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Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

ABSTRACT: Infertility is a growing phenomenon and leads to an increased use of assisted reproductive techniques (ARTs). In recent years, concerns about the safety of these procedures emerged and ARTs were hypothesized to be a risk factor for developing congenital heart diseases (CHDs) in offspring. Our aim is to investigate the association between ART and CHD, specifying results according to various subtypes of defects. We performed a systematic review and random-effects meta-analysis following the PRISMA guidelines. MEDLINE and Google Scholar were searched from January 2011 to May 2022. Data about incidence of CHD in ART were tabulated and extracted from all the studies included. Twenty-four studies were included. Pooled incidence of CHDs after IVF pregnancies was 3% (95% CI 0.3-0.4; I² = 99%), decreasing to 1% (95% CI 0.00-0.01; I² = 93%) for major CHDs only. An increased risk of CHDs, especially minor (i.e., not requiring surgical correction), seems to occur in ART compared with non-ART pregnancies [RR 1.71 (95% CI 1.25-2.34; I² = 99%)]. For major CHDs, not enough evidence is available to assess the real risk. Moreover, some confounding factors (i.e., maternal age and male infertility) seem to play a critical role to determine an increased risk of CHDs. Conflicting results emerged among the studies, setting the need for further research to validate the actual evidence and state the real risk of CHD following ART pregnancies.

SUBMITTER: Gullo G

PROVIDER: S-EPMC10556115 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

Gullo Giuseppe G Scaglione Marco M Laganà Antonio Simone AS Perino Antonio A Andrisani Alessandra A Chiantera Vito V Cucinella Gaspare G Gitas Georgios G Barra Fabio F Riemma Gaetano G

Reproductive sciences (Thousand Oaks, Calif.) 20230505 10

Infertility is a growing phenomenon and leads to an increased use of assisted reproductive techniques (ARTs). In recent years, concerns about the safety of these procedures emerged and ARTs were hypothesized to be a risk factor for developing congenital heart diseases (CHDs) in offspring. Our aim is to investigate the association between ART and CHD, specifying results according to various subtypes of defects. We performed a systematic review and random-effects meta-analysis following the PRISMA ...[more]

PMID: 37145300

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Project description:BackgroundAfter hormonal replacement therapy (HRT) including androgen replacement or sequential therapy of estrogen and progesterone, The combination of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) and pulsatile GnRH, is not sufficient to produce sufficient gametes in some patients with Congenital hypogonadotropic hypogonadism (CHH). A Systematic review and meta-analysis was performed to determine that assisted reproductive techniques (ART) can effectively treat different causes of infertility.MethodsTo determine the effect of ART on fertility of CHH patients and investigate whether outcomes are similar to infertility due to other causes, we conducted a systematic review and meta-analysis of retrospective trials. Clinical trials were systematically searched in Medline, Embase, and the Cochrane central register of controlled trials databases. The keywords and major terms covered "hypogonadotropic hypogonadism", "kallmann syndrome", "assisted reproductive techniques", "intrauterine insemination", "intracytoplasmic sperm injection", "testicular sperm extraction", "in vitro fertilization", "embryo transplantation" and "intra-Fallopian transfer".ResultsA total of 388 pregnancies occurred among 709 CHH patients who received ART (effectiveness 46, 95% confidence interval 0.39 to 0.53) in the 20 studies we included. The I2 in trials assessing overall pregnancy rate (PR) per embryo transfer (ET) cycle was 73.06%. Similar results were observed in subgroup analysis by different gender. Regression indicates pregnancy rate decreases with increasing age. Fertilization, implantation and live birth rates (72, 36 and 40%) showed no significant differences as compared to infertility due to other causes.ConclusionsDespite CHH patients usually being difficult to generate gametes, their actual chances of fertility are similar to subjects with other non-obstructive infertility. ART is a suitable option for CHH patients who do not conceive after long-term gonadotropin treatment.

Project description:ImportanceThe extent to which assisted reproductive technology is associated with increased risk of congenital heart defects independent of its known association with twinning remains uncertain.ObjectiveTo assess the extent to which assisted pregnancy is associated with increased risk of congenital heart defects independent of its known association with twinning.Design, setting, and participantsThis retrospective cohort study linked records of congenital heart defect diagnoses with assisted reproductive technology cycles in 507 390 singleton or twin pregnancies (10 149 assisted pregnancies and 497 241 nonassisted pregnancies), including singleton and twin early pregnancy losses, stillbirths, and live births (follow-up to 1 year of age) in Ontario, Canada, between April 1, 2012, and October 31, 2015. Statistical analysis was performed from January 1, 2017, to September 9, 2019.ExposuresAssisted reproductive technology and its 2 subtypes: intracytoplasmic sperm injection and in vitro fertilization without intracytoplasmic sperm injection.Main outcomes and measuresThe main outcome was congenital heart defects (prevalence and relative risk measured as odds ratios [ORs]). Mediation analysis was performed to assess the extent to which the association between assisted reproductive technology and congenital heart defects was mediated by twinning.ResultsOf 507 390 mother-infant pairs with singleton or twin pregnancies evaluated, the prevalence of congenital heart defects in assisted pregnancies (223 [2.2%]) was higher than that in nonassisted pregnancies (6057 [1.2%]; crude OR, 1.82; 95% CI, 1.59-2.09). The strength of the association between assisted pregnancy and congenital heart defects decreased after adjusting for several risk factors simultaneously (adjusted OR, 1.70; 95% CI, 1.48-1.95). Further mediation analysis indicated that most of the association between assisted pregnancy and congenital heart defects was mediated by twinning (adjusted OR, 1.68; 95% CI, 1.44-1.92), and the natural direct association of assisted pregnancy with congenital heart defects among singleton pregnancies was 1.09 (95% CI, 0.93-1.25). Mediation of twinning accounted for 87.3% of the association.Conclusions and relevanceOur study results suggest that the association between assisted reproductive technology and congenital heart defects may be mediated by twinning.

