Kurachi, K., Aono, T., Minagawa, J., & Miyake, A. (1983). Congenital malformations of newborn infants after clomiphene-induced ovulation. Fertility and sterility, 40(2), 187-189. https://doi.org/10.1016/s0015-0282(16)47235-3
Kurachi K, Aono T, Minagawa J, Miyake A. Congenital malformations of newborn infants after clomiphene-induced ovulation. Fertil Steril. 1983;40(2):187-189. doi:10.1016/s0015-0282(16)47235-3
Kurachi, K., et al. "Congenital malformations of newborn infants after clomiphene-induced ovulation." Fertility and sterility, vol. 40, no. 2, 1983, pp. 187-189.
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The effect of clomiphene citrate (CC) on the incidence of congenital malformations in newborn infants was assessed from the outcome of 1034 pregnancies after CC-induced ovulation recorded at nine university hospitals in a 5-year period. Of these pregnancies, 14.2% ended in abortion, 0.5% in ectopic pregnancy, 0.1% in molar pregnancy, and 1.6% in stillbirth. In all, 935 infants were born, and 21 (2.3%) showed visible malformations. This incidence of malformations was not significantly different from that in 30,033 infants (1.7%) after spontaneous ovulation (spontaneous ovulation group), and the types of malformations after CC treatment were similar to e those in the spontaneous ovulation group. These data indicate that CC has no teratogenic effect.
Sharma S et al., 2014·PloS one·Free full text on PubMed Central
Clomiphene citrate (CC) is the first line drug for ovulation induction but because of its peripheral antiestrogenic effect, letrozole was introduced as the 2nd line drug. It lacks the peripheral antiestrogenic effect and is associated with similar or even higher pregnancy rates. Since letrozole is a drug for breast cancer, its use for the purpose of ovulation induction became controversial in the light of studies indicating an increased incidence of congenital malformations. To evaluate and compare the incidence of congenital malformations among offsprings of infertile couples who conceived naturally or with clomiphene citrate or letrozole treatment. A retrospective cohort study done at a tertiary infertility centre. A total of 623 children born to infertile women who conceived naturally or following clomiphene citrate or letrozole treatment were included in this study. Subjects were sorted out from medical files of both mother and newborn and follow up study was done based on the information provided by parents through telephonic conversations. Babies with suspected anomaly were called and examined by specialists for the presence of major and minor congenital malformations. Other outcomes like multiple pregnancy rate and birth weight were also studied. Overall, congenital malformations, chromosomal abnormalities were found in 5 out of 171 (2.9%) babies in natural conception group and 5 out of 201 babies in the letrozole group (2.5%) and in 10 of 251 babies in the CC group (3.9%). There was no significant difference in the overall rate of congenital malformations among children born to mothers who conceived naturally or after letrozole or CC treatment. Congenital malformations have been found to be comparable following natural conception, letrozole and clomiphene citrate. Thus, the undue fear against letrozole may be uncalled for.
Of 159 pregnancies conceived after clomiphene therapy, 141 ended in childbirth, including seven sets of twins. There was a probable increase in the number of infants born with major malformations. These were exclusively to women who had not previously borne a normal infant. The incidence of malformed infants compares well with that published after gonadotropin therapy. The possibly higher incidence of malformations seen after drug-induced ovulation would therefore seem to be due to the underlying subfertility state and thus not a direct drug effect.
Fifteen years have passed since our group first proposed the use of clomiphene citrate as an ovulation-inducing agent. Our 15-year experience with over 2,000 patients has not dampened our enthusiasm for this drug. The benefits have far outweighted the minor side effects or the possibility of multiple births. Serious birth defects were minimal and have been no greater than what one may expect in the general population. Clomiphene citrate has been a boon to womankind and deserves the confidence of both patient and physician: it is a drug with a record of utility and with but minor risks.
Eighty-six women reached at least 20 weeks' pregnancy in 96 instances, after ovulation induced by clomiphene citrate. Although 37 of the women had 44 previous pregnancies, there had been a high pregnancy wastage (70.5%) producing only 13 live infants prior to the successful clomiphene therapy. After clomiphene therapy, pregnancies were normal except for a high incidence of toxemia (16.7%) and a possibly increased incidence of prediabetes. The pregnancies resulted in 88 single and 8 twin births. The total fetal and neonatal loss was 6.7%. The loss of single births (3.1%) included two stillbirth infants of prediabetic mothers. The twin loss of 25% was due to prematurity. The incidence of congenital malformations was within normal limits.
PMID 6873315 6873315 DOI 10.1016/s0015-0282(16)47235-3 10.1016/s0015-0282(16)47235-3 Kurachi et al. 1983, Kurachi 1983
Cite this article
Kurachi, K., Aono, T., Minagawa, J., & Miyake, A. (1983). Congenital malformations of newborn infants after clomiphene-induced ovulation. Fertility and sterility, 40(2), 187-189. https://doi.org/10.1016/s0015-0282(16)47235-3
Kurachi K, Aono T, Minagawa J, Miyake A. Congenital malformations of newborn infants after clomiphene-induced ovulation. Fertil Steril. 1983;40(2):187-189. doi:10.1016/s0015-0282(16)47235-3
Kurachi, K., et al. "Congenital malformations of newborn infants after clomiphene-induced ovulation." Fertility and sterility, vol. 40, no. 2, 1983, pp. 187-189.
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