OBJECTIVES: To provide updated and more detailed pooled intrauterine device expulsion rates and expulsion risk estimates among women with postpartum intrauterine device placement by timing of insertion, delivery type, and intrauterine device type to inform current intrauterine device insertion practices in the United States. DATA SOURCES: We searched PubMed, Cochrane Library, and ClinicalTrials.gov through June 2019. STUDY ELIGIBILITY CRITERIA: We included all studies, of any study design, that examined postpartum placement of Copper T380A (copper) or levonorgestrel-containing intrauterine devices that reported counts of expulsion. STUDY APPRAISAL AND SYNTHESIS METHODS: We evaluated intrauterine device expulsion among women receiving postpartum intrauterine devices in the "immediate" (within 10 minutes), "early inpatient" (>10 minutes to <72 hours), "early outpatient" (72 hours to <4 weeks), and interval (>= 4 weeks) time periods after delivery. We assessed study quality using the US Preventive Services Task Force evidence grading system. We calculated pooled absolute rates of partial and complete intrauterine device expulsion separately and estimated adjusted relative risks by the timing of postpartum placement, delivery type, and intrauterine device type using log-binomial multivariable regression. RESULTS: We identified 48 level I to II-3 studies of poor to good quality that reported a total of 7661 intrauterine device placements. Complete intrauterine device expulsion rates varied by timing of placement as follows: 10.2% (range, 0.0-26.7) for immediate; 13.2% (3.5-46.7) for early inpatient; 0% for early outpatient; and 1.8% (0.0-4.8) for interval placements. Complete intrauterine device expulsion rates also varied by delivery type: 14.8% (range, 4.8-43.1) for vaginal and 3.8% (0.0-21.1) for cesarean deliveries. Among immediate postpartum vaginal placements, the expulsion rate for levonorgetrel intrauterine devices was 27.4% (range, 18.8-45.2) and 12.4%(4.8-43.1) for copper intrauterine devices. Compared with interval placement, immediate and early postpartum placements (inpatient and outpatient combined) were associated with greater risk of complete expulsion (adjusted risk ratio, 8.33; 95% confidence interval, 4.32-16.08, and adjusted risk ratio, 5.27; 95% confidence interval, 2.56-10.85, respectively). Among immediate postpartum placements, risk of expulsion was greater for placement after vaginal compared with cesarean deliveries (adjusted risk ratio, 4.57; 95% confidence interval, 3.49-5.99). Among immediate placements at the time of vaginal delivery, levonorgestrel intrauterine devices were associated with a greater risk of expulsion compared with copper intrauterine devices (adjusted risk ratio, 1.90; 95% confidence interval, 1.36-2.65). CONCLUSION: Although intrauterine device expulsion rates vary by timing of placement, type, and mode of delivery, intrauterine device insertion can take place at any time. Understanding the risk of intrauterine device expulsion at each time period will enable women to make an informed choice about when to initiate use of an intrauterine device in the postpartum period based on their own goals and preferences.

Objectives To provide updated and more detailed pooled intrauterine device expulsion rates and expulsion risk estimates among women with postpartum intrauterine device placement by timing of insertion, delivery type, and intrauterine device type to inform current intrauterine device insertion practices in the United States. Data Sources We searched PubMed, Cochrane Library, and ClinicalTrials.gov through June 2019. Study Eligibility Criteria We included all studies, of any study design, that examined postpartum placement of Copper T380A (copper) or levonorgestrel-containing intrauterine devices that reported counts of expulsion. Study Appraisal and Synthesis Methods We evaluated intrauterine device expulsion among women receiving postpartum intrauterine devices in the "immediate" (within 10 minutes), "early inpatient" (>10 minutes to <72 hours), "early outpatient" (72 hours to <4 weeks), and interval (≥4 weeks) time periods after delivery. We assessed study quality using the US Preventive Services Task Force evidence grading system. We calculated pooled absolute rates of partial and complete intrauterine device expulsion separately and estimated adjusted relative risks by the timing of postpartum placement, delivery type, and intrauterine device type using log-binomial multivariable regression. Results We identified 48 level I to II-3 studies of poor to good quality that reported a total of 7661 intrauterine device placements. Complete intrauterine device expulsion rates varied by timing of placement as follows: 10.2% (range, 0.0−26.7) for immediate; 13.2% (3.5−46.7) for early inpatient; 0% for early outpatient; and 1.8% (0.0−4.8) for interval placements. Complete intrauterine device expulsion rates also varied by delivery type: 14.8% (range, 4.8−43.1) for vaginal and 3.8% (0.0−21.1) for cesarean deliveries. Among immediate postpartum vaginal placements, the expulsion rate for levonorgetrel intrauterine devices was 27.4% (range, 18.8−45.2) and 12.4% (4.8−43.1) for copper intrauterine devices. Compared with interval placement, immediate and early postpartum placements (inpatient and outpatient combined) were associated with greater risk of complete expulsion (adjusted risk ratio, 8.33; 95% confidence interval, 4.32−16.08, and adjusted risk ratio, 5.27; 95% confidence interval, 2.56–10.85, respectively). Among immediate postpartum placements, risk of expulsion was greater for placement after vaginal compared with cesarean deliveries (adjusted risk ratio, 4.57; 95% confidence interval, 3.49−5.99). Among immediate placements at the time of vaginal delivery, levonorgestrel intrauterine devices were associated with a greater risk of expulsion compared with copper intrauterine devices (adjusted risk ratio, 1.90; 95% confidence interval, 1.36−2.65). Conclusion Although intrauterine device expulsion rates vary by timing of placement, type, and mode of delivery, intrauterine device insertion can take place at any time. Understanding the risk of intrauterine device expulsion at each time period will enable women to make an informed choice about when to initiate use of an intrauterine device in the postpartum period based on their own goals and preferences.

