Birthweight Of Singletons Research Articles

The Association Between Infant Temperament and Breastfeeding Duration: A Cross-Sectional Study.

Little is known about the relationship between infant temperament and breastfeeding. The few studies investigating this report mixed results. Some suggest that difficult infants are breastfed for shorter duration, others report opposing results or no association between the two. This study investigated associations between infant difficult temperament and breastfeeding duration in a nationally representative cohort of Irish 9-month-old infants. Breastfed, normal birth-weight singletons from The Infant Cohort of the Growing Up in Ireland Study (n = 5,955) were considered in this research. The Infant Characteristics Questionnaire (ICQ), completed by the mother, was used to assess four different dimensions of difficult temperament: fussy, unpredictable, unadaptable, and dull. Our main interest was the fussy dimension as this is captured best by the ICQ. Initially, a logistic regression (LR) model having the binary version, short (<90 days) or long breastfeeding (≥90 days) as outcome variable, was constructed. Next, a proportional odds logistic regression (POLR) model examining the five-level categorical version (≤1 week, 2 weeks-<1 month, 1-<3 months, 3-<6 months, and ≥6 months) of breastfeeding duration was developed. All regression models were adjusted for relevant sociodemographic data. A total of 3,119 infants were breastfed for less than 90 days, while 2,836 were breastfed for 90 days or longer. The LR and POLR models showed a mild inverse association between infant fussiness/difficultness and breastfeeding duration (LR: OR = 0.98, 95% CI: 0.97-0.99, POLR: OR = 0.98, 95% CI: 0.97-0.99). Higher infant unpredictability is associated with longer breastfeeding duration (LR: OR = 1.04, 95% CI: 1.02-1.07, POLR: OR = 1.04, 95% CI: 1.02-1.06). In this cross-sectional study, we found that breastfeeding duration was inversely associated with infant fussiness and positively associated with infant unpredictability.

Very Low Birth Weight Monochorionic Diamniotic Twins as a Risk Factor for Symptomatic Patent Ductus Arteriosus

Background: Some prior studies have shown that symptomatic patent ductus arteriosus (sPDA) is highly familial. Although it is estimated that both genetic and environmental factors may contribute to sPDA, evidence is still lacking. Objective: The aim of this study was to determine the risk factors for sPDA, focusing on the genetic and in utero environment by analyzing very low birth weight (VLBW) singletons and twins. Methods: This retrospective case-control study reviewed the medical records of 445 VLBW infants (25 weeks ≤ gestational age <32 weeks, 600 g ≤ birth weight <1,500 g) and compared the incidence of sPDA among monochorionic diamniotic (MD) twins (n = 65), dichorionic diamniotic (DD) twins (n = 66), and singletons (n = 314). Results: Stepwise multiple regression analysis showed that twin siblings (p = 0.001), gestational week (p < 0.001), antenatal steroid use (p = 0.021), and premature rupture of membranes (p = 0.002) were independent predictors of sPDA. Incidence of sPDA in MD twin siblings was significantly higher than that in singletons (p < 0.01), whereas no significant difference was found between singletons and DD twins or between MD and DD twins. Conclusions: The current results show that being a VLBW MD twin is an independent risk factor for sPDA, and that both genetic and in utero environmental factors may contribute to its development.

Culture media influenced laboratory outcomes but not neonatal birth weight in assisted reproductive technology.

Whether the type of culture media utilized in assisted reproductive technology has impacts on laboratory outcomes and birth weight of newborns in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was investigated. A total of 673 patients undergoing IVF/ICSI and giving birth to live singletons after fresh embryo transfer on day 3 from Jan. 1, 2010 to Dec. 31, 2012 were included. Three types of culture media were used during this period: Quinn's Advantage (QA), Single Step Medium (SSM), and Continuous Single Culture medium (CSC). Fertilization rate (FR), normal fertilization rate (NFR), cleavage rate (CR), normal cleavage rate (NCR), good-quality embryo rate (GQER) and neonatal birth weight were compared using one-way ANOVA and χ (2) tests. Multiple linear regression analysis was performed to determine the impact of culture media on laboratory outcomes and birth weight. In IVF cycles, GQER was significantly decreased in SSM medium group as compared with QA or CSC media groups (63.6% vs. 69.0% in QA; vs. 71.3% in CSC, P=0.011). In ICSI cycles, FR, NFR and CR were significantly lower in CSC medium group than in other two media groups. No significant difference was observed in neonatal birthweight among the three groups (P=0.759). Multiple linear regression analyses confirmed that the type of culture medium was correlated with FR, NFR, CR and GQER, but not with neonatal birth weight. The type of culture media had potential influences on laboratory outcomes but did not exhibit an impact on the birth weight of singletons in ART.

