[Show abstract][Hide abstract] ABSTRACT: Study question:
How do the assisted reproductive technology (ART) outcomes of women presenting for ART after cancer diagnosis compare to women without cancer?
The likelihood of a live birth after ART among women with prior cancer using autologous oocytes is reduced and varies by cancer diagnosis but is similar to women without cancer when donor oocytes are used.
What is known already:
Premenopausal patients faced with a cancer diagnosis frequently present for fertility preservation.
Study design, size, duration:
Population-based cohort study of women treated with ART in NY, TX and IL, USA.
Participants/materials, setting, methods:
Women with their first ART treatment between 2004 and 2009 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database and linked to their respective State Cancer Registries based on name, date of birth and social security number. Years were rounded, i.e. year 1 = 6-18 months before treatment. This study used reports of cancer from 5 years, 6 months prior to treatment until 6 months after first ART treatment. Women who only presented for embryo banking were omitted from the analysis. The likelihood of pregnancy and of live birth with ART using autologous oocytes was modeled using logistic regression, with women without prior cancer as the reference group, adjusted for woman's age, parity, cumulative FSH dosage, infertility diagnosis, number of diagnoses, number of ART cycles, State of residency and year of ART treatment. Results of the modeling are reported as adjusted odds ratios (AORs) and (95% confidence intervals).
Main results and the role of chance:
The study population included 53 426 women; 441 women were diagnosed with cancer within 5 years prior to ART cycle start. Mean (±SD) age at cancer diagnosis was 33.4 ± 5.7 years; age at start of ART treatment was 34.9 ± 5.8 for women with cancer compared with 35.3 ± 5.3 years for women without cancer (P = 0.03). Live birth rates among women using autologous oocytes differed substantially by cancer status (47.7% without cancer versus 24.7% with cancer, P < 0.0001), and cancer diagnosis (ranging from 53.5% for melanoma to 14.3% for breast cancer, P < 0.0001. The live birth rates among women using donor oocytes did not vary significantly by cancer status (60.4% for women with any cancer versus 64.5% for women without cancer), or by cancer diagnosis (ranging from 57.9% for breast cancer to 63.6% for endocrine cancer). Women with breast cancer make up about one-third of all cancers in this cohort. Among women with breast cancer, 2.8% of the 106 women who underwent ART within 6 months of being diagnosed with cancer used donor oocytes compared with 34.8% of the 46 women who received ART treatment a longer time after being diagnosed with cancer (P < 0.0001). We conjecture that the former group were either unaware that they had cancer or decided to undergo ART therapy prior to cancer treatment. However, their live birth rate was only 11.7% compared with 28.8%, the overall live birth rate for all women with cancer using autologous oocytes (P < 0.0001). The live birth rate for women diagnosed with breast cancer more than 6 months before ART (23.3%) did not differ significantly from the overall live birth rate for cancer (P = 0.49). If this difference is substantiated by a larger study, it would indicate a negative effect of severe recent illness itself on ART success, rather than the poor outcome being only related to the destructive effects of chemotherapies on ovarian follicles. Alternatively, because of the short time difference between cancer diagnosis and ART treatment, these pre-existing cancers may have been detected due to the increased medical surveillance during ART therapy. In women who only used autologous oocytes, women with prior cancers were significantly less likely to become pregnant and to have a live birth than those without cancer (adjusted odds ratio (AOR): 0.34, [95% confidence interval (CI): 0.27, 0.42] and 0.36 [0.28, 0.46], respectively). This was also evident with specific cancer diagnoses: breast cancer (0.20 [0.13, 0.32] and 0.19 [0.11, 0.30], respectively), cervical cancer (0.36 [0.15, 0.87] and 0.33 [0.13, 0.84], respectively) and all female genital cancers (0.49 [0.27, 0.87] and 0.47 [0.25, 0.86], respectively). Of note, among women with cancer who became pregnant, their likelihood of having a live birth did not differ significantly from women without cancer (85.8 versus 86.7% for women using autologous oocytes, and 85.3 versus 86.9% for women using donor oocytes).
