Background
Embryos with higher morphologic quality grading may have a greater potential to achieve clinical pregnancy that leads to a live birth regardless of the type of cleavage-stage embryos or blastocysts. Few studies have investigated the impacts of embryo grading on the long-term health of the offspring.
Objective
This pilot study aimed to examine the associations between embryo morphologic quality and the physical, metabolic, and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection at preschool age.
Study Design
This matched cohort study included singletons born to infertile couples who underwent fresh cleavage-stage embryo transfer cycles with good- or poor-quality embryos from 2014 to 2016 at the reproductive center of the Women’s Hospital, School of Medicine, Zhejiang University. A total of 144 children, aged 4 to 6 years, participated in the follow-up assessment from 2020 to 2021, and the response rate of poor-quality embryo offspring was 39%. Singletons in the good-quality embryo group were matched with singletons in the poor-quality embryo group at a 2:1 ratio according to the fertilization method and the children’s age (±1 year). We measured the offspring’s height, weight, body mass index, blood pressure, thyroid hormone levels, and metabolic indicators. Neurodevelopmental assessments were performed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Adaptive Behavior Assessment System, Second Edition. We also collected data from the medical records. A linear regression model was used to analyze the association between embryo morphologic quality and offspring health outcomes.
Results
A total of 48 singletons conceived with poor-quality embryo transfer and 96 matched singletons conceived with good-quality embryo transfer were included in the final analysis. Age, sex, height, weight, body mass index, blood pressure, thyroid function, and metabolic indicators were comparable between the 2 groups. After adjustment for potential risk factors by linear regression model 1 and model 2, poor-quality embryo offspring exhibited a tendency toward higher free thyroxine levels than offspring of good-quality embryo transfers (beta, 0.22; 95% confidence interval, 0.09–0.90; beta, 0.22; 95% confidence interval, 0.09–0.91, respectively), but this difference was not clinically significant. Regarding neurodevelopmental assessments, there was no difference in the full-scale intelligence quotient based on the Wechsler Preschool and Primary Scale of Intelligence (109.96±12.42 vs 109.60±14.46; P =.88) or the general adaptive index based on the Adaptive Behavior Assessment System (108.26±11.70 vs 108.08±13.44; P =.94) between the 2 groups. The subindices of the 2 tests were also comparable. These findings remained after linear regression analysis.
Conclusion
At 4 to 6 years of age, singletons born from poor-quality embryo transfers have comparable metabolic and cognitive development as those born from good-quality embryo transfers using fresh cleavage-stage embryos. The results of this pilot study indicate that poor-quality embryos that can survive implantation and end in live birth are likely to have a developmental potential comparable to that of good-quality embryos.
Introduction
It is estimated that more than 8 million children have been conceived through assisted reproductive technology (ART) in recent decades. This number has been increasing by 9.1% annually. The widespread use of ART raises concerns about the short- and long-term health of the offspring. Some studies indicated that children conceived by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) exhibited less favorable cardiometabolic profiles than naturally conceived offspring. Moreover, whether ART offspring have comparable intellectual function remains controversial. ,
Why was this study conducted?
Embryo morphologic quality is a primary predictor of pregnancy for in vitro fertilization and intracytoplasmic sperm injection. Because only a few studies have evaluated the effects of the morphologic quality of an embryo on subsequent childhood health, we aimed to compare the metabolic and cognitive development of preschool children born via poor-quality vs good-quality embryo transfer.
Key findings
Embryo morphologic quality was not associated with height, weight, body mass index, blood pressure, metabolic profiles, or scores on the Wechsler Preschool and Primary Scale of Intelligence and the Adaptive Behavior Assessment System in offspring conceived by in vitro fertilization and intracytoplasmic sperm injection.
What does this add to what is known?
Offspring conceived via poor-quality embryo transfer did not have an increased risk for metabolic abnormalities or low cognitive function when compared with those conceived via good-quality embryo transfer.
Morphologic assessment is the first-line approach to evaluating the quality of embryos for IVF and ICSI. Several studies reported an association between embryo morphologic quality and the chance of pregnancy and live birth from cleavage-stage embryos and blastocysts. Poor-quality embryos (PQEs) with low morphologic grading are often considered to have low developmental potential because of the increased rates of miscarriage , and aneuploidy. Infertile women may receive low-potential embryo transfers (ETs) in an attempt to conceive when only PQEs are available.