Project description:BackgroundAcupuncture is widely used for infertile women without undergoing assisted reproductive techniques (ART) in China but its effect is unclear. We aim to assess whether acupuncture and its combined therapy exert a positive influence on the outcome of female fertility.MethodsWe searched 6 databases, including Medline, EMBASE, the Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure (CNKI), the China Science and Technology Journal Database (VIP), and Wan-Fang Data, from inception to June 2018. Studies of randomized controlled trials (RCTs) on women with infertility treated by acupuncture or its combined therapy were included. A meta-analysis was performed using Revman 5.3. The methodological quality of the studies was assessed through the risk of bias assessment tool by the Cochrane Collaboration.ResultsThe pregnancy rate was significantly improved with treatment (RR = 1.84, 95% CI 1.62 to 2.10, P < .00001), compared to that in the control group. Subgroup analysis showed that comparing with pure western medicine intervention, no matter intervention with acupuncture alone, with acupuncture plus western medicine, with acupuncture plus Chinese medicine, or acupuncture plus Chinese medicine and western medicine, all of these subgroups exhibited significant improvement. The subgroup according to different types of infertility showed a significant improvement in infertility caused by polycystic ovary syndrome, tubal infertility, ovulatory disorder, and other factors. In addition, the ovulation rate and endometrial thickness were significantly increased. The level of LH was obviously decreased. Moreover, with acupuncture, less adverse effects occurred. The funnel plot revealed that publication bias might exist. All trials included had unclear risks in the aspects of allocation concealment, blinding of participants and personnel, blinding of outcome assessment, selective reporting, and other bias. Only 1 study was assessed as unclear risk in random sequence generation. In the incomplete outcome data, all studies were low risk, except 1.ConclusionsAcupuncture and its combined therapy may be effective for treating female infertility. However, the included studies are not robust enough to draw a firm conclusion due to the not robustly sampled quality of the included studies. Future high-quality RCTs are needed to confirm our findings.

Project description:BackgroundCongenital heart disease (CHD) is the commonest birth defect. Studies estimating the prevalence of CHD in school-age children could therefore contribute to quantifying unmet health needs for diagnosis and treatment, particularly in lower-income countries. Data at school age are considerably sparser, and individual studies have generally been of small size. We conducted a literature-based meta-analysis to investigate global trends over a 40-year period.Methods and resultsStudies reporting on CHD prevalence in school-age children (4-18 years old) from 1970 to 2017 were identified from PubMed, EMBASE, Web of Science and Google Scholar. According to the inclusion criteria, 42 studies including 2,638,475 children, reporting the prevalence of unrepaired CHDs (both pre-school diagnoses and first-time school-age diagnoses), and nine studies including 395,571 children, specifically reporting the prevalence of CHD first diagnosed at school ages, were included. Data were combined using random-effects models. The prevalence of unrepaired CHD in school children during the entire period of study was 3.809 (95% confidence intervals 3.075-4.621)/1000. A lower proportion of male than female school children had unrepaired CHD (OR = 0.84 [95% CI 0.74-0.95]; p = 0.001). Between 1970-1974 and 1995-1999, there was no significant change in the prevalence of unrepaired CHD at school age; subsequently there was an approximately 2.5-fold increase from 1.985 (95% CI 1.074-3.173)/1000 in 1995-1999 to 4.832 (95% CI 3.425-6.480)/1000 in 2010-2014, (p = 0.009). Among all CHD conditions, atrial septal defects and ventricular septal defects chiefly accounted for this increasing trend. The summarised prevalence (1970-2017) of CHD diagnoses first made in childhood was 1.384 (0.955, 1.891)/1000; during this time there was a fall from 2.050 [1.362, 2.877]/1000 pre-1995 to 0.848 [0.626, 1.104]/1000 in 1995-2014 (p = 0.04).ConclusionsGlobally, these data show an increased prevalence of CHD (mainly mild CHD conditions) recognised at birth/infancy or early childhood, but remaining unrepaired at school-age. In parallel there has been a decrease of first-time CHD diagnoses in school-age children. These together imply a favourable shift of CHD recognition time to earlier in the life course. Despite this, substantial inequalities between higher and lower income countries remain. Increased healthcare resources for people born with CHD, particularly in poorer countries, are required.

Dataset Information

Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

Publications

Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

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