Assisted Reproductive Group Research Articles

Neurodevelopment at 5 years of age for preterm-born children according to mode of conception: a cohort study

Preterm delivery is a risk factor for suboptimal neurodevelopment. Pregnancies conceived after medically assisted reproduction-which includes invitro fertilization, with or without intracytoplasmic insemination, and induction of ovulation followed by intrauterine insemination or timed intercourse-have a higher risk of preterm delivery. Few studies have evaluated the outcome at >2 years of age of such preterm-born children. To evaluate neurodevelopmental outcome at 5½ years of age of children born preterm according to the mode of conception (spontaneous vs medically assisted reproduction). A total of 4349 children born between 24 and 34 weeks of gestation who survived to 5½ years of age in the 2011 French prospective national cohort study "EPIPAGE-2" were included: 814 in the medically assisted reproduction group (433 by invitro fertilization, with or without intracytoplasmic insemination, and 381 by induction of ovulation) and 3535 in the spontaneously conceived group. The studied neurodevelopmental outcomes were sensory (hearing and vision) impairments, cerebral palsy, cognition, and developmental coordination disorders. Multivariate analyses were performed with generalized estimating equation models adjusted for gestational age, antenatal steroids, and social characteristics. All analyses were performed following multiple imputation. Sensitivity analyses were performed with the populations of singletons and cases with complete data. No differences in cerebral palsy (adjusted odds ratio, 1.00; 95% confidence interval, 0.67-1.49), neurodevelopmental impairment (adjusted odds ratio, 1.09; 95% confidence interval, 0.82-1.45), or developmental coordination disorders (adjusted odds ratio, 0.75; 95% confidence interval, 0.50-1.12) were found between children born following medically assisted reproduction and children born following spontaneous conception after adjustment for sociodemographic factors. For proportions of children with an intelligence quotient below 1 and 2 standard deviations, there were no differences between those born after medically assisted reproduction and those born after spontaneous pregnancy (respectively, adjusted odds ratio, 0.99; 95% confidence interval, 0.80-1.23 and adjusted odds ratio, 1.14; 95% confidence interval, 0.83-1.56). In subgroup analyses, no differences were observed between children born following induction of ovulation or invitro fertilization and those conceived spontaneously. Sensitivity analyses were consistent with the main results. In this cohort of preterm-born children, there was no evidence of an impact of the mode of conception on neurodevelopmental outcomes at 5½ years of age.

The value of transvaginal 4-dimensional hysterosalpingo-contrast sonography in predicting the necessity of assisted reproductive technology for women with tubal factor infertility.

More than 50 million women suffer from infertility worldwide, among whom 30% have associated fallopian tube pathology. Fortunately, the diagnostic accuracy of tubal patency has been enhanced with the consistent development of ultrasound imaging technology, especially the invention of transvaginal 4-dimensional hysterosalpingo-contrast sonography (TV 4D HyCoSy). However, detailed imaging data for evaluating the tubal condition for spontaneous conception and assessing the necessity of assisted reproductive technology (ART) have yet to be amassed. Patients with tubal factor infertility (TFI) who received TV 4D HyCoSy were recruited for this study. They were divided into two groups according to the method of conception: the natural pregnancy group (patients who naturally conceived within 3 months after TV 4D HyCoSy) and the assisted reproduction group (patients who failed to conceive naturally within the 3 months but successfully conceived through ART). Logistic regression analysis was performed to examine the data obtained from participants' medical history and TV 4D HyCoSy investigation. Of the initial 1,433 women, 348 were excluded due to exclusion criteria or lack of follow-up. A total of 1,085 TFI patients were finally included, with individuals in the natural pregnancy group accounting for 27.74% (n=301), and those in the ART group accounting for 37.33% (n=405). The age was younger and the duration of infertility was shorter in the group of women who conceive spontaneously after TV 4D HyCoSy (P<0.05). In terms of imaging data, their endometrial thickness was thinner, right fallopian tube wall was more intact, morphology of the right fallopian tube was smoother, and their ovarian motility (bilateral), fallopian tube visualization (bilateral) and overflow condition of the contrast agent from the fimbriae of fallopian tube (bilateral) were better. In addition, the resistance of the contrast agent injection was less likely to be persistent, reflux was less likely to happen and 0/1 dispersion of the contrast agent around the ovary (bilateral) were more likely to be annular (P<0.05). The imaging data gathered from TV 4D HyCoSy in TFI patients were comprehensive, which suggested that TV 4D HyCoSy could have potential to be used to assess the necessity of post-HyCoSy ART intervention in patients with TFI. This could be of benefit in reducing the incidence of overtreatment and potential complications of ART.

