There is evidence of endocrine disruption and reproductive effects in animals following exposure to certain PBDEs, but human studies are limited. The goal of this study was to investigate the use of serum and follicular fluid as biomarkers of exposure to PBDEs and to explore whether a relationship between PBDE exposure and early pregnancy loss exists. We measured 8 PBDE congeners in archived serum and ovarian follicular fluid samples from 65 women undergoing in-vitro fertilization (IVF). Logistic regression models were used to predict the odds of failed embryo implantation associated with higher levels of PBDEs among the women in the study. There were moderate Kendall's Tau-beta correlations between serum and follicular fluid concentrations of BDE 28, 47, 100 and 154 (T(β)=0.29-0.38, all p-values<0.005), but BDE 99 and 153 were not correlated between the two matrices (T(β)<0.2, p-values>0.05). Women with detectable concentrations of BDE 153 (39% had detectable levels) in follicular fluid had elevated odds of failed implantation compared with women who had non-detectable concentrations (adjusted OR=10.0; 95%CI: 1.9 to 52; p=0.006; adjusted by age and body mass index). These findings suggest that exposure to BDE 153 may be associated with failed embryo implantation. Due to our observation of only moderate correlations between matrices, serum PBDE concentrations may not be a good indicator of follicular fluid concentrations when studying early pregnancy endpoints in women undergoing IVF.

BACKGROUND: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins used in numerous consumer products. In experimental animals, BPA increased embryo implantation failure and reduced litter size. OBJECTIVE: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF). METHODS: In this prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center, urinary BPA concentrations were measured in 137 women by on-line solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry. Logistic regression was used to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum β-human chorionic gonadotropin test (β-HCG <6 IU/L) 17 days after egg retrieval. RESULTS: Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22)µg/L. Overall, 42%(n=75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations (odds ratio (OR)(95% Confidence Interval (CI)) 1.02 (0.35, 2.95), 1.60 (0.70, 3.78), 2.11 (0.84, 5.31) for quartiles 2, 3 and 4, respectively, as compared to the lowest quartile (trend test p-value=0.06). CONCLUSION: There was a positive linear dose-response association between BPA urinary concentrations and implantation failure.

Background: Hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethane (DDE), are persistent chlorinated pesticides with endocrine activity that may adversely affect the early stages of human reproduction. Objective: To determine the association of serum levels of HCB, DDT, and DDE with implantation failure, chemical pregnancy, and spontaneous abortion (SAB) in women undergoing IVF from 1994 to 2003. Methods: Levels of HCB and congeners of DDT and DDE were measured in serum collected during the follicular phase. Multivariable-adjusted statistical models accommodating multiple outcomes and multiple cycles per woman were used to estimate the relation between serum pesticide levels and IVF outcomes. Results: A total of 720 women with a mean age (SD) of 35.4 years (4.2) at enrollment contributed 774 IVF cycles. All samples had detectable levels of HCB, DDT, and DDE, with median levels of 0.087 ng/g serum for HCB, 1.12 ng/g serum for total DDT, and 1.04 ng/g serum for p,p'-DDE. Compared to the lowest quartile of HCB, the lipid- and multivariable-adjusted odds for failed implantation was significantly elevated for those with higher HCB quartiles [Adjusted Odds Ratio (aOR) for Q2: 1.71, 95% confidence interval (CI):1.03, 2.82, aOR for Q3: 2.30, 95% CI:1.39, 3.81; aOR for Q4: 2.32, 95% CI: 1.38, 3.90) and showed a significantly increasing trend (p=0.001). No statistically significant associations were observed between DDT/DDE and IVF outcomes or between HCB and chemical pregnancy or SAB. Conclusions: Serum HCB concentrations were on average lower than that of the general US population and associated with failed implantation among women undergoing IVF.