OBJECTIVE:To estimate expulsion rates among women with postpartum intrauterine device (IUD) placement by timing of insertion, IUD type, and delivery method.DATA SOURCES:We searched PubMed, Cochrane Library, and ClinicalTrials.gov from 1974 to May 2018.METHODS OF STUDY SELECTION:We searched databases for any published studies that examined postpartum placement of a copper IUD or levonorgestrel intrauterine system and reported counts of expulsions. We assessed study quality using the U.S. Preventive Services Task Force evidence grading system. We calculated pooled absolute rates of IUD expulsion and estimated adjusted relative risks (RRs) for timing of postpartum placement, delivery method, and IUD type using log-binomial multivariable regression model.TABULATION, INTEGRATION, AND RESULTS:We identified 48 level I to II-3 studies of poor to good quality. Pooled rates of expulsion varied by timing of IUD placement, ranging from 1.9% with interval placements (4 weeks postpartum or greater), 10.0% for immediate placements (10 minutes or less after placental delivery), and 29.7% for early placements (greater than 10 minutes to less than 4 weeks postpartum). Immediate and early postpartum placements were associated with increased risk of expulsion compared with interval placement (adjusted RR 7.63, 95% CI 4.31-13.51; adjusted RR 6.17, 95% CI 3.19-11.93, respectively). Postpartum placement less than 4 weeks after vaginal delivery was associated with an increased risk of expulsion compared with cesarean delivery (adjusted RR 5.19, 95% CI 3.85-6.99). Analysis of expulsion rates at less than 4 weeks postpartum also indicated that the levonorgestrel intrauterine system was associated with a higher risk of expulsion (adjusted RR 1.91, 95% CI 1.50-2.43) compared with CuT380A.CONCLUSION:Postpartum IUD expulsion rates vary by timing of placement, delivery method, and IUD type. These results can aid in counseling women to make an informed choice about when to initiate their IUD and to help institutions implement postpartum contraception programs.

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OBJECTIVE: To estimate the absolute and relative risk of venous thromboembolism (VTE) among women who initiate depot medroxyprogesterone acetate (DMPA) immediately postpartum compared with those who do not initiate hormonal contraception. METHODS: The IBM MarketScan Commercial Claims and Encounters databases were used to identify delivery hospitalizations among women aged 15-44 years during 2005 through 2014. Diagnosis, procedure, and drug codes were used to identify contraception, VTE, and potential confounding chronic or pregnancy-related conditions. Women who initiated DMPA during days 0 through 7 postpartum were compared with women who did not initiate hormonal contraception during days 0 through 7 postpartum. Women were followed from date of delivery through 12 weeks postpartum for the occurrence of VTE, with censoring at hormonal contraception initiation or prescription, hysterectomy, sterilization, or inpatient death. The incidence rate of VTE and 95% CIs were calculated within each group and the incidence rate ratio was calculated comparing the two groups. RESULTS: The unadjusted VTE incidence rate through 12 weeks postpartum was 0.42/10,000 women-days in the immediate postpartum DMPA group (34 events among 11,159 women contributing 805,999 days of follow-up) and 0.15/10,000 women-days in the control group (3,107 events among 3,102,011 women contributing 206,180,811 days of follow-up). The incidence rate ratio for VTE was 2.87 (95% CI 2.05-4.03) among women in the immediate postpartum DMPA group compared with women in the control group, adjusting for age alone. After adjusting for age and pregnancy-related and chronic conditions, the adjusted incidence rate ratio for VTE was 1.94 (95% CI 1.38-2.72) among women in the immediate postpartum DMPA group compared with women in the control group. CONCLUSION: Initiation of DMPA immediately postpartum is associated with a low incidence but an increased relative risk of VTE compared with nonuse of hormonal contraception.