Recent studies have investigated the health outcomes of PQE newborns. , There was no marked difference in birthweight, gestational age, or the incidence of neonatal complications between singletons born from fresh PQE transfer and those born from fresh good-quality embryo (GQE) transfer. , However, inferior embryo morphologic quality in vitrified-warmed single-blastocyst transfer cycles was found to be associated with a higher risk for low birthweight and preterm birth. , Moreover, one previous retrospective study suggested that there is an increased risk for congenital malformation in PQE offspring following single-blastocyst transfer cycles after reviewing reproductive data in Australia from 2005 to 2015.
To date, most studies have focused on children’s health from birth to infancy, but the possible impacts of embryo morphologic grading on the long-term health of offspring remain unclear. Therefore, this pilot study was conducted to examine the potential association between embryo morphologic quality and the metabolic and neurodevelopmental outcomes of 4- to 6-year-old singletons born from fresh IVF and ICSI.
Materials and Methods
Study design and participants
This pilot cohort study recruited children conceived by IVF and ICSI at the reproductive center of the Women’s Hospital, School of Medicine, Zhejiang University, from January 2013 to December 2016. The follow-up assessments were conducted from December 2020 to September 2021 at the ART Offspring Health Monitoring Center. The maternal medical records were reviewed. Infertile women who underwent fresh cleavage-stage ET that led to a singleton live birth were included. Of the 20,044 women who underwent oocyte retrieval in 2013 to 2016, we excluded women who had no available embryos for transfer (n=7993), those who were <20 years or >40 years (n=490), underwent preimplantation genetic diagnosis or screening (PGD or PGS, n=175), had chromosomal abnormalities from either side of the couple (n=480), underwent transfer of embryos in other stages (n=82), received embryos of inconsistent quality in 1 ET cycle (n=1685), or had missing data on embryo morphologic grading (n=61). Then, according to the morphologic scores of the transferred embryos, 9078 eligible ET cycles were divided into the PQE group (n=1034) and the GQE group (n=8044), ending in 186 and 3128 live births, respectively.
Considering the potential effects of multiple births on offspring health, the compliance of children, and the applicable age range of intelligence tests, we restricted the study participants to singleton children at 4 to 6 years of age. After the exclusion process, 124 women who had received PQE transfers were invited to participate by telephone in this study. A total of 49 women agreed to participate, and 48 children completed the cognitive tests, reaching a response rate of 39% for PQE singletons. Of the 75 children not enrolled in this study, 23 rejected the invitation, 21 could not participate in the study because of the COVID-19 pandemic, 18 had lost contact, 10 relocated to other regions, and 3 died. To improve the statistical efficiency and to control for potential confounding factors, singletons conceived by GQE transfer were matched according to the fertilization method and age (±1 year) of the children at a 2:1 ratio during the follow-up period. If >2 GQE offspring per PQE offspring met the matching criteria and agreed to participate in our study, the 2 GQE offspring who were closest in age to the PQE offspring were enrolled. Ultimately, 48 children in the PQE group and 96 children in the GQE group were included in the final analysis ( Figure 1 ). All of the participant women used autologous oocytes and denied undergoing fetal reduction surgery.
The institutional review board (IRB) of the Women’s Hospital, School of Medicine, Zhejiang University, approved the study (IRB-20200286-R). Written informed consent was obtained from the parents of the children before any research activity.
Embryo quality assessment
Two well-trained and experienced embryologists independently and blindly evaluated the embryo morphologic grading in the ART laboratory of this reproductive center. Based on the Istanbul consensus, we simplified the standard of embryo quality classification. A PQE was defined as only 2 cells on day 2, fewer than 6 cells on day 3, or more than 20% fragmentation. A GQE was defined as 3 to 4 cells on day 2 or 6 to 8 cells on day 3 with fewer than 20% anucleate fragments. The laboratory protocols were the same from 2013 to 2016.
