Perinatal outcomes of singleton live births with and without vanishing twin following transfer of multiple embryos: analysis of 113 784 singleton live births.

STUDY QUESTION: Does transfer of multiple embryos affect perinatal outcomes of resulting singleton live births following ART? SUMMARY ANSWER: There is a higher risk of preterm birth (PTB) and low birthweight (LBW) in singleton live births associated with spontaneous reduction of an initial multiple to singleton gestation following transfer of multiple embryos. WHAT IS KNOWN ALREADY: Singleton pregnancies following ART are at a higher risk of adverse perinatal outcomes compared to spontaneous conceptions. Earlier studies have found an increased risk of PTB and LBW in singletons following transfer of multiple embryos versus single embryo transfer (SET). However, these studies did not address the specific role of vanishing twin, i.e. spontaneous reduction of an initial multiple to singleton gestation. STUDY DESIGN, SIZE, DURATION: Anonymised data on all ART cycles performed in the UK were obtained from the Human Fertilization and Embryology Authority. Data from 1991 to 2011 involving 508 410 fresh and 131 157 frozen autologous ART cycles resulting in 95 779 and 18 005 singleton live births, respectively, were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fresh and frozen ART cycles were analyzed separately to compare perinatal outcomes of PTB and LBW of singleton live births resulting from transfer of multiple (≥2) embryos versus SET. Logistic regression analysis was performed adjusting for confounders. Subgroup analyses were carried out for perinatal outcomes of singleton live births with initial multiple or initial single gestational sacs following transfer of multiple embryos versus singleton live births following SET. MAIN RESULTS AND THE ROLE OF CHANCE: In fresh cycles, there was a significantly higher risk of PTB (adjusted odds ratio (aOR) 2.70, CI 2.37-3.05) and LBW (aOR 2.76, CI 2.44-3.13) in singleton live births with initial multiple gestational sacs but there was no significant difference in the risk of PTB (aOR 1.08, CI 1.00-1.16) or LBW (aOR 1.08, CI 1.00-1.16) in singleton live births with an initial single gestational sac following transfer of ≥2 embryos compared to those following SET. In frozen cycles, there was a significantly higher risk of PTB (aOR 2.13, CI: 1.55-2.93) and LBW (aOR 2.61, CI: 1.87-3.64) in singleton live births with initial multiple gestational sacs but there was no significant difference in the risk of PTB (aOR 1.02, CI: 0.88-1.18) or LBW (aOR 0.91, CI: 0.77-1.07) in the singleton live births with an initial single gestational sac following transfer of ≥2 embryos compared to those following SET. LIMITATIONS, REASONS FOR CAUTION: While the analysis was adjusted for a number of known confounders, the dataset had no information for confounders such as smoking, BMI, previous obstetric history and comorbid medical conditions during pregnancy. The lack of information about the timing of occurrence of the vanishing phenomenon is another limitation because poorer perinatal outcomes of a surviving twin have been reported following second trimester fetal demise compared to the first trimester. WIDER IMPLICATIONS OF THE FINDINGS: The study results suggest that the vanishing twin phenomenon is associated with increased risk of PTB and LBW in the resulting singleton live births and there was no increased risk when there was a single gestational sac from the outset following transfer of multiple embryos. STUDY FUNDING/COMPETING INTERESTS: Nil.

Perinatal outcomes following IVF with use of donor versus partner sperm.

It is a matter of interest whether pregnancies with the use of donor sperm are associated with a higher risk of adverse perinatal outcomes compared with partner sperm. Anonymized data were obtained from the Human Fertilization & Embryology Authority. Data from 1991 to 2011 involving a total of 95,787 singleton births (4523 with donor sperm and 91,264 with partner sperm) following fresh IVF/intracytoplasmic sperm injection (ICSI) were analysed to compare perinatal outcomes of preterm birth (PTB), low birthweight (LBW) and high birthweight (HBW). The risk of LBW was significantly lower (adjusted odds ratio [aOR] 0.88, 95% confidence interval [CI]: 0.79-0.99) following donor sperm versus partner sperm IVF/ICSI. There was no significant difference in the risk of PTB (aOR 0.93, 95% CI: 0.83-1.04), early PTB (aOR 0.86, 95% CI: 0.67-1.11), very LBW (aOR 0.95, 95% CI: 0.75-1.20), HBW (aOR 1.09, 95% CI: 0.98-1.21) and very HBW (aOR 1.15, 95% CI: 0.90-1.45) following donor sperm versus partner sperm IVF/ICSI. The current study did not demonstrate an increased risk of adverse perinatal outcomes following donor sperm compared with partner sperm IVF/ICSI treatment.

Pre-term birth and low birth weight following preimplantation genetic diagnosis: analysis of 88 010 singleton live births following PGD and IVF cycles.

