What is the use of Clomid (Clomiphene citrate)?

From the Guidelines

Clomid (clomiphene citrate) is an acceptable alternative to low-dose gonadotrophins for inducing ovulation, with a lower live birth rate but also lower multiple pregnancy rates and costs, as supported by the most recent and highest quality study 1.

Key Points

• Clomid is used to induce ovulation in women with anovulation or irregular ovulation
• The standard dosage is 50mg taken orally once daily for 5 days, with a maximum recommended dose of 150mg daily
• Clomid works by blocking estrogen receptors in the hypothalamus, stimulating the release of FSH and LH, and promoting ovulation
• Common side effects include hot flashes, mood swings, breast tenderness, and abdominal discomfort
• More serious risks include multiple pregnancy (5-8% chance of twins), ovarian hyperstimulation syndrome, and visual disturbances

Recommendations

• Clomid can be used as an alternative to low-dose gonadotrophins for inducing ovulation, with a lower live birth rate but also lower multiple pregnancy rates and costs 1
• Treatment is typically limited to 3-6 cycles, as extended use doesn't improve pregnancy rates and may increase the risk of ovarian cancer
• Regular monitoring with ultrasound and hormone tests is recommended during treatment to track follicle development and prevent complications

Evidence

• A systematic review and meta-analysis of 14 studies (11,599 IUI cycles) found that multifollicular growth resulted in significantly higher pregnancy rates compared to monofollicular growth, but also increased the risk of multiple pregnancies 1
• A Cochrane systematic review found that gonadotrophins had significantly higher pregnancy rates compared to anti-oestrogens, including clomiphene citrate, but also higher multiple pregnancy rates 1
• A recent RCT confirmed that clomiphene citrate is an acceptable alternative to low-dose gonadotrophins for inducing ovulation, with a lower live birth rate but also lower multiple pregnancy rates and costs 1

From the FDA Drug Label

Clomiphene citrate is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Impediments to achieving pregnancy must be excluded or adequately treated before beginning clomiphene citrate therapy Those patients most likely to achieve success with clomiphene therapy include patients with polycystic ovary syndrome, amenorrhea-galactorrhea syndrome, psychogenic amenorrhea, post-oral-contraceptive amenorrhea, and certain cases of secondary amenorrhea of undetermined etiology.

Clomid Use: Clomid, also known as clomiphene citrate, is used to treat ovulatory dysfunction in women who want to get pregnant.

• It is most effective in patients with polycystic ovary syndrome, amenorrhea-galactorrhea syndrome, psychogenic amenorrhea, post-oral-contraceptive amenorrhea, and certain cases of secondary amenorrhea.
• Before starting Clomid, other impediments to pregnancy must be excluded or treated.
• Clomid is not recommended for male infertility, in vitro fertilization, or combined therapy with other ovulation-inducing drugs 2.

From the Research

Clomid Studies

• The effectiveness of Clomid (clomiphene citrate) in combination with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilization (IVF) has been studied in several trials 3, 4, 5, 6, 7.
• A 2012 study found that the use of Clomid with gonadotropins did not differ significantly from gonadotropins alone in terms of live births or pregnancy rates, but was associated with a reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) 3.
• A 2017 study found that the use of Clomid or letrozole with or without gonadotropins was associated with a reduction in the incidence of OHSS, but the evidence was of low to moderate quality and larger trials are needed to confirm these findings 4.
• A 2021 study found that the addition of Clomid to gonadotropins during the early follicular phase of ovarian stimulation did not affect the number of oocytes retrieved, but was associated with a higher number of blastocysts 5.
• A 1986 study found that combined human menopausal gonadotropin (hMG) and Clomid stimulation was superior to either hMG or Clomid alone in terms of the number of follicles, oocytes, and embryos transferred, but did not improve pregnancy rates 6.
• A 2020 study found that gonadotropins were more expensive than Clomid in couples with unexplained infertility undergoing intrauterine insemination (IUI), without being significantly more effective 7.

Clomid Efficacy

• The efficacy of Clomid in improving live birth rates or pregnancy rates is unclear, with some studies finding no significant difference between Clomid and gonadotropins alone 3, 4.
• Clomid may be associated with a reduction in the incidence of OHSS, but the evidence is of low to moderate quality 3, 4.
• The addition of Clomid to gonadotropins may be associated with a higher number of blastocysts, but the clinical significance of this finding is unclear 5.

Clomid Safety

• Clomid has been associated with a reduction in the incidence of OHSS, a potentially life-threatening condition 3, 4.
• The safety of Clomid in terms of other adverse effects, such as fetal abnormalities, is not well established and requires further study 4.