Assisted Reproductive Technology Births Research Articles

The Risks of Birth Defects and Childhood Cancer With Conception by Assisted Reproductive Technology

ABSTRACT As the proportion of births conceived with assisted reproductive technology (ART) continues to increase, a growing body of literature continues to examine the risks involved such as the higher risk of birth defects. Recently, several studies have suggested that ART-conceived children may have a greater risk of childhood cancer. This population-based cohort study aimed to evaluate the risk of childhood cancer as a function of birth defect status and method of conception. Data were obtained from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, birth certificates (2004–2013), birth defect registries, and cancer registries in 4 states. The Society for Assisted Reproductive Technology Clinic Outcome Reporting System contains comprehensive information on ART procedures from 86% of all clinics and more than 92% of all ART cycles in the United States. Assisted reproductive technology cycles reported from January 2004 to December 2017 that resulted in live births were included in this study. For each ART-conceived delivery, the subsequent 10 deliveries were selected as the non-ART comparison group, and siblings of each ART birth were selected as the ART sibling group. The ART group was divided into 4 subgroups based on the combination of oocyte source (autologous or donor) and embryo state (fresh or thawed). A host of independent variables with established associations on birth defects, cancer, and/or ART were selected a priori for inclusion in statistical models. The total study population included 165,125 ART-conceived children, 31,524 non-ART siblings, 12,451 children born as a result of infertility treatment without ART (ovulation induction/intrauterine insemination [OI/IUI]), and 1,353,440 naturally conceived children. A total of 29,571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect. Compared with naturally conceived children, risks for defects were increased for all other groups for nonchromosomal (adjusted odds ratios [AORs] ranged from 1.20 to 1.24, except for donor-fresh), blastogenesis (AORs, 1.22–1.74), cardiovascular (AORs, 1.04–1.26), gastrointestinal (AORs, 1.28–2.01), musculoskeletal (AORs, 1.10–1.48), and genitourinary among male children (AORs, 1.15–1.40, except for donor-fresh). Orofacial defects were increased in the OI/IUI and autologous-fresh and autologous-thawed groups (AORs, 1.26–1.42). The risk of any cancer was increased among ART autologous-fresh and non-ART siblings (hazard ratios [HRs], 1.31 and 1.34, respectively). A total of 127 children had both birth defects and cancer, with 53 (42%) of these children having leukemia. A Cox proportional hazards regression model identified 2 components for the risk of cancer: method of conception and type and number of birth defects. The presence of chromosomal defects was strongly associated with cancer risk (HRs, 8.70 for all cancers and 21.90 for leukemia), and this was further increased in the presence of both chromosomal and nonchromosomal defects (HRs, 21.29 for all cancers, 64.83 for leukemia, and 4.71 for embryonal tumors). The results of this study demonstrate that compared with naturally conceived children a significantly increased risk of nonchromosomal birth defects was found among children conceived with infertility treatment and that the risk of cancer was increased by greater than 30% among non-ART siblings and ART children born from autologous-fresh cycles. Among both naturally conceived and ART-conceived children, the presence of birth defects was associated with a greater risk of cancer.

Comparative study on risk of birth defects in singleton ART birth under high levels of estrogen after fresh embryo transfer and frozen embryo transfer

Objective To investigate whether high estrogen (E2) levels caused by controlled ovarian hyperstimulation affect the birth defect rate in singleton assisted reproductive technology (ART) birth after conceived by fresh embryo transfer and frozen embryo transfer (FET). Methods This was a retrospective cohort study. A total of 581 women with singletons, as well as those who have become pregnant and have had an unwanted abortion under high E2 levels on trigger day were divided into three groups. Group A received FET and the E2 levels on trigger day were higher than 5000 pg/ml. Group B received fresh embryo transfer and the E2 levels were between 3000 and 5000 pg/ml. Group C received FET and the E2 levels were between 3000 and 5000 pg/ml. Results There were no significant differences in birth weight, delivery mode, preterm birth rate, and fetal sex between the three groups (p > .05). Birth defect rate in Group B was higher than that in Group A and C, and the rate between Group B and C had significant differences (p < .05). After adjusting for maternal age, BMI, and type of infertility, only a FET cycle is significantly associated with decreased birth defect rate. Conclusion Fresh embryo transfer under supraphysiological level of estrogen exposure may increase the birth defect rate of ART singletons. Even after prenatal screening and diagnosis, a part of birth defect could not be detected during pregnancy. When the estrogen levels on trigger day were no lower than 3000 pg/ml, FET should be advocated to reduce the occurrence of such risk.