Independent factors influencing large-for-gestation birth weight in singletons born after in vitro fertilization.

Higher risk for birth of singletons being large for gestational age (LGA) has been revealed after in vitro fertilization (IVF) frozen-thawed embryo-transfer (FET). This phenomenon is now being investigated, since there is a speculation that these neonates could suffer from underlying epigenetic disturbances. The aim of the study was to expose independent LGA risk factors and to identify those connected to the IVF techniques. Altogether, 4508 singleton pregnancies and births were included in the cohort case-matched study. Two hundred eleven singleton pregnancies and births after FET and 916 after fresh embryo transfer (ET) were included into two study groups. The IVF procedures were performed at the University Medical Centre Ljubljana between 2004 and 2011. For each IVF pregnancy, three matched consecutive controls after natural conception were included. Using logistic regression models, we observed LGA connection to maternal parameters (smoking, hypertension, parity, BMI, gestational diabetes, IVF conception, FET, double ET, and ICSI procedure). Singletons born after FET had a significantly higher risk for being LGA (p = 0.032; OR 1.697; 95 % CI 1.047-2.752). BMI 25-30 was a significant independent risk factor for LGA in the IVF groups (FET p = 0.041, OR 2.460, 95 % CI 1.030-5.857 and fresh ET p = 0.003; OR 2.188, 95 % CI 1.297-3.691). ICSI and double ET had no significant effect on LGA occurrence. Besides maternal BMI, FET is a significant independent LGA risk factor in IVF patients. Other observed factors (smoking, hypertension, multiparity, GDM, ICSI procedure, or number of embryos transferred) do not influence LGA risk significantly.

Difference in birth weight of consecutive sibling singletons is not found in oocyte donation when comparing fresh versus frozen embryo replacements

First, to assess if there are any differences in birth weight or gestational length in newborns from egg-donation pregnancies delivering singletons, originating from either fresh or frozen-thawed embryos when they were developed and delivered within the same mothers. Second, to determine if there are any clinical, phenotypic, or laboratory factors influencing this relationship, including the origin of the oocyte (same or different donor), the order of the children (first fresh or first frozen-thawed embryo transfer), the embryo freezing technique (vitrification or slow freezing), the in vitro embryo culture length, and the duration that embryos remained frozen. Retrospective cohorts study. University-affiliated infertility centers. A total of 360 women undergoing oocyte donation (OD), delivering (>28 weeks) at least two babies, each one from a single pregnancy, originating from at least one fresh and one frozen-thawed embryo transfer, controlling maternal and laboratory characteristics, to test the effect of embryo freezing on children size (n = 731). None. Birth weight, gestational age, weight percentile, being large for gestational age (LGA), small for gestational age (SGA), size out of normal range (ONR = LGA + SGA), and macrosomy. From fresh versus thawed embryos, respectively, mean birth weight of children was 3,183.7 g versus 3,226.4 g, gestational age was 272.1 days versus 268.8 days, and mean weight percentiles were 47.6 versus 50.1. The proportions and corresponding odds ratios (ORs) from fresh versus thawed embryos, respectively, were for LGA 13.6% versus 11.3% (OR 0.81), for SGA 9.4% versus 12.5% (OR 1.37), for ONR 23.1% versus 23.8% (OR 1.04), and for macrosomy 0.3% versus 0.8% (OR 3.1). After adjusting for clinically relevant variables, the ORs were for LGA 0.96, for SGA 1.40, for ONR 1.20, and for macrosomy not computable. None of the stated measures were significantly different. Also, independent analyses run on the origin of the oocytes, cryopreservation technique, cleavage stage of the embryos, and time that embryos remained frozen did not reveal any significant trends. This study comparing siblings from OD cycles, and eliminating the independent variables that affect early events in pregnancy, revealed no difference in duration of gestation and live birth weights between fetuses obtained after the replacement of fresh or frozen embryos. Moreover, no clinical, phenotypic, or laboratory factors appeared to be relevant, once statistically controlled.