STUDY QUESTION: Is PGD associated with the risk of adverse perinatal outcomes such as pre-term birth (PTB) and low birth weight (LBW)? SUMMARY ANSWER: There was no increase in the risk of adverse perinatal outcomes of PTB, and LBW following PGD compared with autologous IVF. WHAT IS KNOWN ALREADY: Pregnancies resulting from ART are associated with a higher risk of pregnancy complications compared with spontaneously conceived pregnancies. The possible reason of adverse obstetric outcomes following ART has been attributed to the underlying infertility itself and embryo specific epigenetic modifications due to the IVF techniques. It is of interest whether interventions such as embryo biopsy as performed in PGD affect perinatal outcomes. STUDY DESIGN, SIZE, DURATION: Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1996 to 2011 involving a total of 88 010 singleton live births were analysed including 87 571 following autologous stimulated IVF ± ICSI and 439 following PGD cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on all women undergoing either a stimulated fresh IVF ± ICSI treatment cycle or a PGD cycle during the period from 1996 to 2011 were analysed to compare perinatal outcomes of PTB and LBW among singleton live births. Logistic regression analysis was performed adjusting for female age category, year of treatment, previous IVF cycles, infertility diagnosis, number of oocytes retrieved, whether IVF or ICSI was used and day of embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: There was no increase in the risk of PTB and LBW following PGD versus autologous stimulated IVF ± ICSI treatment, unadjusted odds of PTB (odds ratio (OR) 0.68, 95% CI: 0.46-0.99) and LBW (OR 0.56, 95% CI: 0.37-0.85). After adjusting for the potential confounders, there was again no increase in the risk of the adverse perinatal outcomes following PGD: PTB (adjusted odds ratio (aOR) 0.66, 95% CI: 0.45-0.98) and LBW (aOR 0.58, 95% CI: 0.38-0.88). LIMITATIONS, REASONS FOR CAUTION: Although the analysis was adjusted for a number of important confounders, the data set had no information on confounders such as smoking, body mass index and the medical history of women during pregnancy to allow adjustment. There was no information on the stage of embryo at biopsy, whether blastomere or trophectoderm biopsy. WIDER IMPLICATIONS FOR THE FINDINGS: The demonstration that PGD is not associated with higher risk of PTB and LBW provides reassurance towards its current expanding application. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained. There are no competing interests to declare.

Perinatal outcomes after gestational surrogacy versus autologous IVF: analysis of national data.

Anonymized data were obtained from the Human Fertilization and Embryology Authority to determine whether gestational surrogacy influences perinatal outcomes compared with pregnancies after autologous IVF. A total of 103,160 singleton live births, including 244 after gestational surrogacy, 87,571 after autologous fresh IVF and intractyoplasmic sperm injection (ICSI) and 15,345 after autologous frozen embryo transfers were analysed. Perinatal outcomes of pretern birth (PTB), low birth weight (LBW) and high birth weight (HBW) were compared. No difference was found in the risk of PTB and LBW after gestational surrogacy compared with autologous fresh IVF-ICSI: PTB (adjusted OR 0.90, 95% CI 0.56 to 1.42), LBW (adjusted OR 0.90, 95% CI 0.57 to 1.43) and gestational surrogacy compared with autologous frozen embryo transfers: PTB (adjusted OR 0.96, 95% CI 0.58 to 1.60), LBW (adjusted OR 1.16, 95% CI 0.69 to 1.96). The incidence of HBW was significantly higher after gestational surrogacy compared with fresh IVF-ICSI (adjusted OR 1.94, 95% CI 1.38 to 2.75); no difference was found in HBW between gestational surrogacy and autologous frozen embryo transfers. The dataset is limited by lack of information on confounders, i.e. ethnicity, body mass index, underlying medical history, which could result in residual confounding.

Association of serum 25-Hydroxy vitamin D with total and regional adiposity and cardiometabolic traits.

BACKGROUND: Lower serum 25-hydroxyvitamin D [25(OH)D] is associated with greater adiposity and adverse cardiometabolic risk profile. The evidence is inconsistent among South Asian Indians. We aimed to examine associations between 25(OH)D and cardiovascular (CVD) risk markers in a rural and urban cohort from South India. SUBJECTS/METHODS: In this cross sectional study, 373 individuals (men, n = 205) underwent detailed CVD risk marker assessment including anthropometry [body mass index (BMI), waist, (WC) and hip circumferences (HC)], body composition analysis using dual energy x-ray absorptiometry (DXA), blood pressure and biochemical analysis (glucose, insulin and lipids). The distribution of CVD risk factors were compared across serum 25(OH)D levels, stratified as deficiency (<20 ng/ml), insufficiency (20 to 29 ng/ml) and normal (≥30 ng/ml) levels. Multiple regression analysis, adjusting for potential confounders, was used to study associations of 25(OH)D with adiposity and cardiometabolic traits. RESULTS: The mean and standard deviation (SD) of age, BMI and 25(OH)D levels were 41.4 (1.1) years, 25.5 (4.8) kg/m2 and 23.4 (10.4) ng/ml respectively. The prevalence of 25(OH)D deficiency was 39.9% in this cohort. Individuals in the 25(OH)D deficiency category had significantly higher mean (SD) BMI [26.6 (5.1) kg/m2], waist circumference [89.9 (12.5) cm] and total fat mass [20.6 (7.9) kg] compared with the Vitamin D sufficient group [BMI: 24.0 (4.4); WC 84.7 (12.0); total fat mass: 15.2 (6.8)]. Significantly inverse associations were observed with DXA measured total and regional fat depots with 25(OH)D levels, while anthropometric indices of adiposity showed significant inverse association only in women. After adjusting for total fat mass, no significant associations were observed between 25(OH)D and the cardiometabolic traits. CONCLUSIONS: Our results confirm that lower 25(OH)D is independently associated with both total and regional adiposity, but not with cardiometabolic traits, in this population.

