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Question:

A 34-year-old woman, gravida 0, comes to the office for evaluation of pregnancy.  Menarche was at age 12, and her menstrual cycles are regular; they occur every 30 days with 5 days of menses.  The patient and her husband have been trying to conceive for the past 6 months and plan intercourse during her fertile window according to an ovulation predictor kit.  She has no medical conditions, takes no medications, and has no allergies.  BMI is 23 kg/m2.  Vital signs and physical examination are normal.  If fertilization and implantation occurred in this cycle, when would the β-hCG level first be detectable in the serum?

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Explanation:

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Timing intercourse around a woman's fertility window can help couples achieve pregnancy.  Ovulation predictor kits measure urinary luteinizing hormone levels, and the tests are positive 24 hours before ovulation.

Once an oocyte is released from the ovary, sperm may fertilize it for up to 24 hours.  Following fertilization, the second meiotic division completes, forming a zygote that travels through the fallopian tube while undergoing multiple mitotic divisions (ie, cleavage) and creating smaller cells (blastomeres) known collectively as a morula.  The morula enters the uterus 3-4 days after fertilization and forms a central cavity, converting it into a blastocyst.

The blastocyst implants about 6 days after fertilization (Choices A, B, and E), and the outer cell mass (trophoblast) differentiates into the cytotrophoblast and syncytiotrophoblast.  The syncytiotrophoblast invades the endometrial connective tissue 6-7 days after fertilization and begins secreting β-hCG, which enters the maternal circulation and maintains corpus luteum progesterone secretion.

Accordingly, β-hCG may appear in the maternal serum as early as 6 days after fertilization; however, additional time (typically 8 days) is often required for the serum to rise to a detectable level.  β-hCG is detectable in the maternal serum at <5 IU/L, making serum β-hCG testing the most sensitive method of detecting pregnancy.

(Choice D)  A urine pregnancy test is less sensitive than a serum pregnancy test; it is positive when β-hCG reaches 20 IU/L, which typically occurs 14 days following fertilization.  Therefore, a serum pregnancy test will be positive before a urine pregnancy test.

Educational objective:
β-hCG is produced by the syncytiotrophoblast after implantation, which generally occurs 6-7 days after fertilization at the earliest.  β-hCG typically is detectable in the maternal serum 8 days after fertilization, whereas it is detectable in the urine 14 days after fertilization.