Difference in birth weight of consecutive sibling singletons is not found in oocyte donation comparing fresh versus frozen embryo replacements

First, to assess if there are any differences in birth weight or gestational length in newborns from egg donation pregnancies delivering singletons, originating from either fresh or frozen/thawed embryos, when they were developed and delivered within the same mothers. Second, to determine if there are any clinical, phenotypical or laboratory factors influencing this relationship, including the origin of the oocyte (same or different donor), the order of the children (first fresh or first frozen/thawed embryo transfer), embryo freezing technique (vitrification or slow freezing), the in-vitro embryo culture length, and the duration that embryos remained frozen. Retrospective cohorts study. 360 women undergoing oocyte donation (OD), delivering (>28 weeks) at least two babies, each one from a single pregnancy, originating from at least one fresh and one frozen-thawed embryo transfer, controlling maternal and laboratory characteristics, to test the effect of embryo freezing on children size (n=731). From fresh vs. thawed embryos, respectively, mean birth weight of children was 3183.7g (95%CI: 3115.0-3252.4) vs. 3226.4g (95%CI: 3166.3-3243.2), gestational age (days) was 272.1 days (95%CI: 270.1-274.0) vs 268.8 days (95%CI: 263.1-274.5), and mean percentiles were 47.6th (95%CI: 44.5-50.8) vs 50.1th (95%CI: 46.8-53.3). The proportion and corresponding odds ratio (OR) from fresh vs. thawed embryos, respectively, were for children LGA: 13.6% vs. 11.3% (OR=0.81(0.52-1.27)); SGA: 9.4% vs 12.5% (OR=1.37(0.85-2.2)); ONR 23.1% vs. 23.8% (OR=1.04(0.74-1.47)); and macrosomy 0.3% vs 0.8% (OR 3.1(0.3-29.7)). Mean Z-scores were 0.28(-0.13 to 0.09) vs 0.04(-0.06 to 0.14), respectively. After adjusting for clinically relevant variables, the Adj(OR)LGA=0.96(0.50-1.87); Adj(OR)SGA=1.40(0.72-2.71); Adj(OR)ONR=1.20(0.73-1.97), and Adj(OR)MS=not computable. None of the stated measures were significantly different. Also, independent analyses run on the origin of the oocytes, cryopreservation technique, cleavage stage of the embryos, and time range of embryos remaining frozen did not reveal any significant trends. This study comparing siblings from OD cycles, and eliminating the independent variables which affect early events in pregnancy, revealed no difference in duration of gestation and live birth weights between fetuses obtained after the replacement of fresh or frozen embryos. Moreover, no clinical, phenotypical or laboratory factors appeared relevant, once statistically controlled.

Factors affecting birthweight of singletons from assisted reproductive technology

Factors affecting birthweight of singletons from assisted reproductive technology

Singleton birthweight by gestational age following in vitro fertilization in the United States

Assisted reproductive technology has been reported to account for a disproportionate higher number of low birthweight infants, even in singleton births. Low birthweight infants occur from preterm birth, decreased intrauterine growth, or both. It is unclear whether infants conceived by in vitro fertilization (IVF) have a reduced intrauterine growth rate or intrauterine growth restriction. Growth-restricted newborns have higher perinatal morbidity and are at increased risk for adult-onset illnesses. To date, there are no national standards for birthweight percentiles by gestational week, allowing for fetal growth assessment of singletons conceived by assisted reproductive technology in the United States. The objective of the study was to establish US singleton IVF reference standards using birthweight percentiles by gestational age for singleton live births resulting from IVF in the United States. We studied birthweight by completed weeks of gestation for 93,443 singleton IVF births reported to the Society for Assisted Reproductive Technologies, 2006-2010. The third to 97th birthweight percentiles per completed week of gestation for weeks between 24 and 42 were calculated and were compared with recently published birthweight percentiles by gestational age for 3,812,730 US singleton births in 2011. Smoothed birthweight for gestational age charts and curves were created for all US IVF singletons and female-male singletons from 24 to 42 weeks. Over the span of 31-41 weeks of gestation, the 10th, 50th, and 90th birthweight percentile values of IVF singletons were comparable with recently published birthweight percentile values of US singletons. At 40 completed weeks of gestation, the 10th, 50th, and 90th birthweight percentiles of all IVF singletons were 3078, 3506, and 4053 g, as compared with corresponding 3005, 3499, and 4057 g of US singletons. The 10th, 50th, and 90th birthweight percentile values for female and male IVF singletons were also comparable with US female and male singletons. Birthweight percentiles per completed week of gestation of IVF and US singletons are approximately equal from 31 until 41 completed weeks, suggesting that intrauterine growth is not reduced in IVF singleton infants.

