The study of DNA, its genes and how these express and interact to influence growth and changes in our bodies represents genomics. The changes in DNA are passed through generations which may sometimes lead into inheritable diseases running in families. However, the subject of how our environment influences our genes including for example the diet we eat or the level of our activity we adopt changes chemicals inside our body cells to control how these genes work. This relatively new concept of epigenetics has invited huge interest to understand how these ‘chemical signatures’ result in genetic conditions, and such changes in genes are reversible by changing how these work.
Genomics brings great interest across gynaecology because life begins here, and it is only right that women get to understand genomic medicine. We now have greater understanding how our genetic makeup impacts our health and our approach to manage and treat the disease.
Modern genomics and genetic advances have significantly impacted gynaecology, particularly in the realm of preventive care, by enabling personalised risk assessment, targeted interventions, and early disease detection. Genomic testing helps identify individuals with increased susceptibility to conditions like breast and ovarian cancer, allowing for proactive management strategies such as risk-reducing surgeries or chemoprevention. The advancements in prenatal testing and expanded carrier screening (ECS) have enhanced reproductive health by identifying potential genetic risks for inherited disorders before or during pregnancy Furthermore, epigenetic changes involved in metabolic conditions, disorders affecting brain including Parkinson’s and Alzheimer’s, cancer and autoimmune disorders can all be proactively managed, allowing personalised prevention and precision treatment.
This knowledge of genetics has therefore, fundamentally transformed gynaecological practice, shifting it from reactive symptom management to proactive and personalized approach. Here’s how genetics has reshaped key areas in gynaecology:
Cancer Prevention & Early Intervention
- Hereditary Cancer Syndromes: Genetic testing identifies high-risk women for ovarian/breast cancer, enabling risk-reducing surgeries (bilateral salpingo-oophorectomy and/or mastectomy). Enhanced screening (annual breast MRI + transvaginal ultrasound) may allow use of chemoprevention (tamoxifen).
- Lynch Syndrome (MMR genes): Universal screening of endometrial cancer tissues for mismatch repair defects (e.g., MLH1/PMS2 loss) identifies families needing colonoscopies every 1–2 years and prophylactic hysterectomy/oophorectomy after completion of their family.
- Colorectal cancer gene Panels: Single gene testing for specific genes for Lynch syndrome or multigene panel testing which examines multiple genes simultaneously using next generation sequencing (NGS) are used to identify individuals at higher risk of developing CRC, which allows for earlier and more frequent colonoscopies, potential use of risk reducing medications or even surgery in some cases.
- Polygenic Risk Scores (PRS): This essentiallycombines cumulative effect of multiple genetic variations to predict ovarian/endometrial cancer risk, refining screening thresholds.
Precision Oncology treatments
- Ovarian Cancer: HRD testing in high grade cancers analysestumour’s DNA deficiency to identify cancers which are more sensitive to certain treatments particularly specific chemotherapeutic agents like PARP inhibitors (Olaparib, niraparib) and platinum-based chemotherapy.
- Endometrial Cancer: The introduction of molecular classification of endometrial cancers into POLE-mutated, mismatch repair deficient, p53 abnormal and no specific molecular profile is crucial for understanding tumour biology, prognosis and guiding specific treatment decisions.
Reproductive Genetics & Fertility
- Premature Ovarian Insufficiency (POI): Diagnosing genetic causes (e.g., FMR1 premutation or Fragile X syndrome screen informs fertility preservation timing and possibility of early menopause. This allows genetic testing for individuals and families to understand their risks and reproductive options.
- Recurrent Pregnancy Loss: Identification of thrombophilia (Factor V Leiden), structural variants, or balanced translocations help provide a more accurate prognosis for future pregnancies and guide decisions about treatment options.
- Preimplantation Genetic Testing (PGT): Screens embryos for specific genetic conditions, such as cystic fibrosis or any aneuploidy before implantation in IVF cycles.
Prenatal/Preconception Care
- Expanded Carrier Screening: ECS is a comprehensive genetic test that analyses hundreds of genes to determine if a woman carries mutations associated with autosomal recessive or X-linked disorders. This allows couples planning pregnancy to understand their risk of passing serious genetic conditions to their children. ECS panel screens for more than 300 autosomal recessive/X-linked disorders (e.g., spinal muscular atrophy, cystic fibrosis, Thalassemias, Sickle cell, Osteogenesis Imperfecta, Duchenne muscular dystrophy, Fragile X syndrome, PKU, etc) as pre-pregnancy planning.
- Non-Invasive Prenatal Testing (NIPT): NIPT uses cell-free foetal DNA in maternal blood to screen for chromosomal abnormalities like Down syndrome, Patau syndrome and Edward’s syndrome, three common trisomies with >99% accuracy, reducing invasive procedures.
Ziwig Endotest
This simple non-invasive saliva test utilises next generation sequencing (NGS) of microRNA combined with artificial intelligence, to identify unique biomarkers indicative of endometriosis. This genetic test has high accuracy with studies showing nearly 100% reliability in detecting endometriosis. It is designed to diagnose endometriosis specifically, helping to differentiate it from other conditions that may cause similar symptoms. It can detect endometriosis in all stages, including early stages where imaging may prove difficult to indicate endometriosis.
Whole genome sequencing (WGS)
WGS is proving to be valuable tool for diagnosing rare diseases and uncovering new diagnoses, potentially leading to more personalised treatment plans. Its use is expected to expand in the coming years. WGS can help identify inherited conditions allowing predictive testing in family members and informing about preventive measures. It can assess carrier status for conditions that could affect future children. While powerful, WGS findings can be complex, may reveal unexpected information, and require expert genetic counselling to interpret results and guide personalized healthcare decisions.
Genomics of Rare Disorders
- Müllerian Anomalies: Müllerian duct anomalies (MDAs) are relatively common, affecting around 6.7% of the general female population and 16.7% of women with recurrent miscarriages. Mutations in the WNT4 gene have been linked to mullerian agenesis and can be tested where needed.
- Disorders of Sex Development (DSD): Genetic diagnosis (e.g., SRY, AR, NR5A1) can guide gender assignment and hormone therapy where DSD is suspected.
Frequently asked questions
Q: What are genetic tests used for in gynaecology?
A: They help identify risks or causes for conditions like inherited cancer and rare disorders, reasons for recurrent miscarriages, risks of passing certain diseases to your baby and to screen the foetus for chromosomal conditions.
Q: When might I be offered genetic testing?
A: You might be offered testing if you have a strong family history of certain cancers, have had multiple miscarriages, are planning a pregnancy or are pregnant.
Q: What is expanded carrier screening?
A: Expanded carrier screening (usually done before or during pregnancy) checks if you or your partner carry genes for more than 300 inherited diseases that could affect your baby.
Q: If I have a genetic test, who else in my family needs to know?
A: Your results can impact close blood relatives (parents, siblings, children). Genetic counselling helps discuss this.
Q: Does a negative genetic test result mean I have no risk?
A: No. A negative result means the specific genes tested for were not found. It significantly lowers your risk for those specific conditions but doesn’t eliminate all risk.
eGynaecologist Advice
- You must know your family history and document cancers (type, age diagnosed), reproductive issues, and other genetic conditions in blood relatives on both sides of your family. This information is the biggest trigger for genetic testing.
- You must discuss your history and personal risks with your gynaecologist and ask for genetic testing and counselling which might benefit you.
- You must seek genetic counselling first before testing, who will explain benefits, limitations, potential results including unexpected findings, psychological impact and implications for family.