Dental Status Between Assisted Reproductive Technology And Natural Conceived Children: A Comparative Pilot Study

Objectives: ART children were proven to have low birth weight and some birth defects. However, limited number of studies found concerning dental status of ART children. This research aimed to determine oral health practice and dental status between Assisted-Reproductive (ART) and Natural Conceived (NC) children. Materials And Method: This cross-sectional study consisted of 34 subjects, 17 were ART children and 17 NC children as control. Intraoral examination was conducted and orthopantomogram (OPG) radiograph were obtained from the subjects. Any abnormalities of tooth development such as number and tooth colour were recorded. Oral hygiene practice such as tooth brushing frequency and supervision from the parents during tooth brushing were identified. Caries experience of both groups were recorded using dmft for deciduous teeth and DMFT for permanent teeth. Descriptive analysis, Bivariate analysis were done using Mann-Whitney’s test and Spearman rho test. Results: Most of the participants were girls (58.8%) and majority were aged of 7 – 8 years old (47.1%). 70.6% of ART group used intra-uterine insemination (IUI) technique while 29.4% used in-vitro fertilization (IVF). There was one hypodontia case found in each group. Caries experience in primary teeth showed significantly lower in the ART group with p < 0.05. Conclusions: There was a comparable case of hypodontia in ART and NC group. However, caries experience (dmft) of children in ART group was found significantly lower than NC group.

Neurodevelopmental outcomes of preterm infants conceived by assisted reproductive technology

There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited. This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at <29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally. This retrospective cohort study included inborn, nonanomalous infants, born at <29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of <85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment. Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88). Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at <29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

Unique Associations between Insulin-Like Growth Factor Binding Protein-1, Insulin-Like Growth Factor-1 and T Cell Immunoglobulin Mucin 3 in Successful Twin Pregnancies Conceived with Donor Oocytes.

Background and Objectives: To investigate if pregnancies conceived using an oocyte donor necessitate an alteration in immune regulation, we compared concentrations of insulin-like growth factor binding protein (IGFBP)-1, insulin-like growth factor (IGF)-1 and T cell immunoglobulin mucin-3 (Tim-3) in women with ongoing successful twin pregnancies conceived spontaneously, using assisted reproductive technologies that utilized homologous oocytes or with donor oocytes. Differences in levels of these immune modulatory proteins may be magnified and easier to detect in twin as compared to singleton pregnancies. Methods: In this prospective study IGFBP-1 and IGF-1 were measured in sera and Tim-3 in lysates of peripheral blood mononuclear cells (PBMCs) by ELISA. Results: Median IGFBP-1 levels were lower in women with donor oocytes (41.4 ng/ml) as compared to those with a spontaneous conception (51.2 ng/mL) or who conceived with various assisted reproduction protocols using homologous oocytes (52.4 ng/mL) (p < 0.001). IGF-1 and Tim-3 levels were comparable in each group. The IGFBP-1 level was inversely correlated to the IGF-1 concentration only in women with donor oocytes (p = 0.032). IGFBP-1 and Tim-3 levels were similarly negatively correlated in the donor oocyte group (p = 0. 012). Women in the assisted reproduction group who conceived following intracytoplasmic sperm injection were the only other group in which IGFBP-1 and Tim-3 were negatively correlated (p = 0.018). Conclusions: Down-regulation of IGFBP-1 production in pregnancies conceived with donor oocytes may reduce the extent of pro-inflammatory immunity and contribute to successful outcome in totally allogeneic pregnancies.

