Abstract
ContextClomiphene 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.AimsTo evaluate and compare the incidence of congenital malformations among offsprings of infertile couples who conceived naturally or with clomiphene citrate or letrozole treatment.Settings and DesignA retrospective cohort study done at a tertiary infertility centre.Methods and MaterialA 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.ResultsOverall, 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%).ConclusionsThere 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.Key MessagesCongenital malformations have been found to be comparable following natural conception, letrozole and clomiphene citrate. Thus, the undue fear against letrozole may be uncalled for.
Highlights
Letrozole is a third-generation selective aromatase inhibitor that inhibits the production of estrogen from androstenedione and testosterone substrates
There was no significant difference in the overall rate of congenital malformations among children born to mothers who conceived naturally or after letrozole or Clomiphene citrate (CC) treatment
Infertile women in the age group of 21–35 years who conceived naturally or undergoing ovulation induction or augmentation for timed- intercourse or intrauterine insemination who received either letrozole (5 mg) or CC (100 mg) orally daily for 5 days from day 3 to 7 of the cycles were included in this study
Summary
Letrozole is a third-generation selective aromatase inhibitor that inhibits the production of estrogen from androstenedione and testosterone substrates. It is a widely recommended drug for the treatment of postmenopausal breast cancer and recently it has proven its role as an effective agent for ovulation induction [1]. Letrozole has several distinct advantages over CC. Clomiphene has both estrogen agonistic and antagonistic properties. CC causes depletion of hypothalamic estrogen receptors leading to increased GnRH secretion, thereby increasing pituitary gonadotropin release and ovarian activity [2]. Gonadotropins have been used in cases of clomiphene failure but these are very expensive and can lead to hyperstimulation, need close supervision and monitoring. Pregnancy outcome with letrozole is comparable to gonadotropin but it is cheaper and devoid of complications of gonadotropin [4,5]
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