Male gender explains increased birthweight in children born after transfer of blastocysts.

Does extended embryo culture have a different effect on the birthweight of girls and boys? The mean birthweight of boys born after fresh and frozen-thawed blastocyst transfer was increased compared with those born after cleavage stage embryo transfer. This effect was not detected among girls. Previous studies indicate that newborns from frozen-thawed cleavage stage embryos may present with a higher weight than newborns from fresh embryo transfers. With regard to fresh embryos, newborns after a blastocyst transfer have been reported as having higher birthweights than newborns from cleavage stage embryos. Retrospective multicentre case-control cohort study. All IVF/ICSI treatments were performed in the time-period from January 2008 to March 2014. Birthweight of singletons born at full-term (≥37 weeks), after fresh or frozen blastocyst embryo transfers (n = 277), were compared with weights of children born after fresh or frozen cleavage stage embryo transfers (Day 2-3) (n = 277). The cases and controls were matched by delivery week, and by gender. Data of IVF/ICSI treatments, and the treatments' outcomes were collected and analysed. The birthweight after a fresh blastocyst transfer was significantly higher (mean 3530.6 g) than that after a transfer of cleavage stage embryos (mean 3418.8 g; weight difference 111.8 g, P = 0.047). The weights of newborns after frozen-thawed blastocyst transfers (mean 3647.5 g) and the frozen-thawed cleavage stage embryo transfers (mean 3650.9 g), were similar (weight difference 3.4 g, P = 0.95). The boys born after transfer of frozen-thawed blastocysts had a significantly higher birthweight (mean 3767.9 g) than girls (3525.2 g; weight difference 242.7 g, P = 0.002), whereas the difference of birthweights between genders was only 13.5 g in cleavage stage (P = 0.863). The same effect was seen after fresh blastocyst transfers (weight difference 211.5 g, P = 0.011), but not after fresh Day 2-3 embryo transfers (weight difference 53.6 g, P = 0.478). The study material was large enough to detect differences between birthweights as a whole, but a larger study group would confirm these new findings. To avoid selection bias, the next possible control candidate, fulfilling the selection criteria, was included for matching cases and controls. We have matched the cases and controls by gender and gestational week at birth, with an aim to reduce their impact as confounding factors. Our findings of a similar weight at birth of newborns after frozen-thawed blastocysts and frozen-thawed cleavage stage embryos, when matching for age and duration of pregnancy, are novel. The gender of the newborn has an impact on the birthweight, and the extended embryo culture increases the weight difference between the genders, which is a new finding as well. The study was funded by the Fertility Society of Finland.

Age of G-1 PLUS v5 embryo culture medium is inversely associated with birthweight of the newborn

Does age of G-1 PLUS v5 embryo culture medium affect IVF outcome? Birthweight of singletons born after IVF showed an inverse association with age of the embryo culture medium, while no association was found between age of culture medium and fertilization rate, embryonic development or ongoing pregnancy. It has been reported that IVF culture media can deteriorate during storage, which suggests that the capacity of culture media to support optimal embryo development decreases over time. Some animal studies showed an effect of storage time on embryo development, in contrast to other studies, while the effect of aging culture medium on IVF outcome in humans is unknown. We used data on outcome of 1832 IVF/ICSI cycles with fresh embryo transfer, performed in the period 2008-2012 to evaluate the association of fertilization rate, embryonic development, ongoing pregnancy and birthweight of singletons with age of the culture medium (Vitrolife AB G-1 PLUS v5). Age of the culture medium was calculated by subtracting the production date from the date of ovum retrieval. Data analysis included linear regression and logistic regression on continuous and categorical outcomes, respectively. Age of the culture medium was not associated with fertilization rate (P = 0.543), early cleavage rate (P = 0.155), percentage of embryos containing four or more cells on Day 2 (P = 0.401), percentage of embryos containing eight or more cells on Day 3 (P = 0.175), percentage of embryos with multinucleated blastomeres (P = 0.527), or ongoing pregnancy (P = 0.729). However, birthweight of the newborn was inversely associated with age of the medium (β = -3.6 g, SE: 1.5 g, P = 0.021), after controlling for possible confounders (day of embryo transfer, number of transferred embryos, child's gender, gestational age at birth, parity, pregnancy complications, maternal smoking, height and weight, and paternal height and weight) and the association was not biased by year of treatment, time since first opening of the bottle or batch variations. This indicates a difference of 234 g in birthweight of newborns for media with an age difference of 65 days. The results from this study may be specific for the G-1 PLUS v5 culture medium and extrapolation of the results to other media should be done with caution because of the differences in composition and shelf life. Age of G-1 PLUS v5 medium used to culture human embryos affects birthweight of the respective newborn. This could imply that the preimplantation embryo adapts to its in vitro environment with lasting in vivo consequences. Therefore, it is important that companies are transparent about the exact composition of their embryo culture media, which will allow IVF clinics to further investigate the effects of the media or media components on the health of IVF children. No funding and no competing interests declared. Not applicable.

