The secondary sexual characteristics develop, reproductive functions begin, and sexual dimorphism becomes more obvious during puberty. The pubertal changes are not the same in males and females. In females, the age of presumptive puberty is after 8 years, with the process largely completed by age 16 years. In males, the age of presumptive puberty is after 9 years, with the process largely completed by age 18 years.

Embryology refers to the study of embryonic development; clinically, it refers to embryonic and fetal development and the study of prenatal development. Teratology refers to the study of abnormal embryonic and fetal development. It is the branch of embryology concerned with birth defects and their causes. Embryologic and teratologic studies are applicable to clinical studies because they indicate vulnerable prenatal periods of development.

All of the terms refer to female sexual cells. The term ovum is imprecise because it has been used to apply to stages from the oocyte to the implanting blastocyst. The term ovule is used for the oocyte of mammals (e.g., vertebral animals). A gamete refers to any germ cell, whether it is an oocyte or a sperm. The term oocyte is the internationally preferred term in reference to humans.

Numeric changes in chromosomes arise chiefly from nondisjunction during a mitotic or meiotic cell division. Most clinically important abnormalities in chromosome number develop during the first meiotic division. Nondisjunction is the failure of double-chromatid chromosomes to dissociate during anaphase of cell division. As a result, both chromosomes pass to the same daughter cell, and trisomy results. Trisomy 21 (Down syndrome) is the most common numeric chromosomal disorder resulting in birth defects. This syndrome occurs approximately once in every 1100 births in women 25 to 29 years of age; however, it is more common in older mothers.

A morula with an extra set of chromosomes in its cells is called a triploid embryo . This chromosome abnormality usually results from fertilization of an oocyte by two sperms (dispermy) . A fetus could develop from a triploid morula and be born alive; however, this is unusual. Most triploid fetuses abort spontaneously; if born alive, triploid neonates die within a few days (see Chapter 20 , Fig. 20.10 ).

Blockage of the uterine tubes resulting from infection is a major cause of infertility in women. Because occlusion prevents the oocyte from contacting the sperm, fertilization cannot occur. Infertility in men usually results from defects in spermatogenesis . Non-descent of the testes is one cause of aspermatogenesis (failure of sperm formation); however, normally positioned testes may also not produce adequate numbers of actively motile sperms.

Mosaicism results from nondisjunction of double-chromatid chromosomes during early cleavage of a zygote rather than during gametogenesis. As a consequence, the embryo has two cell lines with different chromosome numbers. Approximately 1% of persons with Down syndrome have mosaic Down syndrome. They have relatively mild stigmata of the syndrome and have a lesser degree of cognitive deficits. Mosaicism can be detected before birth by cytogenetic studies after amniocentesis or chorionic villus sampling.

Postcoital birth control pills (morning-after pills) commonly contain a progestin hormone called levonorgestrel, and if used within 5 days after unprotected sexual intercourse, they may prevent pregnancy, probably by interfering with the function of the corpus luteum and inhibiting ovulation, altering tubal motility, or causing abnormal changes in the endometrium. These hormones prevent implantation, not fertilization.

Many early embryos are spontaneously aborted; the overall early spontaneous abortion rate is approximately 45%. A common cause of early spontaneous abortion is the presence of chromosomal abnormalities , such as those resulting from nondisjunction—failure of one or more pairs of chromosomes to separate.

It is estimated that between 12% and 25% of couples in North America are infertile. In one third to one half of these cases, the cause is male infertility. Male infertility may result from endocrine disorders, abnormal spermatogenesis, or blockage of a genital duct. First, Jerry’s semen should be evaluated (sperm analysis) . The total number, motility, and morphologic characteristics of the sperms in the ejaculate are assessed in cases of male infertility. A man with fewer than 10 million sperms per milliliter of semen is likely to be sterile, especially when the specimen of semen contains immotile and morphologically abnormal sperms.

Yes, a chest radiograph may be taken because the patient’s uterus and ovaries would not be directly in the x-ray beam. The only radiation that the ovaries receive would be a negligible amount from scattering. Furthermore, this small amount of radiation would be highly unlikely to damage the products of conception if the patient happened to be pregnant.

