Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation

Brown, Julie; Farquhar, Cindy; Beck, James I; Boothroyd, Clare; Proctor, Michelle; Hughes, Edward G.

doi:10.1002/14651858.cd002249.pub3

Cited by 32 publications

(12 citation statements)

References 43 publications

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“…Although several approaches are available to induce ovulation in anovulatory PCOS women [3], clomiphene citrate (CC) is still considered the first-line therapy, with lower risk of adverse effects and lower cost [4]. However, evidence has demonstrated that approximately 15–40% of PCOS patients do not respond to CC treatment [5,6], which is termed CC resistance. It has been reported that PCOS women with obesity, hyperandrogenism, and insulin resistance are less likely to respond to CC, suggesting these factors could be prominent causes of CC resistance [7–9].…”

Section: Introductionmentioning

confidence: 99%

Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment

Wang

Baker

et al. 2017

Med Sci Monit

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BackgroundPolycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15–40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown.Material/MethodsWe recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50–100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs.ResultsCC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93–1.95) vs. 1.08 (0.85–1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance.ConclusionsCirculating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation.

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Section: Introductionmentioning

confidence: 99%

Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment

Wang

Baker

et al. 2017

Med Sci Monit

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“…Given its ability to induce ovulation in oligo-ovulatory and anovulatory females, CC is considered a first-line medical approach to improve fertility in this patient population (3)(4)(5). Hammond et al (6) demonstrated that, in a group of anovulatory and oligomenorrheic women treated with CC, 86% ovulated and 49% of those patients conceived.…”

mentioning

confidence: 99%

“…More recently, in a compilation of seven published studies looking at CC and ovulation, Homburg (7) reported an ovulation rate of 73% with a pregnancy rate (PR) of 36%. In addition, Beck et al (5) analyzed 12 randomized controlled trials regarding oral antiestrogen treatment in patients with anovulatory infertility and concluded that CC is effective in increasing the PR when compared with placebo. Thus, CC effectively stimulates both ovulation and greatly improves fertility success in most anovulatory women.…”

mentioning

confidence: 99%

Clomiphene citrate and intrauterine insemination: analysis of more than 4100 cycles

Dovey

Sneeringer

Penzias

2008

Fertility and Sterility

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“…A recent systematic review shows evidence supporting the effectiveness of the current first-line treatment CC. There was no evidence of a difference in effect between CC and TMX [4,7,15] . No review describing adverse effects of CC in infertility patients has been published in the literature.…”

Section: Ovulation Induction and Selective Estrogen Receptor Modulatorsmentioning

confidence: 76%

Association between Clomiphene Citrate and Visual Disturbances with Special Emphasis on Central Retinal Vein Occlusion: A Review

Viola

Meyer

Kruger

2010

Gynecol Obstet Invest

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Objectives: To determine whether clomiphene citrate (CC) can be implicated as a cause for central retinal vein occlusion (CRVO) and other visual disturbances. Methods: For this systematic review, we performed a search of the following databases: PubMed (1976 to November 2009), Medline Plus 2009, Cochrane Library (1996 to November 2009), Google and Google Scholar (1996 to November 2009). Thirty-five relevant titles (25 full papers and 10 abstracts) were identified and read by authors. No review has been published in the literature. The publications included describe adverse effects with clomid and selective estrogen receptor modulators and in particular visual disturbances. The population consisted of infertility patients under ovulation induction with CC. The main outcome measures were loss of vision due to CRVO and other visual changes. Results: CC may predispose to CRVO, but further trials are clearly needed in this area. Conclusion: Physicians should be aware of the potential risk of CC, especially in patients with associated risk factors for CRVO. If visual disturbances occur, therapy should be terminated and the patient referred for specialist ophthalmic care.

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Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation

Abstract: Editorial group: Cochrane Menstrual Disorders and Subfertility Group. Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 4, 2009.

Cited by 32 publications

References 43 publications

Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment

Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment

Clomiphene citrate and intrauterine insemination: analysis of more than 4100 cycles

Association between Clomiphene Citrate and Visual Disturbances with Special Emphasis on Central Retinal Vein Occlusion: A Review

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