OBJECTIVE: To estimate expulsion rates among women with postpartum intrauterine device (IUD) placement by timing of insertion, IUD type, and delivery method. DATA SOURCES: We searched PubMed, Cochrane Library, and ClinicalTrials.gov from 1974 to May 2018. METHODS OF STUDY SELECTION: We searched databases for any published studies that examined postpartum placement of a copper IUD or levonorgestrel intrauterine system and reported counts of expulsions. We assessed study quality using the U.S. Preventive Services Task Force evidence grading system. We calculated pooled absolute rates of IUD expulsion and estimated adjusted relative risks (RRs) for timing of postpartum placement, delivery method, and IUD type using log-binomial multivariable regression model. TABULATION, INTEGRATION, AND RESULTS: We identified 48 level I to II-3 studies of poor to good quality. Pooled rates of expulsion varied by timing of IUD placement, ranging from 1.9% with interval placements (4 weeks postpartum or greater), 10.0% for immediate placements (10 minutes or less after placental delivery), and 29.7% for early placements (greater than 10 minutes to less than 4 weeks postpartum). Immediate and early postpartum placements were associated with increased risk of expulsion compared with interval placement (adjusted RR 7.63, 95% CI 4.31–13.51; adjusted RR 6.17, 95% CI 3.19–11.93, respectively). Postpartum placement less than 4 weeks after vaginal delivery was associated with an increased risk of expulsion compared with cesarean delivery (adjusted RR 5.19, 95% CI 3.85–6.99). Analysis of expulsion rates at less than 4 weeks postpartum also indicated that the levonorgestrel intrauterine system was associated with a higher risk of expulsion (adjusted RR 1.91, 95% CI 1.50–2.43) compared with CuT380A. CONCLUSION: Postpartum IUD expulsion rates vary by timing of placement, delivery method, and IUD type. These results can aid in counseling women to make an informed choice about when to initiate their IUD and to help institutions implement postpartum contraception programs.

ObjectiveTo examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness.Study designA prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350cells/mm3, ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method.ResultsDuring a total of 5233months follow-up among participants not using ART with enrollment CD4 ≥350cells/mm3 (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56–1.48] nor DMPA (aHR 1.28, 95% CI 0.71–2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods.ConclusionHormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.ImplicationsHormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.

OBJECTIVE:To assess the characteristics of IVF cycles for which preimplantation genetic diagnosis (PGD) was used and to evaluate indications for PGD and treatment outcomes associated with this procedure as compared with cycles without PGD with the data from the U.S. National ART Surveillance System. DESIGN:Retrospective cohort study. SETTING:None. PATIENT(S):Fresh autologous cycles that involved transfer of at least one embryo at blastocyst when available. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):PGD indications and age-specific reproductive outcomes. RESULT(S):There were a total of 97,069 non-PGD cycles and 9,833 PGD cycles: 55.6% were performed for aneuploidy screening (PGD Aneuploidy), 29.1% for other reasons (PGD Other), and 15.3% for genetic testing (PGD Genetic). In comparison to non-PGD cycles, PGD Aneuploidy cycles showed a decreased odds of miscarriage among women 35-37 years (adjusted odds ratio [aOR] 0.62; 95% CI, 0.45-0.87) and women >37 years (aOR 0.55; 95% CI, 0.43-0.70); and an increased odds of clinical pregnancy (aOR 1.18; 95% CI, 1.05-1.34), live-birth delivery (aOR 1.43; 95% CI, 1.26-1.62), and multiple-birth delivery (aOR 1.98; 95% CI, 1.52-2.57) among women >37 years. CONCLUSION(S):Aneuploidy screening was the most common indication for PGD. Use of PGD was not observed to be associated with an increased odds of clinical pregnancy or live birth for women <35 years. PGD for aneuploidy was associated with a decreased odds of miscarriage for women >35 years, but an increased odds of a live-birth and a multiple live-birth delivery among women >37 years.

BackgroundBleeding irregularities, such as intermenstrual spotting or heavy or prolonged menstrual bleeding, are common among copper-containing intrauterine device (Cu-IUD) users and are one of the leading reasons for method discontinuation. This review evaluates the evidence for effective therapeutic and preventive treatments for bleeding irregularities during Cu-IUD use.Study DesignWe searched the PubMed database for peer-reviewed articles that were published in any language from inception of the database through March 2012 and were relevant to treatments for irregular bleeding during Cu-IUD use. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence.ResultsFrom 1470 articles, we identified 17 articles that met our inclusion criteria. Evidence from two studies of poor quality demonstrated that antifibrinolytic agents or nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for intermenstrual bleeding or spotting among a small number of Cu-IUD users with mixed results. Evidence from 10 studies of fair to poor quality suggested that some NSAIDs may significantly reduce menstrual blood loss or bleeding duration among Cu-IUD users with heavy or prolonged menstrual bleeding. Antifibrinolytic drugs or antidiuretics may also help reduce blood loss. High-dose aspirin was shown to increase blood loss among those with baseline menorrhagia. Evidence from five studies of fair to poor quality suggested that bleeding irregularities among new Cu-IUD users may be prevented with NSAIDs, although one large study of good quality suggested that prophylactic treatment with ibuprofen does not affect continuation of Cu-IUD use. Evidence from two studies of fair to poor quality suggested that antifibrinolytic agents might be helpful in preventing heavy or prolonged menstrual bleeding among new Cu-IUD users.ConclusionsLimited evidence suggests that NSAIDs may be effective treatments for bleeding irregularities associated with Cu-IUD use; antifibrinolytic agents and antidiuretics have also been studied as possible treatments in a small number of subjects, but their safety has not been well documented. NSAIDs and antifibrinolytics may also prevent bleeding irregularities among new CU-IUD users. Preventive NSAID use, however, does not impact Cu-IUD continuation.

Background: While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required.Study Design: We used data from a multicenter, population-based, case control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC.Results: Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk.Conclusions: These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk. Published by Elsevier Inc.

