Variability in the practice of fertility preservation for patients with cancer.

Fertility is important to women and men with cancer. While options for fertility preservation (FP) are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs). A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases-particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS) in patients with estrogen receptor positive (ER+) breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines-knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14-2.90). These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP.

Adverse effects of obesity and/or high-fat diet on oocyte quality and metabolism are not reversible with resumption of regular diet in mice.

Obesity adversely affects reproduction and results in oocyte defects in both mice and humans. In the present study we used a mouse model to examine whether the adverse effects of an obesogenic diet on oocyte metabolism and morphology can be reversed by return to a control diet. The intervention group consisted of C57BL6/J mice placed on a high-fat diet (HFD; 35.8% fat and 20.2% protein by nutritional content) for 6 weeks and then switched to an isocaloric control diet (CD; 13% fat and 25% protein) for 8 weeks (HFD/CD mice). The control group consisted of age-matched C57BL6/J mice maintained on CD for 14 weeks (CD/CD mice). Although metabolic parameters (weight, glucose tolerance and cholesterol levels) of HFD/CD mice returned to normal after this 'diet reversal' period, several oocyte defects were not reversible. These HFD/CD oocytes demonstrated significantly higher percentages of abnormal meiotic spindles, lower mitochondrial membrane potential and lower ATP and citrate levels, and higher percentages of abnormal lipid accumulation and mitochondrial distribution compared with CD/CD mice. These results suggest that the negative effects of an obesogenic diet on oocyte quality are not reversible, despite reversal of metabolic parameters. These data may provide better insight when counselling obese women regarding reproductive options and success.

DHEA-mediated inhibition of the pentose phosphate pathway alters oocyte lipid metabolism in mice.

Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered hormone levels and suffer from ovarian dysfunction leading to subfertility. We have attempted to generate a model of hyperandrogenism by feeding mice chow supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is often elevated in women with PCOS. Treated mice had polycystic ovaries, low ovulation rates, disrupted estrous cycles, and altered hormone levels. Because DHEA is an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the pentose phosphate pathway, we tested the hypothesis that oocytes from DHEA-exposed mice would have metabolic disruptions. Citrate levels, glucose-6-phosphate dehydrogenase activity, and lipid content in denuded oocytes from these mice were significantly lower than controls, suggesting abnormal tricarboxylic acid and pentose phosphate pathway metabolism. The lipid and citrate effects were reversible by supplementation with nicotinic acid, a precursor for reduced nicotinamide adenine dinucleotide phosphate. These findings suggest that elevations in systemic DHEA can have a negative impact on oocyte metabolism and may contribute to poor pregnancy outcomes in women with hyperandrogenism and PCOS.

Cycle cancellation and pregnancy after luteal estradiol priming in women defined as poor responders: a systematic review and meta-analysis.

STUDY QUESTION: Does a luteal estradiol (LE) stimulation protocol improve outcomes in poor responders to IVF? SUMMARY ANSWER: LE priming is associated with decreased cycle cancellation and increased chance of clinical pregnancy in poor responders WHAT IS KNOWN ALREADY: Poor responders to IVF are one of the most challenging patient populations to treat. Many standard protocols currently exist for stimulating these patients but all have failed to improve outcomes. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis including eight published studies comparing assisted reproduction technology (ART) outcomes in poor responders exposed to controlled ovarian hyperstimulation with and without LE priming. A search of the databases MEDLINE, EMBASE and PUBMED was carried out for studies in the English language published up to January 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies evaluating women defined as poor responders to ART were evaluated. These studies were identified following a systematic review of the literature and data were analyzed using the DerSimonian-Laird random effects model. The main outcomes of interest were cycle cancellation rate and clinical pregnancy. Although the definition of clinical pregnancy varied between studies, the principal definition included fetal cardiac activity as assessed by transvaginal ultrasonography after 5 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 2249 publications were identified from the initial search, and the bibliographies, abstracts and other sources yielded 11 more. After excluding duplications, 1227 studies remained and 8 ultimately met the inclusion criteria. Compared with women undergoing non-LE primed protocols (n = 621), women exposed to LE priming (n = 468) had a lower risk of cycle cancellation [relative risk (RR): 0.60, 95% confidence interval (CI): 0.45-0.78] and an improved chance of clinical pregnancy (RR: 1.33, 95% CI: 1.02-1.72). There was no significant improvement in the number of mature oocytes obtained or number of zygotes obtained per cycle. LIMITATIONS, REASONS FOR CAUTION: These findings are limited by the body of literature currently available. As the poor responder lacks a concrete definition, there is some heterogeneity to these results, which merits caution when applying our findings to individual patients. Furthermore, the increased clinical pregnancy rate demonstrated when using the LE protocol may be principally related to the decreased cycle cancellation rate. WIDER IMPLICATIONS OF THE FINDINGS: The LE protocol may be of some utility in the poor responder to IVF and may increase clinical pregnancy rates in this population by improving stimulation and thereby decreasing cycle cancellation. STUDY FUNDING/COMPETING INTERESTS: NIH K12 HD063086 (ESJ, MGT), NIH T32 HD0040135-11 (KAR), F32 HD040135-10 NIH (KRO), 5K12HD000849-25 (PTJ). No competing interests.