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If becoming pregnant turns into a problem, don’t panic, take Clomid
Delivery of child is one of the most striking and exciting miracles happening in human’s life. Nothing can be compared to giving a birth to a new person, bringing him or her into this world. It’s really a miracle, a wonder when your life suddenly gets filled with meaning and reason, when you know that you will go on in another human looking so alike and so different from you. A baby is always expected with impatience and anxiety and this period in the life of the family is always very special and full of hopes. Unfortunately, things don’t always go this way with getting a baby. Sometimes a couple tries over and over again but in vain. The problem of infertility can discourage anyone but it doesn’t mean that the only way out of this situation is to give up. If follicles are produced but the ovulation never comes there is still a chance for the woman to become pregnant. How? With the help of a medical preparation named Clomid. Clomid contains clomifene – an active component which causes an increase in the amount of hormones responsible for the egg being developed and released. Solving the problem of infertility is easy by buying Clomid online in a very time- and cost-saving way right now.

The findings suggest that using clomiphene citrate for fertility treatment is linked to a slight increase in the risk of both idiopathic generalized epilepsy and focal epilepsy in children. Interestingly, the strongest connection to idiopathic generalized epilepsy appeared in cases where the lowest dose of Clomid was used before conception—but this link disappeared when looking at sibling comparisons. On the other hand, the risk of focal epilepsy seemed to rise with higher total doses of the medication taken prior to conception, and this trend held true even in the sibling analysis.

One of the key strengths of this study was its large sample size, which allowed for highly precise results, detailed subgroup breakdowns, and the inclusion of sibling comparisons. That said, some subgroups included a relatively small number of individuals, and the sibling analyses involved only a limited number of families with differences in both exposure and outcome.

Another notable strength was the use of high-quality, nationwide health registries. These databases provided reliable, detailed information on exposure, health outcomes, and important background factors. Exposure data was based on accurate records of the first day of the women’s last menstrual period (LMP), typically estimated through early pregnancy ultrasounds and recorded in the Danish Medical Birth Registry. Clomiphene citrate is only available with a prescription in Denmark, and every filled prescription is logged in the Danish National Prescription Registry with precise dispensing dates.

Given the nature of infertility treatment, it’s assumed that most women took their prescribed medication as directed. Therefore, the dispensed prescriptions are likely a good reflection of actual usage. However, because Clomid is often taken over multiple cycles and at different dosages, determining the exact level of exposure before conception is challenging. In one sub-analysis that looked at the last dosage taken before conception, there’s a chance that some women who actually took the lowest dose (50 mg/day) were misclassified into higher dose groups (100 or 150 mg/day). For example, a prescription totaling 750 mg might be interpreted as a single cycle at 150 mg/day, when in reality it could represent three cycles at 50 mg/day. This kind of misclassification may have exaggerated the link between higher doses and idiopathic generalized epilepsy.

When analyzing the total amount of Clomid taken in the six months leading up to conception and its relation to focal epilepsy, it’s possible that the dose–response relationship was underestimated. Some women may have filled prescriptions but not used the medication due to becoming pregnant. Additionally, the study couldn’t fully separate the effects of multiple treatment cycles from those of the total dosage received before conception.

Children diagnosed with epilepsy were identified using data from the Danish National Patient Register and by tracking filled prescriptions for antiepileptic medications through the Danish National Prescription Registry. This comprehensive method allowed the study to capture cases diagnosed in both public and private clinics, including children who were diagnosed but not undergoing treatment. Previous research has confirmed the reliability of epilepsy diagnoses from the National Patient Register, showing a positive predictive value of 81% (Christensen et al., 2007).

Epilepsy remains the leading reason for prescribing antiepileptic drugs to children. Requiring at least two filled prescriptions helped ensure that only children with a confirmed epilepsy diagnosis were included. In fact, sensitivity analyses that required both a formal epilepsy diagnosis and prescription use showed consistent results, suggesting minimal misclassification. While specific subtypes of epilepsy haven’t been thoroughly validated, the stronger associations seen with those subtypes suggest they may be more accurately diagnosed than broader, nonspecific epilepsy classifications.

Selection bias in this study was likely minimal. The only participants lost to follow-up were children who died or emigrated, and those cases were properly censored. Data completeness was high, and missing values were handled using multiple imputation. Although maternal smoking data might not be missing at random, it affected only 2.9% of cases, and since its association with epilepsy was weak (data not shown), it likely didn’t have a major impact. However, one limitation is that the study only included live births, which could theoretically introduce bias (Liew et al., 2015).

There’s also a possibility that characteristics associated with parental infertility may influence the child’s risk of developing epilepsy, creating a non-causal link between fertility treatment and childhood epilepsy. To address this, all analyses were adjusted for relevant confounding factors. Socioeconomic status wasn’t adjusted for specifically, as fertility treatment is provided free of charge in Denmark. Moreover, previous research showed that accounting for maternal education didn’t affect the results (Kettner et al., 2017).

A major strength of the study was the inclusion of sibling analyses comparing children exposed and unexposed to Clomid. This approach helps control for unmeasured, stable parental factors—like genetic predispositions—that may influence both infertility and epilepsy risk (Donovan and Susser, 2011). In fact, the link between clomiphene citrate and idiopathic generalized epilepsy disappeared in these sibling comparisons, suggesting that the original association may have been driven by underlying familial traits rather than the fertility medication itself.

Interestingly, the strongest link to idiopathic generalized epilepsy was observed in women who received the lowest dose of Clomid. This suggests the association may stem more from characteristics of the women receiving low doses—such as those with polycystic ovary syndrome (PCOS)—rather than the drug. Women with PCOS or a strong ovarian reserve are often prescribed the lowest doses due to a higher risk of overstimulation. Since PCOS has previously been linked to developmental issues in children, including neurological concerns (Vanky et al., 2019), it’s possible that maternal PCOS, rather than clomiphene itself, played a role.

Unfortunately, the Danish National Prescription Registry doesn’t include the specific reason why clomiphene was prescribed. A sensitivity analysis attempted to adjust for PCOS using diagnostic codes from the Danish National Patient Register. The results stayed largely the same, possibly because PCOS was underreported: only 1.3% of women in the study were identified with PCOS, while the actual prevalence is thought to be as high as 17% among women of reproductive age in Denmark (Lauritsen et al., 2014).

Even so, further analyses showed that maternal PCOS alone is unlikely to fully explain the link between low-dose clomiphene (50 mg/day) and idiopathic generalized epilepsy in children. This makes it unlikely that residual confounding by PCOS accounts for the entire observed association. Given that idiopathic generalized epilepsy is believed to have a strong genetic component, the connection may reflect inherited traits that influence both infertility and epilepsy. Previous research has proposed links between PCOS and epilepsy (Duncan, 2001), suggesting that women with PCOS may themselves be more likely to have epilepsy, which could be passed on to their children.

In this study, however, rates of maternal epilepsy were the same in women who received clomiphene and those who didn’t (Table I), and all analyses were adjusted for maternal epilepsy. Notably, the association between Clomid and focal epilepsy in children remained significant in sibling analyses, with evidence of a dose–response relationship based on cumulative dosage prior to conception.

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