Life,  Tech

The Evolution of Human Fertility: From IVF to Future Technologies Like Artificial Wombs and Stem Cell Gametes

  In the history of human fertility, 1978 was an important year. This year, the Robert Edwards team of the University of Cambridge in the United Kingdom cooperated with the infertile Lesley Brown couple to cultivate the first test-tube baby in human history.
  Prior to this time, all human beings were conceived and born in female bodies. Until the Edwards team discovered that the circadian rhythm level fluctuation of hormones in the human body is crucial for the cells to enter the endometrium, so the scientists selected the implantation period, and the fertilized eggs were successfully implanted. Previous attempts by scientists to implant a fertilized egg into the uterus and achieve a successful pregnancy have all failed.

The world’s first baby born in test tubes, she was born in the UK on July 25, 1978, and is now 45 years old.

  The success of in vitro fertilization combined with embryo transfer (In Vitro Fertilization, IVF, also known as “test-tube baby”) and related technologies means that human gametes can be fertilized outside the mother’s body, and embryos can develop outside the mother’s body. The word Vitro comes from Latin and means “in glass”.
  With the lengthening of years of education, the expansion of childbearing and childcare costs, and the change of concept of marriage and childbearing, women’s postponement of childbearing is becoming a global phenomenon. According to the database of the Organization for Economic Co-operation and Development, since the 1990s, the average age at first marriage of women in each member state has shown a clear upward trend. The same is true for the trend of childbearing age. Between 1990 and 2019, the age of first childbirth for Chinese women increased from 24.3 years to 27.9 years.
  Test-tube baby technology was originally developed for infertile couples – currently 1 out of 175 newborns worldwide comes from a glass vessel. And as women around the world delay their childbearing age, women with late childbearing are also becoming potential users of this reproductive technology.
  In fact, from in vitro fertilization to frozen sperm, frozen eggs, frozen embryos, even delaying ovarian aging and artificial uterus, human assisted reproductive technology has made continuous breakthroughs in the past 50 years. In addition, it also allows contemporary women to obtain a greater degree of freedom of reproduction-at least they do not have to give birth to offspring when they are not ready for career and mind, but their bodies are in the so-called “best reproductive age” in their twenties.
  The history of reproductive technology in the past half century is also the history of women gaining more reproductive autonomy.
creating life in glass

  In the 1970s, Australian reproductive expert Alan Trounson began his work in agriculture, with the task of increasing the reproductive rate of animals. His research target at the time was Merino sheep. Wool production has brought huge benefits to Australia, but while other breeds of sheep can produce two or more lambs, Merino sheep can only produce one lamb, because Merino sheep can only produce a single egg. So Trounson developed hormone therapy to increase egg counts in merino sheep and learned to make fertilized eggs in a petri dish.
  At the same time, Karl Wood, a gynecologist also in Australia, was trying to solve the infertility problem of human women in a similar way. He found that some patients were unable to conceive because of blocked fallopian tubes. If he could fertilize eggs in a petri dish like merino sheep and implant the embryos in the uterus, he could directly bypass this difficulty.
  After learning about Alan Trounson’s method of animal reproduction, Wood found Trounson and tried to apply the technology to humans with reproductive difficulties. In 1973, this fit team successfully cultivated the world’s first human egg fertilized in vitro and implanted it into the mother.
  The mother suffered a miscarriage after three months of pregnancy, but the advance paved the way for the success of Robert Edwards’ team at the University of Cambridge in the UK. In 1978, the Robert Edwards team bred the first test-tube baby in human history. Three years later, Trounson and Wood, not to be outdone, also “manufactured” a test-tube baby. And, unlike Edwards’ team in the UK, which relied on the body’s natural cycles, Trounson and Wood in Australia used hormone therapy, which allowed them to collect more oocytes from which better embryos could be selected. In addition, they also achieved the world’s first frozen embryo pregnancy.

  ”My point is that we should be using fertility drugs. At the time people were looking at the natural cycle and just collecting the eggs that a woman produces every menstrual cycle. We introduced fertility drugs and got multiple eggs and embryos, which I think is A very important step for success.” Alan Trounson told China Business News.
  After two successive cases of IVF were successful, the society did not accept this technology so quickly. There are fears that scientists will breed “Frankenstein”-like aliens. Another layer of controversy comes from how to deal with “abandoned fertilized eggs or embryos”. Human intervention and screening of embryos have also caused researchers to be described as “baby killers”. Attackers have ranged from religious groups and feminists to government agencies and the news media.
  ”It’s so hard to regulate new technology. The government thinks we’re going too fast, so they want us to go slower. But people who are infertile want you to go faster,” said Trounson, who is at the center of the tech ethics debate. He has suffered a lot of trauma. When his daughter was at home when she was young, he didn’t even allow her to answer the phone, because many of them were threats from hostile people.
  But women who want this technology will vote with their feet. Hormone therapy and methods of harvesting more eggs are now commonplace in the medical field. Two weeks before the egg retrieval, doctors start the woman on hormone therapy to get more mature eggs. Once the eggs are obtained, the doctor puts them in a petri dish along with sperm to fertilize them. Common drugs include clomiphene and gonadotropins, and companies including Merck and Baxter are actively developing such drugs.
slow down the biological clock

