In vitro fertilization outcomes and alcohol consumption in at-risk drinkers: the effects of a randomized intervention.

BACKGROUND AND OBJECTIVES: Women's use of alcohol in pregnancy is associated with an increased risk of fetal loss and birth defects. Also, alcohol use in women decreases the success of infertility treatment, such as in vitro fertilization (IVF). Our goal was to determine if there were differences in IVF outcomes and alcohol use parameters among at-risk drinkers randomized to a brief intervention (BI) versus assessment only (AO). METHODS: We conducted a randomized controlled trial to determine the effect of BI or AO among at-risk drinkers on IVF. We studied 37 women (AO = 21; BI = 16). RESULTS: While the BI group had a significantly greater decrease in the number of drinks/drinking day compared to the AO group (p = .04), there were no differences in the likelihood of implantation failure, chemical pregnancy, spontaneous abortion, preterm birth, or live birth. CONCLUSIONS: BI and AO contributed to a decrease in alcohol use and did not demonstrate differences in IVF outcomes. A larger study may confirm these preliminary findings. SCIENTIFIC SIGNIFICANCE: Our results will assist care providers in treating alcohol use in pregnancy in an effective way, such that IVF cycles and the chance of pregnancy are optimized.

Urinary bisphenol A concentrations and implantation failure among women undergoing in vitro fertilization.

BACKGROUND: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size. OBJECTIVE: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF). METHODS: We used online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression 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 ß-human chorionic gonadotropin test (ß-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) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06). CONCLUSION: There was a positive linear dose-response association between BPA urinary concentrations and implantation failure.

Female cancer survivors are low responders and have reduced success compared with other patients undergoing assisted reproductive technologies.

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.

Secondhand tobacco smoke exposure is associated with increased risk of failed implantation and reduced IVF success.

BACKGROUND: Infertility and early pregnancy loss are prevalent as is exposure to secondhand tobacco smoke (STS). Previous research has suggested a relationship between STS exposure and early pregnancy loss, but studies have been limited by small study sizes and/or imprecise methods for exposure estimation. IVF allows for the collection of follicular fluid (FF), the fluid surrounding the pre-ovulatory oocyte, which may be a more biologically relevant sample media than urine or serum in studies of early reproduction. METHODS: In a retrospective analysis of a prospective cohort study, we measured cotinine in FF collected during 3270 IVF treatment cycles from 1909 non-smoking women between 1994 and 2003 to examine the relationship between STS exposure and implantation failure. RESULTS: In adjusted models, we found a significant increase in the risk of implantation failure among women exposed to STS compared with those unexposed [odds ratio (OR) = 1.52; 95% confidence interval (CI) = 1.20-1.92; risk ratio (RR) = 1.17; 95% CI = 1.10-1.25]. We also found a significant decrease in the odds for a live birth among STS-exposed women (OR = 0.75; 95% CI = 0.57-0.99; RR = 0.81; 95% CI = 0.66-0.99). CONCLUSIONS: Female STS exposure, estimated through the measurement of cotinine in FF, is associated with an increased risk of implantation failure and reduced odds of a live birth.

Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization.

OBJECTIVE: To estimate the effect of body mass index (BMI) on oocyte and embryo parameters and cycle outcomes in women undergoing in vitro fertilization (IVF). METHODS: We evaluated a retrospective cohort of 1,721 women undergoing a first IVF cycle with fresh, autologous embryos between 2007 and 2010 in an academic infertility practice. Main outcome measures included number of mature and normally fertilized oocytes, embryo morphology, estradiol on the day of human chorionic gonadotropin administration, clinical pregnancy, spontaneous abortion, and live birth. We performed multivariable analyses, adjusting for potential confounders, including age at cycle start, infertility diagnosis, type of stimulation, total gonadotropin dose, use of intracytoplasmic sperm injection, and number of embryos transferred. RESULTS: Compared with women of normal BMI, women with class II (BMI 35-39.9) and III (BMI 40 or higher) obesity had fewer normally fertilized oocytes (9.3 compared with 7.6 and 7.7, P<.03) and lower estradiol levels (2,047 pg/mL compared with 1,498 and 1,361, P<.001) adjusting for age and despite similar numbers of mature oocytes. Odds of clinical pregnancy (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.31-0.82) and live birth (OR 0.51, 95% CI 0.29-0.87) were 50% lower in women with class III obesity as compared with women of normal BMI. CONCLUSION: Obesity was associated with fewer normally fertilized oocytes, lower estradiol levels, and lower pregnancy and live birth rates. Infertile women requiring IVF should be encouraged to maintain a normal weight during treatment.

Does a woman's educational attainment influence in vitro fertilization outcomes?

