The International Council on Infertility Information Dissemination, Inc

Clomid Use and Abuse

Photo of the medication clomid

Some women can't get pregnant because they don't secrete enough LH and FSH at the right time during the cycle and, as a result, they don't ovulate. For these women, the first drug doctors often prescribe is clomiphene citrate (Clomid, Serophene). This synthetic drug stimulates the hypothalamus to release more GnRH, which then prompts the pituitary to release more LH and FSH, and thus increases the stimulation of the ovary to begin to produce a mature egg.

Clomiphene is a good first choice drug when a woman's ovaries are capable of functioning normally and when her hypothalamus and pituitary are also capable of producing their hormones. In short, the woman's reproductive engine is in working order but needs some revving up.

Structurally like estrogen, clomiphene binds to the sites in the brain where estrogen normally attaches, called estrogen receptors. Once these receptor sites are filled up with clomiphene, they can't bind with natural estrogen circulating in the blood and they are fooled into thinking that the amount of estrogen in the blood is too low. In response, the hypothalamus releases more GnRH, causing the pituitary to pump out more FSH, which then causes a follicle to grow to produce more estrogen and start maturing an egg to prepare for ovulation. Typically, a woman taking clomiphene produces double or triple the amount of estrogen in that cycle compared to pretreatment cycles

If a woman is menstruating, even if irregularly, clomiphene is usually effective, particularly if she develops follicles that aren't reaching normal size. Usually, a mature follicle is about 20 millimeters in diameter, or about the size of a small grape, just before it ruptures and releases its egg. Clomiphene may help small, immature follicles grow to maturity.

A low estradiol level in a woman's blood correlates with an inadequately stimulated, small follicle. A woman having a spontaneous ovulation cycle (that is, ovulating without the aid of fertility drugs) generally has peak estradiol levels ranging from 100 to 300 picograms (one trillionth of a gram)/ml. A woman may have enough hormones to produce an egg, but if her estradiol production by the follicles is low (less than 100 pg/ml), she may not adequately stimulate her cervix to produce fertile mucus or stimulate her endometrium to get ready to accept a fertilized egg for implantation. Clomiphene could boost the weak signals from the hypothalamus to the pituitary to the ovaries.

"A woman who ovulates infrequently, say at six-week intervals or less often, is also a good candidate for clomiphene therapy, since clomiphene will induce ovulation more frequently. The more a woman ovulates, the more opportunities her mature eggs have to be exposed to her husband's sperm and, therefore, the greater her chance to become pregnant.

Clomiphene is also often effective for a woman with a luteal phase defect (LPD). A woman with LPD may begin the ovulation process properly, but her ovarian function becomes disrupted, resulting in low production of the hormone progesterone in the luteal phase of the menstrual cycle. Following ovulation, the ovary produces progesterone, the hormone needed to prepare the uterine lining for implantation of the fertilized egg, which has divided and entered the uterine cavity. A fall in progesterone levels in the blood during this critical time can interfere with early embryo implantation or, even if a fertilized egg has already implanted, cause a woman to menstruate too early and end a pregnancy within a few days after implantation.

Using an LH-urine detector kit or keeping a basal body temperature (BBT) chart can help a woman taking clomiphene determine whether the luteal phase of her cycle is shorter than the normal fourteen days. The luteal phase of the cycle, the length of time from ovulation until she menstruates, has a normal range of thirteen to fifteen days. Clomiphene can often "tune up" the hypothalamus and pituitary so they keep producing the hormones the ovary needs to manufacture progesterone throughout the luteal phase.

"Of women whose only fertility problem is irregular or no ovulation at all, about 80 percent will ovulate and about 50 percent will become pregnant within six months of clomiphene treatments. About three percent of women on clomiphene have multiple pregnancies, usually twins, compared with about one percent in the general population.

If a woman responds to clomiphene and develops a mature follicle (determined by adequate estrogen production and ultrasound examination), but has no LH surge by cycle day 15, then injection of the hormone human chorionic gonadotropin (HCG), which acts like LH, can be given to stimulate final egg maturation and follicle rupture, releasing the egg. The woman tends to ovulate about 36 hours after the LH surge or HCG injection, which can be confirmed by further ultrasound scans.

"Clomiphene is a relatively inexpensive drug, and is taken orally for only five days each month. The doctor attempts to initiate clomiphene therapy so that the woman ovulates on or around day 14 of a regular 28-day cycle. The simplest, most widely used dose starts with one daily 50 mg. tablet for five days starting on cycle day three or five. If a woman ovulates at this dose, there is no advantage to her increasing the dosage. In other words, more of the drug isn't necessarily better. In fact, more may be worse, producing multiple ovulation, causing side effects such as an ovarian cyst or hot flashes, and most commonly, interfering with her fertile mucus production.

If a woman doesn't ovulate after taking one clomiphene tablet for five days, then her doctor will usually double the daily dose to two tablets (100 mg) in her next cycle, and if she still doesn't respond, then triple the daily dose to 150 mg, or add another fertility medication such as human menopausal gonadotropin (Pergonal) in the next cycle. Some doctors increase the dose up to 250 mg. a day, but this is NOT recommended by either of the drug's two manufacturers. Women tend to have side effects much more frequently at higher doses.

If the dose of clomiphene is too high, the uterine lining may not respond completely to estrogen and progesterone stimulation, and may not develop properly. As a result, a woman's fertilized egg may not be able to implant in her uterus.

Side Effects

Because Clomiphene binds to estrogen receptors, including the estrogen receptors in the cervix, it can interfere with the ability of the cervical mucus glands to be stimulated by estrogen to produce fertile mucus. Only "hostile" or dry cervical mucus may develop in the days preceding ovulation. If this occurs, adding a small amount of estrogen beginning on cycle day 10 and continuing until the LH surge may enhance cervical mucus production.

