Teratogenic contraceptives is refered to hormonal contraceptives that act as teratogens which negatively impact reproduction and embryonic development and include radiation, maternal infections, pharmaceuticals, and chemicals. Numerous chemicals act as teratogens that adversely affect human health, with the time period of exposure as a critical factor determining teratogen susceptibility. 

Use of teratogenic contraceptives may affect mainly the pregnancy. The two initial weeks after fertilization, in which the embryo undergoing cell division is called the ‘all-or-nothing’ phase (Pic. 1); in case a contact with a teratogenic agent occurs, it can result either in spontaneous abortion or in a normal embryo-fetal development. If teratogenic exposure occurs between the 3rd and 8th week of gestation, a period in which most of the morphological structures develop, it can lead to considerable phenotypical (signs) changes in the embryo, such as alterations in the central nervous system, limbs and face (Pic. 2). From the 9th week of gestation some organs are still developing, like external genitalia and brain, and exposure to teratogens can culminate in functional abnormalities. However most morphological characteristics are preserved from this phase onward. The use of certain hormones prior to pregnancy, on the other hand, does not lead to an increase in the frequency of chromosomal aberrations or of congenital malformations.

Overall, most drugs cross the placenta to some degree. However, not every medication that may cause birth defects will cause these defects at every stage of pregnancy. Not every pregnancy will be affected despite exposure to a teratogenic substance. 

An estimated 10% of birth defects, therefore, may be caused by teratogens in the environment. Drug exposure accounts for, at most, 2–3% of birth defects. The timing of the exposure to the teratogen is critical: 

  • Pre-embryonic stage In the first two weeks after conception (generally before the woman is even aware that she is pregnant), the “all or none” rule seems to apply. At this stage the embryo is undifferentiated and repair and recovery are possible through multiplication of the still totipotential cells to replace those that are lost. If too many cells are damaged the early embryo will not implant or it will be spontaneously aborted.
  • Embryonic stage (weeks 3–8 of pregnancy) Foetal tissues begin to differentiate and organs and tissues develop. This is the period of maximum susceptibility to teratogens as the tissues differentiate rapidly and damage becomes irreparable. Teratogens ingested in this period affect the system developing at that particular stage. Major organ systems and body features are established by the end of the 8th week.
  • Foetal stage (week 9 to birth) Cell growth and differentiation characterise the remainder of the pregnancy. Teratogens ingested at this stage may cause cell death, retard cell growth or inhibit differentiation. This may cause restricted foetal growth resulting in a decreased birth weight. As parts of the brain are still developing, teratogens ingested at this time may cause disorders in the central nervous system that may not be apparent at birth. The eyes, genitalia, central nervous system and haematopoietic systems (production of the cellular elements of blood) continue to develop and remain susceptible to teratogenic insults.

Although oral contraceptives are over 99% effective with perfect use, an estimated 9% of oral contraceptive users become pregnant in their first year of use, owing to missed or delayed doses, drug interactions, or illness in what is known as a breakthrough pregnancy. Many more women will stop using oral contraceptives when planning a pregnancy and conceive within a few menstrual cycles. In both these instances, a woman could inadvertently expose her fetus to exogenous sex hormones (such as progestins).

Symptoms

A major malformation caused by teratogenic contraceptives is defined as one that is:

  • incompatible with survival, such as anencephaly (absence of parts of the brain and skull; Pic. 3)
  • requiring major surgery for correction, such as cleft palate (Pic. 4) or congenital heart disease
  • producing major dysfunction (e.g., mental retardation)
  • minor malformations, for example ear tags or extra digits

Associated diseases

Uterine malformations

Uterine malformations are associated with genetic and teratogenic factors. Using uncertified contraceptives (e.g. diethylstilbestrol), and any other substance with teratogenic potential, can be seen as problematic. Generally speaking, uterine malformations do not affect the ability to become pregnant. However, it may make it more difficult to carry a baby for the fullterm pregnancy, depending on the abnormality.

Complications

Some studies suggest that oral contraceptive use is associated with certain birth defects - including hypoplastic left heart syndrome (left side of the heart is severely underdeveloped), gastroschisis (intestines extend outside of the body), limb defects, and urinary tract anomalies - while others found no such association. 

Exposure to a synthetic oestrogen (diethylstilbestrol), during pregnancy has also been shown to cause anatomical changes in the genitals of both male and female fetuses and the exposure is associated with breast cancer of the mother and with cancer of the reproductive tract of daughters.

Risk factors

  • uncertified contraceptives
  • anticancer drugs
  • vitamin A
  • parity (number of times a female is or has been pregnant)
  • smoking in pregnancy
  • history of birth defects in a previous pregnancy

Prevention

An exposure during conception is pretty common. About 9% of women on oral contraceptive pills get pregnant. To make matters worse, it takes at least a couple of weeks for a woman to know she is pregnant, and some women won’t realize they are pregnant for some time simply because the pill is already suppressing their periods, which will potentially extend the duration of the exposure. 

If the home pregnancy test is positive, women should stop taking the pill. If taking a home pregnancy test isn't possible, she should stop taking the birth control pill until the pregnancy is confirmed or ruled out.

Maternal and prenatal teratogen exposure is associated with birth defects, spontaneous abortion, and stillbirth, and sometimes cancer in the reproductive tract of progeny. Previous studies demonstrated that acute, high-dose teratogen exposure causes reproductive decline, but the long-term ramifications of low dose teratogen exposure during early development later in life remain unknown.

The primary mode of action for hormonal contraceptives is thought to be suppression of pituitary gonadotropin secretion, secondarily leading to suppression of ovarian function. The pill impedes the follicle-stimulating hormone (FSH) in the pituitary, which doesn't allow for the maturation of follicles in the ovaries. By the human body's feedback loop, the luteinizing hormone (LH) increases, which then prevents ovulation of eggs within the ovary. In addition to the decrease of ovulation, the increase of progesterone in the pill increases the cervical mucus, which creates a harsh environment for sperm.

Fetus is the most vulnerable in the period of 2 to 12 weeks. The duration of adequate post-treatment contraception in females after cessation of a potentially teratogenic drug therapy is a subject of much debate. However, birth defects generally haven't been observed in clinical experience and thus the risk of maternal use of contraceptives just before pregnancy or during pregnancy is very low. In addition, many studies assumed that use of contraceptives during first trimester of pregnancy does not contribute to birth defects.

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