OBJECTIVE: The number of assisted reproductive technology (ART) cycles undertaken by US non-residents (NRs) at US ART clinics increased 79%, 980 in 2004 to 1758 in 2007. Little is known about NRs who seek ART treatment in the US. We examined differences in patient characteristics and treatment outcomes between NR and US ART users with poor prognoses. DESIGN: Retrospective cohort study using CDCs National Assisted Reproductive Technology Surveillance System (NASS). MATERIALS AND METHODS: We restricted analyses to North American, Asian, and European patients with poor prognoses, i.e. > three ART cycles during 2004-2007. NRs from Europe, Asia, Canada, and Mexico accounted for 88% of patients with poor prognoses. Patient characteristics and treatment procedures were compared across regions using chi-square tests. Logistic regression was used to assess live birth delivery rates across regions controlling for age, prior births, pregnancy loss, and type of ART procedure. RESULTS: We selected 807 NR and 44,214 US cycles with > three prior ART attempts. NR cycles were distributed as follows: Europe (36%), Asia (23%), Canada (15%), and Mexico (13%). Compared with US patients, NRs were more likely to be > 40 years (56% vs. 34%, except Mexico), have diagnoses of uterine factor (11% vs. 6.7%), and use donor eggs (56% vs. 26%). NRs were less likely to have a previous birth (34% vs. 49%) or a prior pregnancy loss (42% vs. 51%). All differences were significant at p<0.01. Live birth rates for fresh donor cycles were 42 % for Asia (adjusted odds ratio (AOR) 0.92; 95% confidence interval (CI): 0.60 – 1.40); 59% for Canada (AOR:1.73, 95%CI:0.87-3.44); 46% for Europe(AOR:1.04, 95%CI:0.69-1.57); 30% for Mexico (AOR:0.52, 95%CI:0.20-1.35) compared to 46% for US residents. CONCLUSIONS: Compared to US patients, NRs have significantly different patient characteristics indicative of poorer prognoses but did not have significantly different live birth rates.

OBJECTIVE: To ascertain whether favorable embryo donation (ED) outcome rates reported in small surveys are confirmed by national data collected by the Centers for Disease Control and Prevention (CDC). DESIGN: Analysis of data from the National ART Surveillance System (NASS) maintained by the CDC, and comparison with data from two prior surveys by National Embryo Donation Center (NEDC). MATERIALS AND METHODS: Clinics in the USA must report clinical information on ART procedures on line to CDC, including embryo source, whether pregnancy is achieved, and its outcome. Pregnancy, live delivery, and implantation rates were obtained for ED cycles initiated in 2004-06. These results were compared to rates from a survey of 7 programs previously published by NEDC, and to an additional informal survey of 24 ART centers. Clinic-specific results at 4 ART centers reporting both to CDC and NEDC were also compared. RESULTS: 2,224 ED cycles were reported to CDC with a pregnancy rate of 41.4%, a delivery rate of 33.9%, and an implantation rate of 19.6%.These are similar to the rates previously published by NEDC (44.7%, 35.5%, and 19.9%) and to the informal survey (pregnancy 42.1%, delivery 38.2%). During 2004-2006, the 4 clinics reported 260 ED cycles to NEDC and 268 cycles to CDC. There was 97% agreement between the two systems on the number of cycles, and 96% agreement on the number of live-birth deliveries. Only two significant discrepancies were found: one clinic failed to report to NEDC (but did report to CDC) nine transfers of low-quality embryos done gratis; a second clinic failed to report to CDC ten pregnancies that had miscarried, although they reported the cycles to both systems.Table 1Embryo Donation Outcomes, USA, 2004-06200420052006Donated Frozen Embryo Transfer Cycles666774784Number of Embryos Thawed277331843174Number of Embryos Transferred187020402049Pregnancies271319331Pregnancy Rate Per Embryo Transfer40.741.242.2Pregnancy losses (sacs lost)46 (51)59 (65)58 (64)Implantation Rate18.620.220.5Total deliveries (with at least one live-born)222259272Delivery Rate Per Esfer33.333.534.7Number of clinics167160170 Open table in a new tab CONCLUSIONS: National data from the CDC confirm the favorable outcomes previously reported by the NEDC. The in-depth information gathered by the NEDC provides evidence that the NASS data are of good quality.

