Embryo Project Encyclopedia

Isotretinoin is a molecule and a byproduct (metabolite) of vitamin A, and in greater than normal amounts in pregnant women, it can cause fetal abnormalities including cleft lips, ear and eye defects, and mental retardation. Isotretinoin is commonly called by its trade name Accutane, and it's a chemical compound derived from vitamin A, or retinoic acid. Doctors prescribe isotretinoin to treat severe acne. For pregnant women, too much vitamin A or isotretinoin can also cause greater than normal rates of stillbirths and fetal disintegrations after the ninth week of gestation. Women who use isotretinoin during the first trimester of their pregnancies, even in small amounts, risk defects to their fetuses such as external ear malformations, cleft palates, undersized jaws (micrognathia), a variety of heart defects, buildups of fluids inside the skulls that leads to brain swelling (hydrocephalus), small heads and brains (microcephaly), and mental retardation.

Josef Warkany studied the environmental causes of birth defects in the United States in the twentieth century. Warkany was one of the first researchers to show that factors in the environment could cause birth defects, and he helped to develop guidelines for the field of teratology, the study of birth defects. Prior to Warkany’s work, scientists struggled to explain if or how environmental agents could cause birth defects. Warkany demonstrated that a deficiency or excess of vitamin A in maternal nutrition could cause birth defects. He also established that mercury in teething powders increased infant mortality rates. Warkany showed how substances outside the human body could adversely affect conception, growth, and development of the human fetus in utero.

The article Experimental Studies on Congenital Malformations was published in the Journal of Chronic Diseases in 1959. The author, James G. Wilson, studied embryos and birth defects at the University of Florida Medical School in Gainesville, Florida. In his article, Wilson reviewed experiments on birds and mammals from the previous forty years to provide general principles and guidelines in the study of birth defects and teratogens, which are things that cause birth defects. Those principles included what species are convenient for conducting teratological research, what principles act in human embryological and fetal development, and what agents impact those processes. Wilson's article was one of the first attempts in the twentieth century to synthesize basic research conducted in the field of teratology. The article helped to establish teratology as a field in medicine during the twentieth century.

Sidney Q. Cohlan studied birth defects in the US during the twentieth century. Cohlan helped to discover that if a pregnant woman ate too much vitamin A her fetus faced a higher than normal risk of teratogenic effects, such as cleft palate. A teratogen is a substance that causes malformation of a developing organism. Cohlan also identified the teratogenic effects of several other substances including a lack of normal magnesium and prenatal exposure to the antibiotic tetracycline. Cohlan's experiments with vitamins and other chemicals brought attention to how nutrition and environmental agents adversely affect human pregnancy outcomes.

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.

Hans Peter Dietz and Judy Simpson published, “Levator Trauma is Associated with Pelvic Organ Prolapse,” in the journal BJOG: An International Journal of Obstetrics and Gynecology in 2008. In their article, Dietz and Simpson estimated the risk of pelvic organ prolapse in women who attained injuries to the pelvic levator muscles. The levator muscles, also known as the levator ani, are a major muscle group that comprise the pelvic floor. Along with other muscles, the pelvic floor supports organs in a woman’s pelvis, such as the bladder, uterus, and rectum. Vaginal childbirth can cause a weakening of the pelvic muscles. That can lead to pelvic organ prolapse, which results in the descent of the pelvic organs towards a woman’s vaginal opening. In, “Levator Trauma is Associated with Pelvic Organ Prolapse,” Dietz and Simpson found that women were more likely to have pelvic organ prolapse if they had levator trauma, and called for further research to understand the relationship between levator ani trauma and pelvic organ prolapse.

In 1997, physicians and researchers Ambre Olsen, Virginia Smith, John Bergstrom, Joyce Colling, and Amanda Clark published, “Epidemiology of Surgically Managed Pelvic Organ Prolapse and Urinary Incontinence,” in the journal Obstetrics and Gynecology. In their article, the authors retrospectively analyzed data from patients who underwent surgery for pelvic organ prolapse or urinary incontinence two years prior in 1995. Often due to a weakening of or damage to their pelvic muscles, women with pelvic organ prolapse can experience a descent of pelvic organs into the lower pelvis and vagina. People with urinary incontinence can experience bladder control issues and urinary leaks. According to the authors, an estimated fifty percent of women who have previously given birth have had a prolapse. In their article, Olsen and colleagues analyze factors such as race, age, and weight in women who had surgery to treat pelvic organ prolapse and ultimately advocate for a standard assessment for the severity of those conditions.

In 1996, a team of researchers associated with the International Continence Society published “The Standardization of Terminology of Female Pelvic Organ Prolapse and Pelvic Floor Dysfunction” in American Journal of Obstetrics and Gynecology. Pelvic organ prolapse is characterized by the descent of the pelvic organs into the lower portion of the pelvis and is often caused by a weakening of the muscles and ligaments that normally hold the organs in place. The authors concluded that physicians and researchers needed to develop a system of standardized terms to use to describe the anatomical position of pelvic organ prolapse in women. They propose using terms that emphasize the location of the prolapse rather than just the involved organ. They also suggest that the system utilizes a series of examinations and imaging to uniformly describe and quantify pelvic organ prolapse. The article by Bump and colleagues was one of the first to call for a standardized system using specific terms to communicate findings about pelvic organ prolapse systematically across clinical and academic research settings.

In 2007, physicians John Jelovsek, Christopher Maher, and Matthew Barber published, “Pelvic Organ Prolapse,” in The Lancet. In their article, Jelovsek and colleagues provided an overview of pelvic organ prolapse in women and described the epidemiology, risk factors, symptoms, and management of the condition. Pelvic organ prolapse occurs when a woman’s pelvic floor is weakened or damaged from stress or trauma such as vaginal childbirth. The pelvic floor is a group of muscles that provides support to organs within the lower abdominal region of the body, including the bladder, uterus, and rectum. Disorders of the pelvic floor disrupt its normal function, often causing a feeling of uncomfortable pressure or pain, and incontinence, which is involuntary leakage of urine or feces. In their article, Jelovsek and colleagues reviewed the known information about pelvic organ prolapse as of 2007 and research teams who further studied the causes and management of pelvic organ prolapse in women later used the article as a reference.

Pelvic organ prolapse is a common condition in women that causes the pelvic organs to descend, often resulting from a weakened pelvic floor. Pelvic organs supported by the pelvic floor, such as the bladder, bowel, or uterus, can descend to such a degree that they project out from a woman’s body typically via the vagina. Pelvic floor stress or trauma, like vaginal childbirth, can cause pelvic organ prolapse. Women with pelvic organ prolapse also often experience other conditions, such as incontinence or the involuntary leakage of urine or fecal matter. As a result, while many women experience pressure or fullness from the prolapse itself, other common symptoms of pelvic organ prolapse are those involving the bladder or the bowel. Treatments for prolapse depend on the woman’s symptoms, and include pessaries, surgery, and pelvic floor exercises. As of 2021, researchers and physicians continue to study pelvic organ prolapse to determine how different treatments can be tailored to specific causes or symptoms.