Pregnancy test

Chemical tests for pregnancy look for the presence of the beta subunit of human chorionic gonadotropin (hCG) in the blood or urine. For a qualitative test (yes/no results only), the thresholds for a positive test are generally determined by an hCG cut-off where at least 95% of pregnant women would get a positive result on the day of their first missed period.[5] hCG can be detected in urine or blood after implantation around six to twelve days after fertilization, although some evidence suggests that hCG may be released preimplantation as well.[6][7] Quantitative blood (serum beta) tests can detect hCG levels as low as 1 mIU/mL, and typically clinicians will call a positive pregnancy test at 5mIU/mL.[5] Urine test strips have published detection thresholds of 10 mIU/mL to 100 mIU/mL, depending on the brand.[8] Most home pregnancy tests are based on lateral-flow technology.

With obstetric ultrasonography the gestational sac sometimes can be visualized as early as four and a half weeks of gestation (approximately two and a half weeks after ovulation) and the yolk sac at about five weeks' gestation. The embryo can be observed and measured by about five and a half weeks. The heartbeat may be seen as early as six weeks, and is usually visible by seven weeks' gestation.[9][10]

Although all current pregnancy tests detect the presence of beta hCG, research has identified at least one other possible marker that may appear earlier and exclusively during pregnancy. For example, early pregnancy factor (EPF) can be detected in blood within 48 hours of fertilization, rather than after implantation.[11] That said, its reliable use as a pregnancy test remains unclear as studies have shown its presence in physiological situations besides pregnancy, and its application to humans remains limited.[12]

The control line of this pregnancy test is blank, making the test invalid

The control line on the left of this pregnancy test is visible, suggesting that the test result is valid. A pale purple line has also appeared on the right hand side (the test line) which clearly signifies that the woman is pregnant

A systematic review published in 1998 showed that home pregnancy test kits, when used by experienced technicians, are almost as accurate as professional laboratory testing (97.4%). When used by consumers, however, the accuracy fell to 75%: the review authors noted that many users misunderstood or failed to follow the instructions included in the kits. Improper usage may cause both false negatives and false positives.[13]

Pregnancy tests may be used to determine the viability of a pregnancy. Serial quantitative blood tests may be done, usually 3–4 days apart. Below an hCG level of 1,200 mIU/ml the hCG usually doubles every 48–72 hours, though a rise of 50–60% is still considered normal. Between 1,200 and 6,000 mIU/ml serum the hCG usually takes 72–90 hours to double, and above 6,000 mIU/ml, the hCG often takes more than four days to double. Failure to increase normally may indicate an increased risk of miscarriage or a possible ectopic pregnancy.

Ultrasound is also a common tool for determining viability. A lower than expected heart rate or missed development milestones may indicate a problem with the pregnancy.[10] Diagnosis should not be made from a single ultrasound, however. Inaccurate estimations of fetal age and inaccuracies inherent in ultrasonic examination may cause a scan to be interpreted negatively. If results from the first ultrasound scan indicate a problem, repeating the scan 7–10 days later is reasonable practice.[9]

Jan Steen's The Doctor's Visit. Included in this 17th-century painting is a depiction of a dubious pregnancy test: a ribbon dipped in the patient's urine and then burned.[19]

Records of attempts at pregnancy testing have been found as far back as the ancient Greek and ancient Egyptian cultures. The ancient Egyptians watered bags of wheat and barley with the urine of a possibly pregnant woman. Germination indicated pregnancy. The type of grain that sprouted was taken as an indicator of the fetus's sex. Hippocrates suggested that a woman who had missed her period should drink a solution of honey in water at bedtime: resulting abdominal distention and cramps would indicate the presence of a pregnancy. Avicenna and many physicians after him in the Middle Ages performed uroscopy, a nonscientific method to evaluate urine.

Selmar Aschheim and Bernhard Zondek introduced testing based on the presence of human chorionic gonadotropin (hCG) in 1928.[20] Early studies of hCG had concluded that it was produced by the pituitary gland. In the 1930s, Doctor Georgeanna Jones discovered that hCG was produced not by the pituitary gland, but by the placenta. This discovery was important in relying on hCG as an early marker of pregnancy.[21] In the Aschheim and Zondek test, an infantile female mouse was injected subcutaneously with urine of the person to be tested, and the mouse later was killed and dissected. Presence of ovulation indicated that the urine contained hCG and meant that the person was pregnant. A similar test was developed using immature rabbits. Here, too, killing the animal to check her ovaries was necessary.

At the beginning of the 1930s, Hillel Shapiro and Harry Zwarenstein, who were researchers at the University of Cape Town, discovered that if urine from a pregnant female was injected into the South African Xenopus toad and the toad ovulated, this indicated that the woman was pregnant. This test was used throughout the world from the 1930s to 1960s, with Xenopus toads being exported live in great numbers.[22][23] Shapiro's advisor, Lancelot Hogben, claimed to have developed the pregnancy test himself, but refuted by both Shapiro and Zwarenstein in a letter to the British Medical Journal. A later article, independently authored, granted Hogben credit for the principle of using Xenopus to determine gonadotropin levels in pregnant women's urine, but not for its usage as a functional pregnancy test.[24]

Hormonal pregnancy tests such as Primodos and Duogynon were used in the 1960s and 1970s in the UK and Germany. These tests involved taking a dosed amount of hormones, and observing the response a few days later. A pregnant woman does not react, as she is producing the hormones in pregnancy; a woman not pregnant responds to the absence of the hormone by beginning a new menstrual cycle. While the test was (is) generally considered accurate, research advancements have replaced it with simpler techniques.[25]

Immunologic pregnancy tests were introduced in 1960 when Wide and Gemzell presented a test based on in-vitro hemagglutination inhibition. This was a first step away from in-vivo pregnancy testing[26][27] and initiated a series of improvements in pregnancy testing leading to the contemporary at-home testing.[28] Direct measurement of antigens, such as hCG, was made possible after the invention of the radioimmunoassay in 1959.[29] Radioimmunoassays require sophisticated apparatus and special radiation precautions and are expensive.

Organon International obtained the first patent on a home pregnancy test in 1969, two years after product designer Margaret Crane noticed that the laboratory testing procedure was relatively simple and made a prototype. The product became available in Canada in 1971, and the United States in 1977, after delays caused by concerns over sexual morality and the ability of women to perform test and cope with the results without a doctor.[30]

Another home pregnancy testing kit was based on the work of Judith Vaitukaitis and Glenn Braunstein, who developed a sensitive hCG assay at the National Institutes of Health.[31] That test went onto the market in 1978.[32] In the 1970s, the discovery of monoclonal antibodies led to the development of the relatively simple and cheap immunoassays, such as agglutination-inhibition-based assays and sandwich ELISA, used in modern home pregnancy tests. Tests are now so cheap that they can be mass-produced in a general publication and used for advertising.[33]

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