Growth and metabolic assessment
Weight and height were measured while the children were wearing light clothing and no shoes. Body mass index (BMI, kg/m 2 ) was calculated as weight divided by height squared. According to the BMI growth curve for Chinese children, overweight was defined as a z score of BMI-for-age and sex >1 and <2, and obesity was defined as a z score of BMI-for-age and sex ≥2. Systolic and diastolic blood pressure were measured using an automatic oscillometric device (Mindray BY-29140567, Mindray Medical International Ltd, Shenzhen, China) with an appropriate cuff size adapted to the children’s upper arm perimeter. Fasting venous blood samples were collected to test thyroid hormone, lipid profiles, and glucose levels in the Department of Laboratory Medicine of this hospital. Blood could not be drawn from 1 child in the GQE group and 4 children in the PQE group because of poor vascular condition, and these children were excluded from the blood sample-related analyses. The detailed information of these 5 children is presented in Supplemental Table 1 .
Cognitive function assessment
To evaluate participants’ cognitive performance and adaptive ability, we used the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) and the Adaptive Behavior Assessment System II (ABAS-II), which were translated and adapted by the King-May company with the authorization of NCS Pearson, Inc (Bloomington, MN) and the Western Psychological Services (Torrance, CA). The validity of the 2 adapted scales was demonstrated to be identical to that of the original scales. , The WPPSI-IV test is extensively used in intelligence assessment , and has well-documented psychometric properties. The following 5 main indices provide standardized scores adjusted for the subject’s age and sex: verbal comprehension index (VCI), visual space index (VSI), fluid reasoning index (FRI), working memory index (WMI), and processing speed index (PSI). The full-scale intelligence quotient (FSIQ) was calculated based on the 5 domain subscales. All examiners were trained by a clinician with test qualifications, and the tests were completed in a quiet room. The ABAS-II test is designed as a standardization questionnaire for a child’s parents and teachers to evaluate the practical daily skills required to adapt to the environmental demands that are appropriate for his or her age. Scores from 10 skill areas are grouped into the following 3 domains: conceptual, social, and practical skills. In addition, a General Adaptive Index (GAI) score, which can reflect the child’s overall adaptive behavior, was calculated. For this study, the parents’ version of the ABAS-II was used. All scores of both tests were reported as standardized scores with a mean of 100 and a normalized standard deviation (SD) of 15. ,
Covariates
Parental demographics, ART information, and neonatal characteristics were collected from medical records and standard questionnaire interviews. Supplemental Table 2 presents the time point and source of each variable obtained or assessed, and the time frame was the same for every couple with their child. Parental demographics included age, BMI, parity, educational attainment, occupation, and smoking status before pregnancy. Education level was classified as middle school or below, high school, or college or above. According to the European Socioeconomic Classification (E-SeC), parental occupations were classified into 3 categories, namely more advantaged occupations (higher professionals and managers, higher clerical, service and sales workers, E-SeC classes 1–3), middle occupations (small employers, self-employed individuals, farmers, lower supervisors and technicians, E-SeC classes 4–6), and less advantaged occupations (lower clerical, services, and sales workers, skilled workers, semiskilled and unskilled workers, E-SeC classes 7–9). Annual household income was categorized as more or less than 100,000 Chinese yuan (CHY) based on the household annual income per person of 49,899 CHY in 2019 according to statistical data from the Zhejiang Province government. Medical records provided treatment information, including causes of infertility (principal cause and others), primary IVF or ICSI cycle, number of available embryos, number of embryos transferred, fertilization method, embryo stage, ovary hyperstimulation syndrome (OHSS), maternal estradiol level on human chorionic gonadotropin (hCG) administration day, and vanishing twin syndrome. Available embryos were defined as split embryos available for transfer. We also collected pregnancy and neonatal characteristics, including pregnancy complications (anemia, gestational diabetes mellitus, and gestational hypertension), gestational age at delivery, preterm birth (gestational age <37 weeks), birthweight, mode of delivery, respiratory distress syndrome, congenital anomalies, and breastfeeding patterns.
