Assisted Reproductive Technology (ART) has significantly reshaped the landscape of modern family planning. In the United States alone, ART now accounts for approximately 1.6% of all live births and a staggering 18.3% of all multiple births. While most IVF (In Vitro Fertilization) pregnancies progress normally, research continues to highlight some increased maternal and perinatal risks. This article dives into the complexities of managing IVF pregnancies, with a specific focus on genetic considerations, screening strategies, congenital anomalies, and how best to support healthy outcomes.
Genetic Considerations for IVF Patients
Chromosomal Abnormalities and IVF
Contrary to popular belief, IVF itself does not increase the overall prevalence of chromosomal anomalies when compared to natural conception. However, there is growing evidence that intracytoplasmic sperm injection (ICSI)—a specific IVF technique used to treat male factor infertility—may be linked to an increased rate of de novo (new) chromosomal abnormalities. Several factors contribute to this risk: advanced maternal age, polycystic ovary syndrome (PCOS), and severe male or female infertility. These underlying issues—not the IVF procedure itself—may explain the observed risks.
Risk of Imprinting Disorders
Imprinting syndromes are rare genetic conditions resulting from abnormal gene expression, and some, such as Beckwith-Wiedemann Syndrome (BWS), Angelman and Prader-Willi Syndromes (PWS), and Russell-Silver Syndrome, have been reported at slightly higher rates in children born to subfertile couples. Still, it’s important to note that the absolute risk remains very low.
Fragile X Syndrome and Ovarian Reserve
Women with diminished ovarian reserve or primary ovarian insufficiency (POI) may be premutation or full mutation carriers of the FMR1 gene associated with Fragile X syndrome. Testing for this gene is often performed before IVF in these patients, especially when family history suggests the possibility of X-linked conditions.
The Role of Genetic Counseling
Given the complexity of genetics in fertility treatments, genetic counseling is recommended for all IVF patients, whether or not ICSI is used. A certified counselor can assess risk, explain options, and guide decision-making.
Types of Preimplantation Genetic Testing (PGT)
PGT involves analyzing embryos for genetic conditions before transfer to the uterus. Three primary types exist:
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PGT-A (for aneuploidy): Screens embryos for abnormal chromosome numbers. While widely used, it remains controversial and does not eliminate the need for prenatal genetic screening or diagnostic testing.
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PGT-M (for monogenic disorders): Used when one or both parents carry mutations for single-gene disorders such as cystic fibrosis or Tay-Sachs disease. Ensures only unaffected embryos are transferred.
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PGT-SR (for structural rearrangements): Recommended when a parent carries a balanced chromosomal translocation, duplication, or deletion. It helps avoid transferring embryos with structural chromosomal issues.
For both PGT-M and PGT-SR, confirmatory testing during pregnancy (e.g., chorionic villus sampling or amniocentesis) is advised, although some patients decline due to the risks associated with invasive procedures.
Genetic Screening in IVF Pregnancies
First-Trimester Screening Accuracy
Studies show that IVF may impact the accuracy of early genetic screening, especially with combined first-trimester screening for aneuploidies, which could yield false positives. One contributing factor is a lower fetal fraction in cell-free DNA (cfDNA) testing among IVF pregnancies, increasing the chance of failed tests. However, a failed cfDNA result does not necessarily repeat with a second test, and IVF itself isn’t a consistent cause of failed cfDNA testing upon redraw.
Recommendation: All IVF patients should be informed about the limitations and potential accuracy issues of first-trimester screening tests.
Mosaic Embryo Transfers
Sometimes, when no fully normal (euploid) embryos are available, mosaic embryos—those with both normal and abnormal cells—are transferred. Pregnancies resulting from these embryos should be offered prenatal diagnostic testing, such as CVS or amniocentesis, to better assess the fetus’s genetic status. Note: cfDNA testing is not reliable in pregnancies resulting from mosaic embryo transfers.
Managing Multiple Gestations in IVF
Multiple pregnancies carry increased risk for preterm birth, low birth weight, and maternal complications such as preeclampsia. Even with single embryo transfers, IVF has been linked to a higher risk of monozygotic (identical) twins. If multiple pregnancies do occur, patients should be counseled about the option of multifetal pregnancy reduction, which research shows can reduce risks for both mother and babies.
Congenital Anomalies in IVF Pregnancies
Increased Risk of Birth Defects?
Meta-analyses suggest that IVF, especially with ICSI, is associated with a slightly increased risk of congenital anomalies, including neural tube defects, urogenital abnormalities, and gastrointestinal malformations. The reason for this increase is unclear—it may stem from the IVF process itself, underlying infertility, or a combination of both.
Heart Defects and IVF
Some studies report a higher incidence of congenital heart disease (CHD) in IVF/ICSI babies, although others find no significant difference when controlling for confounding factors.
Recommendations: A detailed obstetric ultrasound (CPT 76811) should be performed for all IVF/ICSI pregnancies. Fetal echocardiography may be offered, especially if there are additional risk factors (GRADE 2C), although universal screening remains debatable.
Placental Abnormalities in IVF
IVF pregnancies carry an increased risk for several placental implantation disorders, including: placenta previa, bilobed placenta, velamentous or marginal cord insertion, and placenta accreta spectrum. These abnormalities are often interrelated and can lead to complications during pregnancy and delivery, including hemorrhage and preterm labor. Early and detailed placental imaging is strongly recommended to manage risks proactively.
Conclusion
While IVF offers incredible hope to many families, it also introduces unique medical considerations. From genetic screening and counseling to managing multiple births and structural abnormalities, individualized care is key. Patients undergoing or who have undergone IVF should have access to a multidisciplinary team that includes reproductive endocrinologists, obstetricians, genetic counselors, and maternal-fetal medicine specialists. By staying informed and making proactive decisions based on current evidence, patients and providers can work together to support healthier outcomes for both mother and baby.
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