Clinical success of intrauterine insemination cycles is affected by the sperm preparation time

To determine the impact of the time interval from the end of sperm preparation (TSP) to intrauterine insemination (IUI) on the outcome. Prospective multicentre cohort study. Seven French centers (assisted reproduction group in northeastern France, four academic centers, and three clinics). Eight hundred sixty-two IUI cycles (709 patients) managed by gonadotropins were studied. Cycles were stimulated by either FSH or hMG, and hCG was administrated when the leading follicle diameter measured >15 mm. IUIs were performed ∼ 36 hours after ovulation triggering. Generalized linear mixed models for binary outcomes were used to model clinical pregnancy (CP) to assess the effect of TSP adjusted for other predictors (such as maternal age, semen quality, and indication of IUI treatment). The TSP effect was significant, featuring an inverse U-shaped curve admitting an optimum interval of ∼ 40-80 minutes improving CP compared with other values. Other significant predictors were total motile spermatozoa inseminated, maternal age, and unexplained infertility. The observance of TSP in the range of 40-80 minutes has a potential positive effect on pregnancy rate, while not requiring the investment of supplemental resources. This finding awaits confirmation in randomized trials.

Stress and anxiety‐depression levels following first‐trimester miscarriage: a comparison between women who conceived naturally and women who conceived with assisted reproduction

To compare the psychological impact following early miscarriage between women who conceived naturally and women who conceived following assisted reproduction. Prospective cohort study. Assisted reproduction clinic and general gynaecological unit in a university-affiliated, tertiary referral hospital. A cohort of 150 women (75 after natural conception; 75 after assisted reproduction). Completed semi-structured interviews using two standard questionnaires [the 12-item General Health Questionnaire (GHQ-12) and the 22-item Revised Impact of Events Scale (IES-R)], at 1, 4, and 12 weeks after a diagnosis of first-trimester miscarriage. The GHQ-12 and IES-R scores for the two groups of women. The GHQ-12 and IES-R scores were significantly higher in the assisted reproduction group than the scores in the natural conception group, at 4 weeks and 12 weeks after miscarriage. Further breakdown of the scores revealed significantly higher hyperarousal symptoms at 4 and 12 weeks in the assisted reproduction group, indicating the traumatic effect of miscarriage to these women. Following first-trimester miscarriage, subfertile women who conceived after assisted reproduction had higher stress and anxiety-depression levels, and experienced more traumatic impact from the event, than those after natural conception. A timely support and psychological intervention would be beneficial in the management of this group of women.