Effects of the early phase of the COVID-19 pandemic on natural and ART-mediated birth rates in Lombardy Region, Northern Italy

Research questionWhat effects did the early phase of the COVID-19 pandemic have on natural and assisted reproductive technology (ART)-mediated birth rates? DesignRegional registries were consulted with permission from the Health Authorities of Lombardy Region, Northern Italy, an area particularly affected by the early phase of the epidemic. Deliveries occurring in the area between 1 January 2019 and 31 December 2020 from women beneficiaries of the National Health System and resident in Lombardy were identified. Comparisons mainly focused on December 2020, when women who conceived after 8 March (the start of the stringent lockdown imposed by the authorities) were expected to deliver. ResultsWhen comparing the periods January to November in 2019 and 2020, a 5.1% reduction of monthly general birth rate (from 5732 in 2019 to 5438 in 2020) was observed. The contribution of ART births was similar in 2019 and 2020, being 4.4% and 4.5%, respectively. In December 2020, a notable drop in natural (–17.8%), ART-mediated (–86.6%) and overall (–21.0%) births was observed compared with December 2019. After adjusting for the expected 5.1% reduction, the inferred effect of the COVID-19 crisis corresponded to a 16.7% reduction in birth rate, of which 76% was related to natural (707 births) and 24% to ART (218 births) conceptions. ConclusionsThis is the first study providing population-based evidence on the effects of COVID-19 and its related stringent restrictions on birth rates. The birth rate was dramatically reduced following the critical period, and the closure of ART centres played only a marginal role (24%) in the overall detrimental effect.

Retinopathy of Prematurity and Assisted Reproductive Technology: Is There an Association?

PurposeThis study aimed to determine the incidence of retinopathy of prematurity (ROP) and to assess whether assisted reproductive technology (ART) is a risk factor for ROP independent of the generation of multiple births by determining the occurrence and severity of ROP and the need for treatment. We will also evaluate other risk factors associated with the development of ROP among preterm infants.Patients and MethodsWe conducted a retrospective chart review for all premature infants who were screened for ROP according to the screening guidelines of the American Academy of Ophthalmology and born at King Abdulaziz University Hospital from 2015 to 2019. In addition to ophthalmological results, data on gestational age (GA), birth weight (BW), type of pregnancy (singleton or multiple), type of conception (natural or ART), infantile factors, and maternal factors were recorded.ResultsA total of 229 preterm babies met our criteria. The mean GA at birth was 29.35 weeks. Notably, 175 neonates were conceived naturally and 54 were conceived by ART. Furthermore, 33 infants in the natural conception group were products of multiple pregnancies, as were 49 infants in the ART group. ROP was noted in 96 of 229 infants (41.92%). No significant difference was found in the occurrence of ROP between multiple neonates in the natural and ART groups. However, ART birth babies in general were significantly associated with the development of ROP (P=0.045). On multiple regression analysis, early GA, low BW, and extended oxygen therapy were the variables most significantly associated with ROP (P≤0.001).ConclusionIn our sample, ART in multiple birth babies per se did not seem to be a risk factor for ROP. However, ART babies were more prone to develop ROP than natural conception birth babies, which seemed to be more severe.

Associated factors of secondary sex ratio of offspring in assisted reproductive technology: a cross-sectional study in Jilin Province, China

BackgroundThe aim of this study was to determine the secondary sex ratio (SSR) of offspring in assisted reproduction technology (ART) in Jilin Province, China, and to analyse the influencing factors associated with SSR.MethodsA cross-sectional study of 3833 babies including singletons and twins born to 2990 couples treated by ART between May 2011 and December 2018 was performed.ResultsThe main outcomes of this study were that the SSR of ART babies in Jilin Province was 50.64% and the SSR was associated with fertilization methods (p < 0.05). Comparing to in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) (OR = 0.808, 95%CI: 0.681–0.958) decreased the percentage of male babies.ConclusionsThis study suggests that the SSR of ART births in Jilin Province was lower than the normal level and ICSI had a significant effect on SSR. Though we need more samples to study in the future, we still need to think about the impact of ICSI on SSR in ART.

Validation of Assisted Reproductive Technology in the Medical Birth Registry of Norway Versus the Norwegian Prescription Database.

