Reproductive Science and Engineering

Summary

Reproductive science and engineering is concerned with the examination and regulation of the physiological mechanisms involved in human reproduction, such as conception and birth, and with diagnosing and treating disorders of reproduction, such as male and female infertility. Because the ability to successfully bear offspring is the core objective driving the success of all animal species, reproductive research is of profound importance on a purely scientific level. In addition, by providing methodologies that enable infertile couples to conceive, such as artificial insemination and in vitro fertilization, this discipline has profound effects on both individual human lives and the population trends of societies, nations, and the world.

Definition and Basic Principles

Reproductive science and engineering studies the physical and chemical processes that underlie human reproduction. It involves the application of scientific technologies to treat disorders of reproduction, such as infertility. It also includes the development and use of methods to interfere with or prevent impregnation, such as contraception and sterilization. Among the many approaches reproductive scientists take to these issues, three of the most significant involve mechanical, chemical, and genetic strategies for engaging with reproduction. Micromanipulation is an umbrella term for any reproductive assistance technique that involves the physical handling of sperm, oocytes, or embryos on a microscopic scale using specialized tools. Another key tool that reproductive scientists widely use is a set of pharmaceutical products that mimic or interfere with the chemical signals naturally produced by the body. These artificial hormones can be used to manipulate the human reproductive system in various ways. Reproductive genetics is a rapidly expanding subfield of reproductive science that applies the tools of genetic research and deoxyribonucleic acid (DNA)-based technologies to issues of conception, childbirth, and inheritance.

Background and History

Written records indicate that humans have struggled with infertility since ancient times. For example, infertility is mentioned in texts from ancient Greece and Persia. For much of European history, infertility was generally attributed to women, not men, and was considered a sign of impiety because bearing children was considered a blessing from God. The first experiments with artificial insemination were carried out in the middle of the nineteenth century by the American gynecologist J. Marion Sims, who also carried out surgical procedures designed to widen the cervix and thus facilitate the entry of sperm. In the late nineteenth century, scientists began to acknowledge the potential role of male infertility, using microscopes to test the potency of sperm.

The first half of the twentieth century witnessed the discovery of the three most important hormones involved in reproduction: the female hormones estrogen and progesterone and the male hormone testosterone. Soon after, companies began to manufacture the first synthetic hormones for the treatment of infertility. In 1944, the first laboratory test showed human oocytes could be fertilized in vitro. Thirty-four years later, the first so-called test-tube baby was born in England, and sperm banks became more common. The late twentieth century saw two more milestones in infertility treatment: the first successful implantation and pregnancy with an egg that had been cryopreserved and the development of intracytoplasmic sperm injection technology.

How It Works

Micromanipulation. The basic setup of a micromanipulator is a microscope connected to robotic arms powered by electric motors and moved by hydraulic or pneumatic controls that may require foot pedals, joysticks, or both. The robotic arms are, in turn, connected to incredibly tiny glass tools. By looking through the microscope, which magnifies the cells hundreds of times, and manipulating the controls, the operator can tinker with the gametes and embryos with great precision—in essence, performing a kind of microsurgery. Some micromanipulation techniques involve lasers, which can move segments of a cell from place to place and slice open the thick membrane around an oocyte. This membrane, known as the zona pellucida, is often slit open to facilitate the entry of sperm. Other techniques involve using electric currents that can cause the membranes of two different cells to join together or transfer genetic material from one cell to another. Intracytoplasmic sperm injection is the most common micromanipulation procedure.