Implantation is regulated by a delicate balance between estrogen and progesterone. The large doses of estrogen would upset this balance. Progesterone makes the endometrium grow thicker and more vascular so that the blastocyst may become embedded and adequately nourished. When media commentators refer to the “abortion pill,” they are usually referring to RU486 (mifepristone). This drug interferes with the implantation of a blastocyst by blocking the production of progesterone by the corpus luteum. Early pregnancy tests are sensitive enough to detect levels of human chorionic gonadotropin (hCG) 6 days before a missed menstrual period. The accuracy of such a test varies from approximately 76% when done 6 days before a missed period to 99% when carried out on the first day of the missed period. Early pregnancy can also be detected by ultrasonography .

More than 95% of ectopic pregnancies are in the uterine tube, and 60% of those are in the ampulla. Endovaginal sonography is often used to detect ectopic tubal pregnancies. The surgeon would likely perform a laparoscopic (minimally invasive) surgical procedure to remove the uterine tube containing the ectopic conceptus.

No, the surgery would not have produced the defect of the brain. Exposure of an embryo during the second week of development to the slight trauma that might be associated with abdominal surgery would not cause a birth defect. Furthermore, the anesthetics used during the operation would not induce a defect in the brain. Maternal exposure to teratogens during the first 2 weeks of development will not induce birth defects, but the conceptus may spontaneously abort.

Women older than 40 years of age are more likely to have a baby with a birth defect, such as Down syndrome; however, women older than 40 years may have normal children. Prenatal diagnosis will tell whether the embryo has severe chromosomal abnormalities (e.g., trisomy 13) that could cause its death shortly after birth. Ultrasound examination of the embryo may also be performed for the detection of certain morphologic anomalies (e.g., defects of the limbs and central nervous system). In most cases, the embryo is normal, and the pregnancy continues to full term.

The hormones in contraceptive pills prevent ovulation and development of the luteal (secretory) stage of the menstrual cycle. Severe chromosomal abnormalities may have caused the spontaneous abortion. The incidence of birth defects in early abortions is high in women who become pregnant shortly after discontinuing the use of birth control pills. A pronounced increase in polyploidy (cells containing three or more times the haploid number of chromosomes) has been observed in embryos expelled during spontaneous abortions when conception occurred within 2 months after discontinuing oral contraception. Polyploidy is fatal to developing embryos. This information suggests that it is wise to use some other type of contraception for one or two menstrual cycles before attempting pregnancy. Some women have become pregnant 1 month after discontinuing the use of contraceptive pills and have given birth to normal babies.

A highly sensitive radioimmune test would likely indicate that the woman was pregnant. The presence of embryonic and/or chorionic tissue in the endometrial remnants would be an absolute sign of pregnancy. By 5 days after the expected menses (approximately 5 weeks after the start of the last normal menstrual period), the embryo would be in the third week of its development. The embryo would be approximately 2 mm in diameter and could be detected with transvaginal ultrasound techniques .

The central nervous system (brain and spinal cord) begins to develop during the third embryonic week. Meroencephaly , in which most of the brain and calvaria are absent, may result from environmental teratogens acting during the third week of development. This severe defect of the brain occurs because of failure of the cranial part of the neural tube to develop normally, which usually results from nonclosure of the rostral neuropore. The physician might explain that there is no known safe amount or safe time to drink alcohol during pregnancy and that she should refrain from drinking further alcohol to minimize additional risk.

Sacrococcygeal teratomas are the most common tumor in the newborn and arise from remnants of the primitive streak. Because cells from the primitive streak are pluripotent (may affect more than one organ or tissue), the tumors contain various types of tissue derived from all three germ layers in varying stages of development. These tumors are three to four times more frequent in females than in males.

Transvaginal (endovaginal) sonography is an important technique for assessing pregnancy late in the third week and during the fourth week because the conceptus (embryo and membranes) can be visualized. It is therefore possible to determine whether the embryo is developing normally. A negative pregnancy test in the third week does not rule out an ectopic pregnancy. The serum human chorionic gonadotrophin (hCG) assay is the basic element of pregnancy tests and early diagnosis of an ectopic pregnancy, but because ectopic pregnancies produce hCG at a slower rate than intrauterine pregnancies, the test may be inaccurate.