Increasing attention has been given to the long-term effects of assisted reproductive technology (ART). This study assessed the validity and completeness of ART as registered in the Medical Birth Registry of Norway (MBRN) using drug prescription data from the Norwegian Prescription Database (NorPD) as reference. In this nationwide registry validation study, we included all pregnancies recorded in the MBRN between 2005 and 2017. We estimated sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the MBRN, using data from the NorPD as reference. We obtained the total percentage of ART pregnancies that could be identified (completeness) from both registries using the capture-recapture method. We analyzed subgroups by maternal age, gestational length, mode of ART treatment, health region, and mode of registration of ART (ART institution or birth notification form). Twenty-three thousand seven hundred eighteen of a total 765,789 pregnancies were registered as ART pregnancies through the MBRN and 20,807 as ART pregnancies through the NorPD. The sensitivity of the MBRN was 85.1% (95% confidence interval [CI] = 84.7, 85.6) and the PPV was 74.7% (74.1-75.2). Sensitivity declined with increasing maternal age: 71.5% (69.4-73.7) in the age group 40-44 years, and 40.7% (22.2-59.3) in the ages above 45 years. Completeness when combining data was 96.2% (96.0-96.5). Our analysis shows that, when identifying women pregnant through ART, NorPD data complemented MBRN data to obtain a more complete count of all women giving birth after ART in Norway.

Number of embryos transferred and diagnosis of preeclampsia

BackgroundMultiple births and first pregnancy are associated with higher preeclampsia risk. It is unknown if the transfer of multiple embryos or first embryo transfer with assisted reproductive technology (ART) is also associated with greater preeclampsia risk.MethodsWe performed a retrospective cohort study of IVF clinics and hospitals in Massachusetts. We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data for 21,188 births, considering resident singleton (12,810) and twin (8378) live-births from autologous or donor eggs from 2005 to 2012. We used log binomial and Poisson regression to calculate adjusted relative risks (aRRs) and 95% confidence intervals (CI) for the association between preeclampsia and predictors of preeclampsia. Outcomes were stratified by singleton and twin birth, donor versus autologous cycles, and use of fresh versus cryopreserved embryos.ResultsConsidering all singleton births, the transfer of multiple embryos increased the risk of preeclampsia [aRR = 1.10 (95% CI: 1.01–1.19)]. Relative risks were greatest for fresh non-donor cycles [aRR = 1.14 (95% CI: 1.03–1.26)]. Vanishing twin and number of prior ART cycles was not associated with preeclampsia among singleton births [aRR = 1.18 (95% CI: 0.91–1.53)], and aRR = 1.01 (95% CI: 0.96–1.05)], respectively. Considering all twin births, the transfer of > 2 embryos increased the risk of preeclampsia [aRR = 1.09 (95% CI: 1.001–1.19)]. Vanishing triplet and number of prior ART cycles were not associated with preeclampsia among twin births [aRR = 0.93 (95% CI: 0.69–1264), and aRR = 0.98 (CI: 0.95–1.02)], respectively.ConclusionsAmong ART births, the transfer of more than 1 embryo for singleton gestations and more than 2 embryos for twin gestations increased the risk for preeclampsia diagnosis.

The demographics of assisted reproductive technology births in a Nordic country.