Reproductive Pharmacology. Reproductive pharmacology makes use of synthetic hormones to produce a desired effect—whether contraceptive in nature or intended to increase fertility. For example, most birth control pills use some combination of artificial forms of the female hormones estrogen and progesterone. These substances interfere with the normal cycle of ovulation and menstruation, thus suppressing the ability to conceive. For example, the chemical signals the pill sends may prevent the pituitary gland from releasing a chemical signal that induces ovulation, so the ovaries do not release any oocytes. Or it may prevent the lining of the uterus from thickening, thus inhibiting the implantation of a fertilized egg. Other ways in which artificial hormones may prevent pregnancy include thickening the mucus found in the cervix so that it is more difficult for sperm to travel through it and reducing the rate at which oocytes migrate from the ovaries toward the uterus. Endometriosis (overgrowth of the endometrium), amenorrhea (absent menstruation), and dysmenorrhea (painful menstruation) are also sometimes treated using artificial hormones, which can help regulate menstrual timing, duration, and severity.

Artificial hormones can also be used to treat female infertility. For example, injections of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) stimulate the process of ovulation, while gonadotropin-releasing hormone alters the timing of ovulation, making the fertile period more regular and ensuring that an oocyte is not released into the uterus until it has developed properly. These and other pharmaceutical tools can help physicians correct problems associated with common female fertility disorders. The most common disorder leading to female infertility is polycystic ovary syndrome (PCOS), which results in excessively high levels of androgen (a male hormone) and ovulation that is irregular or absent.

Genetics. Some infertility disorders are associated with a genetic defect of one kind or another. Male infertility has been linked with microdeletions, or tiny missing parts, in the Y chromosome and with mutations in particular genes. To identify these genetic components of infertility, scientists often conduct what is known as a genome-wide association study or whole-genome association study. This is a technique by which the entire set of genetic material belonging to each member of a group of subjects is scanned and compared to pinpoint specific genetic variations that are more prevalent in people with a certain trait, such as infertility.

Screening Tests. Another common tool of reproductive genetics is using screening tests to identify genetic traits in embryos produced by in vitro fertilization before they are implanted in the uterus. After a cell sample has been retrieved from the blastocyst or embryo, various techniques can be used to screen its DNA for possible genetic abnormalities associated with diseases, such as Down syndrome or cystic fibrosis. For example, short pieces of DNA can be artificially produced and specially designed to bind to and mark mutated DNA in the sample if it exists. Alternatively, the DNA in the sample can be directly examined to look for known mutations. Tests can also be carried out to reveal enzymes and proteins produced by specific genes.

Applications and Products

In Vitro Fertilization. In vitro fertilization (IVF) is one of the most common applications of assisted reproduction technology. The Latin term in vitro literally means “in glass.” In vitro fertilization is a medical procedure in which egg cells are fertilized not inside the body (in vivo) but within an artificial laboratory environment. Because this procedure is both complex and expensive, it is often employed to help couples for whom other infertility treatments have already failed.

The first step in an IVF cycle involves the use of artificial hormones, such as FSH and hCG, in drug form. During regular ovulation, the ovaries produce a single egg. This treatment, known as superovulation, causes the ovaries to produce multiple oocytes. Next, the oocytes, along with some follicular fluid, are retrieved from the patient's ovaries via a needle. They are allowed to incubate under controlled laboratory conditions, with sperm collected from the patient's partner or with donor sperm. After a day or two, the eggs are examined to determine which have been successfully fertilized. If necessary, intracytoplasmic sperm injection may be used to inseminate the eggs. This is a micromanipulation procedure that can be used to artificially induce fertilization when sperm have low motility (do not move well). In this process, a micromanipulator with a thin glass pipette on the end is used to pick up and inject a single sperm directly into an oocyte. Next, the fertilized eggs—now known as embryos—are either frozen for later use or transferred into the uterus using a speculum and a catheter. Typically, multiple embryos are inserted into the uterus to increase the chances of at least one successful implantation. This also increases the possibility of multiple births.

Because the success of any given cycle of IVF treatments is by no means guaranteed, many couples choose to use cryopreservation techniques to freeze embryos produced in one cycle for future use. This streamlines the process a couple must go through if treatment does have to be repeated. It also reduces the need for performing invasive procedures on the female patient.