OBJECTIVE To determine the association between patient characteristics at diagnosis of premenopausal breast cancer, including gravidity, parity, age at menarche, age at first birth, alcohol use, smoking history, weight, height, and body mass index (BMI), with the development of persistent chemotherapy-related amenorrhea (CRA) in follow-up. DESIGN Retrospective cohort study. SETTING Dana Farber Cancer Institute and Brigham and Women's Hospital. PATIENT(S) Premenopausal women with breast cancer. INTERVENTION(S) We identified all premenopausal women who received standard adjuvant chemotherapy during 1997-2005 for whom menstrual data were available. Multivariable logistic regression models evaluating persistent amenorrhea at ≥6 month after completion of chemotherapy were conducted. MAIN OUTCOME MEASURE(S) Persistent chemotherapy-related amenorrhea (CRA) at ≥6 months from completion of chemotherapy. RESULT(S) A total of 431 women met eligibility criteria and had ≥6-months' follow-up. Women with older (>13 years) vs. younger (12-13 years) age at menarche were more than twice as likely to remain amenorrheic. Current smokers had 2.4 greater odds of CRA vs. never smokers, although this association was not statistically significant (95% confidence interval, 0.86-6.75). CONCLUSION(S) Few identifiable factors contribute to the variability in CRA among premenopausal women after adjuvant chemotherapy for breast cancer. Further research to improve the prediction of CRA, premature menopause, and infertility in young breast cancer survivors is warranted.

OBJECTIVE: To investigate the effect of prior chemotherapy and radiation on assisted reproductive technology (ART) outcomes. DESIGN: Retrospective cohort study. SETTING: University-based infertility clinic. PATIENT(S): Female cancer survivors who had received chemotherapy or radiation and all other women undergoing first-fresh IVF/intracytoplasmic sperm injection (ICSI) cycles. INTERVENTION(S): Survivors' ART outcomes were compared with all women undergoing first-fresh IVF/ICSI cycles and those with male-factor infertility only. Multivariate logistic and Poisson regression analyses were used to estimate the effect of cancer therapy on ART outcomes. MAIN OUTCOMES MEASURE(S): Number of oocytes retrieved and embryos obtained; odds of cycle cancelation, clinical pregnancy, and live birth. RESULT(S): Compared with others undergoing IVF/ICSI, survivors had significantly fewer oocytes retrieved and embryos available for transfer. In addition, survivors were significantly more likely to be canceled (odds ratio [OR] 5.60, 95% CI 2.94-10.66) and had lower pregnancy and live birth rates (OR 0.30, 95% CI 0.13-0.68; and OR 0.27, 95% CI 0.10-0.69; respectively). Odds ratios were stronger when the comparison group was restricted to those with male-factor infertility only. CONCLUSION(S): Women who have received systemic therapy for malignancy should be considered to be low responders and counseled that their per-cycle live birth rate is lower than that of their peers. These data strongly support offering fertility preservation before cancer therapy when possible.

STUDY OBJECTIVE: To evaluate the efficacy and tolerability of norethindrone acetate (NA) as single-agent hormonal therapy for suppression of endometriosis symptoms in adolescents and young adults. DESIGN: Retrospective study. SETTING: Two academic medical centers. PARTICIPANTS: A keyword search using the query 'NA' was applied to the electronic medical records of all women treated by one gynecologist (M.R.L.) from 1992 to 2010. IRB-approved chart review was then conducted on the index records. INTERVENTIONS: Continuous treatment with NA (5-15 mg daily). MAIN OUTCOME MEASURES: Postoperative bleeding and pain scores; adverse effects. RESULTS: One hundred and ninety-four patients with surgically diagnosed endometriosis initiated NA postoperatively during the study period. Median patient age was 18.9 years. 92.2% of patients had stage 1 or 2 disease, and distribution was similar among those excluded. Median pain scores decreased from 5 at NA initiation to 0 at follow-up (P =.0001) and bleeding scores from 2 to 0, respectively (P =.001) for all stages of endometriosis. Post-NA bleeding scores were improved regardless of prior hormonal regimen, and post-NA pain scores improved in all patients except for those previously prescribed GnRH-agonist plus add-back. Most patients (55.2%) did not report any side effects. The most common adverse effect was weight gain (16.1%), with a mean increase in BMI of 1.2 ± 1.6 kg/m(2) at 12 months. CONCLUSION: NA alone is a well-tolerated, effective option to manage pain and bleeding for all stages of endometriosis. Among those on prior hormonal therapy, symptoms improved after NA initiation.