Maternal and neonatal health outcomes following assisted reproduction

This study assessed the risk for maternal complications in women and neonatal outcomes in children conceived following assisted reproductive treatment as compared with spontaneously conception and also separately evaluated conventional IVF and intracytoplasmic sperm injection (ICSI). The prospective cohort included 1161 women with singleton pregnancies: 561 who conceived following assisted reproduction (223 following IVF and 338 following ICSI) and 600 who conceived spontaneously. No differences were observed in pregnancy complications (including spontaneous abortion, pregnancy-induced hypertension, gestational diabetes and Caesarean delivery) except for significantly increased risk for excess vaginal bleeding in assisted reproduction pregnancies (21.4% versus 12.9%; OR 1.67, 95% CI 1.18–2.37), which was prominent in women who reported polycystic ovary syndrome. Neonates born following assisted reproduction had increased risk for prematurity (10.6% versus 5.3%; OR 1.72, 95% CI 1.04–2.87), and IVF, but not ICSI, was associated with significantly increased risk for prematurity (OR 2.36, 95% CI 1.28–4.37) and low birthweight (OR 1.89, 95% CI 1.03–3.46). In conclusion, this study observed only an increased risk for excess vaginal bleeding as a pregnancy-associated complication in singleton pregnancies following assisted compared with spontaneous conception. However, singleton neonates born following IVF, but not ICSI, were at increased risk for prematurity.The current study evaluated the risk for maternal complications in women and outcomes of children conceived following assisted reproduction treatment as compared with spontaneously conceived pregnancies. In addition, conventional IVF and intracytoplasmic sperm injection (ICSI) were separately evaluated against spontaneously conceived pregnancies. The study cohort included 1161 women with singleton pregnancies: 561 who conceived following assisted reproduction (223 following IVF and 338 following ICSI) and 600 women who conceived spontaneously. No differences were observed in the risk for complications during pregnancy including spontaneous abortion, pregnancy-induced hypertension, gestational diabetes and Caesarean delivery, except for a significantly increased 1.6-fold risk for vaginal bleeding in assisted reproduction treatment. A 1.7-fold excess risk for prematurity was present in the assisted reproduction group. When the two assisted reproduction methods were compared separately with spontaneous conception, IVF cycles were associated with significantly increased risk for prematurity and low birthweight. However, no significantly increased risk was found in preterm birth or low birthweight following ICSI as compare to spontaneous conception. In conclusion, this study did not show increased risk of pregnancy-associated complications in singleton pregnancies following assisted reproduction compared with spontaneous pregnancies except for excess vaginal bleeding. However, singleton neonatals born following IVF, but not ICSI, were at increased risk for prematurity.

Clinical features of abnormal chromosome karyotypes in twin pregnancies complicated with structural abnormalities

To investigate the clinical features of the abnormal chromosome karyotypes in twin pregnancies complicated with fetal malformations. Totally 181 twin pregnancies (362 fetuses) in which one or two fetuses had abnormalities diagnosed by ultrasound were referred to the First Affiliated Hospital of Sun Yat-Sen University from January, 2000 to September, 2010. They were divided into different groups according to (1) maternal age: the cases with maternal age ≥ 35 were divided into advanced pregnancy group (105 fetuses), and those with maternal age < 35 were divided into young pregnancy group (203 fetuses); (2) conceived method: those conceived by assisted reproductive technology were divided into assisted reproductive group (81 fetuses), and the natural conception pregnancies were divided into natural conception group (227 fetuses); (3) chorionicity: the monochorionic twin (MCT) pregnancies were divided into MCT group (123 fetuses), and the dichorionic twin (DCT) pregnancies were divided into DCT group (185 fetuses); (4) structural abnormalities: 205 fetuses with structural abnormalities were divided into the abnormal fetal group, and 103 fetuses without structural abnormalities were divided into the normal fetal group. All fetuses were examined by the ultrasound and chromosomes were examined in 308 fetuses. (1) The karyotype of fetuses: among 181 twin pregnancies, 23 cases had chromosomal abnormalities in 1 or 2 fetuses (12.7%, 23/181), and chromosomes were examined in both fetuses in 20 of 23 cases. Twenty-six of 308 fetuses were found with abnormal chromosomes (8.4%, 26/308), and the aneuploid was the most common type of abnormal karyotypes (53.8%, 14/26). Twenty-one of 205 fetuses with malformations were found with abnormal karyotypes (10.2%, 21/205). (2) Seven of 123 fetuses in MCT group were with abnormal karyotypes (5.7%, 7/123), and 19 of 185 fetuses in DCT group were with abnormal karyotypes (10.3%, 19/185). There was no statistical difference of abnormal chromosome incidence between the two groups. There were 14 fetuses with aneuploid in DCT group (7.6%, 14/185); but there was no fetus with aneuploid in MCT group. There was statistical difference between these two groups. In two cases of DCT group, only one fetus with malformation received chromosome examination because another fetus was dead, and the karyotypes were trisomy 21 and trisomy 18 respectively. Both fetuses of the rest 17 cases received chromosome examination, and the chromosomes of both fetuses in each pregnancy were different. Fifteen of 19 fetuses with abnormal chromosomes in DCT group were complicated with structural abnormalities, and 7 fetuses of 4 twin pregnancies in MCT group were with chromosomal abnormalities. (3) The comparison of the abnormal karyotype incidence between the advanced pregnancy group and young pregnancy group: the abnormal karyotype incidence of the advanced pregnancy group was 7.6% (8/105), and that was 8.9% (18/203) in young pregnancy group. There was no statistical difference between the two groups (P > 0.05). Six of 105 fetuses in advanced pregnancy group were aneuploids (5.7%, 6/105), and 8 of 203 fetuses in young pregnancy group were aneuploids (3.9%, 8/203). The aneuploid incidence in advanced pregnancy group was significantly higher than that in young pregnancy group (P < 0.05).(4) The comparison of the abnormal karyotype incidence between the assisted reproductive group and the natural conception group: 11 of 81 fetuses were with the abnormal karyotypes in assisted reproductive group (13.6%, 11/81), and 15 of 227 fetuses were with the abnormal karyotypes in assisted reproductive group (6.6%, 15/227). There was statistical difference between the two groups (P < 0.05). There were 7 fetuses with the aneuploid in assisted reproductive group (8.6%, 7/81) and 7 fetuses with the aneuploid in natural conception group (3.1%, 7/227), which showed no statistical difference (P > 0.05). (5) The comparison of the abnormal karyotype incidence between the abnormal fetal group and normal fetal group: 21 of 205 fetuses in abnormal fetal group were with abnormal karyotypes (10.2%, 21/205), and 5 of 103 fetuses in normal fetal group were with abnormal karyotypes (4.9%, 5/103). There was no statistical difference (P > 0.05). 13 fetuses in abnormal fetal group were with the aneuploid (6.3%, 13/205), and only one fetus in normal fetal group was aneuploid (1.0%, 1/103). There was statistical difference between the two groups (P < 0.05). Aneuploid is the most common abnormal karyotype in twin pregnancy complicated with fetal abnormalities, especially trisomy 21. Aneuploid mainly occurs in only one fetus of DCT, and chromosomal discordance is usually found in DCT. While in MCT, the twin fetuses with the same abnormal karyotype may have different phenotypes. The results suggest that it is necessary to analyze both karyotypes of twins even if only one fetus is complicated with structural abnormalities.

