Understanding Infertility
As stated in the “History of Assisted Reproductive Technology (ART)” section, the ART process has only been around for a relatively short amount of time. However, within that time period, breakthroughs in reproductive technology have been almost mind-blowing. This now begs the question: where does ART go from here?
Some current research has gone in the direction of stem cells and the effect it has on reproductive uses. Ovarian stem cells, which have been found in the ovaries of reproductive aged women, may be one case for the future. Although still in pre-human testing using mice, stem cells found in these ovaries may help those with diminished ovarian reserve (DOR) – a condition in which the ovaries prematurely age. Stem cells can help by reinforcing eggs (oocytes) with mitochondria. Additionally, reduced quality eggs could have improvement in both biological and chemical factors by using these mitochondria to enrich ATP production in eggs (oocytes.)[1] In trials with mice, when healthy ovarian stem cells were transferred into mouse ovaries, the mouse ovarian stem cells could produce embryos and offspring once again. Around 80% of treated mice using adult ovarian stem cells and neonatal stem cells produced offspring who were also fertile.[2]
Additionally, stem cells are being looked at for answers to male infertility. Spermatogonial stem cells (SSCs), which have self-renewing properties, have been used to make sperm in vitro using mice.[5] The first successful meiosis (cell division) of a generated germ cell using stem cells was reported in 2016. The research team from China changed embryonic stem cells (ESCs) into primordial germ cells (cells that generate into sperm or egg stem cells); these germ cells were then exposed to testicular cells. This helped create a natural environment for testosterone and the germ cells, leading to complete meiosis and production of sperm-like cells. These sperm-like cells, when injected into mouse eggs, produced healthy embryos that later birthed healthy offspring.[6] While ethical concerns and risks are still debated, this may be a step toward helping men who suffer from male infertility.
Artificial gametes are another area in which extensive research is being done. Gametes are sexual reproductive haploid cells needed for fertilization and conception (sperm and eggs.) Scientists have looked into production of gametes using stem cells, bone marrow and fetal skin.[7] These gametes can then produce sperm and eggs using the stem cells of the males and females. This could combat infertility in those with egg issues by creating gametes from dead or stored tissue.[8] Post menopausal women and gay couples could conceive genetically related children as well. Artificial sperm and eggs created from stem cells in animals have already been produced and led to viable offspring. Artificial sperm in humans has been produced from female stem cells, but there has been no reported offspring birth yet.[9]
Another area of interest in regards to stem cell research and infertility is within the realm of cancer. In one study by Sara Mohamed et. al, they used bone marrow mesenchymal stem cells (BMSCs) to treat chemotherapy induced ovarian failure. Using mice, their results showed that the groups which was treated with stem cells show re-population of growing follicles and a significant increase in pregnancy numbers compared to the other groups.[3]
However, these treatments are not without their critics. The presence of ovarian stem cells is still a highly debated topic (as the original thought is that a woman is born with the amount of eggs she has until she dies.) Other groups have published contradictory results that said ovarian stem cells do not exist in normal, adult human ovaries or that follicle regrowth does not exist.[4] This discourse has led to multiple reports and experiments on the matter and is shaping the scope of future infertility research.
Another new technique used in the last few years is IMSI – intracytoplasmic morphologically elected sperm injection. During the in vitro fertilization (IVF) process, there are two ways for egg fertilization. The first is conventional insemination – in which the male’s sperm is placed over the woman’s retrieved eggs so that the sperm can naturally penetrate the eggs. The second method is intracytoplasmic sperm injection (ICSI) – in which embryologists select a single sperm from a semen sample and inject it into the egg via a small glass needle.[10]
During IMSI, embryologists look at the sperm more magnified than the ICSI process. While the ICSI process look at sperm at 200-400x, IMSI looks at sperm from 6100x to up to 13,000x. This allows a closer look to ensure the best sperm during selection.[11] However, the effectiveness of IMSI for clinical practice is still a hot topic. Despite initial studies showing that IMSI had better pregnancy rates[12], further studies have been done that show similar outcomes for ICSI and IMSI.[13] More research is needed to test the effectiveness of IMSI vs. ICSI in the future.[14]
Another part of the IVF process can include preimplantation genetic screening (PGS). PGS is a process in which embryos are sent for testing to determine if they have chromosomal abnormalities. Women over 35, those with recurrent pregnancy loss (RPL) and those with multiple failed IVF cycles are recommended for the process.[15] For more information on PGS, please visit the PGS section under the IVF tab in the menu.