Intrafallopian Transfer.Gamete intrafallopian transfer (GIFT) is a procedure that resembles in vitro fertilization. The main difference between the two applications is that with GIFT, fertilization occurs not within a laboratory setting but inside the female patient's body. GIFT is a minimally invasive surgical procedure in which a catheter is placed through a small keyhole incision. Oocytes and semen are inserted through the catheter into the Fallopian tubes. At this point, fertilization and implantation of the embryo may or may not occur.

Zygote intrafallopian transfer (ZIFT) is a procedure that combines elements of both in vitro fertilization and GIFT. First, gametes are extracted and fertilized under controlled laboratory conditions. Next, they are inserted into the Fallopian tubes using the same method as in GIFT. Because GIFT and ZIFT are more invasive and expensive than in vitro fertilization, they are much less commonly performed. They may be recommended for couples whose struggles with infertility are more severe or who have not responded positively to previous cycles of IVF treatment.

Artificial Insemination. Artificial insemination is a widely used, minimally invasive procedure used to help couples with a variety of infertility problems, such as a partner with low sperm count or motility, the existence of natural antibodies in either partner that attack sperm, or characteristics of the cervix shape that make fertilization difficult. Artificial insemination can be carried out using either the intended father's sperm or that of a donor obtained from a sperm bank. In either case, once the sperm has been collected, it is physically inserted via a catheter into the cervix. Though the technique is simple, timing is crucial—artificial insemination must take place either just before or on the day of ovulation to be successful. In practice, it is often carried out on two consecutive days to increase the chances of fertilization.

Surrogacy. Surrogacy is an attractive option for those who are infertile because their uterus is abnormal or has been removed or who are believed to be at high risk for miscarriage or other complications of pregnancy. In gestational surrogacy, an embryo fertilized through in vitro fertilization is implanted into the uterus of someone who is healthy and fertile and has agreed to act as a surrogate. In some cases, the surrogate donates her own egg to be fertilized via in vitro fertilization with the biological father's sperm or that of a donor, then carries the baby to term. Some surrogates perform this service out of pure altruism or generosity; these are usually close friends or relatives of the intended mother. Others are unrelated strangers who are compensated financially by the parents. Surrogacy invokes many ethical issues and is illegal in many countries worldwide. 

Contraception and Sterilization. Some applications of reproductive science are intended to prevent, not facilitate, impregnation. Most of the available contraceptive methods are designed for use by a female partner alone, although a few are meant for shared use or use by a male partner alone. Barrier methods, such as the sponge, the diaphragm, the male and female condoms, and the cervical cap, prevent sperm from reaching the egg inside the Fallopian tube. Hormonal methods, such as the pill, the vaginal ring, injected or implanted devices, and certain intrauterine devices, release artificial hormones into a woman's body to interfere with the process of ovulation and prevent eggs from being released into the Fallopian tubes. Emergency contraception, which can be used up to three days after intercourse, uses high doses of estrogen to prevent a fertilized egg from being implanted in the uterus.

Other contraceptive methods are less reliable. These include the rhythm method, in which partners carefully monitor the woman's body temperature and menstrual cycle to determine the date of ovulation and avoid intercourse during this time. Sterilization is the most decisive method of preventing impregnation. A vasectomy is a reversible surgical procedure that results in sterility for the male partner. It involves cutting or otherwise sealing both the right and the left vas deferens, the tubes through which sperm travel into the penis. A tubal ligation is an irreversible surgical procedure that results in female sterility. It involves sealing the Fallopian tubes so that eggs cannot pass from them into the uterus.