Statistical analysis
Statistical analysis was performed using SPSS 25.0 (IBM, Armonk, NY). Comparative analysis was performed using the chi-square test or Fisher exact test for categorical variables and a t test for continuous variables. The association of embryo quality with test scores and metabolic measurements of offspring was assessed using a linear regression model. We adjusted for parental age, parental BMI, paternal smoking, ART information (polycystic ovary syndrome [PCOS], primary infertility, number of embryos transferred, fertilization method, embryo stage, OHSS), child age and sex, neonatal characteristics (gestational age, birthweight, cesarean delivery, respiratory distress syndrome, breastfeeding patterns), and pregnancy complications in model 1. Additional adjustments were made for parental educational levels, occupations, and household income in model 2. The effects are presented as beta coefficients and 95% confidence intervals (CIs). A 2-sided P value of <.05 was considered indicative of statistical significance. PASS 15 software (NCSS LLC, Kaysville, UT) was used to estimate the sample size according to a previous publication. To reach a power ≥0.80 (α=0.05; ratio=1:2), 28 PQE subjects and 56 GQE subjects were needed to detect a 1 kg/m 2 difference in BMI between the 2 groups, and 48 PQE subjects and 96 GQE subjects were required to detect a difference of 5 in the FSIQ. Therefore, at least 48 PQE subjects and 96 GQE subjects were needed to reach satisfactory statistical power.
Results
A total of 9078 women underwent fresh cleavage-stage ET with consistent embryo grading per cycle from January 2013 to December 2016. Of these, 1034 received PQEs and 8044 received GQEs, ending in 186 and 3128 live births, respectively. As presented in Supplemental Table 3 , GQE transfer showed a 2-fold increase in clinical pregnancy and live birth rates when compared with PQE transfer, and gestational age, birthweight, and the cesarean delivery rates were similar between neonates conceived by GQE and those conceived by PQE transfer. We also compared the characteristics between the included children and all singleton offspring in the PQE group and GQE group, respectively. There was no significant difference between the 48 PQE subjects that were included and all 124 PQE singletons ( Supplemental Table 4 ), whereas the 96 included GQE subjects had higher parental education levels than all 1813 singletons born from GQE transfer ( Supplemental Table 5 ).
Baseline characteristics of the 2 groups
A total of 48 children born from PQE transfers with a response rate of 39% and 96 matched children from GQE transfers were included in this study. Women in the PQE group had fewer available embryos than those in the GQE group (3.3±1.9 vs 5.0±3.0; P <.001). There was no significant difference in parental age, BMI, parity, smoking status, education level, occupation, household income, principal cause of infertility, PCOS, IVF/ICSI treatments, or pregnancy complications between the 2 groups ( Table 1 ). The singletons in the 2 groups were similar in gestational age, birthweight, mode of delivery, incidence of respiratory distress syndrome, congenital anomalies, and breastfeeding patterns. All mothers of the included children denied cigarette smoking.
| Characteristics | GQE group (n=96) | PQE group (n=48) | P value |
|---|---|---|---|
| Maternal age (y), mean±SD | 30.8±3.9 | 31.1±3.9 | .65 |
| Maternal BMI (kg/m 2 ), mean±SD | 22.4±2.6 | 22.0±3.0 | .41 |
| Nulliparous, n (%) | 82 (85.4) | 40 (83.3) | .74 |
| Maternal education level, n (%) | .93 | ||
| Middle school or below | 22 (22.9) | 10 (20.8) | |
| High school | 39 (40.6) | 19 (39.6) | |
| College or above | 35 (36.5) | 19 (39.6) | |
| Maternal occupation, n (%) | .52 | ||
