Observational study of the development and evaluation of a fertility preservation patient decision aid for teenage and adult women diagnosed with cancer: the Cancer, Fertility and Me research protocol.

INTRODUCTION: Women diagnosed with cancer and facing potentially sterilising cancer treatment have to make time-pressured decisions regarding fertility preservation with specialist fertility services while undergoing treatment of their cancer with oncology services. Oncologists identify a need for resources enabling them to support women's fertility preservation decisions more effectively; women report wanting more specialist information to make these decisions. The overall aim of the 'Cancer, Fertility and Me' study is to develop and evaluate a new evidence-based patient decision aid (PtDA) for women with any cancer considering fertility preservation to address this unmet need. METHODS AND ANALYSIS: This is a prospective mixed-method observational study including women of reproductive age (16 years +) with a new diagnosis of any cancer across two regional cancer and fertility centres in Yorkshire, UK. The research involves three stages. In stage 1, the aim is to develop the PtDA using a systematic method of evidence synthesis and multidisciplinary expert review of current clinical practice and patient information. In stage 2, the aim is to assess the face validity of the PtDA. Feedback on its content and format will be ascertained using questionnaires and interviews with patients, user groups and key stakeholders. Finally, in stage 3 the acceptability of using this resource when integrated into usual cancer care pathways at the point of cancer diagnosis and treatment planning will be evaluated. This will involve a quantitative and qualitative evaluation of the PtDA in clinical practice. Measures chosen include using count data of the PtDAs administered in clinics and accessed online, decisional and patient-reported outcome measures and qualitative feedback. Quantitative data will be analysed using descriptive statistics, paired sample t-tests and CIs; interviews will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Research Ethics Committee approval (Ref: 16/EM/0122) and Health Research Authority approval (Ref: 194751) has been granted. Findings will be published in open access peer-reviewed journals, presented at conferences for academic and health professional audiences, with feedback to health professionals and program managers. The Cancer, Fertility and Me patient decision aid (PtDA) will be disseminated via a diverse range of open-access media, study and charity websites, professional organisations and academic sources. External endorsement will be sought from the International Patient Decision Aid Standards (IPDAS) Collaboration inventory of PtDAs and other relevant professional organisations, for example, the British Fertility Society. TRIAL REGISTRATION NUMBER: NCT02753296; pre-results.

Effect of increased body mass index on oocyte and embryo quality in IVF patients.

Obesity may have an adverse effect on the outcome of IVF/intracytoplasmic sperm injection (ICSI) treatment. In this study, the effects of increased body mass index (BMI) on oocyte and embryo quality during IVF cycles were studied. A retrospective analysis of 426 IVF/ICSI cycles was performed. Cycles were classified according to the BMI: normal BMI (19-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (> or = 30 kg/m(2)). Cycles were further stratified based on age (group 1, < 35 years; group 2, > or = 35 years). Markers of oocyte quality (number of oocytes inseminated and fertilization rate) and embryo quality (utilization rate, number of embryos discarded and cryopreserved, and mean embryo grade) were examined. In group 1, obesity had a significant adverse effect on the mean embryo grade (P = 0.02), the embryo utilization rate (P = 0.01), number of embryos discarded (P = 0.007) and cryopreserved (P < 0.05). In group 2, there was no difference in markers of embryo quality between the three BMI ranks. Obesity did not have any significant effect on markers of oocyte quality or clinical pregnancy rates. In conclusion, obesity may adversely affect embryo quality in young women (<35 years) undergoing IVF/ICSI, while the oocyte quality is not affected.

Evaluation of the utility of multiple endocrine and ultrasound measures of ovarian reserve in the prediction of cycle cancellation in a high-risk IVF population.

