Risk of neural tube defects in relation to maternal fertility and fertility drug use

Potential association between infertility and spinal neural tube defects in offspring

“…Despite early reports linking clomiphene citrate and NTDs (Cornel et al,1989; Lancaster,1987; Robert et al,1991), the majority of research has not supported this association (Cuckle and Wald,1989; Czeizel,1989; Dhont et al,1999; Greenland and Ackerman,1995; Kurachi et al,1983; Lammer,1995; Mills et al,1990; Stromberg et al,2002; Werler et al,1994; Whiteman et al,2000). A meta‐analysis performed in 1995 found that studies performed in Europe, which together supported the association between clomiphene citrate and NTDs, uniformly analyzed the periconceptional use of clomiphene citrate (Greenland and Ackerman,1995).…”

“…A meta‐analysis performed in 1995 found that studies performed in Europe, which together supported the association between clomiphene citrate and NTDs, uniformly analyzed the periconceptional use of clomiphene citrate (Greenland and Ackerman,1995). In contrast, other studies either included clomiphene citrate use in the 6–12 months prior to conception (Lammer,1995; Mills et al,1990; Werler et al,1994), or did not specify the timing of the medication (Kurachi et al,1983; Medveczky et al,2004; Whiteman et al,2000). Our preliminary finding of an association between periconceptional clomiphene citrate use and spinal NTDs supports the results from studies using a similar definition of exposure, although it can not be determined from our study whether the observed association is due to the underlying infertility or to infertility treatment effects.…”

“…The possibility that infertility and clomiphene citrate might increase the risk of neural tube defects (NTDs) was raised in the 1970s when several case reports suggested a possible association (Ahlgren et al,1976; Dyson and Kohler,1973; Field and Kerr,1974; Singh and Singhi,1978; Ylikorkala,1975). Subsequently, studies in Europe, Australia, and the United States provided conflicting results (Cornel et al,1989; Cuckle and Wald,1989; Lancaster,1987; Mills et al,1990; Robert et al,1991; Whiteman et al,2000), and a pooled analysis of all studies performed prior to 1995 concluded that the existing data were “insufficient to either confirm or refute an effect of clomiphene citrate on neural tube defect risk” (Greenland and Ackerman,1995, p. 940). Recently, in the largest case‐control study reported to date, investigators found an OR of 2.1 (95% CI 1.0–4.5) for clomiphene citrate and NTDs (Medveczky et al,2004).…”

Paediatric outcome following infertility management/genetic outcome

“…Controlled ovarian stimulation in itself (without other fertility treatment) has been claimed to be responsible for a higher malformation rate [11], but this was not confirmed by other studies [12].…”

Reproductive History in Mothers of Children with Neural Tube Defects

“…Changes in fertility of NTD mothers have been suggested, either due to biological or social factors [13], although there is no agreement on this point [14,15]. Short intervals have been observed or predicted before affected outcomes [3,5,8,13].…”