However, scientists want to take PGS a step further. Preimplantation genetic diagnosis (PGD) is the process of profiling embryos before implantation. This process can screen for specific diseases (compared to PGS which can only screen for abnormalities.) PGD is recommended for those who are carriers of genetics diseases or those with balanced translocation.[16]
Of course, PGD is not without controversy. Many ethical issues surround the practice – the thought of playing “God” with the test embryos still prevails. While PGD for genetic disease and disorder screening is seen as ethical, the practice of PGD for gender selection is still heavily debated. As PGD in this instance is nonmedical, the practice is seen as highly controversial. Further, many people question the extent PGD can go in the future. With more technology, genetic tests for sexual orientation, height, intelligence, or other traits could arise. However, this is still unlikely for a long time due to the difficulty in finding a basis for these traits.[17]
Additionally, embryo destruction is an issue that can arise due to PGD. Around 20% of the time, PGD can cause embryo damage, leading to the arresting (stopped growth) of the embryo. According to Michael Tucker, PhD, chief embryologist at Georgia Reproductive Specialists in Atlanta, it is important to note that PGD is an invasive procedure and embryo viability can be compromised.[18] PGD is also not a 100% guarantee – abnormal embryos can appear normal while normal embryos may appear normal and be destroyed.[19]
While ART is not even half a century old, many advancements have been made to make the process as smooth as possible. With such a successful past, we can only guess where the future will lead. However, with such a bright present, the future of ART looks to be even brighter.
[1] Silvestris, Erica, et al. "Perspective in infertility: the ovarian stem cells." Journal Of Ovarian Research 8, no. 1 (August 2015): 1-9. Academic Search Complete, EBSCOhost (accessed April 14, 2018).
[2] Ozakpinar, Ozlem Bingol. "Ovarian Stem Cells: From Basic to Clinical Applications." World Journal of Stem Cells 7, no. 4 (May 26, 2015): 757-68. doi:10.4252/wjsc.v7.i4.757.
[3] Mohamed, Sara A., Shahinaz M. Shalaby, Mohamed Abdelaziz, Soumia Brakta, William D. Hill, Nahed Ismail, and Ayman Al-Hendy. "Human Mesenchymal Stem Cells Partially Reverse Infertility in Chemotherapy-Induced Ovarian Failure." Reproductive Sciences 25, no. 1 (May 1, 2017): 51-63. Accessed April 15, 2018. doi:10.1177/1933719117699705.
[4] Evron, Ayelet, and Zeev Blumenfeld. "Ovarian Stem Cells–-the Pros and Cons." Clinical Medicine Insights: Reproductive Health 7 (March 20, 2013): 43-47. Accessed April 15, 2018. doi:10.4137/cmrh.s11086.
[5] Kobayashi, Hideyuki, Koichi Nagao, and Koichi Nakajima. "Stem cell research for male infertility." Reproductive Medicine & Biology 10, no. 3 (September 2011): 171-174. Academic Search Complete, EBSCOhost (accessed April 14, 2018).
[6] Brazier, Yvette. "Sperm Created from Stem Cells Offer Hope in Cases of Male Infertility." Medical News Today. February 26, 2016. Accessed April 15, 2018. https://www.medicalnewstoday.com/articles/307044.php.
[7] Bhartiya, Deepa, Indira Hinduja, Hiren Patel, and Rashmi Bhilawadikar. "Making Gametes from Pluripotent Stem Cells – a Promising Role for Very Small Embryonic-like Stem Cells." Reproductive Biology and Endocrinology 12, no. 1 (November 24, 2014): 114. Accessed April 14, 2018. doi:10.1186/1477-7827-12-114.