  In 2012, the American Society for Reproductive Medicine removed the “experimental” standard for egg freezing, making egg freezing an industry open to the public.
  In January 2014, Facebook announced that it would subsidize the cost of freezing eggs for female employees, with each reimbursement of $20,000. Technology giants such as Apple, Google, and Amazon followed suit. In 2018, Ctrip, a Chinese online travel company, announced that the company would provide egg freezing fees ranging from 100,000 yuan to 2 million yuan for middle- and senior-level female managers.
  The reason why this assisted reproductive technology is sought after is also related to its “autonomy” of women’s reproductive rights.

  During the period when Silicon Valley companies successively offered egg freezing benefits, a survey of female employees in the IT industry stated that in the IT industry, two-thirds of female employees would choose to leave the industry after giving birth, and many of them were middle-level employees. Female managers believe that having children can be an obstacle to career advancement.
  Many American reproductive clinics have responded to the psychological and physical needs of women in their advertisements. According to one of the clinics, “Modern women have more choices than ever before. And we offer another option: allowing you to start your family only when you are ready.” Quality and quantity come with
  age Lowered, which is characteristic of both sperm and egg cells. As early as 1948, British cryobiologist Christopher Polge took the wrong bottle from the refrigerator in an experiment of cryopreservation of chicken sperm, and accidentally discovered that glycerin was an effective storage medium, thus opening the “frozen sperm” industry. history.
  Egg freezing is much more difficult than sperm freezing. Egg cells contain a greater proportion of water than sperm, and this water tends to form ice crystals during freezing—sharp ice crystals can damage the structure of the cell. In the 1980s, scientists discovered that when an egg cell is rapidly cooled in liquid nitrogen, the egg will immediately turn into a glass state, thereby eliminating the ice crystal factor. Soon, in 1986, Australian scientists completed the world’s first in vitro fertilization and successful pregnancy of frozen eggs.
  Egg freezing technology was not originally developed to return reproductive autonomy to women. The original purpose of reproductive scientists studying this technology was to preserve fertility for women suffering from cancer or other diseases. In addition to freezing eggs, they have also tried a direction, which is to freeze ovarian tissue, and when a woman is seriously ill, old, and can no longer have children, the slices preserved when she is healthy are transplanted back to the ovary.
  ”Ovarian tissue does not need to go to war like liver transplantation and kidney transplantation. It does not need anastomosis of blood vessels. When transplanting, it is only necessary to cut open the ovaries that remain in the body, and then put the ovary slices that have been frozen and revived, and put them in a place with rich blood vessels. If it is sutured properly, it will grow back soon.” Ruan Xiangyan, executive deputy director of the Department of Obstetrics and Gynecology at Capital Medical University, told China Business News.
  In 1960, British endocrinologist Parrott et al. transplanted the frozen ovaries of a healthy mouse to irradiated mice, and the latter regained their fertility. This is the earliest successful case of ovarian tissue freezing and transplantation in the world, which shows that ovarian tissue has excellent regeneration ability.
  Later medical experiments proved that the regenerative ability of ovaries not only exists in mice, but also in human ovaries, which are also mammals. After successful transplantation, the patient’s ovarian function and fertility can be extended for about 20 years.
  Ruan Xiangyan first encountered ovarian tissue cryopreservation in 2010. At that time, she observed an 18-year-old female patient’s breast cancer operation in Germany. German doctors took part of her ovarian tissue while removing her sentinel lymph nodes. After the patient recovered, the doctor transplanted the ovarian tissue back into the female patient’s ovaries, and she could still have children in the future.
  The difficulty of this ovarian tissue freezing and transplantation lies in “how to maintain the activity of ovarian tissue during the process of freezing and thawing”. The ovary is only the size of an apricot. After the doctor takes out part of the ovarian tissue with a laparoscope, it needs to be quickly processed into several or dozens of cortical slices ranging from 7 to 8 mm long and 4 to 5 mm wide, and finally divided into cryovials containing cryopreservation solution inside. “This is tissue engineering. Ovary slices contain cells at different levels. Freezing needs to consider how to ensure the survival of different cell follicles under the same cryopreservation conditions.” Ruan Xiangyan said.
  After returning from studying in Germany, Ruan Xiangyan established the first ovarian tissue cryopreservation bank in Beijing Obstetrics and Gynecology Hospital. In 2016, she helped a bone marrow transplant patient cryopreserve part of her ovarian tissue; two years later, she transplanted this part of ovarian tissue back into the patient; The first baby born from ovarian tissue freezing and transplantation.
  This technology is no less important to enhancing women’s reproductive autonomy than freezing eggs. At present, this technology has been legalized in some countries such as Israel and Denmark. It has a success rate of about 23% to 41%, according to data provided by a 2020 review published in the journal “Chinese Reproduction and Contraception”. As of 2021, the number of babies successfully conceived using this technology will reach about 200 worldwide. Most of these cases are concentrated in European countries such as Belgium and Denmark.
  In China, a number of delayed fertility technologies, including egg freezing and ovarian tissue freezing, are currently only aimed at female patients who suffer from diseases and may have difficulty in bearing children in the future, and are not open to the public.
Artificial uterus, or no opposite sex at all