Preterm birth or small for gestational age in a singleton pregnancy and risk of recurrence in a subsequent twin pregnancy.

To evaluate whether a history of preterm birth or small for gestational age (SGA) in a singleton pregnancy is associated with an increased risk of recurrence of the same condition in a subsequent twin pregnancy. Retrospective cohort study of twin pregnancies delivered in one maternal-fetal medicine practice from 2005 to 2014. Patients with a history of singleton preterm birth at less than 37 weeks of gestation were compared with patients with a history of singleton term birth and nulliparous patients. A similar analysis was performed for a history of SGA (birth weight less than 10%). Six hundred forty-seven twin pregnancies were included. The prior singleton gestational age at delivery was significantly positively correlated with the twin gestational age at delivery (P<.001), and the prior singleton birth weight was significantly positively correlated with the birth weight of the larger twin (P<.001) and the smaller twin (P<.001). The rate of twin preterm birth before 32 weeks of gestation was 3.5% in patients with a prior term birth, 9.2% in nulliparous patients, and 26% in patients with a prior preterm birth (P<.001). The rate of SGA in patients with a prior birth not complicated by SGA was 42.1%, in nulliparous women it was 54.4%, and in patients with a history of SGA it was 65.2% (P=.007). On regression analysis, prior preterm birth and SGA of a singleton pregnancy were independently associated with recurrence of the same condition in a subsequent twin pregnancy. Prior preterm birth and SGA in a singleton pregnancy increase the risk of the same condition in a subsequent twin pregnancy. We postulate that the extrinsic mechanism responsible for the pathophysiology of adverse outcomes in twin pregnancies overlaps with that in singleton pregnancies.

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles.

To investigate the impact of elevated serum estradiol (E2) levels on the day of hCG trigger on the birth weight of term singletons after fresh In Vitro Fertilization (IVF)-Embryo Transfer (ET) cycles. Retrospective cohort study of all patients initiating fresh IVF-ET cycles resulting in live births between January 2004 and February 2013. The incidence of low birthweight (LBW) term singletons in patients with E2 levels on day of hCG trigger above or below the 95 % cutoff for E2 values in our clinic (3,069.2 pg/mL) was estimated. Multiple gestations and vanishing twin pregnancies were excluded. Two thousand nine hundred thirty-nine singleton live births were identified for inclusion. One hundred forty seven (5 %) and 2792 (95 %) live singleton births occurred in patients with peak E2 levels above and below 3,069.2 pg/mL, respectively. The overall incidence of term LBW was 5.4 % in the >3,069.2 pg/mL group compared to 2.4 % in the ≤3,069.2 pg/mL group (P = .038). An E2 level >3,069.2 pg/mL on the day of hCG administration was associated with increased odds of LBW term singletons (OR = 2.29; 95 % CI = 1.03-5.11). The increased odds remained unchanged when adjusting for maternal age (aOR = 2.29; 95 % CI = 1.02-5.14; P = .037), gestational age at delivery (aOR = 2.04; 95 % CI = 1.22-3.98; P = .025), and day 3 versus blastocyst transfer (aOR = 2.5; 95 % CI = 1.11-5.64; P = .023). Peak E2 level >3,069.2 pg/mL is associated with increased odds of LBW term singletons after fresh IVF-ET cycles. Conservative stimulation protocols aiming not to exceed an E2 level of 3,000 pg/mL may be advantageous for placentation and fetal growth if a fresh transfer is planned.