| Less advantaged | 29 (30.2) | 19 (39.6) | |
| Middle | 43 (44.8) | 18 (37.5) | |
| Most advantaged | 24 (25.0) | 11 (22.9) | |
| Paternal age (y), mean±SD | 32.5±4.8 | 33.6±5.1 | .24 |
| Paternal BMI (kg/m 2 ), mean±SD | 24.2±3.4 | 23.5±3.9 | .28 |
| Paternal education level, n (%) | .76 | ||
| Middle school or below | 19 (19.8) | 9 (18.8) | |
| High school | 40 (41.7) | 23 (47.9) | |
| College or above | 37 (38.5) | 16 (33.3) | |
| Paternal occupation, n (%) | .25 | ||
| Less advantaged | 24 (25.0) | 10 (20.8) | |
| Middle | 51 (53.1) | 32 (66.7) | |
| Most advantaged | 21 (21.9) | 6 (12.5) | |
| Paternal smoking, n (%) | 26 (27.1) | 11 (22.9) | .59 |
| Annual household income, n (%) | .90 | ||
| >100,000 CHY | 69 (71.9) | 34 (70.8) | |
| ≤100,000 CHY | 27 (28.1) | 14 (29.2) | |
| Principal cause of infertility, n (%) a | .64 | ||
| Male infertility | 18 (18.8) | 9 (18.8) | |
| Tubal factor infertility | 54 (56.3) | 25 (52.1) | |
| Endometriosis | 10 (10.4) | 4 (8.3) | |
| Ovulation disorder | 9 (9.4) | 4 (8.3) | |
| Unexplained | 5 (5.2) | 6 (12.5) | |
| Maternal PCOS, n (%) | 5 (5.2) | 1 (2.1) | .66 |
| IVF/ICSI-ET details | |||
| Primary infertility, n (%) | 48 (50.0) | 23 (47.9) | .81 |
| Primary IVF/ICSI cycle, n (%) | 74 (77.1) | 35 (72.9) | .58 |
| Number of available embryos, mean±SD | 5.0±3.0 | 3.3±1.9 | <.001 b |
| Number of embryos transferred, n (%) | .19 | ||
| 1 | 17 (17.7) | 13 (27.1) | |
| 2 | 79 (82.3) | 35 (72.9) | |
| ICSI, n (%) | 24 (25.0) | 12 (25.0) | >.99 |
| Embryo stage, n (%) | .13 | ||
| Day 2 | 11 (11.5) | 10 (20.8) | |
| Day 3 | 85 (88.5) | 38 (79.2) | |
| OHSS, n (%) | 10 (10.4) | 7 (14.6) | .47 |
| Maternal estradiol level on hCG administration day (pmol/L), mean±SD c | 9896.5±5483.0 | 9851.5±7353.6 | .97 |
| Vanishing twin syndrome, n (%) | 2 (4.2) | 6 (5.9) | >.99 |
| Complications of pregnancy, n (%) | |||
| Anemia | 13 (13.5) | 9 (18.8) | .41 |
| Gestational diabetes mellitus | 11 (11.5) | 10 (20.8) | .13 |
| Gestational hypertension disorders | 6 (6.3) | 1 (2.1) | .27 |
| Neonatal characteristics | |||
| Gestational age (wk), mean±SD | 38.5±1.9 | 38.8±1.4 | .24 |
| Preterm birth, n (%) | 10 (10.4) | 1 (2.1) | .10 |
| Birthweight (g), mean±SD | 3332.6±565.1 | 3348.1±461.6 | .87 |
| Low birthweight, n (%) d | 6 (6.3) | 2 (4.2) | .72 |
| Macrosomia, n (%) e | 8 (8.3) | 3 (6.3) | .75 |
| Cesarean delivery, n (%) | 55 (57.3) | 33 (68.8) | .18 |
| Respiratory distress syndrome, n (%) | 5 (5.2) | 1 (2.1) | .66 |
| Congenital anomaly, n (%) | 5 (5.2) | 6 (13.6) | .10 |
| Breastfeeding patterns, n (%) | .96 | ||
| Breastfeeding only | 62 (64.6) | 32 (66.7) | |
| Artificial only | 25 (26.0) | 12 (25.0) | |
| Mixed | 9 (9.4) | 4 (8.3) |
a Principal cause of infertility means the leading cause exclusively
b Statistically significant value
c One value was missing for maternal estradiol level on hCG administration day in the GQE group
d Low birthweight is defined as birthweight <2500 g
Growth and metabolic profiles of offspring
Age, sex, height, weight, BMI, blood pressure, thyroid function, lipid profiles, and glucose level were similar between the 2 groups ( Table 2 ). However, the PQE offspring had slightly higher free thyroxine (FT4) levels than the GQE offspring (14.41±1.00 pmol/L vs 14.03±1.09 pmol/L; P =.05). After adjustment for potential risk factors in linear regression model 1 ( Table 3 ), the beta value of the FT4 levels was 0.22 (95% CI, 0.09–0.90) for PQE children when compared with GQE children. This difference remained significant in linear regression model 2 (beta, 0.22; 95% CI, 0.09–0.91), which additionally adjusted for socioeconomic features. There was no association between embryo morphologic quality and other metabolic profiles.
