Infertility is a struggle for many individuals nowadays. According to the World Health Organization (WHO), 1 in 6 people experience infertility, showing the increasing need for the use of alternative options to overcome these challenges and high-quality fertility care through assisted reproductive treatment (ART) (1). In vitro fertilization (IVF) is one treatment solution for infertility, offering a beacon of hope for those struggling to conceive naturally.
While IVF is a powerful tool that can significantly increase pregnancy success rates, it does not always guarantee successful pregnancy and live birth. The field of infertility has seen many advancements in recent years, offering individuals a wider range of options to consider, which potentially increases the possibility of conceiving and at the same time shortens and simplifies the overall fertility journey. One example is Preimplantation Genetic Testing (PGT).
In this blog, you will find information about IVF and the challenges that can arise during this process. In addition, we describe PGT and its importance in reducing miscarriage rates, as well as who is suitable for PGT and the different tests that can be performed to increase the success of pregnancy.
Contents
What is IVF and what are the challenges that can occur?
In vitro fertilization (IVF) is the process in which eggs are fertilized with sperm in vitro (“in glass”). During IVF, eggs are retrieved from the ovaries and fertilized with sperm outside the body, in a petri dish. This process can take several months as it requires hormonal stimulation of the ovaries via injections to produce mature eggs, which will ultimately fuse with sperm and create the embryo. Following fertilization, embryologists carefully examine embryos through visual observation. They assess the embryo’s physical appearance (morphology) and development stage. This evaluation aims to identify the embryo with the most optimal features and the highest chance of leading to a successful pregnancy. The chosen embryo is then implanted into the uterus. Pregnancy occurs when the embryo successfully implants in the uterus and survives (2, 3).
IVF has revolutionized the field of ART and continues to provide an alternative option for individuals who are unable to conceive naturally. However, there are many challenges that individuals could face until a successful pregnancy is achieved. The success of an IVF treatment depends on many factors such as maternal age and lifestyle (3, 4).
In addition, a critical factor for successful embryo implantation is its genetic makeup, and the correct number of chromosomes (4). Traditionally, embryos were solely evaluated according to their morphology and development to select the best embryo for implantation. However, these assessments don’t always guarantee a successful pregnancy because they don’t provide any information about the embryo’s genetic makeup (5). For example, certain genetic abnormalities such as trisomy of chromosome 16, could prevent implantation or hinder the survival of the embryo in the uterus. Therefore, additional genetic testing is needed to ensure embryos have the correct genetic status, increasing the chance of successful implantation and pregnancy.
PGT and its significance
While IVF has been a game-changer, the introduction of PGT has taken the IVF process one step further. PGT allows for the genetic screening of IVF-fertilized embryos before they are transferred into the uterus (6).
During PGT, cells from the fertilized egg are extracted through biopsy by experienced embryologists and genetically analyzed. This is usually done on day 3 or day 5 post-fertilization, at the cleavage or blastocyst stage of the embryo, respectively (7). The extracted cells, which do not affect embryo development, are sent to a specialized laboratory for genetic testing analysis to check for any genetic abnormalities. If no abnormalities are identified, the embryo is considered euploid and has a higher chance of successful implantation. In addition to this, by identifying embryos with a higher chance of successful implantation and development, PGT can potentially shorten the overall time it takes to achieve pregnancy and reduce the risk of miscarriage (8).
Types of PGT
There are different PGT options that screen for various genetic abnormalities that might lead to failed IVF as well as miscarriages:
1. PGT-A (PGT for aneuploidy)
PGT-A focuses on identifying chromosomal abnormalities in embryos and whether the embryos have a total of 46 chromosomes. These abnormalities are a leading cause of miscarriage and birth defects. By analyzing the genetic makeup of embryos, PGT-A can help identify whether an embryo is euploid or aneuploid. The key difference between them lies in their chromosome count. Euploids have a correct genetic status with the correct number of chromosomes, 46 in total, whereas aneuploid embryos might have an incorrect genetic status or chromosome number (9). Euploid embryos are more likely to implant and result in a child with no chromosomal abnormalities, whereas aneuploid embryos might lead to miscarriage or result in a child with a genetic disorder such as Down syndrome. In certain cases, mosaic embryos can result during fertilization, in which some of the cells have the correct number of chromosomes whereas others do not. Mosaic embryos can also lead to miscarriage or a child with a genetic condition (10). PGT-A allows for the selection of euploid embryos, significantly improving their implantation potential and reducing the risk of miscarriage (8, 11).
2. PGT-SR (PGT for structural rearrangements):
PGT-SR analyzes embryos to identify those with a balanced genetic makeup in which they have the correct number of chromosomes but not in the correct location. By avoiding unbalanced embryos, PGT-SR reduces the risk of miscarriage or having a child with a genetic disorder while increasing IVF success rates, and offering individuals valuable information for informed family planning decisions (8, 11).