OBJECTIVE: Preimplantation Genetic Diagnosis (PGD) is used to test human embryos during in vitro fertilization (IVF) to detect genetic defects. Studies suggest that PGD could be used to select "healthier" embryos and improve IVF outcomes, especially among women with advanced age, previous IVF failure, or recurrent pregnancy loss. The purpose of this study was to compare the success rates and selected adverse outcomes of IVF in PGD and non-PGD cycles.DESIGN: Retrospective study of data from CDC's National Assisted Reproductive Technology (ART) surveillance system (NASS).MATERIALS AND METHODS: Data analysis was limited to fresh IVF cycles that progressed to retrieval. Outcomes included termination of the cycle before transfer, clinical pregnancy, spontaneous pregnancy loss, live-birth delivery, pre-term delivery and low birth weight. Logistic regression models compared PGD and non-PGD cycles adjusting for potential confounders.RESULTS: PGD was used in 13,961(5%) of 254,872 IVF cycles that progressed to retrieval. PGD cycles were more likely than non-PGD cycles to be performed in women with advanced age, previous IVF failure, and recurrent pregnancy loss. The odds of terminating the cycle before transfer were 3 to 9 times higher in PGD than in non-PGD cycles, depending on age, suggesting that PGD successfully prevented the transfer of embryos with genetic defects. Among women <35 years, PGD cycles were less likely than non-PGD cycles to result in a clinical pregnancy (odds ratio (OR):0.85, 95% confidence interval (95%CI):0.79-0.91) or live birth (OR:0.89, 95%CI:0.82-0.95). By contrast, among women >40 years, PGD cycles were more likely than non-PGD cycles to result in a clinical pregnancy (OR:1.48, 95%CI:1.28-1.71) or live birth (OR:1.59, 95%CI:1.35-1.87). PGD cycles were less likely than non-PGD cycles to result in a pregnancy loss regardless of the women's age (OR:0.75, 95% CI:0.66-0.84). There was no association between PGD and the risk of pre-term delivery. Low birth weight was more common among infants born to PGD cycles than infants born to non-PGD cycles for women >38 years.CONCLUSIONS: PGD cycles were more likely than non-PGD cycles to be terminated before transfer. Among cycles progressing to transfer, there is an age-dependent, crossover association between PGD and clinical pregnancy or live birth rates. PGD cycles have lower rates of pregnancy loss. Pre-term delivery is not associated with the use of PGD, while low birth-weight infants are more common in PGD cycles, especially among older women. OBJECTIVE: Preimplantation Genetic Diagnosis (PGD) is used to test human embryos during in vitro fertilization (IVF) to detect genetic defects. Studies suggest that PGD could be used to select "healthier" embryos and improve IVF outcomes, especially among women with advanced age, previous IVF failure, or recurrent pregnancy loss. The purpose of this study was to compare the success rates and selected adverse outcomes of IVF in PGD and non-PGD cycles. DESIGN: Retrospective study of data from CDC's National Assisted Reproductive Technology (ART) surveillance system (NASS). MATERIALS AND METHODS: Data analysis was limited to fresh IVF cycles that progressed to retrieval. Outcomes included termination of the cycle before transfer, clinical pregnancy, spontaneous pregnancy loss, live-birth delivery, pre-term delivery and low birth weight. Logistic regression models compared PGD and non-PGD cycles adjusting for potential confounders. RESULTS: PGD was used in 13,961(5%) of 254,872 IVF cycles that progressed to retrieval. PGD cycles were more likely than non-PGD cycles to be performed in women with advanced age, previous IVF failure, and recurrent pregnancy loss. The odds of terminating the cycle before transfer were 3 to 9 times higher in PGD than in non-PGD cycles, depending on age, suggesting that PGD successfully prevented the transfer of embryos with genetic defects. Among women <35 years, PGD cycles were less likely than non-PGD cycles to result in a clinical pregnancy (odds ratio (OR):0.85, 95% confidence interval (95%CI):0.79-0.91) or live birth (OR:0.89, 95%CI:0.82-0.95). By contrast, among women >40 years, PGD cycles were more likely than non-PGD cycles to result in a clinical pregnancy (OR:1.48, 95%CI:1.28-1.71) or live birth (OR:1.59, 95%CI:1.35-1.87). PGD cycles were less likely than non-PGD cycles to result in a pregnancy loss regardless of the women's age (OR:0.75, 95% CI:0.66-0.84). There was no association between PGD and the risk of pre-term delivery. Low birth weight was more common among infants born to PGD cycles than infants born to non-PGD cycles for women >38 years. CONCLUSIONS: PGD cycles were more likely than non-PGD cycles to be terminated before transfer. Among cycles progressing to transfer, there is an age-dependent, crossover association between PGD and clinical pregnancy or live birth rates. PGD cycles have lower rates of pregnancy loss. Pre-term delivery is not associated with the use of PGD, while low birth-weight infants are more common in PGD cycles, especially among older women.