Limitations, reasons for caution:
Women may not have been residents of the individual States for the entire 5-year pre-ART period, and therefore some cancers may not have been identified through this linkage. As a result, the actual observed number of cancers may be an underestimate. In addition, the overall prevalence is low due to the age distributions. Also, because we restricted the pre-ART period to 5 years prior, we would not have identified women who were survivors of early childhood cancers (younger than age 13 years at cancer diagnosis), or who had ART more than 5 years after being diagnosed with cancer. Additional analyses are currently underway evaluating live birth outcomes after embryo banking among women with cancer prior to ART, cycles which were excluded from the analyses in this paper. Future studies are planned which will include more States, as well as linkages to vital records to obtain information on spontaneous conceptions and births, to further clarify some of the issues raised in this analysis.
Wider implications of the findings:
Since the live birth rates using donor oocytes were not reduced in women with a prior cancer, but were reduced with autologous cycles, this suggests that factors acting in the pre- or peri-conceptional periods may be responsible for the decline.
Study funding/competing interests:
The study was funded by grant R01 CA151973 from the National Cancer Institute, National Institutes of Health, USA. B.L. is a research consultant for the Society for Assisted Reproductive Technology. All other authors report no conflict of interest.
Human Reproduction 11/2015; DOI:10.1093/humrep/dev288 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to develop and validate a computer simulation model for coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM) that reflects current medical and surgical treatments.
We modified the structure of the CHD submodel in the Michigan Model for Diabetes to allow for revascularization procedures before and after first myocardial infarction, for repeat myocardial infarctions and repeat revascularization procedures, and for congestive heart failure. Transition probabilities that reflect the direct effects of medical and surgical therapies on outcomes were derived from the literature and calibrated to recently published population-based epidemiologic studies and randomized controlled clinical trials. Monte Carlo techniques were used to implement a discrete-state and discrete-time multistate microsimulation model. Performance of the model was assessed using internal and external validation. Simple regression analysis (simulated outcome=b0+b1×published outcome) was used to evaluate the validation results.
For the 21 outcomes in the six studies used for internal validation, R(2) was 0.99, and the slope of the regression line was 0.98. For the 16 outcomes in the five studies used for external validation, R(2) was 0.81, and the slope was 0.84.
Our new computer simulation model predicted the progression of CHD in patients with T2DM and will be incorporated into the Michigan Model for Diabetes to assess the cost-effectiveness of alternative strategies to prevent and treat T2DM.
[Show abstract][Hide abstract] ABSTRACT: Objective
To model morphological assessments of embryo quality that are predictive of live birth.
Longitudinal cohort using cycles reported in the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) between 2007 and 2011.
Fresh autologous assisted reproductive technology (ART) cycles with ETs on day 3 or day 5 and morphological assessments reported (25,409 cycles with one embryo transferred and 96,093 cycles with two embryos transferred). Live-birth rates were modeled by morphological assessments using backward-stepping logistic regression for cycle 1 and over five cycles, separately for day 3 and day 5 transfers and number of embryos transferred (1 or 2). Additional models for each day of transfer also included the number of oocytes retrieved and the number of embryos cryopreserved.
Main Outcome Measure(s)
Morphological assessments of grade, stage, fragmentation, and symmetry were significant for the day 3 models; grade, stage, and trophectoderm were significant in the day 5 model; inner-cell mass was significant in the models when two embryos were transferred. Number of oocytes retrieved and number of embryos cryopreserved were significant for both day 3 and day 5 models.
These findings confirm the significant association between embryo quality parameters reported to SART CORS and live-birth rate after ART.
Fertility and Sterility 09/2014; 102(5). DOI:10.1016/j.fertnstert.2014.07.1242 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: To develop a model predictive of live-birth rates (LBR) and multiple birth rates (MBR) for an individual considering assisted reproduction technology (ART) using linked cycles from Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) for 2004-2011. Design: Longitudinal cohort. Setting: Clinic-based data. Patient(s): 288,161 women with an initial autologous cycle, of whom 89,855 did not become pregnant and had a second autologous cycle and 39,334 did not become pregnant in the first and second cycles and had a third autologous cycle, with an additional 33,598 women who had a cycle using donor oocytes (first donor cycle). Intervention(s): None. Main Outcome Measure(s): LBRs and MBRs modeled by woman's age, body mass index, gravidity, prior full-term births, infertility diagnoses by oocyte source, fresh embryos transferred, and cycle, using backward-stepping logistic regression with results presented as adjusted odds ratios (AORs)and 95% confidence intervals. Result(s): The LBRs increased in all models with prior full-term births, number of embryos transferred; in autologous cycles also with gravidity, diagnoses of male factor, and ovulation disorders; and in donor cycles also with the diagnosis of diminished ovarian reserve. The MBR increased in all models with number of embryos transferred and in donor cycles also with prior full-term births. For both autologous and donor cycles, transferring two versus one embryo greatly increased the probability of a multiple birth (AOR 27.25 and 38.90, respectively). Conclusion(s): This validated predictive model will be implemented on the Society for Assisted Reproductive Technology Web site (www.sart.org) so that patients considering initiating a course of ART can input their data on the Web site to generate their expected outcomes. (C) 2014 by American Society for Reproductive Medicine.