The association between educational level and cycle outcomes was quantified by applying multivariable logistic and linear regression within a prospective cohort of 2,569 women commencing their first in vitro fertilization (IVF) cycle. Although a woman's educational attainment was not associated with the likelihood of implantation failure, chemical pregnancy, spontaneous abortion, or live birth, the odds of cycle cancellation before egg retrieval were 40% lower among those with an college degree and 48% lower among those with graduate school attendance compared with women who had no college degree, suggesting that educational attainment is inversely associated with the likelihood of cycle cancellation.

Effect of time between human chorionic gonadotropin injection and egg retrieval is age dependent.

OBJECTIVE: To investigate whether egg retrieval at ≥36.5 hours improves IVF outcomes in women aged ≥40 years. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): First-attempt autologous IVF cycles without preimplantation genetic diagnosis, IUI conversion, or intentional delayed egg retrieval were included (n=3,231). Cycles were stratified by age and hCG exposure (<36.5 vs. ≥36.5 hours). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Oocyte yield, maturity, fertilization, embryo quality, implantation, clinical pregnancy, and live birth were analyzed, controlling for age and gonadotropins. Stimulation type, hMG use, stimulation days, day-3 FSH level, and diagnosis were evaluated as potential confounders. Multivariable regression analyses were performed and Wald tests for trend calculated. RESULT(S): No consistent differences in oocyte yield, maturity, fertilization, or embryo quality were detected. No absolute differences in outcomes were noted among group comparisons. However, as age increased, significant trends toward improved implantation, clinical pregnancy, and live birth were detected at ≥36.5 hours. CONCLUSION(S): Extending exposure to hCG for ≥36.5 hours may be beneficial in patients aged≥40 years. A prospective, randomized study is warranted to determine whether retrieval time merits revision for patients of advanced age, as well as the age cutoffs at which such protocols should be applied.

Serum concentrations of polychlorinated biphenyls in relation to in vitro fertilization outcomes.

BACKGROUND: Human exposure to polychlorinated biphenyls (PCBs) remains widespread. PCBs have been associated with adverse reproductive health outcomes including reduced fecundability and increased risk of pregnancy loss, although the human data remain largely inconclusive. OBJECTIVE: Our goal was to explore the relationship between serum PCB concentrations and early pregnancy loss among a large cohort of women undergoing in vitro fertilization (IVF) between 1994 and 2003. METHODS: Concentrations of 57 PCB congeners were measured in serum samples collected during 827 IVF/intracytoplasmic sperm injection cycles from 765 women. Joint statistical models that accommodate multiple outcomes and multiple cycles per woman were used to assess the relationship between serum PCB quartiles and implantation failure, chemical pregnancies (human chorionic gonadotropin level > 5.0 mIU/mL) that did not result in clinical pregnancy, or spontaneous abortion, while also adjusting for confounders. RESULTS: PCB-153 was the congener present in the highest concentration (median, 46.2 ng/g lipid). Increasing quartiles of PCB-153 and the sum of all measured PCB congeners (ΣPCBs) were associated with significantly elevated dose-dependent odds of failed implantation. Adjusted odds ratios (95% confidence interval) for highest versus lowest quartile were 2.0 (1.2-3.4) for PCB-153 and 1.7 (1.0-2.9) for ΣPCBs. There were suggestive trends for increased odds of implantation failure for PCB-118 and cytochrome P450-inducing congeners (p-values for trend = 0.06). No statistically significant associations between PCBs and chemical pregnancy or spontaneous abortion were found. CONCLUSIONS: Serum PCB concentrations at levels similar to the U.S. general population were associated with failed implantation among women undergoing IVF. These findings may help explain previous reports of reduced fecundability among women exposed to PCBs.

Effect of alcohol consumption on in vitro fertilization.

OBJECTIVE: To estimate whether alcohol use at the initiation of an in vitro fertilization (IVF) cycle is associated with IVF outcomes. METHODS: In this prospective cohort study, men and women completed a self-administered questionnaire before their first IVF cycle. Participants reported alcohol type, amount, and frequency consumed. Discrete survival analysis was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) for live birth-the primary outcome. Secondary outcomes were cycle characteristics and points of failure in the IVF process (cycle cancellation, failed fertilization, implantation failure, and spontaneous abortion). We conducted multicycle analyses with final models adjusted for potential confounders that included cycle number, cigarette use, body mass index, and age. RESULTS: A total of 2,545 couples contributed 4,729 cycles. Forty-one percent of women and 58% of men drank one to six drinks per week. Women drinking at least four drinks per week had 16% less odds of a live birth rate compared with those who drank fewer than four drinks per week (OR 0.84, CI 0.71-0.99). For couples in which both partners drank at least four drinks per week, the odds of live birth were 21% lower compared with couples in which both drank fewer than four drinks per week (OR 0.79; CI 0.66-0.96). CONCLUSION: Consumption of as few as four alcoholic drinks per week is associated with a decrease in IVF live birth rate. LEVEL OF EVIDENCE: II.