Careers and Course Work

Preparing for a future career in reproductive science and engineering should begin with a thorough grounding in science and mathematics at the high school level. Students should be sure to advance through the highest available levels of biology and chemistry. The next step is to earn a Bachelor of Science at the undergraduate level, preferably with a concentration in biology or biomedicine. Courses particularly significant to this field include developmental biology, andrology, embryology, endocrinology, urology, bioengineering, and genetics. In addition, it is important to spend some time acquiring hands-on laboratory research experience, which can come through internships or independent studies. Some may choose to complete a degree in medicine and become a practicing physician specializing in fertility or embryology. Alternatively, many professionals in reproductive science and engineering are physician-investigators who have pursued training in both medicine and scientific research. This path involves obtaining a dual Doctor of Medicine (MD) and Doctoral degree (PhD) after completing a Bachelor of Science degree at the undergraduate level. Typical MD-PhD candidates require about seven to eight years to complete this program. This path is ideal for anyone considering conducting original research in an academic setting, serving as a clinician-researcher at a hospital, or working in a private laboratory dedicated to assisted reproductive technologies.

Professional careers in reproductive science and engineering can take a variety of other shapes. For instance, many opportunities exist in the context of fertility clinics, including jobs for nurses, medical assistants, and technicians, such as ultrasonographers. Salaries in the medical fields vary greatly depending on a person’s specific discipline.

Social Context and Future Prospects

Perhaps the most significant social impact of reproductive science and engineering is how it has transformed the opportunities available to women in the workplace and, more broadly, the shape of families themselves. Because technologies, such as in vitro fertilization, enable people to bear children successfully later in their lives, many choose to delay parenthood until they have established themselves fully within their careers. Artificial insemination has not only enabled infertile heterosexual couples to fulfill their desire to bear children but also—because sperm can be acquired through donor banks—has facilitated the rise of the modern phenomenon of single parenthood by choice. Also, assisted reproductive technologies have provided a means for same-sex couples to become biological parents.

Some beneficial technologies created by reproductive science and engineering have the potential to be turned into what some observers fear are unethical applications. For example, preimplantation genetic diagnosis has profound benefits because it enables couples to raise their chances of having healthy babies. However, it has also generated a certain amount of controversy because the same techniques could, in theory, be used to allow couples to select embryos with certain very specific traits. For example, embryos could be chosen or engineered to have genes encoding eye or hair color or traits, such as intelligence or physical beauty—the so-called designer baby concept. It can be used to allow couples to favor children of one sex over another. Other ethical questions provoked by assistive reproductive technologies include the question of what to do with leftover frozen embryos, whether a divorcee can use a frozen embryo over the objection of the former partner, and whether and how much someone should be compensated for egg or embryo donation or surrogacy. Finally, cloning remains a controversial and often misunderstood area in biomedical research. Reproductive cloning, which involves creating a precise genetic copy of an existing organism through a process known as somatic cell nuclear transfer, is banned from being done with humans in most countries. Similarly, the reported births of "three-parent" children, created through a process that combines healthy mitochondria from a donor oocyte, the sperm of the intended father, and an oocyte nucleus from the intended mother, has raised ethical and safety concerns about "heritable genetic modification." The United States government barred the practice, while the United Kingdom government gave limited approval for further research.

An ongoing area of research in reproductive science and engineering is easily reversible male contraception. Clinical trials have been conducted to test artificial hormones in pill, topical gel, and injection forms, and a nonhormonal polymer block for the vas deferens that would serve as a reversible vasectomy. Appropriate regulation of testosterone levels, the fast metabolism and clearance of artificial male hormones, and concerns regarding side effects have long complicated efforts to develop and commercialize a safe, effective male contraceptive. The most promising options included a topical combination of progestin and testosterone and an oral formulation of dimethandrolone undecanoate. However, in the mid-2020s, there were no federally approved male birth control drugs, and condoms and vasectomies remained the only options for male birth control. Mitochondrial transfer, transplants of the uterus, and using CRISPR-Cas9 to modify DNA are just a few of the emerging technologies in reproductive technology. In the twenty-first century, reproductive technology continued to be a rapidly developing field where science and ethics collided. 

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