BACKGROUND: Unexpectedly poor response leading to IVF cycle cancellation is a distressing treatment outcome. We have prospectively assessed several markers of ovarian reserve in a high risk IVF population to determine their utility in predicting IVF cycle cancellation. METHODS: Eighty-four women at high risk of cycle cancellation due to raised FSH, previous poor response and/or age > or =40 years attending for high-dose short protocol IVF treatment had baseline measures of FSH, inhibin B, anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume. A GnRH agonist was then administered and, 24 h later, estradiol (E(2)) and inhibin B measures were repeated. RESULTS: Fifty-seven per cent of patients in this study had a poor response to stimulation, and 15% were cancelled. Using multivariate logistic regression, we found that day 3 inhibin B levels were the best predictor of cycle cancellation with an area under the receiver operating curve (ROC AUC) = 0.78 (P = 0.017). When only considering baseline variables, mean ovarian volume was the best predictor of cycle cancellation (ROC AUC = 0.78; P = 0.016). AMH concentrations were the best predictor of a poor response (P = 0.003), and AMH was also predictive of cycle cancellation (P = 0.007) with very little inter-cycle variability. None of the parameters studied were predictive of ongoing pregnancy. CONCLUSIONS: This group of at-risk patients had a high rate of poor response to simulation and cancellation. Although several measures of ovarian reserve were able to predict cycle cancellation, none were able to predict pregnancy. AMH was predictive of both cycle cancellation and poor response with little inter-cycle variability.

Pregnancy outcome is not affected by antiphospholipid antibody status in women referred for in vitro fertilization.

OBJECTIVE: To determine the prevalence of antiphospholipid (aPL) and anti-beta 2 glycoprotein I (anti-beta2-GPI) antibodies in women referred for IVF and to prospectively evaluate the effect of these antibodies on IVF outcome. DESIGN: Prospective observational study. SETTING: A university hospital and IVF unit. PATIENT(S): Three hundred eighty consecutive women referred for IVF. INTERVENTION(S): Blood samples taken before commencement of IVF cycles were tested for the presence of aPL (lupus anticoagulant [LA], anticardiolipin [aCL], and antiphosphatidyl serine antibodies [aPS]) and anti-beta2-GPI antibodies. MAIN OUTCOME MEASURE(S): Antibody prevalence, pregnancy rates, and live birth rates. RESULT(S): Of the total 380 women, 89 tested persistently positive for aPL (23.4%). None of 176 women tested for IgG aPS antibodies had a positive titer. Only 3.3% (11 of 329) tested positive for anti-beta2-GPI antibodies. Pregnancy rate, live birth rate, gestational age at delivery, and birth weight were not affected by aPL status. CONCLUSION(S): Although women referred for IVF have a high prevalence of aPL, these antibodies do not affect the outcome of treatment. Screening women undergoing IVF for aPL is not justified.

Measurement of ovarian volume by transvaginal sonography before ovulation induction with human menopausal gonadotrophin for in-vitro fertilization can predict poor response.

The study tests the hypothesis that small ovaries measured on transvaginal sonography (TVS) are associated with a poor response to ovulation induction by human menopausal gonadotrophin (HMG) for in-vitro fertilization (IVF). A total of 140 infertile patients with morphologically normal ovaries undergoing IVF was studied. The mean ovarian volume of each patient was measured on TVS before starting HMG. Subsequent routine IVF management was conducted without knowledge of the results of TVS. The mean ovarian volume was 6.3 cm3 (range 0.5-18.9, SD= 3.1). Patients (n = 17; group A) with small ovaries of < 3 cm3 (i.e. overall mean volume - 1 SD) were compared to patients (n = 123; group B) with ovaries > or = 3 cm3. Both groups were of similar age (mean 35.8 versus 34.4 years). Early basal FSH concentrations were increased in group A (9.5 versus 7.0 mIU/ml, P = 0.025). The cycle was abandoned before planned oocyte recovery in nine patients (52.8%) from group A and in 11 patients (8.9%) from group B because of poor response to ovulation induction (P < 0.001). Increased age and ovarian volume were associated independently with cancellation of the cycles. The remaining eight patients from group A who had oocytes retrieved required higher doses of HMG (87.5 versus 53.8 ampoules, P < 0.01), yielded fewer follicles (10.3 versus 14.5, P < 0.05) and fewer oocytes were recovered from them (6.8 versus 11.0, P < 0.05) compared with group B. There was no difference in the fertilization or pregnancy rates or the number of embryos available for transfer in either group. Our results indicate a strong association between ovarian volume and ovarian reserve. Small ovaries are associated with poor response to HMG and a very high cancellation rate during IVF. Assessment of ovarian size should be an integral part of infertility evaluation.