Fertility and Sterility 06/2014; 102(3). DOI:10.1016/j.fertnstert.2014.05.020 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate factors associated with monozygosity (MZ) (number of fetal heartbeats on early ultrasound greater than the number of embryos transferred) and the risk of recurrence in subsequent pregnancies using a national assisted reproduction database.
Historical cohort study.
197,327 pregnancies (including 2,824 with evidence of MZ) from cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) between 2004 and 2010.
Evidence of MZ, adjusted odds ratios and their 95% confidence intervals computed from logistic regression models.
In the univariate analysis, the risk of MZ was increased with ovulation disorders, donor oocytes, gonadotropin-releasing hormone agonist (GnRH-a) suppression, assisted hatching (AZH), and day 5-6 transfer, and was decreased with higher follicle-stimulating hormone (FSH) doses (≥3,000 IU). In the multivariate analysis, the risk of MZ was increased with GnRH-a suppression, AZH, and decreased with intracytoplasmic sperm injection (ICSI) and higher FSH dose. The interaction showed that although MZ was more likely with day 5-6 embryos, AZH had a minimal nonsignificant effect, whereas in day 2-3 embryos, AZH had a substantial statistically significant effect. Only one woman had a recurrence of MZ in a subsequent assisted reproduction pregnancy, which is consistent with randomness.
The risk of MZ was higher with fresh day 5-6 embryos, donor oocytes, GnRH-a suppression, lower FSH doses, and AZH (particularly with day 2-3 embryos).
Fertility and sterility 01/2014; 101(3). DOI:10.1016/j.fertnstert.2013.11.034 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate the effect of a prior assisted reproductive technology (ART) live birth on subsequent live-birth rates.
Historical cohort study.
The study population included 297,635 women with 549,278 cycles from 2004 to 2010 from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Try 1 refers to ART cycles up to and including the first live birth, try 2 to ART cycles after a first live birth.
Main Outcome Measure(s)
Live-birth rates by cycle number, try number, and oocyte source.
Younger women at try 1 are more likely to return for try 2. Women returning for try 2 were more likely to have had an ART singleton versus multiple birth (33.2% after a try 1 singleton versus 8.1% after twins and 4.9% after triplets) and were less likely to have a diagnosis of diminished ovarian reserve or tubal factors. Live-birth rates were significantly higher for try 2 compared with try 1 for autologous fresh cycles, averaging 7.7 percentage points higher over five cycles. Live-birth rates were not significantly different for try 2 versus try 1 with thawed autologous cycles or either fresh or thawed donor cycles.
These results indicate that when fresh autologous oocytes can be used, live-birth rates per cycle are significantly greater after a prior history of an ART live birth.
Fertility and Sterility 12/2013; 100(6):1580–1584. DOI:10.1016/j.fertnstert.2013.07.1993 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study examined mealtime behaviors in families of young children with type 1 diabetes (T1DM) on intensive insulin therapy. Behaviors were compared to published data for children on conventional therapy and examined for correlations with glycemic control. Thirty-nine families participated and had at least three home meals videotaped while children wore a continuous glucose monitor. Videotaped meals were coded for parent, child, and child eating behaviors using a valid coding system. A group difference was found for child request for food only. There were also associations found between children's glycemic control and child play and away. However, no associations were found between parent and child behaviors within meals and children's corresponding post-prandial glycemic control. Results reinforce existing research indicating that mealtime behavior problems exist for families of young children even in the context of intensive therapy and that some child behaviors may relate to glycemic control.