STUDY QUESTIONWhat are the socio-demographic characteristics of families in Norway who have children after assisted reproductive technology (ART), and have these characteristics changed over time?SUMMARY ANSWERParents who conceive through ART in Norway tend to be advantaged families, and their socio-demographic profile has not changed considerably over the period 1985–2014.WHAT IS KNOWN ALREADYA small number of studies show that couples who conceive through ART tend to be socio-economically advantaged.STUDY DESIGN, SIZE, DURATIONNorwegian Population Register, the Medical Birth Register and the national data bases were linked to study all live births in Norway between 1985 and 2014.PARTICIPANTS/MATERIALS, SETTING, METHODSThe sample consisted of 1 757 768 live births. Simple bivariate analyses were performed to describe the socio-demographic characteristics of parents who conceived through ART and changes in these characteristics over the time period 1985–2014. We used linear probability models to estimate the association between parental income and giving birth after ART from 2000 to 2014, before and after adjustment for maternal age at delivery, education and area of residence.MAIN RESULTS AND THE ROLE OF CHANCEParents conceiving through ART were more likely to be older, with the highest levels of income and education, and married. Their socio-demographic profiles did not change considerably during the period 1985–2014. In the unadjusted model, parents belonging to the top income quartile were 4.2 percentage points more likely (95% CI: 4.1 to 4.3) to have conceived through ART than parents who belonged to the bottom income quartile. Adjustment for maternal age only partially reduced the income disparities (for the top income quartile by 35% (β = 2.7 with 95% CI: 2.5 to 2.8)). Additional adjustment for maternal education, marital status and area of residence did not further attenuate the associations.LIMITATIONS, REASONS FOR CAUTIONThe data does not enable us to tell whether the lower numbers of children conceived through ART amongst more disadvantaged individuals is caused by lower success rates with ART treatment, lower demand of ART services or barriers faced in access to ART. The study focuses on Norway, a context characterised by high subsidisation of ART services.WIDER IMPLICATIONS OF THE FINDINGSEven though in Norway access to ART services is highly subsidised, the results highlight important and persisting social inequities in use of ART. The results also indicate that children born after ART grow up in resourceful environments, which will benefit their development and well-being.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by European Research Council agreement n. 803959 (to A.G.), by Economic and Social Research Council grant ES/M001660/1 and by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The authors have no conflict of interest to declare.TRIAL REGISTRATION NUMBERNot applicable.

Assisted reproductive technology use in the United States: a population assessment

To study social and demographic differentiation of assisted reproduction technology (ART) use at the population level in the United States. Population-based study. Not applicable. Women 15-49years old in the American Community Survey and National Vital Statistics Birth Certificate data from 2010-2017. Not applicable. Birth rate after ART by major sociodemographic categories and likelihood of having an ART birth. Net of education, age, period, and marital status, the incidence rates of ART births are lower for black women (0.57 times; 95% CI, 0.52-0.62) and Hispanic women (0.67 times; 95% CI, 0.57-0.62) relative to white women's rates; for Asian women, the incidence rates are 1.21 times that of white women's rates. Further, the incidence rates of ART births are higher for women with more than a 4-year degree (2.08 times; 95% CI, 1.90-2.27) relative to women with a 4-year degree, and are lower for women with less education. Women who are married have an incidence rate of ART that is 5.72 times (95% CI, 5.37-6.09) that of unmarried women. The incidence rates for 2013-2016 are statistically significantly higher than for 2010 by a factor of 1.16 (95% CI, 1.02-1.31), 1.16 (95% CI, 1.03-1.31), 1.27 (95% CI, 1.12-1.43), and 1.51 (95% CI, 1.43-1.82), respectively. The educational differences in ART exist across all age groups from 20 to 49, but are the largest among the 35-39 and 40-44 age groups. Large differences in the risk of an ART birth and the proportion of births and the total fertility rate due to ART exist across period, age, race, education, and marital status groups in the United States. Current measures of ART births may disguise an unmet need for ART.

Development of assisted reproductive technology services in Thailand between 2008 and 2014 before the new law: Results generated from the National ART Registry, Royal Thai College of Obstetricians and Gynecologists

Abstract Background While the assisted reproductive technology (ART) relieves the burden of infertility in many couples, it presents significant public health challenges due to the substantial risk for multiple birth delivery and preterm birth, which are associated with poor maternal and fetal health outcomes. For this reason, it is important to monitor the development and effectiveness of ART services in Thailand. Objective To analyze the trends of ART services in Thailand between 2008 and 2014. Methods ART clinics in Thailand are required to submit data to the Royal Thai College of Obstetricians and Gynecologists via the National Reporting System. The data from 2008 to 2014 were collected and analyzed. Results The number of ART centers was increased from 35 to 47. The total fresh ART cycles were also increased from 3,723 to 6,516. The percentage values of intracytoplasmic sperm injection (ICSI), in vitro fertilization, gamete intrafallopian transfer, and zygote intrafallopian transfer cycles were changed from 77.87 to 95.59, 21.43 to 4.31, 0.21 to 0.09, and 0.45 to 0.05, respectively. The clinical pregnancy rates were 28.79–33.19, 22.84–51.34, 14.29–42.86, and 0.00–26.67, respectively. The clinical pregnancy rates in fresh vs. frozen-thawed cycles were 31.01–36.33 vs. 31.54–37.34 (P &lt; 0.05). The clinical pregnancy rates in female age &lt;35 vs. 35–39 vs. ≥40 years were 36.97–40.70 vs. 32.74–33.42 vs. 21.08–31.34, respectively (P &lt; 0.001), and the percentage values of multifetal pregnancy rate were 18.75 vs. 13.30 and 13.69, respectively (P &lt; 0.001). There were increasing preimplantation genetic screening (PGS) cycles, with the percentage of the clinical pregnancy rate (25.90–42.63, P &lt; 0.05). The clinical pregnancy rates in medium-sized ART centers (100–300 cycles per year) vs. in small and large centers were 30.79–41.14 vs. 28.01–34.04 and 8.70–40.35, respectively (P &lt; 0.001). Trends of increasing percentage of ART birth rate to total birth rate ratio were 0.24–0.34 (P &lt; 0.05). Conclusions There were higher clinical pregnancy rates in frozen-thawed cycles. Higher multifetal pregnancy rate and clinical pregnancy rate were also found in younger females. There were increasing uses of ICSI and PGS. A trend toward increasing ART birth to total birth ratio was observed.

