Abstract
Background: Anovulation is a common cause of infertility and induction of ovulation with oral agents such as clomifene is the treatment of choice in women with normogonadotropic anovulation. While such treatment is able to achieve ovulation in many, some women fail to respond thus termed as having clomifene resistance. Knowledge on factors associated with such resistance would enable us to counsel patients more accurately and offer alternative treatment modalities without undue delays. This study was aimed at identifying factors associated with clomifene resistance among infertile women with WHO group II anovulation at a teaching hospital in Sri Lanka. Method: A case control study was done at the Infertility clinic of the North Colombo teaching hospital, Ragama conducted by the department of obstetrics & Gynaecology of the University of Kelaniya. Women with WHO group II anovulation (n=128) were included and underwent induction of ovulation with clomifene citrate starting at a dose of 50mg per day, increased up to 150mg till ovulation was achieved. Those who fail to respond to a maximum dose of 150mg were termed as clomifene resistant. The factors known to be associated with clomifene resistance were compared between the two groups who responded and those who failed to respond. The study was registered with the Sri Lankan clinical trial registry maintained by the Sri Lanka Medical association. The study was funded by the National Science foundation of Sri Lanka through a research grant (Grant No: RG/2007/HS/08) Results: Ovulation was achieved in 77.3% (n=99) of subjects and therefore the prevalence of clomifene resistance was 22.8% (n=29). Among those who responded, 41 did so at a dose of 50mg per day while 40% did with 100mg, thus over 80% achieving ovulation at a dose of 100mg per day or less. The factors associated with clomifene resistance in this population included infertility of more than three years (OR 2.06, 95%CI 1.51-9.14), presence of hirsutism (OR 2.76, 95%CI 1.18-6.46), a higher AFC (16 vs 13, p=0.04), PCOS (OR 2.99, 95%CI 1.06-8.41) and an LH:FSH ratio of > 1(OR3.11, 95%CI 1.33-7.24). Other factors that have been described to be associated with clomifene resistance such as advanced age, a BMI > 25, and a higher ovarian volume did not show any significant associations in this study. Discussion: This study was able to identify factors associated with clomifene resistance in a local population. Most factors identified included clinical and laboratory findings of PCOS thus highlighting the limitations in treatment success of clomifene among women with PCOS. This information may be used in clinical practice to counsel patients prior to treatment or to consider other alternative treatment options such as Letrozole or gonadotropins. DOI: http://dx.doi.org/10.4038/sljog.v36i3.7715 Sri Lanka Journal of Obstetrics and Gynaecology 2014; 36: 71-73
Highlights
Anovulation is the commonest cause of female infertility[1] and is seen in approximately 20-30% of couples[2,3].The WHO classification defines WHO group II anovulation as anovulation in the presence of normal levels of gonadotropins
The factors associated with clomifene resistance in this population included infertility of more than three years, presence of hirsutism, a higher antral follicle count (AFC) (16 vs 13, p=0.04), Polycystic ovary syndrome (PCOS) and an LH:FSH ratio of > 1(OR3.11, 95%CI 1.33-7.24)
Other factors that have been described to be associated with clomifene resistance such as advanced age, a BMI > 25, and a higher ovarian volume did not show any significant associations in this study
Summary
Anovulation is the commonest cause of female infertility[1] and is seen in approximately 20-30% of couples[2,3].The WHO classification defines WHO group II anovulation as anovulation in the presence of normal levels of gonadotropins. Clomifene citrate is the most commonly used oral ovulation induction agent worldwide It is an anti-oestrogen, which blocks the oestrogen receptors at the level of the hypothalamus inducing FSH secretion from the anterior pituitary by interfering with the negative feedback of oestrogen. It is often used as the first line agent and other methods such as gonadotropins are reserved for patients who do not respond to clomifene citrate or fail to conceive with such treatment. Anovulation is a common cause of infertility and induction of ovulation with oral agents such as clomifene is the treatment of choice in women with normogonadotropic anovulation.
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