[Show abstract][Hide abstract] ABSTRACT: This study uses linked cycles of assisted reproductive technology (ART) to examine cumulative live birth rates, birthweight, and length of gestation by diagnostic category.
We studied 145,660 women with 235,985 ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System during 2004-2010. ART cycles were linked to individual women by name, date of birth, social security number, partner's name, and sequence of ART treatments. The study population included the first four autologous oocyte cycles for women with a single diagnosis of male factor, endometriosis, ovulation disorders, diminished ovarian reserve, or unexplained infertility. Live birth rates were calculated per cycle, per cycle number (1-4), and cumulatively. Birthweight and length of gestation were calculated for singleton births.
Within each diagnosis, live birth rates were highest in the first cycle and declined with successive cycles. Women with diminished ovarian reserve had the lowest live birth rate (cumulative rate of 28.3 %); the live birth rate for the other diagnoses were very similar (cumulative rates from 62.1 % to 65.7 %). Singleton birthweights and lengths of gestation did not differ substantially across diagnoses, ranging from 3,112 to 3,286 g and 265 to 270 days, respectively. These outcomes were comparable with national averages for singleton births in the United States (3,296 g and 271 days).
Women with the diagnosis of diminished ovarian reserve had substantially lower live birth rates. However, singleton birthweights and lengths of gestation outcomes were similar across all other diagnoses.
Journal of Assisted Reproduction and Genetics 09/2013; 30(11). DOI:10.1007/s10815-013-0092-0 · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: To estimate the direct medical costs associated with type 2 diabetes, its complications, and its comorbidities among US managed carepatients. Study Design: Data were from patient surveys, chart reviews, and health insurance claims for 7109 people with type 2 diabetes from 8 health plans participating in the Translating Research Into Action for Diabetes (TRIAD) study between 1999 and 2002. Methods: A generalized linear regression model was developed to estimate the association of patients' demographic characteristics, tobaccouse status, treatments, related complications, andcomorbidities with medical costs. Results: The mean annualized direct medical cost was $2465 for a white man with type 2 diabetes who had been diagnosed fewer than 15 yearsearlier, was treated with oral medication or dietalone, and had no complications or comorbidities. We found annualized medical costs to be 10% to 50% higher for women and for patients whose diabetes had been diagnosed 15 or moreyears earlier, who used tobacco, who were being treated with insulin, or who had several other complications. Coronary heart disease, congestive heart failure, hemiplegia, and amputation were each associated with 70% to 150% higher costs. Costs were approximately 300% higher for end-stage renal disease treated with dialysis and approximately 500% higher for end-stage renal disease with kidney transplantation. Conclusions: Most medical costs incurred by patients with type 2 diabetes are related to complications and comorbidities. Our cost estimatescan help when determining the most cost-effectiveinterventions to prevent complications and comorbidities.
The American journal of managed care 05/2013; 19(5):421-30. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: We report the 10-year effectiveness and within-trial cost-effectiveness of the Diabetes Prevention Program (DPP) and its Outcomes Study (DPPOS) interventions among participants who were adherent to the interventions. Study Design: DPP was a 3-year randomized clinical trial followed by 7 years of open-label modified intervention follow-up. Methods: Data on resource utilization, cost, and quality of life were collected prospectively. Economic analyses were performed from health system and societal perspectives. Lifestyle adherence was defined as achieving and maintaining a 5% reduction in initial body weight, and metformin adherence as taking metformin at 80% of study visits. Results: The relative risk reduction was 49.4% among adherent lifestyle participants and 20.8% among adherent metformin participants compared with placebo. Over 10 years, the cumulative, undiscounted, per capita direct medical costs of the interventions, as implemented during the DPP, were greater for adherent lifestyle participants ($4810) than adherent metformin participants ($2934) or placebo ($768). Over 10 years, the cumulative, per capita non-interventionrelated direct medical costs were $4250 greater for placebo participants compared with adherent lifestyle participants and $3251 greater compared with adherent metformin participants. The cumulative quality-adjusted life-years (QALYs) accrued over 10 years were greater for lifestyle (6.80) than metformin (6.74) or placebo (6.67). Without discounting, from a modified societal perspective (excluding participant time) and a full societal perspective (including participant time), lifestyle cost < $5000 per QALY-gained and metformin was cost saving compared with placebo. Conclusions: Over 10 years, lifestyle intervention and metformin were cost-effective or cost saving compared with placebo. These analyses confirm that lifestyle and metformin represent a good value for money.