Assisted reproductive technology and risk of ovarian cancer and borderline tumors in parous women: a population-based cohort study

The study aimed to investigate if assisted reproductive technology (ART) treatment or a diagnosis of infertility were associated with the risk of ovarian cancer or borderline ovarian tumors (BOT) in parous women. In a population-based register study of 1,340,097 women with a first live birth in Sweden 1982–2012, the relationship between ART treatments, infertility and incidence of ovarian cancer or BOT were investigated using Cox regression analysis. In the cohort, 38,025 women gave birth following ART, 49,208 following an infertility diagnosis but no ART and 1,252,864 without infertility diagnosis or ART. During follow-up, 991 women were diagnosed with ovarian cancer and 747 with BOT. Women who gave birth following ART had higher incidence of both ovarian cancer (adjusted hazard ratio [aHR] 2.43, 95% confidence interval [CI] 1.73–3.42) and BOT (aHR 1.91, 95% CI 1.27–2.86), compared to women without infertility. Compared to women with infertility diagnoses and non-ART births, women with ART births also had a higher incidence of ovarian cancer (aHR 1.79, 95% CI 1.18–2.71) and BOT (aHR 1.48, 95% CI 0.90–2.44). Our results suggest that women who have gone through ART have a higher risk of ovarian cancer and BOT. At least part of that risk seems to be due to the underlying infertility and not the treatment per se, since the increased risk was smaller when comparing to other infertile women. As ART treatments are becoming more common and ovarian cancer usually occur in women of advanced age, larger studies with longer follow-up are needed in order to confirm or refute our findings.

Use of assisted reproductive technologies before and after the Artificial Reproduction Act in Taiwan.

BackgroundLow birth rates and infertility are growing concerns for many countries. The Artificial Reproduction Act (ARA) was implemented in 2007 to better support the use of assisted reproductive technology (ART) in Taiwan. This study aims to examine trends in the use of ART and to determine impacts of the ARA on ART use.MethodThis study used data from the Health Promotion Administration in Taiwan. We used auto-regression models to examine the recent trends (1998–2017) in fertility related indicators and the use of ART. An interrupted time series design and segmented linear regression models were applied to analyze the changes in number of ART treatment cycles and birth rates by ART following the ARA.ResultsThe number of births by ART has gradually increased, with an annual growth rate of 21.55%. The rate of births by ART increased from 0.86% in 1998 to 1.44% in 2007, and to 4.33% in 2016 (annual growth rate: 41.23%). We estimated a relative increase of 78.51% (95%CI: 46.13%, 110.90%) in the number of births by ART and a relative increase of 35.67% (95%CI: 18.87%, 52.47%) in rate of births by ART 5 years following the ARA was implemented.ConclusionART has been seen as an approach to improve fertility. Our analysis suggests that the ART use and births associated from ART use both increased in Taiwan following the implementation of ARA. This experience in Taiwan may offer important lessons for other countries that are facing low fertility challenges.

