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)
Mussa et al. (Pediatrics, 2017) examined the prevalence of Beckwith-Wiedemann syndrome (BWS) in children born through ART to further refine relative risk
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
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)
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
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
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)
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
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
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
euploid embryo: 1 blastocyst
4 cleavage stage embryos
euploid embryo: 1 blastocyst
≥ 43 years
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.
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.
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
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
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.
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
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.
Prospective Cohort Study
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.
OBG Project CME requires a modern web browser (Internet Explorer 10+, Mozilla Firefox, Apple Safari, Google Chrome, Microsoft Edge). Certain educational activities may require additional software to view multimedia, presentation, or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Apple QuickTime, Adobe Acrobat, Microsoft PowerPoint, Windows Media Player, or Real Networks Real One Player.
Disclosure of Unlabeled Use
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.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
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.
Jointly provided by
NOT ENOUGH CME HOURS
It appears you don't have enough CME Hours to take this Post-Test. Feel free to buy additional CME hours or upgrade your current CME subscription plan