Are Offspring of IVF/ICSI Pregnancies at Higher Risk for Congenital Heart Defects?
BACKGROUND AND PURPOSE:
There have been studies that suggest an increased risk for cardiac defects in IVF/ICSI pregnancies
There are no meta-analyses that specifically look at the incidence of CHD in the IVF/ICSI
Giorgione et al. (Ultrasound in Obstetrics & Gynecology, 2018) examined whether there was a higher risk of congenital heart defects (CHD) in offspring conceived through IVF/ICSI
METHODS:
Systematic review and meta-analysis
Literature search of studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously
For the meta-analysis, the authors selected cohort studies to estimate the pooled odds ratio (OR) with 95% CI
RESULTS:
Data was pooled from 8 cohort studies for meta-analysis
25,856 children were conceived using IVF/ICSI techniques and 287,995 children conceived spontaneously
Both singleton and multiple gestations were included
1.30% of patients in the IVF/ICSI group and 0.68% in the spontaneous conception group had CHD events
The risk of CHD was significantly increased in the IVF/ICSI group
Pooled OR, 1.45; 95% CI, 1.20–1.76 (P = 0.0001)
In the subgroup of singleton pregnancies, a significant difference was also evident
Pooled OR, 1.29; 95% CI, 1.03–1.60; P = 0.02
CHD subtypes
VSD was more frequent in IVF/ICSI
TOF (tetralogy of Fallot) and TGA (transposition of great arteries) were more common in pregnancies conceived spontaneously
CONCLUSION:
The risk of CHD in IVF/ICSI pregnancies is significantly increased by approximately 50%
CHD subtypes
VSD was more frequent in IVF/ICSI
TOF and TGA were more common in pregnancies conceived spontaneously
These results held in subgroup analyses even after adjusting for confounding factors, including maternal age
The authors cite results of this paper as evidence to support fetal echocardiography in IVF/ICSI pregnancies
Does ART increase the risk for imprinting disorders such as BWS?
BACKGROUND AND PURPOSE:
There have been reports of an association between assisted reproductive techniques (ART) and imprinting disorders, for example (clinical findings and management for syndromes can be found in ‘Learn More – Primary Sources below)
Beckwith-Wiedemann syndrome (BWS)
Russell-Silver syndrome
Angelman syndrome
Mussa et al. (Pediatrics, 2017) examined the prevalence of Beckwith-Wiedemann syndrome (BWS) in children born through ART to further refine relative risk
METHODS:
BWS patients were identified and matched with general demographic data and corresponding regional ART registry
BWS criteria included at least 2 of the following
Abdominal wall defect, macroglossia, macrosomia, embryonal tumor, ear malformations, organ enlargement, nevus flammeus, hemihyperplasia, nephron/urological malformations, hypoglycemia, or family history of BWS
RESULTS:
Out of a total population of 379,872 live births, 7884 ART live births were studied
Within the total population, there were 38 patients with BWS (7 from ART and 31 naturally)
BWS birth prevalence was significantly higher in the ART group
In the ART group the relative risk was higher in BWS compared to non-ART at 10.7 (887.9 per 1,000,000 vs 83.3 per 1,000,000 risk)
CONCLUSION:
There is an approximately ten-fold increased risk of BWS in ART children
Does Maternal Subfertility Impact Outcomes in Twin Pregnancies?
BACKGROUND AND PURPOSE:
Multiple gestation associated with assisted reproductive technology (ART) is declining but still accounts for approximately 40% of all twin births.
There is a greater risk of adverse outcomes in twin vs. singleton pregnancies
There is ongoing controversy if adverse outcomes using ART is related to the treatment or parental characteristics such as subfertility and limited data in twin vs. singleton pregnancies
This study by Luke et al. (AJOG, 2017) sought to determine if a mother’s fertility status impacts the risk of adverse outcomes in twin pregnancies
METHODS:
Longitudinal Retrospective Cohort Study
10,352 women with twin pregnancies were included in the study
6,090 ‘fertile’ women who conceived twins naturally
724 ‘subfertile’ women (e.g., use of fertility drugs or ART, diagnosis of infertility) who conceived twins without IVF
3,538 women who conceived twins with IVF
Adverse pregnancy and infant outcomes were examined
RESULTS:
Women in the subfertile and IVF group were older and had more chronic health conditions
There were higher rates of gestational diabetes, gestational hypertension, uterine bleeding, placental complications, prenatal hospitalizations, and primary C-sections among the subfertile and IVF groups
Uterine bleeding (adjusted relative risk ratios, 1.92 for subfertile and 2.58 for IVF) and placental complications (adjusted relative risk ratios, 2.07 for subfertile and 1.83 for IVF) were the highest risks
Subfertile women had increased risk for very preterm birth (< 32 weeks) and neonatal and infant death (adjusted relative risk ratios, 1.36, 1.89, and 1.87, respectively)
In the IVF group, women were at increased risk for very preterm birth, preterm birth (<37 weeks), and birth defects (adjusted relative risk ratios, 1.28, 1.07, and 1.26, respectively)
CONCLUSION:
The risk of adverse maternal and infant outcomes was increased among subfertile and IVF twins
Especially increased risk of bleeding and placental complications is a consistent finding among studies
These data are in keeping with guidelines promoting single embryo transfer and cautious use of ovulation induction to limit multiple gestation with ART
ASRM guidance: ART and recommended number of embryos to transfer
Summary:
ASRM and SART have released updated guidance on assisted reproductive technologies (ART) and the number of embryos to transfer to prevent twin and higher order multiple births. The guideline promotes elective single-embryo transfer (eSET). The rationale for this guidance is based on evidence that demonstrates:
Multiple gestations lead to higher maternal and newborn complication rates, including twins
Approximately 50% of multiple gestations from ART are occurring women < 35 years of age and 23% of of women < 38 years of age
When financial barriers are removed, IVF is associated with fewer embryos transferred, thereby implicating economic factors in the transfer of multiple embryos
eSET in women < 38 years of age resulted in decreased rates of multiple gestations but no impact on live-birth rates
Preimplantation genetic screening (PGS) may also be helpful
In women < 42 years of age, transferring a tested (euploid) blastocyst resulted in the same pregnancy rate as the transfer of 2 untested blastocysts
Recommendations:
In the case of favorable prognosis which, aside from younger age, may include the following features (1) one or more high-quality embryos will be available for cryopreservation; (2) euploid embryos; (3) previous live birth after IVF; (4) frozen embryos – availability of high quality day-5 or day-6 blastocysts for transfer, recommendations are as follows:
Any age: euploid embryo
Transfer 1 embryo
< 35 years:
Transfer 1, regardless of embryo stage
35 – 37 years:
strong consideration for 1 embryo
38 – 40 years:
3 cleavage-stage embryos
2 blastocysts
euploid embryo: 1 blastocyst
41-42 years:
4 cleavage stage embryos
3 blastocysts
euploid embryo: 1 blastocyst
≥ 43 years
Insufficient data
Risks associated with multiple gestations increase with age
Consider transferring additional embryos depending on clinical circumstances such as
This study by Nyfløt et al. (BJOG, 2016) aimed to determine if a relationship exists between assisted reproductive technology (ART) and postpartum hemorrhage.
METHODS:
Case-Control Study
RESULTS:
1,064 cases of severe postpartum hemorrhage and 2,059 controls were included in the study. Women who had conceived using ART had a significantly increased risk of severe postpartum hemorrhage. Anticoagulant medication and mode of delivery had confounding effects. Risks were seen in both singleton and multiple births, with an even higher risk for multiples. This evidence supports the argument for being prepared for hemorrhage at delivery and the value of single embryo transfer during ART to avoid twins and higher order births.
Vasa previa is defined as fetal vessels that run through the fetal membranes, over or near the endocervical os (2 cm or less) and are unprotected by placenta or umbilical cord.
CLINICAL ACTIONS:
Deliver by cesarean section before the onset of labor and before rupture of membranes
Scheduled delivery 34w0d to 37w0d
Deliver by cesarean section in the case of PPROM and viability
Antenatal corticosteroids 28 to 32 weeks gestation
SMFM guidance states to consider hospitalization at 30 to 34 weeks
Benefit is unproven and there have been good outcomes reported with outpatient management
When considering hospitalization, individualize based on the following
Symptoms
History of preterm birth
Logistics in getting to hospital with transfusion capabilities
Patients with normal cervical lengths are the best candidates for possible outpatient management
Repeat ultrasound in the third trimester is suggested if vasa previa is suspected in the second trimester, as approximately 20% of apparent vasa previa will resolve by the late third trimester
SYNOPSIS:
Vasa previa occurs in 1/2500 to 1/5000 pregnancies and is associated with an increased risk of preterm birth and the associated complications of prematurity. There is a 97% survival rate when diagnosed by prenatal ultrasound and a 44% survival rate when the diagnosis is made intrapartum.
KEY POINTS:
Risk factors:
Velamentous cord insertion (Type 1 vasa previa)
Succinturate or bilobed placenta connecting vessels (Type 2 vasa previa)
Placenta previa or low lying placenta in the second trimester
Multiple gestation
IVF (1/250 risk of Type 1 vasa previa)
In cases of low lying placenta, bilobed placenta, succinturate placenta or velamentous cord insertion, a targeted ultrasound for vasa previa should be performed
Screening possible at 2nd trimester fetal anatomy ultrasound
If detected on 2nd trimester ultrasound, 20% will resolve
Document cord insertion site if possible
Diagnosis is made by ultrasound, ideally with transvaginal and color flow Doppler
Ultrasound findings include a linear tubular echolucent body overlying the endocervical os with color flow doppler demonstrating flow through the structure and pulsed doppler showing fetal vascular wave forms
Risk of perinatal loss due to fetal exsanguination – watch for sinusoidal pattern on FHT tracing
Plan for delivery at a center that can perform neonatal transfusion if required
Note: Center should have negative blood available for neonate in case rapid transfusion is necessary
This study by Yeung et al. (JAMA Pediatrics, 2016) aimed to assess if there exists a link between type of infertility treatment and children’s development. The authors’ noted a lack of data from the U.S.
METHOD
Prospective Cohort Study
RESULTS:
1,422 mothers underwent infertility treatments including assisted reproductive technology (ART), ovulation induction, or intrauterine insemination. Parents completed the Ages and Stages Questionnaires at 4, 8, 12, 18, 24, 30, and 36 months of age in order to test their children’s development. The authors found no difference in children’s development at 3 years of age, regardless of infertility treatment or type.
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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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