| Characteristics | GQE group (n=96) | PQE group (n=48) | P value |
|---|---|---|---|
| Age at examination (y), mean±SD | 4.9±0.5 | 4.9±0.7 | .57 |
| Sex (male), n (%) | 58 (60.4) | 29 (60.4) | >.99 |
| Height (cm), mean±SD | 109.3±5.5 | 109.5±4.9 | .86 |
| Weight (kg), mean±SD | 18.6±3.3 | 18.5±3.1 | .87 |
| BMI (kg/m 2 ), mean±SD | 15.4±1.8 | 15.3±1.8 | .74 |
| Overweight, n (%) | 12 (12.5) | 3 (6.3) | .39 |
| Obese, n (%) | 8 (8.3) | 4 (8.3) | >.99 |
| Systolic blood pressure (mmHg), mean±SD | 99.3±8.9 | 99.2±10.4 | .95 |
| Diastolic blood pressure (mmHg), mean±SD | 57.7±8.1 | 57.8±7.6 | .92 |
| Children’s thyroid function, mean±SD a | |||
| FT4 (pmol/L) | 14.03±1.09 | 14.41±1.00 | .05 |
| TSH (mIU/L) | 2.42±1.06 | 2.63±1.37 | .33 |
| Children’ metabolic indicators (mmol/L), mean±SD a | |||
| Triglyceride | 0.72±0.25 | 0.74±0.24 | .58 |
| Cholesterol | 4.57±0.83 | 4.49±0.78 | .58 |
| High-density lipoprotein | 1.55±0.27 | 1.49±0.31 | .23 |
| Low-density lipoprotein | 2.66±0.63 | 2.66±0.56 | .95 |
| Glucose | 4.84±0.36 | 4.81±0.37 | .66 |
a A total of 95 children in the GQE group and 44 children in the PQE group underwent fasting venous blood sample tests.
| Offspring characteristics | GQE group (n=95) a | PQE group (n=44) b | Unadjusted | Adjusted model 1 c | Adjusted model 2 d | |||
|---|---|---|---|---|---|---|---|---|
| Beta (95% CI) | P value | Beta (95% CI) | P value | Beta (95% CI) | P value | |||
| Children’s thyroid function, mean±SD | ||||||||
| FT4 (pmol/L) | 14.03±1.09 | 14.41±1.00 | 0.38 (−0.01 to 0.72) | .05 | 0.22 (0.09 to 0.90) | .02 | 0.22 (0.09 to 0.91) | .02 |
| TSH (mIU/L) | 2.42±1.06 | 2.63±1.37 | 0.21 (−0.21 to 0.63) | .33 | 0.03 (−0.37 to 0.53) | .73 | 0.01 (−0.43 to 0.47) | .93 |
| Children’ metabolic indicators, mean±SD | ||||||||
| TG (mmol/L) | 0.72±0.25 | 0.74±0.24 | 0.03 (−0.06 to 0.12) | .58 | 0.07 (−0.07 to 0.14) | .49 | 0.07 (−0.07 to 0.14) | .48 |
| TC (mmol/L) | 4.57±0.83 | 4.49±0.78 | −0.08 (−0.38 to 0.21) | .58 | −0.06 (−0.44 to 0.22) | .52 | −0.04 (−0.41 to 0.26) | .67 |
| HDL (mmol/L) | 1.55±0.27 | 1.49±0.31 | −0.06 (−0.16 to 0.04) | .23 | −0.16 (−0.21 to 0.02) | .09 | −0.13 (−0.19 to 0.03) | .16 |
| LDL (mmol/L) | 2.66±0.63 | 2.66±0.56 | 0.01 (−0.21 to 0.22) | .95 | 0.00 (−0.24 to 0.25) | .98 | 0.02 (−0.22 to 0.27) | .84 |
| GLU (mmol/L) | 4.84±0.36 | 4.81±0.37 | −0.03 (−0.16 to 0.10) | .66 | −0.01 (−0.14 to 0.12) | .90 | −0.00 (−0.13 to 0.13) | .97 |
a A total of 95 of 96 children in the GQE group underwent fasting venous blood sample tests
b All 48 children in the PQE group underwent fasting venous blood sample tests
c Model 1 adjusted for parental age, parental BMI, paternal smoking, ART information (PCOS, primary infertility, primary IVF/ICSI cycle, number of embryos transferred, fertilization method, embryo stage, OHSS), child age and sex, neonatal characteristics (gestational age, birthweight, cesarean delivery, respiratory distress syndrome, breastfeeding patterns), and pregnancy complications (anemia, gestational diabetes, gestational hypertension)
d Model 2 additionally adjusted for parental educational level, occupation, and annual household income.
