Reproductive health is a fundamental aspect of human well-being, affecting individuals and communities worldwide [1]. It encompasses a wide range of issues, from understanding one’s body and fertility to making informed decisions about contraception, pregnancy, and childbirth. Yet, despite its importance, reproductive health is often overlooked or stigmatized [2].
This blog will explore the various types of reproductive genetic testing and their benefits, aiming to empower individuals with knowledge to evaluate their choices about their reproductive plans.
Contents
The role of genetic testing
Genetic testing analyzes a person’s DNA, helping us understand the genetic makeup of an individual, and identify changes in genes that may cause disease or affect health. It can help diagnose conditions, predict risks, and guide treatment decisions. Reproductive genetic testing has revolutionized the way we understand and manage inherited conditions. There are various types of genetic tests available, each assisting in different parts of the patient’s journey, from thinking about starting a family to trying to have a family, and finally, during pregnancy. These tests include:
- Carrier screening: For identifying individuals who carry a gene for a recessive disorder.
- Infertility testing: For identifying individuals with genetic mutations that are associated with infertility.
- Preimplantation genetic testing (PGT): For screening embryos for genetic abnormalities before implantation during in vitro fertilization (IVF) cycles.
- Prenatal screening: For assessing the risk of genetic conditions in a developing fetus during pregnancy.
Carrier screening
Carrier screening is a non-invasive genetic test, usually performed with a buccal swab or blood sample, that helps identify individuals who carry a gene for a recessive genetic disorder and are known as carriers [3]. Recessive genetic disorders occur when two copies – one from each parent – of a mutated gene are inherited. While carriers may not be affected by the condition, and subsequently present no symptoms, if both parents are carriers, there’s a 25% chance their child could inherit the disorder [4]. Most common disorders tested by carrier screening include cystic fibrosis, sickle cell disease, Tay-Sachs disease, and spinal muscular atrophy.
Professional societies mention that carrier screening should be offered as an option to all individuals but especially recommend it to those planning to have children and have a family history of specific genetic disorders such as cystic fibrosis, hemoglobinopathies, and spinal muscular atrophy [5]. Additionally, carrier screening is specifically recommended for couples from ethnic or racial groups that have a higher risk for certain disorders. By understanding their carrier status, couples can make informed decisions about family planning.
Benefits of carrier screening
- Early detection: Allows couples to identify potential genetic risks before conception.
- Informed family planning: Empowers couples to make well-considered decisions prior to starting their families.
- Reduced risk: If both partners are carriers, they can explore options like prenatal testing, PGT-M, or adoption.
Infertility Genetic Testing
Infertility can be a complex issue with various underlying causes, affecting 1 in 6 couples worldwide [6]. Infertility genetic testing is essential in the clinical assessment and management of infertility. It can help identify genetic factors associated with infertility in both men and women that are often overlooked and not able to be detected by traditional biochemical and instrumental testing [7]. This information can help couples gain a better understanding of their reproductive health, guide and explore appropriate treatment options, and improve the chances of conception. Some of the disorders tested by infertility genetic testing include premature ovarian failure and ovarian hyperstimulation syndrome in women, and hypogonadotropic hypogonadism and Y chromosome microdeletions in men.
Infertility genetic testing is applicable for all couples and individuals experiencing delay in conceiving, women with menstruation abnormalities, men with sperm abnormalities, individuals with external characteristics indicating a sex development syndrome, and individuals with a family history of infertility. Additionally, infertility genetic testing is applicable for couples and individuals who will undergo any assisted reproductive technology (ART), such as IVF.
Benefits of infertility genetic testing
- Diagnosis: Helps identify the underlying genetic cause of infertility.
- Treatment options: Tailors treatment plans to address specific genetic factors.
- Improved success rates: Increases the chances of conception and healthy pregnancy.
Preimplantation genetic testing (PGT)
PGT is a technique used in conjunction with IVF. It involves testing embryos for genetic disorders before implantation [8]. This allows couples at risk of passing on serious genetic conditions or those with a history of recurrent miscarriages to select embryos free of those conditions and embryos with higher chances of successful implantation.
There are different types of PGT, depending on the needs of the couple. These types include:
- PGT for aneuploidies (PGT-A): This test screens embryos for abnormal chromosome numbers. Euploid embryos, which have the correct number of chromosomes, have the best prospect of achieving pregnancy [9]. Aneuploid embryos, which have an abnormal number of chromosomes, can lead to miscarriages or the birth of children with genetic conditions such as Down syndrome or Turner syndrome. PGT-A is applicable to all couples undergoing IVF.
- PGT for structural rearrangements (PGT-SR): This test screens embryos’ chromosomes for structural rearrangements (translocations). Structural rearrangements are when a person has the correct number of chromosomes but not in the correct location. This can lead to difficulty in conceiving, recurrent pregnancy loss, or having a child with the same translocation. PGT-SR can help identify embryos that are euploid or balanced for the translocation and optimize the chances of a successful pregnancy and live birth.
- PGT for monogenic disorders (PGT-M): This test is used when couples are at risk of passing on a single-gene disorder, such as cystic fibrosis. By analyzing specific genes, PGT-M can identify embryos unaffected by the disorder. This test is usually recommended to couples where a carrier screening test has found that both of them have certain genetic mutations that could result in a disorder.
