Reference:

  1. Dr. RPS Maternal and Newborn Care: A Comprehensive Guide and Source Book for Teaching and Learning, 2nd Edition, ISBN 9789719822653, by Rosalinda Parado Salustiano (Ch. 4, 64–79)

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Fertilization

Fertilization (conception, fecundation, impregnation) is the union of a mature egg cell (ovum) and sperm cell in the ampulla (outer third) of the fallopian tube. The resulting fertilized egg is called the zygote.

Sperm move within the female reproductive system through flagellar action. Each sperm often reach the ampulla within 5 minutes, up to 4 to 6 hours after ejaculation. From 400 million or more sperm, only ~200 actually reach the ampulla. Sperm often remain for 4 to 6 hours before being able to fertilize an egg, as this period is when sperm capacitation and acrosomal reaction occurs:

  1. Sperm Capacitation: the sperm becomes hypermobile, and the acrosomal membrane/covering of the sperm head becomes exposed, allowing it to bind with the zona pellucida of the ovum.
  2. Acrosomal Reaction: the deposition of minute amounts of hyaluronidase in the corona radiata, allowing the sperm to penetrate the ovum.

As soon as the sperm penetrates the zona pellucida and makes contact with the vitelline membrane of the ovum, a cellular change occurs in the ovum that inhibits other sperm cells from entering. This process is mediated by the release of materials from cortical granules (organelles) just under the egg surface.

Fertilization occurs when the male pronucleus units with the female pronucleus; thus, the chromosome diploid number (46) is restored and a new cell, the zygote, is created with a new combination of genetic material, which creates a unique individual different from the parents and anyone else.

The zygote undergoes cleavage/mitosis, in sequential order:

  1. Zygote: the cell that results from fertilization of the ovum by a spermatozoa. This cell undergoes mitosis, which is the process of cell replication where each chromosome splits longitudinally to form a double-stranded structure.
  2. Cleavage: a series of mitotic cell divisions by the zygote
  3. Blastomere: daughter cells arising from the mitotic cell division of the zygote (2-cell, 4-cell, and 8-cell blastomeres).
  4. Morula: a solid ball of cells produced by 16 or so blastomeres; called the “traveling” form because it is in this form when it migrates through the fallopian tube (oviduct) and reaches the uterine cavity about 3 to 4 days after fertilization.
  5. Blastocyst: a fluid-filled cavity that reaches the uterine cavity.

Morula Reformation

The morula reforms to become the blastocyst; the cavity within the morula is the blastocoele. This cavity expands, and the outer cells of the morula become the trophoblast. It is after this reformation that energy becomes necessary, and the blastocyst implants into the uterine wall for further development.


Implantation

Implantation, also known as nidation, occurs within 6 to 9 days (average 7 days) after fertilization. In a normal implantation, the site is in the upper fundal portion or upper one-third of the uterus, either anteriorly or posteriorly. Abnormal implantation sites are the fallopian tubes (ectopic pregnancy) and the lower uterine segment (placenta previa).

Blastocyst

While the blastocyst is in the stage of implantation, its outer layer, the trophoblast, is responsible for actual implantation (nidation). The trophoblast gives rise to the placenta.


Teratology

The study of the etiology and defects of birth. Teratogenesis is the dysgenesis of fetal organs as evidenced either structurally or functionally. Any agent that produces permanent alterations of form or function during embryonic or fetal development is a teratogen. These can cause premature birth, stillbirth, or other pregnancy complications. Teratogens vary; drugs, medicine, chemicals, alcohol, toxic substances, and certain infections.

  • Cigarette smoking is associated with fetal growth retardation (intrauterine growth restriction; IUGR), premature birth, and miscarriage. It also affects fetal lung tissue and brain.

The typical manifestations of teratogenesis is restricted growth or death of the fetus, carcinogenesis, and malformations. These vary in severity, and major malformation may be life-threatening, or may have cosmetic functional effects and require major surgery.

Pharmacology

Because any medication can present risks in pregnancy and because not all risks are known, the safest pregnancy-related pharmacy is as little pharmacy as possible. Each drug should be assessed, and its risks and benefits should be weighed.

Take only prescribed drugs, do not self-medicate, do not take over-the-counter drugs, including vitamins and minerals, and avoid hot tubs, saunas, and anything that raises internal body temperature.

Alcohol

Do not take alcohol, no matter how slight.

Known Teratogenic DrugsTeratogenic Effect
Anticholinergic DrugsNeonatal meconium ileus
Antithyroid Drugs (Prophylthiouracil, methimazole)Fetal and neonatal goiter, hypothyroidism
CyclophosphamideCNS malformation, secondary cancer
DiethylstilbestrolVaginal cancer, other genitourinary defects in male or female offspring
Hypoglycemic DrugsNeonatal hypoglycemia
MethotrexateCNS and limb malformations
NSAIDsConstriction of ductus arteriosus, necrotizing enterocolitis
PhenytoinGrowth retardation, CNS defects
Psychoactive Drugs (Barbiturates, opioids, benzodiazepines)Neonatal withdrawal syndrome when given in late pregnancy
TetracyclineTeeth staining and bone defects
ThalidomideLimb defects/shortening, internal organ defects
Warfarin (Coumadin)Skeleton and CNS effects. Heparin is the drug of choice as an anticoagulant, as it does not cross the placental barrier.

The drug, substance, or toxin asserts varying severities depending on length of exposure, amount of exposure, gestational age during exposure, and hereditary factors that could increase fetal risk.