The American journal of managed care 03/2013; 19(3):194-202. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
To estimate the health utility scores associated with type 2 diabetes, its treatments, complications, and comorbidities.
RESEARCH DESIGN AND METHODS
We analyzed health-related quality-of-life data, collected at baseline during Translating Research Into Action for Diabetes, a multicenter, prospective, observational study of diabetes care in managed care, for 7,327 individuals with type 2 diabetes. We measured quality-of-life using the EuroQol (EQ)-5D, a standardized instrument for which 1.00 indicates perfect health. We used multivariable regression to estimate the independent impact of demographic characteristics, diabetes treatments, complications, and comorbidities on health-related quality-of-life.
The mean EQ-5D–derived health utility score for those individuals with diabetes was 0.80. The modeled utility score for a nonobese, non–insulin-treated, non-Asian, non-Hispanic man with type 2 diabetes, with an annual household income of more than $40,000, and with no diabetes complications, risk factors for cardiovascular disease, or comorbidities, was 0.92. Being a woman, being obese, smoking, and having a lower household income were associated with lower utility scores. Arranging complications from least to most severe according to the reduction in health utility scores resulted in the following order: peripheral vascular disease, other heart diseases, transient ischemic attack, cerebral vascular accident, nonpainful diabetic neuropathy, congestive heart failure, dialysis, hemiplegia, painful neuropathy, and amputation.
Major diabetes complications and comorbidities are associated with decreased health-related quality-of-life. Utility estimates from our study can be used to assess the impact of diabetes on quality-of-life and conduct cost-utility analyses.
Diabetes care 07/2012; 35(11):2250-6. DOI:10.2337/dc11-2478 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure.
We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment.
The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used.
Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology.).
New England Journal of Medicine 06/2012; 366(26):2483-91. DOI:10.1056/NEJMoa1110238 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite recent advances in critical care and ventilator management, acute lung injury and acute respiratory distress syndrome continue to cause significant morbidity and mortality. Granulocyte-macrophage colony stimulating factor may be beneficial for patients with acute respiratory distress syndrome.
To determine whether intravenous infusion of granulocyte-macrophage colony stimulating factor would improve clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome.
A randomized, double-blind, placebo-controlled clinical trial of human recombinant granulocyte-macrophage colony stimulating factor vs. placebo. The primary outcome was days alive and breathing without mechanical ventilatory support within the first 28 days after randomization. Secondary outcomes included mortality and organ failure-free days.
Medical and surgical intensive care units at three academic medical centers.
One hundred thirty individuals with acute lung injury of at least 3 days duration were enrolled, out of a planned cohort of 200 subjects.
Patients were randomized to receive human recombinant granulocyte-macrophage colony stimulating factor (64 subjects, 250 μg/M) or placebo (66 subjects) by intravenous infusion daily for 14 days. Patients received mechanical ventilation using a lung-protective protocol.
There was no difference in ventilator-free days between groups (10.7 ± 10.3 days placebo vs. 10.8 ± 10.5 days granulocyte-macrophage colony stimulating factor, p = .82). Differences in 28-day mortality (23% in placebo vs. 17% in patients receiving granulocyte-macrophage colony stimulating factor (p = .31) and organ failure-free days (12.8 ± 11.3 days placebo vs. 15.7 ± 11.9 days granulocyte-macrophage colony stimulating factor, p = .16) were not statistically significant. There were similar numbers of serious adverse events in each group.
In a randomized phase II trial, granulocyte-macrophage colony stimulating factor treatment did not increase the number of ventilator-free days in patients with acute lung injury/acute respiratory distress syndrome. A larger trial would be required to determine whether treatment with granulocyte-macrophage colony stimulating factor might alter important clinical outcomes, such as mortality or multiorgan failure. (ClinicalTrials.gov number, NCT00201409 [ClinicalTrials.gov]).
Critical care medicine 09/2011; 40(1):90-7. DOI:10.1097/CCM.0b013e31822d7bf0 · 6.31 Impact Factor