Melanie Davies

Predictors of ovarian reserve in young women with breast cancer

Ovarian reserve can be diminished following treatment for breast cancer. This study evaluated biochemical and biophysical parameters of ovarian reserve in these patients. Biochemical and biophysical tests of ovarian reserve were performed simultaneously in young (age 22–42 years), regularly menstruating women with breast cancer (n=22) and age-matched controls (n=24). All tests were performed before (baseline) and after transient ovarian stimulation in the early follicular phase. Patients were recruited both before and after completion of chemotherapy, with some patients being followed up prospectively. Serum samples were analysed for follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E2), inhibins A and B, and antimullerian hormone (AMH). Biophysical (ultrasound) tests included ovarian volume, antral follicle count (AFC), ovarian stromal blood flow and uterine dimensions. Significant differences were revealed (when compared with the controls) for basal FSH (11.32±1.48 vs 6.62±0.42 mIU ml−1, P<0.001), basal AMH (0.95±0.34 vs 7.89±1.62 ng ml−1, P<0.001) and basal inhibin B (19.24±4.56 vs 83.61±13.45 pg ml−1, P<0.001). Following transient ovarian stimulation, there were significant differences in the increment change (Δ) for inhibin B (3.02±2.3 vs 96.82±16.38 pg ml−1, P<0.001) and E2 (107.8±23.95 vs 283.2±40.34 pg ml−1, P<0.01). AFC was the only biophysical parameter that was significantly different between patients and the controls (7.80±0.85 vs 16.77±1.11, P<0.001). Basal and stimulated biochemical (serum AMH, FSH, inhibin B and E2) and biophysical (AFC) tests may be potential markers of ovarian reserve in young women with breast cancer.

Fertility Preservation in Women Undergoing Treatment for Breast Cancer in the UK: A Questionnaire Study

OBJECTIVE 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. METHOD 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. RESULTS n = 306 respondents. Factors which influenced whether fertility preservation options were discussed with a patient included the following: patients 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). CONCLUSIONS 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.

The Turner Syndrome Life Course Project: Karyotype-phenotype analyses across the lifespan.

Turner syndrome (TS) is associated with a variety of morbidities affecting nearly every body system, some of which increase in prevalence in adult life. The severity of clinical features in TS is roughly in parallel with the magnitude of the deficit of X‐chromosome material. The aim of this study was to extend the established karyotype‐phenotype relationships using data from a large adult cohort.

Preservation of fertility in women undergoing reduced-intensity conditioning allogeneic transplantation with a fludarabine-based regime.

Infertility is a major late effect in patients receiving either conventional or high-dose chemotherapy or hematopoietic stem-cell transplantation (SCT) for hematological malignancies and nonmalignant disorders (1). Most of the published data in relation to patients undergoing a hematopoietic SCT come from studies reporting the deleterious effect of the conditioning in recipients of primarily myeloablative regimens (2, 3). Reduced-intensity conditioning SCT (RIC-SCT) has minimized the use of total-body irradiation as part of the pretransplantation conditioning regime and has therefore reduced the short-term and long-term toxicity. We have previously reported low rate of nonrelapse mortality and low incidence of graftversus-host disease with a RIC protocol based on a fludarabine, melphalan, and campath-1H combination (4). The present study aimed to document the effect of RIC on ovarian function. Female patients of reproductive age who underwent an RIC transplantation from 2001 to 2009 were identified from our clinical database. We retrospectively collected data on female patients who were being followed up in the late effects clinic and identified those who had (i) maintained menstruation; (ii) normal luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels; (iii) radiologic evidence of ovarian follicles; and (iv) went on to conceive. Ovarian function was assessed by measuring basal serum FSH, LH, estradiol, and antral follicle count. Ovarian activity and fertility potential was considered optimal if FSH and LH values were less than 10 IU/L and antral follicle count were greater than 8. Thirty female patients aged 19 to 44 years who underwent an RIC transplantation were identified. Of these, 26 had already sustained gonadal damage (as it was demonstrated by increased FSH, LH, and amenorrhea) from antecedent chemotherapy before the transplantation and were excluded from further study. Two of 30 patients had preserved fertility (normal FSH, LH, and cycling) before the transplantation and retained ovarian function even after the transplantation. In addition, two more patients who were heavily pretreated before the transplantation became pregnant at 11 and 37 months after transplantation despite the fact that the hormonal profile after transplantation was consistent with menopause (Table 1). The ages of the patients were 19, 25, 33, and 35 years (Table 1). Diagnoses were Hodgkin lymphoma in two patients and myelodysplastic syndromes in two patients. The patients received either a sibling allograft (n=1) or matched unrelated-donor transplant (n=3) with RIC that consisted of fludarabine/ melphalan/campath-1H (n=3) and fludarabine/tresulfan/campath-1H (n=1). Of these four patients, two went on to become pregnant despite documented high gonadotrophins. The remaining two patients both had menstruation after transplantation and relative preservation of ovarian function as evidenced by LH, FSH, and estradiol. Ultrasound imaging

Factors which Determine the Age of the Menopause

Menopause is the final cessation of menstruation. Humans are the only primates to experience a menopause, and its origins and purpose remain unclear. The age of menopause has remained constant since Aristotle, although the age of menarche has fallen in the past 100 years. The incidence of natural premature ovarian failure before age 40 is 1%. The factors controlling the timing of the menopause are not well understood. The possession of two X chromosomes is essential for normal ovarian function. Genetic, reproductive and lifestyle factors, chemotherapy and radiation, pelvic surgery, infection, and autoimmunity have all been implicated. There is an association between age of menopause of mothers and daughters and greater concordance with identical than non-identical twins. However, with the exception of smoking which advances menopause by two years, these factors have failed to show a consistent influence on age at menopause.