their fertility, but the availability of all approaches varies widely. Effective approaches for prepubertal boys are also required.

150 INVITED Frozen Hope – Fertility Preservation for Women With Cancer

150 INVITED Frozen Hope – Fertility Preservation for Women With Cancer