Clomiphene Citrate and Pregnancy Outcome

Abstract

Data from Australia and elsewhere have shown consistently that adverse perinatal outcomes such as preterm birth and perinatal mortality are more common in pregnancies resulting from assisted conception with IVF and GIFT than normally conceived pregnancies. Factors that may contribute to the excess of poor outcomes include maternal factors, the assisted conception procedures themselves and possibly the influence of drugs used to induce superovulation. This review examines the medical literature describing pregnancies following ovulation induction with one of the drugs used to induce superovulation, clomiphene citrate, and compares their outcomes with Australian IVF and GIFT pregnancy outcomes. The review shows that whilst some studies have suggested higher rates of ectopic pregnancy, spontaneous abortion and congenital malformations in clomiphene citrate induced pregnancies, the findings are inconsistent and the data are flawed. There are only very poor data available on the incidence of preterm birth. Multiple pregnancy is a well-recognized adverse outcome of clomiphene citrate induced pregnancies. Attempts to improve perinatal outcomes of pregnancies following assisted conception will be helped by a better understanding of the relative contributions of maternal and treatment factors and further studies of pregnancy outcome after ovulation induction are needed.

Health of children born after ovulation induction

“…We could not analyze separately OI with and without IUI, because IUI is not registered with a specific code in the files of the SII. The evidence on the association between the use of CC and infant outcomes (25) is still lacking. The evidence on the use of gonadotrophins combined with IUI suggests that one effect might be lower birth weights of infants (26,27).…”

Pregnancy outcomes with increased clomiphene citrate dose

“…Although a number of authors have reported higher rates of spontaneous abortion when clomiphene-induced pregnancies were compared to spontaneous pregnancies, the studies lacked appropriate size and comparisons were not made to subfertile patients, a more appropriate control group 7 . Only one study of sufficient size compared the incidence of spontaneous abortion following clomiphene administration to that of infertile patients.…”

Pregnancy Outcome Among Twins Conceived After Subfertility Treatment Compared With Natural Twins: A Population-Based Study

“…Of most concern is the observation of a 50 g difference in mean birthweight, and slightly earlier gestation of our treated twins, particularly since average smoking was considerably lower among treated women. We are not in a position to unravel why this might be so, but the finding that subfertile (treated) women deliver lighter babies on average has been repeatedly demonstrated (Berkowitz et al, 1990;Ghazi et al, 1991;Hull, 1995;McElrath & Wise, 1997;Scialli, 1986;Venn & Lumley, 1993;Venn & Lumley, 1994). However, few studies have examined birthweight in twins following subfertility treatment and it is less clear that such twin babies are lighter than their naturally conceived counterparts Helmerhorst et al, 2004;Schieve et al, 2002).…”