OBJECTIVE: Use of intracytoplasmic sperm injection (ICSI) for IVF has increased in the U.S. since the mid 1990's. Initially limited to the treatment of male infertility, ICSI is now also used to treat couples with female infertility only. We examine the impact of this expanded use of ICSI on ART success rates. DESIGN: Retrospective cohort study using data from CDC's National Assisted Reproductive Technology (ART) surveillance system (NASS). MATERIALS AND METHODS: We analyzed data on IVF's performed in 2004-2006 in U.S. Cumulative logit models were used to compare the outcomes of ICSI and non-ICSI cycles for couples with no indication of male infertility. The outcome was measured by whether or not the cycle was terminated at different stages. Indicators of poor female prognosis were adjusted for the analysis, including advanced age, previous pre-term delivery, pregnancy loss, prior IVF failure, and few embryos available for transfer. RESULTS: Approximately 60% of 323,231 fresh IVF cycles (from donors and non-donors) performed in 2004-2006 used ICSI. Among those, 47% was to treat cases of male-factor infertility, 22% with no male-factor but poor female prognosis, and 31% with neither. Among couples with no male-factor infertility, after adjusting for prognostic factors and types of IVF procedures, cycles using ICSI were less likely to fail prior to transfer (odds ratio (OR):0.91, 95% confidence interval (95%CI):0.88-0.94); but more likely to result in no implantation (OR: 1.14, 95%CI: 1.12-1.16) and in pregnancy loss (OR: 1.15, 95%CI: 1.11-1.19). The odds of a live birth delivery were lower with ICSI (OR: 0.84, 95%CI: 0.83-0.86) than non-ICSI. Additional analyses were limited to women with previous IVF without ICSI, whose cycles were terminated prior to transfer. Success rates for this group were not higher in the next cycle with ICSI than without (data not shown). Couples with no male-factor infertility were more likely to use ICSI if treatment costs were covered by their insurance program (OR: 1.46, 95%CI: 1.42-1.49). CONCLUSIONS: Treatment of couples with solely female factor infertility accounted for only a portion of increased use of ICSI-IVF cycles in recent years. The data suggest no benefit for use of ICSI for this group of women. Limitations of the NASS data include the inaccuracy of diagnoses reported, and lack of detailed information on male-factor diagnosis. Despite these limitations, it seems unlikely that expanded use of ICSI, as currently practiced in the U.S., has improved ART success rates.

OBJECTIVE: Nonrandomized studies suggest that IVF cycles in which embryos are transferred at the blastocyst stage (day-5 transfers) have higher success rates than day-3 transfers, whereas randomized trials fail to show an advantage. Nonrandomized studies may overestimate the advantage of day-5 transfers by computing success rates only for procedures that progress to transfer, thus ignoring failures due to short embryo survival. This study expand previous analyses to include procedures that failed before a transfer.DESIGN: Retrospective cohort study using data from CDC's National Assisted Reproductive Technology (ART) surveillance system (NASS).MATERIALS AND METHODS: We analyzed data on IVF's of fresh non-donors from ART programs that perform most transfers either on day 5 or on day 3 in the U.S. Outcome was measured by whether or not the cycle was terminated at different stages of the procedure. Cumulative logit models with adjustment for patient and clinic factors were used to compare the outcomes of day5 and day3 programs.RESULTS: A total of 9,273 procedures from 35 clinics were identified in the study as the day-3 group; and 9,007 IVF cycles from 19 clinics as the day-5 group. Compared to the day3 group, procedures in the day5 group were less likely to be cancelled prior before retrieval(odds ratio (OR): 0.84, 95% confidence interval(95%CI): 0.77-0.91); but were more likely to be terminated before transfer, particularly for women over age 40 (OR: 1.85, 95% CI: 1.53-2.25). The odds of implantation failure were generally lower in day-5 programs than in day-3 programs (OR:0.92, 95%CI:0.87-0.98), as were the odds of pregnancy loss (OR:0.91, 95%CI:0.85-0.97), but not among women over 40 years of age (implantation failure, OR:1.48, 95%CI:1.11-1.97; pregnancy loss, OR:1.38, 95%CI:0.97-1.97). Live birth rates were slightly higher for the day-5 group (OR: 1.10, 95% CI: 1.03-1.18), but not among women over 40 years (OR:0.72, 95%CI:0.51-1.03). As expected, restricting the analysis to procedures that progressed to transfer exaggerated the advantage of day-5 transfer (data not shown).CONCLUSIONS: In this analysis, ART programs that offer mostly day-5 transfer yielded slightly higher odds of successful outcomes compared to programs that offered mostly day-3 transfer, after controlling for patient characteristics. The advantage seemed to be limited to younger women. This analysis confirms that comparisons limited to cycles that progress to transfer tend to overestimate the advantage of extended embryo culture. OBJECTIVE: Nonrandomized studies suggest that IVF cycles in which embryos are transferred at the blastocyst stage (day-5 transfers) have higher success rates than day-3 transfers, whereas randomized trials fail to show an advantage. Nonrandomized studies may overestimate the advantage of day-5 transfers by computing success rates only for procedures that progress to transfer, thus ignoring failures due to short embryo survival. This study expand previous analyses to include procedures that failed before a transfer. DESIGN: Retrospective cohort study using data from CDC's National Assisted Reproductive Technology (ART) surveillance system (NASS). MATERIALS AND METHODS: We analyzed data on IVF's of fresh non-donors from ART programs that perform most transfers either on day 5 or on day 3 in the U.S. Outcome was measured by whether or not the cycle was terminated at different stages of the procedure. Cumulative logit models with adjustment for patient and clinic factors were used to compare the outcomes of day5 and day3 programs. RESULTS: A total of 9,273 procedures from 35 clinics were identified in the study as the day-3 group; and 9,007 IVF cycles from 19 clinics as the day-5 group. Compared to the day3 group, procedures in the day5 group were less likely to be cancelled prior before retrieval(odds ratio (OR): 0.84, 95% confidence interval(95%CI): 0.77-0.91); but were more likely to be terminated before transfer, particularly for women over age 40 (OR: 1.85, 95% CI: 1.53-2.25). The odds of implantation failure were generally lower in day-5 programs than in day-3 programs (OR:0.92, 95%CI:0.87-0.98), as were the odds of pregnancy loss (OR:0.91, 95%CI:0.85-0.97), but not among women over 40 years of age (implantation failure, OR:1.48, 95%CI:1.11-1.97; pregnancy loss, OR:1.38, 95%CI:0.97-1.97). Live birth rates were slightly higher for the day-5 group (OR: 1.10, 95% CI: 1.03-1.18), but not among women over 40 years (OR:0.72, 95%CI:0.51-1.03). As expected, restricting the analysis to procedures that progressed to transfer exaggerated the advantage of day-5 transfer (data not shown). CONCLUSIONS: In this analysis, ART programs that offer mostly day-5 transfer yielded slightly higher odds of successful outcomes compared to programs that offered mostly day-3 transfer, after controlling for patient characteristics. The advantage seemed to be limited to younger women. This analysis confirms that comparisons limited to cycles that progress to transfer tend to overestimate the advantage of extended embryo culture.