Benefits of PGT
- Reduced risk of miscarriages: Increases the chances of a successful pregnancy by identifying euploid embryos with no structural rearrangements.
- Healthy offspring: Reduces the risk of having a child with a genetic disorder.
- Reduced need for multiple IVF cycles: By transferring only healthy embryos, PGT can increase the efficiency of IVF and reduce the need for multiple cycles.
- Personalized family planning: Allows couples to make informed decisions about their reproductive journey.
Non-invasive prenatal genetic screening
Prenatal genetic testing is offered to pregnant women to assess the risk of their fetus having a genetic disorder. Several types of prenatal testing are available, including non-invasive prenatal testing (NIPT) and invasive tests like amniocentesis and chorionic villus sampling (CVS). NIPT is a genetic test that has revolutionized prenatal care by offering a safer and more accurate way to screen for chromosomal abnormalities in a developing fetus to women of all ages [10]. Unlike invasive methods, NIPT is performed using maternal blood, in which the fetal DNA circulates freely. By analyzing the fetal DNA, scientists can determine the risk of chromosomal abnormalities in the fetus. The most common chromosomal abnormalities screened by NIPT include:
- Autosomal aneuploidies:
- Down syndrome (trisomy 21)
- Edwards syndrome (trisomy 18)
- Patau syndrome (trisomy 13)
- Sex chromosome abnormalities such as Turner syndrome and Klinefelter syndrome
- Microdeletions
Benefits of NIPT
- Safe: NIPT does not pose any risks to the mother or fetus, unlike amniocentesis and CVS, which carry a small risk of miscarriage.
- Early detection: Allows for early diagnosis and planning as it can be performed as early as the 10th week of pregnancy.
- High accuracy: Most NIPTs have a very high detection rate for the most common chromosomal abnormalities.
- Informed decision-making: Helps parents make choices about their pregnancy.
- Medical management: Provides opportunities for prenatal care and treatment.
While NIPT is highly accurate, it is a screening test, and thus does not offer a definitive diagnosis. A high-risk NIPT result for a genetic abnormality should always be followed up with a confirmatory test, such as amniocentesis or CVS.
Conclusion
Genetic testing has significantly advanced reproductive health by providing couples with valuable information about their genetic risks and offering personalized options for family planning. As technology continues to advance, genetic testing is likely to play an even more significant role in addressing infertility challenges and family planning. By understanding the benefits of carrier screening, infertility genetic testing, PGT, and prenatal genetic testing, individuals can make informed decisions about their reproductive health and increase their chances of having a healthy family.
References
[1] World Health Organization: WHO. “Sexual and reproductive health and rights.” www.who.int, https://www.who.int/health-topics/sexual-and-reproductive-health-and-rights#tab=tab_1 (Accessed November 2024)
[2] Mann, S., & Stephenson, J. (2018). “Reproductive health and wellbeing – addressing unmet needs.” British Medical Association (BMA 20180500). Retrieved October 29, 2024, from https://www.bma.org.uk/media/2114/bma-womens-reproductive-health-report-aug-2018.pdf
[3] Solomon, Benjamin. “Carrier screening.” Genome.gov, updated 09. Nov. 2024, https://www.genome.gov/genetics-glossary/Carrier-Screening (Accessed November 2024)
[4] CDC. “Genetic disorders.” Genomics and Your Health. 15 May 2024, https://www.cdc.gov/genomics-and-health/about/genetic-disorders.html (Accessed November 2024)
[5] American College of Obstetricians and Gynecologists “Carrier screening.” Www.acog.org, Dec. 2020, https://www.acog.org/womens-health/faqs/carrier-screening (Accessed November 2024)
[6] Agarwal, A., Mulgund, A., Hamada, A. et al. “A unique view on male infertility around the globe.” Reproductive Biology and Endocrinology, 13, 37 (2015). https://doi.org/10.1186/s12958-015-0032-1
[7] Cariati, F., D’Argenio, V., & Tomaiuolo, R. “The evolving role of genetic tests in reproductive medicine.” Journal of Translational Medicine, 17, 267 (2019). https://doi.org/10.1186/s12967-019-2019-8
[8] Johns Hopkins Medicine. “Infertility services: Preimplantation Genetic Testing (PGT).” Www.hopkinsmedicine.org, https://www.hopkinsmedicine.org/gynecology-obstetrics/specialty-areas/fertility-center/infertility-services/preimplantation-genetic-testing (accessed November 2024)
[9] Kim, J. G., Murugappan, G., Lathi, R. B., et al. (2019). “Preimplantation genetic testing for aneuploidy (PGT-A) reduces miscarriage and improves live birth rates in recurrent pregnancy loss patients.” Fertility and Sterility, 112(3), e401, Sept. 2019, https://doi.org/10.1016/j.fertnstert.2019.07.1141
[10] Medline Plus. “What is noninvasive prenatal testing (NIPT) and what disorders can it screen for?: MedlinePlus Genetics.” Medlineplus.gov, 28 Jul. 2021 https://medlineplus.gov/genetics/understanding/testing/nipt/ (Accessed November 2024)