Obstetric outcomes in pregnancies resulting from in vitro fertilization (IVF) are not different in fertile, sterilized patients compared to infertile women: a society for assisted reproductive technology (SART) database analysis

This study aims to compare obstetric outcomes resulting from assisted reproductive technology (ART) in couples with a history of female sterilization compared to those with other infertility diagnoses. Retrospective Cohort Study. All 760,705 fresh, autologous embryo transfer cycles with partner ejaculated sperm from 2004 to 2013 in the SART database were reviewed. Cycles in women with prior female sterilization were compared to cycles with other infertility diagnoses. After excluding cycles with male sterilization, day of transfer >7, prior sterilization with an additional infertility diagnosis, and unknown method of ICSI or IVF, 4,174 cycles in patients with history of female sterilization were compared to 179,605 cycles in patients with other causes of infertility. Multiple linear regression analyses and generalized estimating equations were performed to assess whether gestational length and birthweight were significantly different between groups in singleton and twin pregnancies after controlling for BMI, age, parity, and type of ART procedure (traditional IVF vs ICSI). Previously sterilized women were older with significantly higher parity and body mass indices than women in couples with all other causes of infertility. Number of oocytes retrieved, timing of embryo transfer, pregnancy and live birth rates were not significantly different between the two groups. Women with a history of sterilization had significantly shorter gestations and lower birth weights than women with other causes of infertility. However, there was no significant difference between these groups after controlling for singleton and twin gestations except in birth weight for twins.Tabled 1All Women (N=183779)Women with history of female sterilization (N=4174)Women with all other causes of infertility (N=179605)P-ValueAge (years)35.281 ± 4.05934.507 ± 4.604<0.0001Parity2.425 ± 1.1720.469 ± 0.710<0.0001Body Mass Index (BMI) (kg/m2)27.155 ± 5.50225.414 ± 15.321<0.0001Number of oocytes retrieved12.734 ± 7.48612.817 ± 7.6980.4794Day of Embryo Transfer3.712 ± 1.0483.705 ± 1.0440.6583Clinical Pregnancy Rate Per Cycle, n (%)1864 (44.66%)81689 (45.48%)0.2897Live Birth Rate Per Cycle, n (%)1544 (36.99%)67972 (37.85%)0.2605Lengthof Gestation, days250.479 ± 1.046252.667 ± 1.3780.0364Singletons Twins270.220 ± 1.051270.662 ± 1.3420.6739236.024 ± 1.924239.780 ± 2.7820.0509Live Birth Weight, grams2100.348 ± 37.1292275.679 ± 53.150<0.0001Singletons Twins3027.401 ± 139.1713142.228 ± 177.8790.40931978.822 ± 48.0002140.158 ± 73.5060.0008 Open table in a new tab Evidence has linked pregnancies resulting from ART with increased risk of adverse obstetric outcomes, including low birthweight; however, it is unclear if this is due to the ART procedures or to subfertility itself.1 This study provides a rare opportunity to evaluate the effects of ART in a population without an underlying infertility diagnosis. This analysis demonstrates no significant differences in neonatal birthweight or gestational age among ART births from women with infertility and tubal sterilization. The results suggest that differences in outcomes between ART and natural conceptions may be due to the procedures of ART itself.

Gestational age-specific perinatal mortality rates for assisted reproductive technology (ART) and other births.

Is perinatal mortality rate higher among births born following assisted reproductive technology (ART) compared to non-ART births? Overall perinatal mortality rates in ART births was higher compared to non-ART births, but gestational age-specific perinatal mortality rate of ART births was lower for very preterm and moderate to late preterm births. Births born following ART are reported to have higher risk of adverse perinatal outcomes compared to non-ART births. This population-based retrospective cohort study included 407 368 babies (391 952 non-ART and 15 416 ART)-393 491 singletons and 10 877 twins or high order multiples. All births (≥20 weeks of gestation and/or ≥400 g of birthweight) in five states and territories in Australia during the period 2007-2009 were included in the study, using National Perinatal Data Collection (NPDC). Primary outcome measures were rates of stillbirth, neonatal and perinatal deaths. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were used to estimate the likelihood of perinatal death. Rates of multiple birth and low birthweight were significantly higher in ART group compared to the non-ART group (P < 0.01). Overall perinatal mortality rate was significantly higher for ART births (16.5 per 1000 births, 95% CI 14.5-18.6), compared to non-ART births (11.3 per 1000 births, 95% CI 11.0-11.6) (AOR 1.45, 95% CI 1.26-1.68). However, gestational age-specific perinatal mortality rate of ART births (including both singletons and multiples) was lower for very preterm (<32 weeks' gestation) and moderate to late preterm births (32-36 weeks' gestation) (AOR 0.61, 95% CI 0.53-0.70 and AOR 0.61, 95% CI 0.53-0.70, respectively) compared to non-ART births. Congenital abnormality and spontaneous preterm were the most common causes of neonatal deaths in both ART and non-ART group. Due to different cut-off limit for perinatal period in Australia, the results of this study should be interpreted with cautions for other countries. Australian definition of perinatal period commences at 20 completed weeks (140 days) of gestation and ends 27 completed days after birth which is different from the definition by World Health Organisation (commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth) and by Centers for Disease Control and Prevention (includes infant deaths under age 7 days and fetal deaths at 28 weeks of gestation or more). Preterm birth is the single most important contributing factor to increased risk of perinatal mortality among ART singletons compared to non-ART singletons. Further research on reducing early preterm delivery, with the aim of reducing the perinatal mortality among ART births is needed. Couples who access ART treatment should be fully informed regarding the risk of preterm birth and subsequent risk of perinatal death. There was no funding associated with this study. No conflict of interest was declared.