3. PGT-M (PGT for monogenic diseases):
PGT-M is specifically designed for individuals with a family history of certain genetic disorders and individuals who are carriers of a disease-causing genetic mutation. PGT-M analyzes embryos for the presence of those specific mutations that can be passed down from parents to children, enabling the selection of embryos that did not inherit the genetic condition (8, 12)
When can PGT be considered?
PGT testing is applicable to:
- Any individual or couple going through IVF
- Any individual or couple with a history of unsuccessful fertility treatments
- Any individual who is at high risk of passing on a specific single gene disorder
- Women who have experienced at least one miscarriage
- Individuals with structural chromosomal rearrangements (translocations)
- Women who have experienced a previous pregnancy with a chromosomal aneuploidy
- Women over 35 years old going through IVF
Why should someone consider PGT?
There are several reasons to consider PGT alongside IVF. Firstly, PGT can increase the success rates of pregnancy by focusing on embryos that do not have genetic abnormalities and have higher implantation potential. In addition, it reduces the risk of chromosomal abnormality-associated miscarriage. Therefore, PGT could reduce failed IVF cycles, as well as reduce emotional and financial strain.
Conclusion
PGT is a significant breakthrough in IVF technology. It offers hope to individuals seeking to build a family through IVF by increasing their chances of a successful pregnancy, while potentially reducing both the emotional and financial burden. However, the decision to undergo PGT is personal and should be carefully discussed with a fertility specialist and genetic counselor. As technology advances, PGT is expected to become even more sophisticated, offering more options and shaping the future of family building planning for many individuals.
References
[1] World Health Organization. “1 in 6 people globally affected by infertility: WHO”. Www.who.int, 4 Apr. 2023, https://www.who.int/news/item/04-04-2023-1-in-6-people-globally-affected-by-infertility. Accessed 10 Jul. 2024.
[2] Mayo Clinic Staff “In vitro fertilization (IVF)” Mayo Clinic, Mayo Foundation for Medical Education and Research, 1 Sept. 2023, https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716. Accessed 10 Jul. 2024.
[3] Nordqvist, Joseph. “IVF: What Does It Involve?” Medicalnewstoday.com, Medical News Today, 05 Feb. 2018, www.medicalnewstoday.com/articles/262798. Accessed 10 Jul 2024.
[4] “Why Does IVF Fail? 6 Reasons for IVF Failure.” The Fertility & Gynaecology Academy, https://www.fertility-academy.co.uk/blog/why-does-ivf-fail/. Accessed 10 Jul. 2024.
[5] Fesahat, Farzaneh et al. “Frequency of chromosomal aneuploidy in high quality embryos from young couples using preimplantation genetic screening.” International journal of reproductive biomedicine vol. 15,5 (2017): 297-304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510583/.
[6] Parikh, Firuza Rajesh et al. “Preimplantation Genetic Testing: Its Evolution, Where Are We Today?.” Journal of human reproductive sciences vol. 11,4 (2018): 306-314, doi:10.4103/jhrs.JHRS_132_18 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333033/.
[7] Vlajkovic, Tijana et al. “Day 5 versus day 3 embryo biopsy for preimplantation genetic testing for monogenic/single gene defects.” The Cochrane database of systematic reviews vol. 11,11 CD013233. 24 Nov. 2022, doi:10.1002/14651858.CD013233.pub2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690144/.
[8] “Preimplantation Genetic Testing (PGT) | Fertility & Reproductive Medicine Center.” Fertility.wustl.edu, Washington University Physicians, https://fertility.wustl.edu/treatments-services/genetic-counseling/preimplantation-genetic-testing-pgt
[9] “Euploid Embryo vs Aneuploid Embryo I TRIO Fertility.” TRIO Fertility Treatment Practice, 28 Feb. 2024, https://triofertility.com/euploid-embryo-vs-aneuploid-embryo/. Accessed 10 Jul 2024.
[10] Muñoz Elkin, Bronet Fernando, Lledo Belen, et al. “To transfer or not to transfer: the dilemma of mosaic embryos – a narrative review.” Reprod Biomed Online [Internet]. Mar 2024;48(3):103664. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1472648323007630.
[11] Viotti Manuel. “Preimplantation Genetic Testing for Chromosomal Abnormalities: Aneuploidy, Mosaicism, and Structural Rearrangements.” Genes (Basel). vol. 11,6 602. 29 May. 2020, doi:10.3390/genes11060602. PMID: 32485954; PMCID: PMC7349251. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349251/pdf/genes-11-00602.pdf.
[12] Zanetti, Bianca Ferrarini et al. “Preimplantation genetic testing for monogenic diseases: a Brazilian IVF centre experience.” JBRA assisted reproduction vol. 23,2 99-105. 30 Apr. 2019, doi:10.5935/1518-0557.20180076, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501745/.