OBJECTIVE: To estimate the number of multiple pregnancies and related adverse pregnancy outcomes that could be prevented by promoting elective single embryo transfer (e-SET) among women who meet criteria set by the American Society for Reproductive Medicine (ASRM), compare with the expected loss in ART success rates, and assess potential savings to society.DESIGN: Retrospective analysis of data on Assisted Reproductive Technology (ART) procedures reported to the National ART Surveillance System (NASS) maintained by the Centers for Disease Control and Prevention (CDC).MATERIALS AND METHODS: We evaluated 159,269 fresh, non-donor ART cycles reported to the NASS during 2005-2006, which progressed to embryo transfer. Of these, 23,010 cycles (14.5%) met a definition of e-SET eligibility (Age <35 years, no prior ART, extra embryos designated for cryopreservation) consistent with the 2004 ASRM guidelines. We estimated the numbers of ART failures, singleton and multiple deliveries among that would have occurred if e-SET had been used in all eligible cases, assuming that the outcomes would be a function of the per-embryo live birth rate within each embryo transfer category. We developed estimates of the long-term costs associated with multiple deliveries to assess potential savings.RESULTS: E-SET was performed in only 6.4% of the eligible ART cycles, two embryos were transferred in 78.4%, and ≥3 embryos were transferred in 15.2%. In this group of cycles, the live birth rate per transfer was 34.9%, and 31.3% of the deliveries were multiple. If e-SET had been performed in all eligible cycles, the live birth rate would have been 32.4%, and the multiple delivery rate would have been 24.6%. Thus, universal adoption of e-SET would have resulted in 3,849 additional cycle failures, but also in 4,697 fewer multiple deliveries. Whereas universal adoption of e-SET would have entailed additional charges to patients between $20 million and $60 million to achieve the same total success rate, prevention of the multiple deliveries and subsequent charges would have saved $491 million -$1.12 billion to society.CONCLUSIONS: A large number of multiple deliveries could be prevented by increasing adherence to e-SET, because eligible patients experience high multiple delivery rates even with the transfer of two embryos. The decrease in success rates associated with e-SET could be offset by offering subsequent thawed e-SET cycles. Societal savings would be large. OBJECTIVE: To estimate the number of multiple pregnancies and related adverse pregnancy outcomes that could be prevented by promoting elective single embryo transfer (e-SET) among women who meet criteria set by the American Society for Reproductive Medicine (ASRM), compare with the expected loss in ART success rates, and assess potential savings to society. DESIGN: Retrospective analysis of data on Assisted Reproductive Technology (ART) procedures reported to the National ART Surveillance System (NASS) maintained by the Centers for Disease Control and Prevention (CDC). MATERIALS AND METHODS: We evaluated 159,269 fresh, non-donor ART cycles reported to the NASS during 2005-2006, which progressed to embryo transfer. Of these, 23,010 cycles (14.5%) met a definition of e-SET eligibility (Age <35 years, no prior ART, extra embryos designated for cryopreservation) consistent with the 2004 ASRM guidelines. We estimated the numbers of ART failures, singleton and multiple deliveries among that would have occurred if e-SET had been used in all eligible cases, assuming that the outcomes would be a function of the per-embryo live birth rate within each embryo transfer category. We developed estimates of the long-term costs associated with multiple deliveries to assess potential savings. RESULTS: E-SET was performed in only 6.4% of the eligible ART cycles, two embryos were transferred in 78.4%, and ≥3 embryos were transferred in 15.2%. In this group of cycles, the live birth rate per transfer was 34.9%, and 31.3% of the deliveries were multiple. If e-SET had been performed in all eligible cycles, the live birth rate would have been 32.4%, and the multiple delivery rate would have been 24.6%. Thus, universal adoption of e-SET would have resulted in 3,849 additional cycle failures, but also in 4,697 fewer multiple deliveries. Whereas universal adoption of e-SET would have entailed additional charges to patients between $20 million and $60 million to achieve the same total success rate, prevention of the multiple deliveries and subsequent charges would have saved $491 million -$1.12 billion to society. CONCLUSIONS: A large number of multiple deliveries could be prevented by increasing adherence to e-SET, because eligible patients experience high multiple delivery rates even with the transfer of two embryos. The decrease in success rates associated with e-SET could be offset by offering subsequent thawed e-SET cycles. Societal savings would be large.

