Measuring ovarian toxicity in clinical trials: an American Society of Clinical Oncology research statement.

Anticancer agents can impair ovarian function, resulting in premature menopause and associated long-term health effects. Ovarian toxicity is not usually adequately assessed in trials of anticancer agents, leaving an important information gap for patients facing therapy choices. This American Society of Clinical Oncology (ASCO) statement provides information about the incorporation of ovarian toxicity measures in trial design. ASCO recommends: (1) measurement of ovarian toxicity in relevant clinical trials of anticancer agents that enrol post-pubertal, pre-menopausal patients; (2) collection of ovarian function measures at baseline and at 12-24 months after anticancer agent cessation, as a minimum, and later in line with the trial schedule; and (3) assessment of both clinical measures and biomarkers of ovarian function. ASCO recognises that routine measurement of ovarian toxicity and function in cancer clinical trials will add additional complexity and burden to trial resources but asserts that this issue is of such importance to patients that it cannot continue to be overlooked.

Results of a pilot study in the U.S. and Vietnam to assess the utility and acceptability of a multi-level pregnancy test (MLPT) for home monitoring of hCG trends after assisted reproduction.

BACKGROUND: To evaluate the utility and acceptability of using multi-level pregnancy tests (MLPTs) at home to monitor hCG trends following assisted reproductive technology (ART). METHODS: One hundred and four women presenting for ART at either Stanford Medicine Fertility and Reproductive Health Clinic (Stanford, CA) or Hung Vuong Hospital (Ho Chi Minh City, Vietnam) participated in this pilot study. Women were asked to perform the MLPT at home, primarily on days when they were also scheduled to receive standard clinic-based serum hCG testing. These tests were administered up to 6 times over the 6-week period following embryo transfer or intrauterine insemination (IUI). Concordance of serial hCG readings for each time point was assessed by comparing trends in urine MLPT results with trends in serum hCG. Stable or increasing hCG level was interpreted as an indication of a progressing pregnancy, while a declining hCG was interpreted as a lack of established or progressing pregnancy. At study end, all participants were asked about the acceptability and convenience of using the MLPT at home for monitoring hCG trends following ART. RESULTS: Data from both urine and serum testing are available for 156 of 179 clinic visits (87.2%). There was high concordance of serial trend results between the two types of tests: among the 156 sets of serum and urine hCG data points, 150 (96.2%) showed a matching trend in hCG pattern and 6 (3.8%) resulted in a discordant trend. Seventy-three percent of women reported being satisfied or very satisfied with using the MLPTs at home. Almost all (96.6%) said that the MLPT was easy or very easy to use. CONCLUSION: The MLPT offers women and health care providers a client-friendly diagnostic tool to detect very early pregnancy and monitor its progress. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov as NCT01846403 (May 1, 2013), and NCT01919502 (August 5, 2013).

Does an increased body mass index affect endometrial gene expression patterns in infertile patients? A functional genomics analysis.

OBJECTIVE: To analyze the transcriptomic profile of endometrial gene alterations during the window of implantation in infertile obese patients. DESIGN: Multicenter, prospective, case-control study. SETTING: Three academic medical centers for reproductive medicine. PATIENT(S): Infertile patients, stratified into body mass index (BMI) categories according to the World Health Organization guidelines, were included in the study. INTERVENTION(S): Endometrial samples were obtained from women undergoing standardized estrogen and P replacement cycles after 5 days of vaginal P supplementation. MAIN OUTCOME MEASURE(S): To identify endometrial gene expression alterations that occur during the window of implantation in infertile obese patients as compared with infertile normal-weight controls using a microarray analysis. RESULT(S): XCL1, XCL2, HMHA1, S100A1, KLRC1, COTL1, COL16A1, KRT7, and MFAP5 are significantly dysregulated during the window of implantation in the receptive endometrium of obese patients. COL16A1, COTL1, HMHA1, KRCL1, XCL1, and XCL2 were down-regulated and KRT7, MFAP5, and S100A1 were up-regulated in the endometrium of obese patients. These genes are mainly involved in chemokine, cytokine, and immune system activity and in the structural extracellular matrix and protein-binding molecular functions. CONCLUSION(S): Obesity is associated with significant endometrial transcriptomic differences as compared with non-obese subjects. Altered endometrial gene expression in obese patients may contribute to the lower implantation rates and increased miscarriage rates seen in obese infertile patients. CLINICAL TRIAL REGISTRATION NUMBER: NCT02205866.

Increased body mass index negatively impacts blastocyst formation rate in normal responders undergoing in vitro fertilization.

PURPOSE: The aim of this study is to investigate the effect of female BMI and metabolic dysfunction on blastocyst formation rate. METHODS: This was a retrospective cohort study that was performed in an academic center for reproductive medicine. Patients who were normal weight, overweight with metabolic dysfunction, or obese who had ≥6 oocytes retrieved in a fresh IVF cycle were included in the study. The blastocyst formation rate was calculated from the number of ≥5 cell embryos on day 3 observed in culture until day 5 or day 6. Only good quality blastocysts were included in the calculation as defined by a morphologic grade of 3BB or better. RESULTS: The blastocyst formation rate was significantly better in the normal-weight controls versus overweight/obese patients (57.2 versus 43.6 %, p < 0.007). There was no difference in blastocyst formation between the patients with a BMI 25-29.9 kg/m(2) with metabolic dysfunction and those with a BMI ≥30 kg/m(2). CONCLUSION: The maternal metabolic environment has a significant impact on embryo quality as measured by blastocyst formation. A decreased blastocyst formation rate is likely a significant contributor to poorer reproductive outcomes in overweight and obese women with infertility.

Drug-Induced Thrombocytopenia following a Transvaginal Oocyte Retrieval for In Vitro Fertilization.

Drug-induced immune thrombocytopenia has been associated with hundreds of medications and can lead to devastating consequences for the patient. We present a case of a healthy 33-year-old female undergoing in vitro fertilization who developed a severe drug-induced thrombocytopenia, petechiae, and a large hemoperitoneum after receiving Cefazolin antibiotic prophylaxis for a transvaginal oocyte retrieval. The patient was admitted to the intensive care unit for resuscitation with blood products. The presence of drug-dependent platelet antibodies to Cefazolin was confirmed serologically.