A Case Control Study on Risk Factors Associated with Low Birth Weight Babies in Eastern Nepal.

Background. This study was done to assess the maternal and sociodemographic factors associated with low birth weight (LBW) babies. Methods. An unmatched case control study was done involving 159 cases (mothers having LBW singleton babies) and 159 controls (mothers having normal birth weight singleton babies). Results. More than 50% of LBW babies were from the mothers with height ≤145 cm while only 9.43% of NBW babies were from the mothers with that height. Finally, after multivariate logistic regression analysis, maternal height, time of first antenatal care (ANC) visit, number of ANC visits, iron supplementation, calcium supplementation, maternal education, any illness during pregnancy, and hypertension were found as the significant predictors of LBW. However, maternal blood group AB, normal maternal Body Mass Index (BMI), mother's age of 30 or more years, and starting ANC visit earlier were found to be protective for LBW. Conclusion. Study findings suggest that selectively targeted interventions such as delay age at first pregnancy, improving maternal education and nutrition, and iron and calcium supplementation can prevent LBW in Nepal.

Prolonged saltatory fetal heart rate pattern leading to newborn metabolic acidosis

Purpose: The saltatory pattern, characterized by wide and rapid oscillations of the fetal heart rate (FHR), remains a controversial entity. The authors sought to evaluate whether it could be associated with an adverse fetal outcome. Material and Methods: The authors report a case series of four saltatory patterns occurring in the last 30 minutes before birth in association with cord artery metabolic acidosis, obtained from three large databases of internally acquired FHR tracings. The distinctive characteristics of this pattern were evaluated with the aid of a computer system. Results: All cases were recorded in uneventful pregnancies, with normal birthweight singletons, born vaginally at term. The saltatory pattern lasted between 23 and 44 minutes, exhibited a mean oscillatory amplitude of 45.9 to 80.0 beats per minute (bpm) and a frequency between four and eight cycles per minute. Conclusions: A saltatory pattern exceeding 20 minutes can be associated with the occurrence of fetal metabolic acidosis.

Relationship of birth weight with congenital cardiovascular malformations in a population-based study.

A known comorbidity of congenital cardiovascular malformations is low birth weight, but the reasons for this association remain obscure. This retrospective study examines the relationship between congenital cardiovascular malformations and the birth weight of singletons, taking into account differences in gestational age and other factors. Using data from the retrospective, population-based Baltimore-Washington Infant Study, six types of congenital cardiovascular malformations were investigated in comparison with controls (n=3519) through linear regression: d-transposition of the great arteries (n=187), other conotruncal heart defects (n=361), endocardial cushion defects (n=281), left heart obstructive lesions (n=507), atrial septal defects (n=281), and membranous ventricular septal defects (n=622). Infants with conotruncal heart defects (-218 g), endocardial cushion defects with Down syndrome (-265 g), endocardial cushion defects without Down syndrome (-194 g), left heart obstructive lesions (-143 g), atrial septal defects (-150 g), and membranous ventricular septal defects (-127 g) showed significant birth weight deficits, adjusting for gestational age, and other covariates. Infants with d-transposition of the great arteries (-67 g) did not show significant birth weight deficits compared with the control group. The degree of birth weight decrement appears to be highly related to the specific type of congenital cardiovascular malformation. As a whole, these infants do not exhibit low birth weights solely because of being premature, and thus other mechanisms must underlie these associations.

Maternal glucose level and body mass index measured at gestational diabetes mellitus screening and the risk of macrosomia: results from a perinatal cohort study

ObjectiveTo examine the impact of maternal blood glucose (BG) level and body mass index (BMI) measured at gestational diabetes mellitus (GDM) screening on the risk of macrosomia.DesignA perinatal cohort of...

The safety of long-term cryopreservation on slow-frozen early cleavage human embryos

To evaluate the impact of cryopreservation storage time on cleavage-stage embryo survival rate, pregnancy rate, implantation rate, singleton birth weight, and live birth rate. This study was a retrospective analysis, including 867 thaw cycles and 3,367 embryos. Women who underwent IVF-FET cycles between 2005 and 2012 were analyzed. The patients were divided into four groups, as follows: group 1 (12-23 months); group 2 (24-35 months); group 3 (36-48 months); and group 4 (≥48 months). The storage time did not have a significant effect on survival, damage rate of the blastomeres, implantation rate, pregnancy rate, singleton birth weight, and live birth rate for embryos frozen at cleavage stages. Storage time did not influence the survival and pregnancy outcomes of slow-frozen early cleavage human embryos. The developmental potential of cryopreserved human embryos with different storage times does not appear to have a negative influence on further development.

Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep

Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

Number of Embryos Transferred After In Vitro Fertilization and Good Perinatal Outcome

To assess the association between number of embryos transferred and a measure of assisted reproductive technology success that emphasizes good perinatal outcome. We analyzed assisted reproductive technology cycles initiated in 2011 that progressed to fresh embryo transfer among women using autologous oocytes and reported to the U.S. National Assisted Reproductive Technology Surveillance System (n=82,508). Percentages of good perinatal outcome (live birth of a term [at or after 37 weeks of gestation], normal birth weight [2,500 g or greater] singleton) were stratified by prognosis (favorable, average, less favorable), age, embryo stage (day 3, day 5), and number of embryos transferred. Differences in the percentages by number of embryos transferred were evaluated using Fisher's exact test with Bonferroni correction. Among patients younger than 35 years with a favorable prognosis, chances of a good perinatal outcome were higher with transferring a single (compared with double) day 5 (43% compared with 27%) or day 3 embryo (36% compared with 30%). Likewise, a higher chance of a good perinatal outcome was observed with transferring a single day 5 embryo in patients 35-37 years old with a favorable prognosis (39% compared with 28%) or patients younger than 35 years old with an average prognosis (35% compared with 26%). A higher chance of good perinatal outcome was associated with transferring two (compared with one) day 3 embryos among patients aged 40 years or younger with an average prognosis or patients younger than 35 years old with a less favorable prognosis. The association between number of embryos transferred and the birth of a term, normal birth weight singleton is described. Among patients younger than 35 years of age undergoing in vitro fertilization with a favorable prognosis, the highest chance of good perinatal outcome is associated with a single embryo transfer. II.

Effect of in vitro culture period on birthweight of singleton newborns

Does prolonged in vitro culture influence newborn birthweight? The absolute mean birthweight and gestational age- and gender-adjusted birthweight (Z scores) of singletons born from blastocyst transfer are higher than singletons born from Day 3 transfer. An increased proportion of large-for-gestational age (LGA) newborns occurs after blastocyst transfer compared with Day 2 transfer, and Z scores for newborns after blastocyst transfer are higher than newborns after transfer on Day 2 or Day 3. This study was a retrospective analysis of newborn birthweight, including 2929 singletons at the Reproductive Medical Center of Peking University Third Hospital between January 2009 and June 2012. The number of singletons after Day 3 transfer was 2833 and the number of singletons after blastocyst transfer (Day 5-6) was 96. Only cycles with fresh embryo transfer were included. Patients ≤40 years of age with a BMI < 30 kg/m(2) were analyzed. Only data from singleton newborns born alive after the 20th week of gestation were included in the data analysis. Patients with more than one fetal sac diagnosed by ultrasound but who delivered singletons were excluded. Patients who received PGD and cycles with donor oocytes were excluded. Multiple linear regression analysis was performed to determine the significance of individual factors on absolute birthweight of singleton newborns. The absolute birthweight and Z scores of singletons were compared. Multiple linear regression analysis indicated that maternal age, maternal BMI, paternal BMI, type of infertility, gestational age, infant gender and culture period were significantly associated with birthweight. The absolute birthweight for singletons resulting from blastocyst transfer was significantly greater than singletons resulting from Day 3 transfer (3465.31 ± 51.36 versus 3319.82 ± 10.04 g respectively, P = 0.009). The Z scores for singletons after blastocyst transfer were significantly higher than singletons after Day 3 transfer (0.347 versus 0.029 respectively, P = 0.016). In our clinic, blastocyst culture is mainly offered to patients with unsuccessful IVF cycles but also to patients with uterine malformations, and therefore this protocol introduced a potential selection bias in our study. Moreover, as certain culture media are associated with fetal overgrowth, the media used may be also a confounding factor, even though the absolute birthweights of singletons were comparable. Our study suggests that a prolonged (5-6 days) in vitro culture period has a significant effect on the mean absolute birthweight and Z scores of singleton newborns. The effect of prolonged in vitro culture on epigenetic changes in the embryo needs further study. National Natural Science Foundation of China for Young Scholars (81300483). The authors have no conflicts of interest to declare. Not applicable.