Embryo cryopreservation and preeclampsia risk

To determine whether assisted reproductive technology (ART) cycles involving cryopreserved-warmed embryos are associated with the development of preeclampsia. Retrospective cohort study. IVF clinics and hospitals. A total of 15,937 births from ART: 9,417 singleton and 6,520 twin. We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data, considering resident singleton and twin births from autologous or donor eggs from 2005-2010. We compared the frequency of preeclampsia diagnosis for cryopreserved-warmed versus fresh ET and used multivariable logistic regression to adjust for confounders. Among pregnancies conceived with autologous eggs resulting in singletons, preeclampsia was greater after cryopreserved-warmed versus fresh ET (7.51% vs. 4.29%, adjusted odds ratio = 2.17 [95% CI 1.67-2.82]). Preeclampsia without and with severe features, preeclampsia with preterm delivery, and chronic hypertension with superimposed preeclampsia were more frequent after cryopreserved-warmed versus fresh ET (3.99% vs. 2.55%; 2.95% vs. 1.41%; 2.76 vs. 1.48%; and 0.95% vs. 0.43%, respectively). Among pregnancies from autologous eggs resulting in twins, the frequency of preeclampsia with severe features (9.26% vs. 5.70%) and preeclampsia with preterm delivery (14.81% vs. 11.74%) was higher after cryopreserved versus fresh transfers. Among donor egg pregnancies, rates of preeclampsia did not differ significantly between cryopreserved-warmed and fresh ET (10.78% vs. 12.13% for singletons and 28.0% vs. 25.15% for twins). Among ART pregnancies conceived using autologous eggs resulting in live births, those involving transfer of cryopreserved-warmed embryos, as compared with fresh ETs, had increased risk for preeclampsia with severe features and preeclampsia with preterm delivery.

Trends and correlates of male sex among assisted reproductive technology births in the united states

To assess United States national trends in the proportion of males among live births in the assisted reproductive technology (ART) population and in the general population, investigate the sex distribution among ART live births stratified by preimplantation genetic diagnosis or screening (PGD/PGS) use, and identify predictors of offspring sex.

Assisted reproductive technology & risk of childhood cancer

To compare the incidence of childhood cancer in children born from assisted reproductive technology (ART) to the general population. Longitudinal cohort of children in 14 States (CA, CO, CT, FL, IL, MA, MI, NC, NJ, NY, OH, PA, TX, and VA). Women who were residents of participating study States and who underwent in vitro fertilization cycles resulting in a live birth between 2004 and 2013 (three States to 2009 and one State to 2010) were linked to their birth certificates; 10:1 random sample of births from non-ART deliveries were selected as controls. All children were linked to their respective State cancer registries through 2013 (three States through 2012); additional data are expected from one State. Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CI) of the risk of cancer in children conceived by ART versus controls, adjusting for State and year of birth, and mother’s age, race, and education, stratified by plurality. Controls were compared to all ART births, to those using fresh embryos and to those using thawed embryos. The study included 2,275,341 children with 2,142 cancers, including 204,655 ART children with 242 cancers. The singleton HR for ART births using fresh embryos was marginally increased relative to controls, but not increased using thawed embryos. The HR confidence intervals for twins included the estimates for singletons, indicating no statistical difference between the two groups. This large study shows that the potential increases in cancer rates among ART children are small. However, these results warrant further surveillance and continued research into the association between ART treatment and cancer.Tabled 1N, ChildrenN, CancersRate/1,000 BirthsHazard Ratio95% CIp-ValueSingletonsControls2,005,7921,8430.921.00Reference--All ART114,8621321.151.170.97, 1.410.102Fresh ART90,2431111.231.220.99, 1.490.054Thawed ART24,619210.850.950.61, 1.470.804TwinsControls64,894570.881.00Reference--All ART89,7931101.231.160.18, 1.680.41Fresh ART75,389891.181.090.75, 1.590.65Thawed ART14,404211.461.550.87, 2.760.13 Open table in a new tab

Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births.