Prevalence, incidence and predictors of cardiovascular risk factors: longitudinal data from rural and urban South India and comparison with global data.

INTRODUCTION: India has high mortality rates from cardiovascular disease (CVD). Understanding the trends and identifying modifiable determinants of CVD risk factors will guide preventive strategies and policy making. RESEARCH DESIGN AND METHODS: CVD risk factors (obesity, central obesity, and type 2 diabetes (T2D), hypertension, hypercholesterolemia and hypertriglyceridemia) prevalence and incidence were estimated in 962 (male 519) non-migrant adults from Vellore, South India, studied in: (1) 1998-2002 (mean age 28.2 years) and (2) 2013-2014 (mean age 41.7 years). Prevalence was compared with the Non-Communicable Disease Risk Collaboration (global) data. Incidence was compared with another Indian cohort from New Delhi Birth Cohort (NDBC). Regression analysis was used to test baseline predictors of incident CVD risk factors. RESULTS: The prevalence at 28 and 42 years was 17% (95% CI 14% to 19%) and 51% (95% CI 48% to 55%) for overweight/obesity, 19% (95% CI 17% to 22%) and 59% (95% CI 56% to 62%) for central obesity, 3% (95% CI 2% to 4%) and 16% (95% CI 14% to 19%) for T2D, 2% (95% CI 1% to 3%) and 19% (95% CI 17% to 22%) for hypertension and 15% (95% CI 13% to 18%) and 30% (95% CI 27% to 33%) for hypertriglyceridemia. The prevalence of T2D at baseline and follow-up and hypertension at follow-up was comparable with or exceeded that in high-income countries despite lower obesity rates. The incidence of most risk factors was lower in Vellore than in the NDBC. Waist circumference strongly predicted incident T2D, hypertension and hypertriglyceridemia. CONCLUSIONS: A high prevalence of CVD risk factors was evident at a young age among Indians compared with high and upper middle income countries, with rural rates catching up with urban estimates. Adiposity predicted higher incident CVD risk, but the prevalence of hypertension and T2D was higher given a relatively low obesity prevalence. Preventive efforts should target both rural and urban India and should start young.

Comparison of Perinatal Outcomes of Singletons Following Vanishing Twin Phenomenon and Singletons with Initial Single Gestational Sac Conceived Following Assisted Reproductive Technology: A Retrospective Analysis.

AIM: The aim of the study was to compare the perinatal outcomes between singletons following vanishing twin phenomenon and singletons arising from initial single gestational sac following assisted reproductive technology (ART) treatment. SETTING AND DESIGN: This was a retrospective cohort study. MATERIALS AND METHODS: A retrospective cohort study included analysis of all singleton births following ART over a period of 7 years (January 2010 -December 2016). All women who underwent fresh or frozen embryo ART cycles were followed up. The study population included all singleton births following spontaneous reduction of one of the gestational sacs in dichorionic diamniotic twin pregnancies. The perinatal outcome of this group was compared with those of singletons arising from the initial single gestational sac. RESULTS: A total of 521 singleton births were recorded during the study period. In the study group, 72 singleton births had spontaneous reduction of one of the gestational sacs (vanishing twin group) and the remaining 449 had an initial single gestational sac. The risk for low birth weight (LBW) (14/72, 19.4% vs. 96/449, 21.6%) and preterm birth (PTB) (17/72, 23.6% vs. 134/449, 29.8%) was not significantly different between those singletons who had spontaneous reduction from two gestational sacs to single sac compared to those with initial single sac. The miscarriage rate was significantly lower in vanishing twin group compared to control group (7/84, 8.3% vs. 157/622, 25.2%; P = 0.01). The subgroup analysis based on spontaneous reduction occurring before or after the appearance of the embryonic pole also showed similar risk of PTB (11/41, 26.8.% vs. 9/31, 29.0%) and LBW (7/41, 17.1% vs. 9/31, 29.0%). CONCLUSION: Perinatal outcomes in singleton live births following vanishing twin phenomenon are similar to those pregnancies with an initial single gestational sac following ART.