Helping women to ovulate
David J Cahill in Practical Patient Management in Reproductive Medicine, 2019
Clomifene citrate is a (relatively ineffective) nonsteroidal anti-oestrogen medication. It works by simulating a low oestrogen status to the hypothalamus, which responds by increasing GnRH pulses to the pituitary, driving FSH production upwards and thereby driving follicular development and ovulation. It only works in the presence of some circulating oestrogen – it is not effective in either WHO Type I or Type III, only in Type II, which includes women with PCOS. Clomifene has both oestrogenic and anti-oestrogenic effects. Centrally, it induces follicular development, but peripherally, in the cervix and in the endometrium, it appears to have largely anti-oestrogen effects, reducing the amount of cervical mucus and the thickness of the endometrium. Clomifene is produced in two isomers, enclomifene [(E)-clomifene] and zuclomifene [(Z)-clomifene]. Clomifene's half-life is reported as 5–7 days, but the zuclomifene isomer can be present for up to 6–8 weeks afterwards, and certainly beyond the time in which an embryo would be exposed it, should the woman get pregnant. There are, however, no reports of an increase in miscarriage rates or congenital anomalies associated with its use. Clomifene does have side effects which include multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) (see Section 8.7.1 in Chapter 8).
Unexplained infertility
David M. Luesley, Mark D. Kilby in Obstetrics & Gynaecology, 2016
Oral clomiphene citrate therapy has been commonly used for management of unexplained infertility. It is thought to correct subtle ovulatory dysfunction. Clomiphene is a selective oestrogen receptor modulator (SERM) that inhibits the negative feedback effect of oestrogen on the hypothalamus, resulting in increased gonadotrophin secretion and induction of ovulation. It can lead to multiple ovulation and is associated with a risk of multiple pregnancy. Treatment is usually initiated with a dose of 50 mg once daily from days 2–6 of a menstrual cycle, although higher doses have been used. Common side effects of clomiphene include hot flushes, abdominal discomfort or blurring of vision. Concerns regarding potential risk of ovarian cancer have not been confirmed. Clomiphene has been popular because it is inexpensive, non-invasive and needs less clinical monitoring.
Medical Treatment of Male Infertility
Botros Rizk, Ashok Agarwal, Edmund S. Sabanegh in Male Infertility in Reproductive Medicine, 2019
Clomiphene citrate is a selective estrogen receptor modulator responsible for the inhibition of the negative feedback at the level of hypothalamus and pituitary. This action enhances the excretion from the anterior pituitary of LH and FSH, resulting in increased testosterone production and spermatogenesis, respectively. Therefore, it is not recommended for men with already increased gonadotropins from the initial presentation. Enclomiphene and zuclomiphene are the two isoforms that comprise the racemic mixture of clomiphene citrate. Clomiphene citrate is most commonly used in normogonadotropic men with low testosterone and normal T/E2 ratio [51]. In a recent study, the reported adverse effects were headache, gynecomastia, skin rash, testicular enlargement, visual disturbances, dizziness, impotence, and decreased libido. Although all of these were categorized as nonserious side effects (CHUA), pulmonary embolism and venous thrombosis have been reported in men taking clomiphene citrate [52,53].
Effect of serum vitamin D level on endometrial thickness and parameters of follicle growth in infertile women undergoing induction of ovulation
Published in Journal of Obstetrics and Gynaecology, 2018
An ultrasound was performed to determine endometrial thickness and antral follicle size in the day of hCG injection. Clinical pregnancy was defined by the presence of a heartbeat of an intra-uterine gestational sac. The treatment used in this study has been clomiphene citrate. Typically, one clomiphene citrate 50 mg tablet was taken orally for 5 days, from cycle day 3 to cycle day 7. On day 11 or 12 of the menstrual cycle, ultrasound monitoring was conducted to determine if an ovarian follicle or follicles have developed and to measure the endometrial lining. In order for ovulation induction to be successful, when 2–3 follicles with 18–30 mm diameter were visible, an injection of hCG was performed and a form of the progesterone was given via vaginal tablets. If ovulation occurred, a timed intercourse or IUI was performed.
Ultrasound monitoring during first-cycle treatment with clomifene citrate: a national survey of compliance with NICE
Published in Human Fertility, 2020
Heather Garthwaite, Jane Stewart, Kathryn King, Ken McGarry, Scott Wilkes
Clomifene citrate has been the first-line medical treatment for polycystic ovarian syndrome-related (WHO class II) infertility for over 30 years. It acts by up-regulating follicle stimulating hormone, which encourages follicular development (Wallach & Adashi, 1984). However, more than one follicle may result, thus increasing the risk of multiple pregnancy from the background rate of 1.6% to approximately 5–8% (Legro, 2016; Office for National Statistics, 2017). The majority are dichorionic twins, with the risk of triplets reported as 0.3–0.5%, quadruplets 0.3% and quintuplets 0.13% (McDowell, Kroon, & Yazdani, 2013).
Multiple pregnancy rate in patients undergoing treatment with clomifene citrate for WHO group II ovulatory disorders: a systematic review
Published in Human Fertility, 2022
Heather Garthwaite, Jane Stewart, Scott Wilkes
Clomifene citrate has been the first-line medical treatment for polycystic ovary syndrome (PCOS)-related (WHO group II) subfertility for over 30 years. It acts by up-regulating follicle-stimulating hormone (FSH), which encourages follicular development (Wallach & Adashi, 1984). Potential multifollicular development raises concerns about an increased risk of multiple pregnancy, which is commonly quoted in clinical practice as 8–10% (Homburg, 2005; Macgregor et al., 1968).
Related Knowledge Centers
- Infertility
- Liver Disease
- Pelvic Pain
- Polycystic Ovary Syndrome
- Ovarian Cancer
- Anovulation
- Twin
- Hot Flash
- Seizure
- Vaginal Bleeding