Intellectual and adaptive evaluation in offspring
Children born from PQE transfers achieved FSIQ scores in the WPPSI-IV test that were comparable with those of children in the GQE group (109.60±14.46 vs 109.96±12.42; P =.88). Only 1 child (2.1%) in the PQE group and 1 child (1.0%) in the GQE group obtained an FSIQ score of <80 (marginal intelligence score). Similarly, there was no significant difference between the groups in terms of VCI, VSI, FRI, WMI, and PSI scores. Moreover, the GAI score, conceptual skills, social skills, and practical skills measured in the ABAS-II test for the PQE group were not different from those in the GQE group. Only 1 child in the PQE group obtained a GAI score <80. No significant difference was found after adjusting for these covariates in linear regression models 1 and 2 ( Table 4 ). The distributions of the FSIQ and GAI scores in two groups were also comparable ( Figure 2 ).
| Offspring characteristics | GQE group (n=96) | PQE group (n=48) | Unadjusted | Adjusted model 1 a | Adjusted model 2 b | |||
|---|---|---|---|---|---|---|---|---|
| Beta (95% CI) | P value | Beta (95% CI) | P value | Beta (95% CI) | P value | |||
| WPPSI-IV, mean±SD | ||||||||
| FSIQ | 109.96±12.42 | 109.60±14.46 | −0.35 (−4.94 to 4.24) | .88 | −0.06 (−6.72 to 3.16) | .48 | −0.04 (−5.78 to 3.58) | .64 |
| FSIQ <80, n (%) | 1 (1.0) | 1 (2.1) | ||||||
| VCI | 107.81±13.44 | 107.69±15.09 | −0.13 (−5.02 to 4.77) | .96 | −0.04 (−6.60 to 4.11) | .65 | −0.01 (−5.52 to 4.69) | .87 |
| VSI | 107.50±13.84 | 108.71±15.36 | 1.21 (−3.81 to 6.23) | .64 | −0.01 (−5.77 to 5.24) | .92 | 0.01 (−5.13 to 5.79) | .91 |
| FRI | 108.21±12.91 | 109.54±12.76 | 1.33 (−3.16 to 5.83) | .56 | 0.03 (−3.89 to 5.37) | .75 | 0.04 (−3.52 to 5.71) | .64 |
| WMI | 103.32±10.91 | 101.35±12.37 | −1.97 (−5.96 to 2.02) | .33 | −0.15 (−7.72 to 0.71) | .10 | −0.13 (−7.33 to 1.12) | .15 |
| PSI | 103.16±11.30 | 104.38±10.61 | 1.22 (−2.65 to 5.09) | .54 | 0.04 (−3.21 to 5.21) | .64 | 0.04 (−3.16 to 5.05) | .65 |
| ABAS-II, mean±SD | ||||||||
| GAI | 108.26±11.70 | 108.08±13.44 | −0.18 (−4.48 to 4.12) | .94 | 0.01 (−5.05 to 4.58) | .92 | 0.01 (−4.42 to 5.07) | .89 |
| GAI <80, n (%) | — | 1 (2.1) | ||||||
| Conceptual skills | 106.96±13.30 | 107.15±14.07 | 0.19 (−4.55 to 4.93) | .94 | 0.00 (−5.19 to 5.40) | .97 | 0.03 (−4.44 to 5.91) | .78 |
| Social skills | 109.43±10.70 | 107.90±13.90 | −1.53 (−5.68 to 2.61) | .47 | −0.07 (−6.48 to 2.69) | .41 | −0.07 (−6.26 to 2.79) | .45 |
| Practical skills | 106.15±11.95 | 106.77±12.87 | 0.63 (−3.66 to 4.91) | .77 | 0.02 (−4.21 to 5.37) | .81 | 0.04 (−3.73 to 5.90) | .66 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