PURPOSE To examine sexual orientation group disparities in the Papanicolaou (Pap) and sexually transmitted infection (STI)/human papillomavirus (HPV) tests among adolescents and young adult females. METHODS Survey data from 4,224 adolescents and young adults aged 17-25 years who responded to the 2005 wave questionnaire of the Growing Up Today Study were cross-sectionally examined with multivariate generalized estimating equations regression. We examined associations between sexual orientation and reproductive healthcare utilization as well as abnormal results with completely heterosexual as the referent group, controlling for age, race/ethnicity, geographic region, and sexual history. RESULTS After accounting for sociodemographics and sexual history, mostly heterosexual/bisexual females had 30% lower odds of having a Pap test within the last year and almost 40% higher odds of being diagnosed with an STI, as compared with the completely heterosexual group. Additionally, lesbians had very low odds of having a Pap test in their lifetime (odds ratio =.13, p ≤ .0001) and having a Pap test within the last year (odds ratio =.25, p =.0002), as compared with completely heterosexuals. CONCLUSIONS Our study demonstrates that sexual minority adolescent and young adult women underutilize routine reproductive health screenings, including Pap smears and STI tests. Providers and health educators should be aware of these disparities so that they can provide appropriate care to young women and their families and ensure that all young women receive reproductive health screening. Further research is needed to explore reasons sexual minority females are not accessing care as recommended because this may suggest opportunities to improve reproductive health screenings as well as broader healthcare access issues.

OBJECTIVE: The purpose of this prospective study was to study the association between rotating nightshift work and endometriosis risk within the Nurses' Health Study II. STUDY DESIGN: We found 89,400 women without diagnosed endometriosis at baseline; the 2062 laparoscopically confirmed cases that were documented during 16 years of follow-up evaluation formed our study population. RESULTS: Overall, there was no association between rotating nightshift work and risk of endometriosis. When the cases were categorized by infertility status, risk was elevated among women with concurrent infertility and ≥5 years of rotating nightshift work (rate ratio, 1.71; 95% confidence interval, 1.18-2.49; P(trend)=.005), compared with women with no rotating nightshift work. In contrast, there was no association among women without reported infertility (P(heterogeneity)=.003). CONCLUSION: Women who work rotating nightshifts for ≥5 years may have a modestly elevated risk of endometriosis if concurrently infertile. However, the relation between shiftwork, endometriosis, and infertility is complex, and the potential for bias because of a healthy or infertile worker effect must be considered.

The scientific literature on endometriosis specific to the adolescent population is limited, and the existing data are retrospective and descriptive in nature. It is possible that the disease has a different pathophysiology in adolescents, but little epidemiologic or molecular data exist to support or refute this speculation. In addition, the limited literature does not yet confirm that intervening in the adolescent population prevents long-term sequelae such as pain and infertility as adults. Case-control and cohort studies to identify risk factors, as well as prospective observational and intervention studies to assess treatment outcome, are required to further knowledge about endometriosis in the adolescent population. The scientific literature on endometriosis specific to the adolescent population is limited, and the existing data are retrospective and descriptive in nature. This review summarizes studies that have been done to date and suggests areas for future investigation.

OBJECTIVE To evaluate the effect of increasing female obesity on response to and outcome of assisted reproductive technology (ART) treatment. DESIGN Historical cohort study. SETTING Clinic-based data. PATIENT(S) A total of 152,500 ART cycle starts from the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System for 2007-2008, limited to women with documented height and grouped by body mass index (BMI,[weight/height(2)]). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Cycle cancellation overall, cycle cancellation due to low response, treatment failure (not pregnant vs. pregnant), and pregnancy failure (fetal loss or stillbirth vs. live birth), as adjusted odds ratios and 95% confidence intervals, with cycles among normal-weight women as the reference group. RESULT(S) Cycle cancellation overall and cancellation due to low response using autologous oocytes significantly paralleled increasing BMI. The odds of treatment failure rose significantly with autologous-fresh cycles, from 1.03 for cycles among overweight women (BMI 25.0-29.9) to 1.53 for cycles among women with BMIs ≥ 50.0 kg/m(2). Likewise, the odds of pregnancy failure were most significant with increasing BMI among women with autologous-fresh cycles, increasing from 1.10 for cycles to overweight women to 2.29 for cycles to women with BMI ≥ 50.0 kg/m(2). CONCLUSION(S) These results indicate significantly higher odds of cycle cancellation. In addition, treatment and pregnancy failures with increasing obesity significantly increased starting with overweight women.