In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies

The maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) were reduced in hormonally stimulated pregnancies in the in vitro fertilization and intracytoplasmic sperm injection groups (N=176; PAPP-A: 0.82) and in the entire assisted reproduction group (N=282; PAPP-A: 0.83) as compared with controls (N=24,783; PAPP-A: 0.94). However, the false-positive rate of first-trimester combined screenings was not statistically significantly increased in assisted reproduction pregnancies after adjustment for maternal age.

Pregnancy, obstetric and neonatal outcome after assisted reproduction in Nigerians

Purpose. To evaluate the pregnancy, obstetric and neonatal outcome after assisted reproduction in Nigerians.Methods. Case control study of all confirmed pregnancies following assisted reproduction managed at the Havana Specialist Hospital (HSH), Lagos over a 7 year period.Results. Adverse obstetric and neonatal outcome occurred in 30.8% of pregnancy following assisted reproduction compared to 12.6% in spontaneously conceived pregnancy (p = 0.0003). Multiple pregnancy (<0.001), preterm delivery (p < 0.000), placenta praevia (0.00002), antenatal admission (0.02), early pregnancy bleeding (0.04), miscarriage (0.001) and caesarean delivery (<0.001) were significantly commoner in the assisted reproduction group. After adjustment for confounding variables, preterm delivery (OR: 5.95), miscarriage (OR: 5.84), multiple pregnancy (OR: 4.58), placenta praevia (OR: 4.13), caesarean delivery (OR: 3.57), early pregnancy bleeding (OR: 2.18) and antenatal admission (OR: 2.01) retained their significance.Conclusion. This study has provided the first evidence from our part of the world showing that assisted pregnancy is associated with poorer obstetric outcome when compared with spontaneously conceived pregnancy.