Pregnancy test

  A pregnancy test is a test to determine whether or not a woman is pregnant.

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Modern tests

The earliest test for pregnancy is a rosette inhibition assay for early pregnancy factor (EPF). EPF can be detected in blood within 48 hours of fertilization.^[1] However, testing for EPF is expensive and time consuming.

Most chemical tests for pregnancy look for the presence of the beta subunit of hCG or human chorionic gonadotropin in the blood or urine. hCG can be detected in urine or blood after implantation, which occurs six to twelve days after fertilization.^[2] Quantitative blood (serum beta) tests can detect hCG levels as low as 1 mIU/mL, while urine tests have published detection thresholds between 20 mIU/mL and 100 mIU/mL, depending on the brand.^[3] Qualitative blood tests generally have a threshold of 25 mIU/mL, and so are less sensitive than some available home pregnancy tests. Most "home" pregnancy tests are based on Lateral flow technology.

With obstetric ultrasonography the gestational sac can sometimes 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 6 weeks, and is usually visible by 7 weeks gestation.^[4][5]

History

  The ancient Egyptians watered bags of wheat and barley with the urine of a possibly pregnant woman. Germination indicated pregnancy, and based on what type of grain sprouted they predicted the gender of the fetus. 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.

Early studies of hCG had concluded that it was produced by the pituitary gland. In the 1930s Dr. 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.^[7] Selmar Aschheim and Bernhard Zondek introduced testing based on the presence of human chorionic gonadotropin (hCG) in 1928.^[8] In the Aschheim and Zondek test an infantile female mouse was injected subcutaneously with urine of the person to be tested, and some time later the mouse 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, the rabbit test. Here, too, it was necessary to kill the animal to check its ovaries. An improvement arrived with the frog test that was still used in the 1950s. A female frog was injected with serum or urine of the patient. If the frog produced eggs within the next 24 hours, the test was positive. In the frog test, the animal remained alive, and could be used again.

Direct measurement of antigens such as hCG was made possible with the invention of the radioimmunoassay in 1959,^[9] although radioimmunoassays require sophisticated apparatus, special precautions to deal with radiation, and are expensive. The discovery of monoclonal antibodies in the 1970s led to the development of the comparatively simple and cheap immunoassays used in modern home pregnancy tests.

Timing of test

False negative readings can occur when testing is done too early. Quantitative blood tests and the most sensitive urine tests usually detect hCG shortly after implantation, which can occur anywhere from 6 to 12 days after ovulation.^[2] Less sensitive urine tests and qualitative blood tests may not detect pregnancy until three or four days after implantation. Menstruation occurs on average 14 days after ovulation, so the likelihood of a false negative is low once a menstrual period is late.

Ovulation may not occur at a predictable time in the menstrual cycle, however. A number of factors may cause an unexpectedly early or late ovulation, even for women with a history of regular menstrual cycles. Using ovulation predictor kits (OPKs), or charting the fertility signs of cervical mucus or basal body temperature give a more accurate idea of when to test than day-counting alone.

The accuracy of a pregnancy test is most closely related to the day of ovulation, not of intercourse. It is normal for sperm to live up to five days after intercourse^[10] in the fallopian tubes, waiting for ovulation to occur.^[11] It could take up to twelve further days for implantation to occur, meaning even the most sensitive pregnancy tests may give false negatives up to seventeen days after the act of intercourse that caused the pregnancy. Because some home pregnancy tests have high hCG detection thresholds (up to 100 mIU/mL), it may take an additional three or four days for hCG to rise to levels detectable by these tests — meaning false negatives may occur up to three weeks after the act of intercourse that causes pregnancy.

False positives

Evaporation lines may appear on many home pregnancy tests if read after the suggested 3–5 minute window or reaction time, independent of an actual pregnancy. Therefore, it is imperative that a pregnancy test be interpreted within the reaction time specified by the test manufacturer. False positives may also appear on tests used past their expiration date.

A woman who has been given an hCG injection as part of infertility treatment will test positive on pregnancy tests, regardless of her actual pregnancy status. Common infertility drugs like clomid do not contain the hCG hormone.^[12]

When taken according to package directions, by women who have not received an hCG injection, false positive pregnancy test results are rare. Some diseases may cause a false positive pregnancy test: choriocarcinomas, IgA deficiencies, heterophile antibodies, enterocystoplasties, gestational trophoblastic diseases (GTD), gestational trophoblastic neoplasms (GTN), testicular germ cell malignancies, and even other forms of cancer, e.g. lung cancer.^{[citation needed]}

Viability

Pregnancy tests may be used to determine the viability of a pregnancy. Serial quantitative blood tests may be done, usually 2–3 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 72–96 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.^[5] 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.^[4]

References

1. ^ Fan XG, Zheng ZQ (1997). "A study of early pregnancy factor activity in preimplantation". Am. J. Reprod. Immunol. 37 (5): 359-64. PMID 9196793.
2. ^ ^{a b} Wilcox AJ, Baird DD, Weinberg CR (1999). "Time of implantation of the conceptus and loss of pregnancy.". New England Journal of Medicine 340 (23): 1796–1799. PMID 10362823.
3. ^ Waddell, Rebecca Smith (2006). FertilityPlus.org. Home Pregnancy Test hCG Levels and FAQ. Retrieved on 2006-06-17.
4. ^ ^{a b} Woo, Joseph (2006). Why and when is Ultrasound used in Pregnancy?. Obstetric Ultrasound: A Comprehensive Guide. Retrieved on 2007-05-27.
5. ^ ^{a b} Boschert, Sherry (2001-06-15). "Anxious Patients Often Want Very Early Ultrasound Exam". OB/GYN News. FindArticles.com. Retrieved on 2007-05-27.
6. ^ Clark, Stephanie Brown. (2005). Jan Steen: The Doctor's Visit. Literature, Arts, and Medicine Database. Retrieved 2007-05-27.
   Lubsen-Brandsma, M.A. (1997). Jan Steen's fire pot; pregnancy test or gynecological therapeutic method in the 17th century?. Ned Tijdschr Geneeskd, 141(51), 2513–7. Retrieved 2006-05-24.
   "The Doctor's Visit." (n.d.). The Web Gallery of Art. Retrieved 2006-05-24.
7. ^ Damewood, Marian D.; John A. Rock (August 2005). "In memoriam: Georgeanna Seegar Jones, M.D.: her legacy lives on". Fertility and Sterility 84 (2): 541-2. American Society for Reproductive Medicine. Retrieved on 2007-12-31.
8. ^ Speert, Harold (1973). Iconographia Gyniatrica. Philadelphia: F. A. Davis. ISBN 978-0803680708. 
9. ^ Yalow, RS; SA Berson (July 1960). "Immunoassay of endogenous plasma insulin in man". Journal of Clinical Investigation 69: 1157-75. PMID 13846364.
10. ^ Weschler, Toni (2002). Taking Charge of Your Fertility, Revised Edition, New York: HarperCollins, p.374. ISBN 0-06-093764-5. 
11. ^ Ellington, Joanna (2004). Sperm Transport to the Fallopian Tubes. Frequently Asked Questions with Dr. E. INGfertility Inc. Retrieved on 2006-08-13.
12. ^ Phillips, Pat (2007). Early Pregnancy Tests. Pregnancy Test FAQ. Retrieved on 2007-03-04.