OBJECTIVE: In 2004, ASRM/SART recommended that women with good prognosis (age<35 using fresh non-donor eggs, no prior ART failure, and extra embryos for cryopreservation) consider single embryo transfer (SET). Although a general trend towards fewer embryos transferred following the guideline have resulted in fewer multiple deliveries, overall, multiple births still account for one third of IVF births in the U.S. This may be due to a slow adoption of the guideline, but may also be due to a restrictive definition of "good prognosis" cycles. The purpose of this study is to identify additional criteria of eligibility for SET. DESIGN: Retrospective cohort study using data from CDC's National ART surveillance system (NASS). MATERIALS AND METHODS: Based on NASS data (2005-2006), women with multiple live-birth deliveries from IVF and among whom, each embryo transferred had resulted in a successful implantation were selected for analysis of SET population profile. RESULTS: In 2005-2006, 23,010 IVF's were performed on women who met ASRM SET criteria but with a low SET adoption rate of 6%. Hypothetically, if the remaining 94% of the cycles had also adopted SET, 4,697 multiple birth deliveries could have been avoided. This, however, would only have translated in a decrease of multiple-birth rate of IVF from 31% to 26%. In contrast, if all women who had multiple-birth deliveries and did not experience embryo loss had adopted SET, multiple-birth rates would have dropped to 13% with no affect on overall live birth rates. Analysis of the predictors of 100% per-embryo success identified two other characteristics that may be considered for expanding SET eligibility: blastocyst transfer and first IVF cycles with donor eggs. By adoption of ASRM SET guideline with additions of these two characteristics (including cycles with embryo transfer loss), multiple-birth rate would have dropped to 18% with a minimal offset on the national average live birth rate (<2%) in 2005-2006. CONCLUSIONS: Current recommendation only covers a proportion of SET candidates resulting in limited reduction in multiple births from IVF. ART professional society needs to consider additional criteria for viable SET. With advanced screening techniques for "best" quality embryos for transfer, the number of IVF's where each embryo transferred results in a successful implantation will continue to grow. Patient and treatment profiles associated with these cycles can be further defined to develop a more comprehensive set of criteria for the selection of SET candidates.

PROBLEM/CONDITION:Assisted reproductive technology (ART) includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART procedures are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). This report presents the most recent national data and state-specific results.REPORTING PERIOD COVERED:2005.DESCRIPTION OF SYSTEM:In 1996, CDC initiated data collection regarding ART procedures performed in the United States, as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Beginning with 2004, CDC has contracted with a statistical survey research organization, Westat, Inc., to obtain data from ART medical centers in the United States. Westat, Inc., maintains CDC's web-based data collection system called the National ART Surveillance System (NASS).RESULTS:In 2005, a total of 134,260 ART procedures were reported to CDC. These procedures resulted in 38,910 live-birth deliveries and 52,041 infants. Nationwide, 73% of ART procedures used freshly fertilized embryos from the patient's eggs, 15% used thawed embryos from the patient's eggs, 8% used freshly fertilized embryos from donor eggs, and 4% used thawed embryos from donor eggs. Overall, 42% of ART transfer procedures resulted in a pregnancy, and 35% resulted in a live-birth delivery (delivery of one or more live-born infants). The highest live-birth rates were observed among ART procedures that used freshly fertilized embryos from donor eggs (52%). The highest numbers of ART procedures were performed among residents of California (18,655), New York (12,032), Illinois (9,449), New Jersey (9,325), and Massachusetts (8,571). These five states also reported the highest number of live-birth deliveries. Of 52,041 infants born through ART, 49% were born in multiple-birth deliveries. The multiple-birth risk was highest for women who underwent ART transfer procedures that used freshly fertilized embryos from either donor eggs (41%) or their own eggs (32%). Approximately 1% of U.S. infants born in 2005 were conceived through ART. Those infants accounted for 17% of multiple births nationwide. Approximately 9% of ART singletons, 57% of ART twins, and 95% of ART triplets or higher-order multiples were low birthweight. Similarly, 15% of ART singletons, 66% of ART twins, and 97% of ART triplets or higher-order multiples were born preterm.INTERPRETATION:Whether an ART procedure resulted in a pregnancy and live-birth delivery varied according to different patient and treatment factors. ART poses a major risk for multiple births that are associated with adverse maternal and infant outcomes (e.g., preterm delivery, low birthweight, and infant mortality). This risk varied according to the patient's age, the type of ART procedure performed, the number of embryos available for transfer to the uterus, the number actually transferred, and the day of transfer (day 3 or day 5).PUBLIC HEALTH ACTIONS:ART-related multiple births represent a sizable proportion of all multiple births nationwide and in selected states. To minimize the adverse maternal and child health effects that are associated with multiple pregnancies, ongoing efforts to limit the number of embryos transferred in each ART procedure should be continued and strengthened. Adverse maternal and infant outcomes (e.g., low birthweight and preterm delivery) associated with ART treatment choices should be explained fully when counseling patients who are considering ART.