The physician would likely tell the patient that her baby was undergoing a critical stage of its development and that it would be best for her to stop smoking. The physician would also likely tell her that heavy cigarette smoking is known to cause intrauterine growth restriction and underweight babies and that the incidence of prematurity increases with the number of cigarettes that are smoked. The physician would also recommend that she not consume alcohol (individuals who smoke are more likely to use alcohol) during her pregnancy because of its known teratogenic effects (see Chapter 20 , Fig. 20.17 ).

One cannot necessarily predict how a drug will affect the human embryo because human and animal embryos may differ in their response to drugs; for example, thalidomide is extremely teratogenic to human embryos, but it has very little effect on some experimental animals, such as rats and mice. However, drugs known to be strong teratogens (agents that can produce birth defects) in animals should not be used during human pregnancy, especially during the embryonic period. The germ layers form during gastrulation. All tissues and organs of the embryo develop from the three germ layers: ectoderm, mesoderm, and endoderm. Formation of the primitive streak and notochord are important events during morphogenesis (development of the shape, size, and other features of a particular organ or part of the body).

Information about the starting date of a pregnancy may be unreliable because it depends on the patient’s recall of an event (last menses) that occurred 2 or 3 months earlier. In addition, she may have had breakthrough bleeding at the time of her last normal menstrual period and may have thought that it was a light menses. Transvaginal ( endovaginal) ultrasound at 4 to 6 weeks of gestation may be carried out for estimating the probable starting date of a pregnancy and embryonic age.

Taking a sleeping pill may not harm the embryo, but a physician should be consulted about any medications. To cause severe limb defects, a known teratogenic drug would have to act during the critical period of limb development (24 to 36 days after fertilization). Teratogens interfere with differentiation of tissues and organs, often disrupting or arresting the embryo’s normal development.

Physicians cannot always rely on information about the time of the last normal menstrual period provided by their patients. This is especially important in cases in which determination of fertilization age is important, for example, in high-risk pregnancies in which expedient induction of labor may be required. The expected date of delivery can be determined with reasonable accuracy by using diagnostic ultrasonography to measure the size of the fetal head and abdomen.

Chorionic villus sampling would likely be performed for the study of the fetal chromosomes. Also, isolation of fetal cells in maternal blood for DNA-based fetal testing may also be used. The most common chromosomal disorder detected in fetuses of women older than 40 years of age is trisomy 21 (Down syndrome). If the fetal chromosomes were normal but birth defects of the brain or limbs were suspected, ultrasonography would likely be performed. These methods allow one to look for morphologic abnormalities while scanning the entire fetus. The sex of the fetus could be determined by examining the sex chromosomes in cells obtained by chorionic villus sampling. At 10 or more weeks, the obstetric radiologist can determine fetal sex using ultrasonography.

There is considerable danger when uncontrolled drugs (over-the-counter drugs), such as aspirin and cough medicines, are consumed excessively or indiscriminately by pregnant women. Withdrawal seizures have been reported in infants born to mothers who are heavy drinkers. Fetal alcohol syndrome is present in some of these infants (see Chapter 20 , Fig. 20.17 ). The physician would likely tell the patient not to take any drugs that are not prescribed. Drugs that are most detrimental to her fetus are under legal control and are prescribed with great care.

Many factors (fetal, maternal, and environmental) may reduce the rate of fetal growth (intrauterine growth retardation). Examples of such factors are intrauterine infections, multiple pregnancies, and chromosomal abnormalities. Cigarette smoking, narcotic addiction, and consumption of large amounts of alcohol are also well-established causes of intrauterine growth retardation. A mother interested in the growth and general well-being of her fetus consults her doctor frequently; eats a good-quality diet; and does not use illicit drugs, smoke, or drink alcohol.

Amniocentesis is relatively devoid of risk. The chance of inducing an abortion is estimated to be approximately 0.5% to 1.0%. Chorionic villus sampling can also be used for obtaining cells for chromosome study. In percutaneous umbilical cord blood sampling , a needle is inserted into the umbilical vein with the guidance of ultrasonography. Chromosome and hormone studies can be performed with the blood obtained.