[8] Mackellar, Calum. "Representative Aspects of Some Synthetic Gametes." New Bioethics 21, no. 2 (November 2015): 105-116. Academic Search Complete, EBSCOhost (accessed April 14, 2018).
[9] Hendriks, Saskia, Eline A.f. Dancet, Ans M.m. Van Pelt, Geert Hamer, and Sjoerd Repping. "Artificial Gametes: A Systematic Review of Biological Progress towards Clinical Application." Human Reproduction Update 21, no. 3 (May/June, 2015): 285-96. Accessed April 14, 2018. doi:10.1093/humupd/dmv001.
[10] "Typical IVF Schedule." Advanced Fertility Care. 2017. Accessed April 15, 2018. https://www.azfertility.com/your-miracle/ivf-in-vitro-fertilization/typical-ivf-cycle/.
[11] "Regular (ICSI) versus Ultra‐high Magnification (IMSI) Sperm Selection for Assisted Reproduction." National Center for Biotechnology Information. July 25, 2013. Accessed April 15, 2018. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0057740/.
[12] Knez, Katja, Branko Zorn, Tomaz Tomazevic, Eda Vrtacnik-Bokal, and Irma Virant-Klun. "The IMSI Procedure Improves Poor Embryo Development in the Same Infertile Couples with Poor Semen Quality: A Comparative Prospective Randomized Study." Reproductive Biology and Endocrinology 9, no. 1 (August 29, 2011): 123. doi:10.1186/1477-7827-9-123.
[13] Setti, Amanda Souza, Daniela Paes De Almeida Ferreira Braga, Assumpto Iaconelli, Tsutomu Aoki, and Edson Borges. "Twelve Years of MSOME and IMSI: A Review." Reproductive BioMedicine Online 27, no. 4 (October 2013): 338-52. doi:10.1016/j.rbmo.2013.06.011.
[14] Teixeira, D.m., M. Barbosa, R.a. Ferriani, P.a. Navarro, N.j. Raine-Fenning, C.o. Nastri, and W.p. Martins. "EP27.02: Ultra-high Magnification (IMSI) vs Standard Sperm Selection (ICSI) for Assisted Reproduction." Ultrasound in Obstetrics & Gynecology 50, no. S1 (September 16, 2017): 384. doi:10.1002/uog.18754.
[15] "Pre-implantation Genetic Screening (PGS)." Pre-implantation Genetic Screening (PGS) | Human Fertilisation and Embryology Authority. Accessed April 15, 2018. https://www.hfea.gov.uk/treatments/embryo-testing-and-treatments-for-disease/pre-implantation-genetic-screening-pgs/.
[16] Thornhill, A.r., C.e. Dedie-Smulders, J.p. Geraedts, J.c. Harper, G.l. Harton, S.a. Lavery, C. Moutou, M.d. Robinson, A.g. Schmutzler, P.n. Scriven, K.d. Sermon, and L. Wilton. "ESHRE PGD Consortium ‘Best Practice Guidelines for Clinical Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS)’." Human Reproduction 20, no. 1 (January 01, 2005): 35-48. doi:10.1093/humrep/deh579.
[17] Robertson, J. A. "Extending Preimplantation Genetic Diagnosis: The Ethical Debate: Ethical Issues in New Uses of Preimplantation Genetic Diagnosis." Human Reproduction 18, no. 3 (March 01, 2003): 465-71. doi:10.1093/humrep/deg100.
[18] "Bust a Myth about PGD/PGS." Bust a Myth About PGD and PGS. Accessed April 15, 2018. https://www.fertilityauthority.com/articles/bust-myth-about-pgd-pgs.
[19] "Preimplantation Genetic Diagnosis." BioCentre. Accessed April 15, 2018. https://www.bioethics.ac.uk/topics/preimplantation-genetic-diagnosis.php.