  Childbirth is a long process. Regardless of egg freezing or ovary slices, or the combination of sperm and eggs in a petri dish outside the body, after the success of these technologies, the reproductive process is not over, and the final birthplace of life still needs the uterus.
  Many animals are not as dependent on their mother’s womb as human young children are. For example, kangaroos, it only takes about a month to give birth to small kangaroos, and at this time the small kangaroos are less than 5 grams, about the size of our little finger, they will follow the reproductive tract licked by the female kangaroo, Slowly climb into the pouch, and then grow in the pouch until it can live out of the pouch.
  Some scientists are already developing “brood pouches”, or “artificial wombs”, for human embryos. The “EXTEND” of the Children’s Hospital of Philadelphia in the United States, the “EVE” of Tohoku University in Japan, and the EctoLife project launched in Berlin, Germany in 2022 are typical representatives. These artificial wombs try to simulate the environment in the mother’s womb. The core function is to provide oxygen and nutrients to the embryo, and deal with the waste produced by the fetus, allowing the embryo to grow in an environment that can monitor fetal development and vital indicators at any time.
  According to the vision of Hashem AI-Ghaili, the founder of the EctoLife project in Germany, his company will have 75 well-equipped laboratories in the future, each of which can accommodate 400 artificial wombs, and the number of newborns born each year can reach 30,000.
  However, the maturity of this technology is still far away compared with frozen eggs and IVF. The results of the Weizmann Institute in Israel show that the mouse embryos cultivated in vitro can grow to the sixth day (about 1/3 of the entire gestation period), grow hearts, stomachs, limbs and other organs, but then die up. The research team of the Children’s Hospital of Philadelphia in the United States successfully allowed the premature lamb fetus to continue to develop in the artificial womb for 4 weeks.
  One of the reasons the technique has been so difficult to fully succeed is that scientists don’t yet know exactly how babies need different nutrients at different stages of their lives inside a real womb. “It’s like you know that you need flour, butter, eggs, and sugar to make a cake, but if you just give you these ingredients, you can’t make a cake because you don’t know the proportion and timing of adding each ingredient.” Microbiology and Biology Informatics expert Sam Westreich said.
  Furthermore, “Limited knowledge is available on the possible long-term psychological and emotional effects of the use of artificial wombs on parents and future offspring. The impact of this technology on the concept of ‘fertility’ needs to be further explored.” Study by Center for Epidemiological Research in Afghanistan Director Ahmad Neyazi told China Business News. “Despite progress, we are still not at the stage where we can fully rely on this technology.”
  During traditional childbirth, the mother’s body plays a central role in conceiving and sustaining the growth of the fetus. If artificial wombs become a reality, human understanding of childbirth and the role of the mother may be reshaped when the process of childbirth becomes an external event for women.
  The artificial womb is not the most “fantastic” idea in the field of assisted reproduction. Some companies are still trying to use stem cells to customize sperm and eggs. This technology called in-Vitro Gametogenesis (IVG) is being used by some researchers. Seen as the future of reproductive science.
  It works by taking blood cells from a person’s blood and reprogramming them into stem cells, which are then reprogrammed into germ cells. In theory, induced pluripotent stem cells can be transformed into any cell in the human body, including germ cells. This could be good news for gay people, meaning women can also produce sperm cells and men can produce eggs.
  Despite initial success in mouse experiments, some researchers have expressed concern that some apparently healthy and functional cells may have unknown errors in their genomes, and that prolonged cultures in petri dishes may also May result in misretouching.
  ”There’s been talk of stem cells being used to create embryos, I don’t think that’s going to happen. Maybe something like an embryo can be made, but it won’t be an embryo. Not in my lifetime, nor in your lifetime, but later, who knows. What happened.” Trounson, who created the third human test-tube baby, told China Business News.

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