Assisted reproductive technology (ART) has been associated with birth defects, but the contributions of multiple births and underlying subfertility remain unclear. We evaluated the effects of subfertility and mediation by multiple births on associations between ART and nonchromosomal birth defects. We identified a retrospective cohort of Massachusetts live births and stillbirths from 2004 to 2010 among ART-exposed, ART-unexposed subfertile, and fertile mothers using linked information from fertility clinics, vital records, hospital discharges, and birth defects surveillance. Log-binomial regression was used to estimate prevalence ratios and 95% confidence intervals (CIs). Mediation analyses were performed to deconstruct the ART-birth defects association into the direct effect of ART, the indirect effect of multiple births, and the effect of ART-multiples interaction. Of 17,829 ART-exposed births, 355 had a birth defect, compared with 162 of 9431 births to subfertile mothers and 6183 of 445,080 births to fertile mothers. The adjusted prevalence ratio was 1.5 (95% CI, 1.3-1.6) for ART and 1.3 (95% CI, 1.1-1.5) in subfertile compared with fertile deliveries. We observed elevated rates of several birth defects with ART, including tetralogy of Fallot and hypospadias. Subfertility and multiple births affect these associations, with multiple births explaining 36% of the relative effect of ART on nonchromosomal birth defects. Although the risk of birth defects with ART is small, a substantial portion of the relative effect is mediated through multiple births, with subfertility contributing an important role. Future research is needed to determine the impact of newer techniques, such as single embryo transfer, on these risks. Birth Defects Research 109:1144-1153, 2017. © 2017 Wiley Periodicals, Inc.

The long-term health risks of ART: Epidemiological data and research on animals indicate that in vitro fertilization might create health problems later in life.

Potential health risks associated with assisted reproduction technology (ART) have been suspected ever since the first IVF baby, Louise Brown, was born in the UK in 1978. These risks have constantly been reassessed in light of epidemiological data as well as animal studies. Yet, even 39 years is not long enough to obtain conclusive proof of significantly increased levels of serious conditions, including cancer, cardiac, or metabolic diseases. However, evidence has been more than sufficient to stimulate further research across the whole spectrum of treatments for sub‐fertility, given that demand continues to grow around the globe. A number of factors combine to drive up assisted reproduction rates, including rising awareness among infertile couples, technical advances, growing medical tourism, and, above all, the trend among women, especially in developed countries, toward delaying pregnancy into the 30s. As a result, of the 6 million or so babies conceived via ART since 1978, about half were born during the past decade. In the USA, 72,913 babies were born via ART in 2015 representing 1.6% of all births, according to the US Centers for Disease Control and Prevention. > The risk of multiples alone means that ART babies are far more likely to suffer subsequent health problems associated with the greater incidence of being born prematurely. The situation is similar in Europe, where numbers of ART births increased by 7% between 2012 and 2013, according to the European Society of Human Reproduction and Embryology (ESHRE; https://focusonreproduction.eu/2016/07/05/6-5-million-ivf-babies-since-louise-brown/). The study also noted that ICSI (intra‐cytoplasmic sperm injection) now accounted for two‐thirds of all ART treatments in Europe, mainly owing to male infertility. In ICSI, the embryologist injects a single sperm directly into an ovum, compared with IVF where fertilization takes place in a dish and many sperm swarm around one or a few eggs. The ESHRE emphasized …

Contribution of Assisted Reproductive Technology to Overall Births by Maternal Age in the United States, 2012-2014

Assisted reproductive technology (ART) contributes to 1.6% of births in the United States,1 and utilization varies across several dimensions, including patient age.2 Delayed childbearing and age-related fertility declines may be associated with increasing ART use. Also, success rates for patients using their own oocytes decline with increasing maternal age, leading to higher use of donated oocytes by older women.2 The proportion of ART births among US multiple births by maternal age has been reported3; however, to our knowledge, age-specific estimates of the contribution of ART to total US births have not been previously published.