SUMMARY:

Use of assisted reproductive technology (ART) accounts for 1.6% of singletons and 18.3% of multiple pregnancies in the United States. Although most IVF pregnancies are uncomplicated, there is an association with increased risks of maternal, fetal, and perinatal outcomes. Some of these risks are affected by specific IVF techniques.

Genetic Outcomes

• IVF
  • Not associated with increased risk for chromosomal anomalies
  • Factors associated with an increased risk for chromosomal anomalies include
    • Older age | PCOS | Severe male or female infertility
• Intracytoplasmic sperm injection (ICSI)
  • Is associated with an increased rate of de novo chromosomal abnormalities
  • Allows for chromosomal or gene defects to be transmitted that might be naturally lost or eliminated
• Patients with reduced ovarian reserve and primary ovarian insufficiency
  •  Associated with increased risk of premutation or full mutation for Fragile X
• Increased risk of imprinting syndromes
  • Beckwith-Wiedemann | Angelman | Prader-Willi | Russel Silver
• Genetic counseling should be offered to all IVF patients

Preimplantation Genetic Testing (PGT)

• PGT does not replace guidance to offer prenatal screening and diagnostic testing
  • Misdiagnosis is possible with PGT and confirmatory testing is recommended
• PGT-A: PGT for aneuploidy
  • Detection of aneuploidies increases implantation and pregnancy rates, and lowers miscarriage rates
  • Samples obtained from trophoectoderm (placenta) and not the inner cell mass (fetus)
    • Possibility for discordant aneuploidy findings
• PGT-M: PGT for monogenic disorders
  • Used when previous offspring has been affected by a single-gene disorder or both parents test positive as carriers for a mutation associated with disease (e.g., cystic fibrosis)
  • Other scenarios: HLA-compatible child (stem cell therapy) | Sex selection (sex-linked disorders) | Late-onset autosomal dominant disorders
• PGT-SR: PGT for structural rearrangements
• Known carrier of balanced translocation, deletion, or duplication

First Trimester Genetic Screening

• Potential risk for false-positive results for aneuploidies in first-trimester combined screening
  • Decreased PAPP-A | Increased total hCG 
  • Accuracy of first trimester screening tests, including cfDNA for aneuploidy, should be discussed with patients
• Increased nuchal translucency
• Lower fetal fraction of cfDNA

Fetal Outcomes

Multifetal Pregnancy

• Even with single embryo transfer, risk of monozygotic twins is increased
• Multifetal reduction should be offered
  • Reduces risks of preterm birth, neonatal morbidity and maternal complications

Congenital Anomalies

• Associations between IVF (with and without ICSI) and congenital malformations
• Unclear if related to infertility, procedure, or both
• Distinction of risk between IVF alone and IVF and ICSI is also unclear
• Should perform detailed ultrasound for all IVF pregnancies
• Not all organ systems are equally affected
  • Higher difference in rates of malformations in GI, musculoskeletal and urogenital systems
• Higher rates of congenital heart disease
  • Highest risk with ICSI/subfertility
  • Offer fetal echocardiography for IVF with ICSI pregnancies

Fetal Growth

• Increased risk for SGA infants
• Higher risk after IVF from fresh cycles than with frozen cycles
• Effect on fetal growth is particularly evident near term
• Optimal gestational ages for fetal growth scans and their frequency in the presence of additional risk factors is unknown
• Fetal growth assessment advised in third trimester
• Serial growth scans for IVF alone not indicated

Placental Findings

• Several placental implantation disorders are more common with IVF
• Higher risk for abnormal placental structure   
  • Bilobed | Accessory placental lobes
• Increased risk for
  • Marginal or velamentous cord insertion
  • Placenta previa
  • Vasa previa
  • Placenta accreta spectrum
• Anatomy scan should include comment on
  • Placental location | Placental shape | Cord insertion site
• Ultrasound at 32 weeks
  • Assessment for vasa previa including placental location

Pregnancy Outcomes 

• Higher risk for
  • Preterm birth | Low birth weight | Very low birth weight
• Risks are more than doubled in IVF twin gestations
• Utility of serial cervical length measurement is unknown when sole indication is IVF
  • Serial cervical length assessment not recommended
• Progesterone supplementation for the sole purpose of IVF is not indicated >12 weeks
• Cervix should be visualized between18w0d and 22w6d either abdominally or vaginally during anatomical survey

Hypertensive Disorders

• IVF is a moderate risk-factor for preeclampsia
• Risk appears to depend on specific technique
  • Higher risk with oocyte donation than with autologous IVF
  • Increased risk with IVF from frozen embryo than with fresh embryo transfer
• No significant reduction in rates with prepregnancy initiation of low-dose aspirin
• Low-dose aspirin is recommended ONLY if an additional moderate risk factor is found

Stillbirth

• 2- to 3-fold increased risk
• Lower risk with frozen embryo than with fresh embryo transfer
• Weekly antenatal testing should begin no later than 36 weeks

Elective Induction at 39 Weeks

• Risk reduction compared to expectant management is unknown
• In asymptomatic uncomplicated singleton pregnancies, induction between 39w0d and 40w6d
  • Does not increase risk for cesarean delivery
  • Does not reduce rates of adverse perinatal outcomes such as perinatal death, low 5 minute Apgar score or need for NICU admission

KEY POINTS:

• Genetic counseling should be offered to all patients undergoing or who have undergone IVF
• Regardless of whether PGT has been performed, all patients should be offered prenatal screening and diagnostic testing via chorionic villus sampling or amniocentesis
• Careful examination of placental location, placental shape and cord insertion site should be performed at time of fetal anatomy ultrasound, including evaluation for vasa previa
• Fetal echocardiography should be offered in pregnancies achieved with IVF and ICSI
• Assessment of fetal growth should be performed in the third trimester
• Weekly antenatal fetal surveillance beginning by 36w0d

Learn More – Primary Sources:

SMFM Consult Series #60: Management of pregnancies resulting from in vitro fertilization

SMFM: Special Statement: Checklist for pregnancies resulting from in vitro fertilization

Related ObG Topics:

ACOG Addresses Preimplantation Genetic Testing

Are Offspring of IVF/ICSI Pregnancies at Higher Risk for Congenital Heart Defects?

Does ART Increase Risk of Postpartum Hemorrhage?

Infertility Treatment and Childhood Development

Does ART increase the risk for imprinting disorders such as BWS?

ASRM guidance: ART and recommended number of embryos to transfer

Vanishing Twin Pregnancy: Outcomes with IVF-ICSI vs Natural Conception

Is IVF an Independent Risk Factor for Placenta Accreta Spectrum?

Frozen or Fresh Embryos for IVF Transfer?

How Have Preimplantation Genetic Testing Trends Changed in the US?

RCT Results: Fresh vs Frozen Strategy for Embryo Transfer?