Alpha-fetoprotein is produced by the yolk sac, gut, and hepatic cells of the fetus. Neural tube defects (spina bifida and anencephaly) are indicated by high levels of alpha-fetoprotein . Diagnostic studies during the second trimester for chromosomal disorders would be done to monitor the levels of alpha-fetoprotein. Further studies and confirmation could be done using ultrasonography. Low levels of alpha-fetoprotein may indicate Down syndrome. Chromosome studies may also be done to check the chromosome complement of the fetal cells.

Polyhydramnios is an excessive amount of amniotic fluid that surrounds the fetus in the amniotic sac. This condition occurs in 1% to 2% of pregnancies. When it occurs over the course of a few days, there is an associated high risk of severe fetal birth defects, especially of the central nervous system (e.g., meroencephaly and spina bifida cystica ). Fetuses with gross brain defects do not ingest the usual amounts of amniotic fluid; hence, the amount of liquid increases. Atresia (blockage) of the esophagus is almost always accompanied by polyhydramnios because the fetus cannot swallow and absorb amniotic fluid. Twinning or a multiple pregnancy is also a predisposing cause of polyhydramnios.

There is a tendency for twins to “run in families.” It appears unlikely that there is a genetic factor in monozygotic twinning, but a disposition to dizygotic twinning is genetically determined. The frequency of dizygotic twinning increases sharply with maternal age up to 35 years and then decreases; however, the frequency of monozygotic twinning is affected very little by the age of the mother. Determination of twin zygosity can usually be made by examining the placenta and fetal membranes. One can later determine zygosity by looking for genetically determined similarities and differences in a twin pair. Differences in DNA studies prove that twins are dizygotic.

A single umbilical artery occurs in approximately 1 of every 200 umbilical cords. This abnormality is accompanied by a 15% to 20% incidence of cardiovascular abnormalities and other anomalies. A single artery can be also be associated with chromosomal anomalies (trisomy 21, trisomy 18, and trisomy 13).

Two zygotes were fertilized. The resulting blastocysts implanted close together, and the placentas fused. The sample of chorionic villi was obtained from the chorionic sac of the female twin. If two chorionic sacs had been observed during ultrasonography, dizygotic twinning would have been suspected.

Amniotic bands form when the amnion tears and delaminates during pregnancy. The fibrous, sticky bands surround and entangle parts of the embryo’s body and produce birth defects, such as the absence of a hand or deep grooves in a limb. This constitutes the amniotic band syndrome or the amniotic band disruption complex. An alternative causative theory for amniotic band syndrome is vascular disruption (reduced blood supply).

A diagnosis of congenital diaphragmatic hernia (CDH) is most likely. The birth defect in the diaphragm that produces this hernia usually results from failure of the left pericardioperitoneal canal to close during the sixth week of development; consequently, herniation of the intestinal loops into the thorax occurs. This compresses the lungs, especially the left one, and results in respiratory distress. The diagnosis can usually be established by a radiographic or sonographic examination of the chest. The defect can also be detected prenatally using ultrasonography. Characteristically, there are air- or fluid-filled loops of intestine in the left hemithorax of a neonate with CDH.

Pericardial defects are extremely rare and are caused by a failure in the formation of the pleuropericardial membrane that separates the pericardial cavity from the peritoneal cavity. This defect can be on one or both sides. The intestine may herniate into the pericardial sac, or, conversely, the heart may be displaced into the superior part of the peritoneal cavity.

Congenital diaphragmatic hernia (CDH) occurs in approximately 1 of every 2200 births. A neonate diagnosed with CDH would immediately be positioned with the head and thorax higher than the abdomen to facilitate inferior displacement of the abdominal organs from the thorax. After a period of preoperative stabilization, an operation is performed with reduction of the abdominal viscera and closure of the diaphragmatic defect. Neonates with CDH may die because of severe respiratory distress from poor development of the lungs. However, most infants with this condition survive as a result of improvements in ventilator care.

Gastroschisis and epigastric hernias occur in the median plane of the epigastric region; these hernias are uncommon, occurring once in every 2000 births. The defect, usually on the right side of the umbilicus, results from failure of the lateral body folds to fuse in this region during the fourth week of gestation. Herniation of the intestinal loops and other abdominal structures may occur through the opening.