Some women taking clomiphene experience hot flashes and premenstrual-type symptoms, such as migraines and breast discomfort (particularly if they have fibrocystic disease of the breasts). Visual symptoms such as spots, flashes or blurry vision are less common and indicate that treatment should stop.

Clomiphene is a very safe medication with relatively few contraindications. Preexisting liver disease is one contraindication since clomiphene is metabolized by the liver. Enlarged ovaries are also a contraindication since clomiphene may occasionally produce hyperstimulation of the ovaries.

The hot flashes are just like the hot flashes women experience at menopause when the level of estrogen circulating in the blood is low. The clomiphene fools the brain into thinking that blood estrogen levels are low.

Clomiphene Abuse

Too often, doctors give clomiphene to women with unexplained infertility before the couple has a fertility workup, or even after they have a workup, but there is no evidence of an ovulation disorder. This empiric therapy may create new problems, such as interfering with fertile mucus production and often delays further evaluation that can lead to a specific diagnosis and proper treatment.

For a woman who has normal, spontaneous ovulation, driving the pituitary harder with clomiphene won't make ovulation any more normal. If a woman has taken clomiphene for several cycles without becoming pregnant, then she and her fertility specialist should investigate other conditions that may be preventing her pregnancy.

After noting a good postcoital test (PCT) during a fertility workup, some doctors fail to repeat the test after placing a woman on clomiphene. A PCT needs to be repeated to check the quality of the woman's cervical mucus while she is on clomiphene, since 25 percent or more of women who take the drug develop cervical mucus problems. It's important for a woman to monitor her cervical mucus production during every cycle while trying to become pregnant, including her cycles while taking clomiphene.

 

How Separating Children Damages the Brain

Many parents coming to the US border with their children are seeking asylum and protection under international law. (See Refugee Act of 1980). Asylum is a humanitarian protection and part of the American value system particularly since the Holocaust of the mid-twentieth century. Those who seek asylum in the United States are afraid to return to their countries fleeing war, violence, and persecution in their native countries.

Under federal law, ANYONE from another country can “legally” seek asylum. Immigrants are eligible to apply for asylum for up to one year after entering the US. Many come here, literally, to save the lives of their children and themselves. 
According to the United State Government, "To obtain asylum through the affirmative asylum process you must be physically present in the United States. You may apply for asylum status regardless of how you arrived in the United States or your current immigration status."

Recently immigrants LEGALLY seeking asylum, and following the rules, who have committed no crimes, are being separated from their children, some of which are infants. These damaging and punitive separations are the product of cruel policies set by the current administration’s Department of Justice. Attorney General, Jeff Sessions outlined the Trump administration policies. Contrary to what AG Sessions says, there are no laws on the books directing this policy [separating children from their families] and the only blame for this vindictive, punishing action rests squarely on the choices and policies of those in charge. The Trump administration is not only separating children from their caregivers but also, now, cannot account for almost 1500 of those children.

The ramifications for children being damaged because of the separation from their parents is significant. This article takes a deeper look at the physiological reaction of children when they are traumatized.
 

Defining Trauma

 

 

Psychological trauma refers to a unique individual experience or event or continuing conditions, where a child’s ability to absorb and incorporate an emotional experience is trounced and exhausted. These individuals face (based on their perception) a threat to life and bodily safety.  In other words, the child’s perception is a threat to their life and safety. Remember, these children have already (most probably) been exposed to threats, and traumas by virtue of their beginnings in countries where wars and violence were part of their daily lives.

What are the neurophysiological results for the child?

Fight/Flight/Freeze.

To understand the insult to a child’s brain, one must first understand the physiological response and reaction of the fight, flight and/or freeze. The fight, flight, freeze response is a normal reaction or alarm reaction to perceived danger. We all need this reaction to keep us out of the pathway of a speeding car or to alert us to danger so we can react quickly, often without thinking, to protect ourselves. Once there is a threat (real or perceived) our bodies are hyper-aroused and a series of physiological changes begin. The Central Nervous System begins the process of releasing hormones such as cortisol and adrenaline. Central and peripheral nervous system activity responsible for processing threat information becomes involved. The reaction is an automatic survival response, directly correlated with the behavior of the child. (Bruce Perry, M.D., Ph.D., The Child Trauma Academy, 2002)

 Hyper-aroused children become hyper-vigilant children. Hyper-vigilance becomes the baseline for children who are chronically hyper-aroused, so even without active triggers, their hyper-vigilant or hyper-arousal starting point involves a constantly heightened state of high arousal. The result is that it takes little to nothing to set them off into freeze/fight/flight.

The chronically hyper-aroused brain shifts from processing in the pre-frontal cortex where executive functioning takes place to the limbic system or the emotional seat of the brain. The brains of these students cannot filter out the

overwhelming bombardment of all kinds of sensory, environmental and extraneous information. The result is the brain's self-preservation response. Young children are virtually helpless as they are not in control of their environments. Children are small with limited physical strength. Instead of fighting or fleeing, they may freeze when there is a perceived threat. As a result of a lack of safety and control from the child's perspective, they may shut down.

 

 

Toxic Stress Affects the Brain

The younger a child’s brain the more damaging the toxic stress. Environmental experiences, interactions, and relationships that expose a child to toxic stress make a child’s brain incredibly vulnerable to chemical changes and even structural changes in that brain. These changes are not only damaging but also can cause long-term or even life-long changes.  

Read more about Toxic Stress by visiting the Center on the Developing Child at Harvard University

Separating children from their families is wrong. Those who separate infants and children from mothers, inflicting physical, long-term and possibly life-long harm. Toxic stress shortens the lives of these children and endangers their current and future welfare. To intentionally inflict this harm is child abuse.