Guideline:
Use of clomiphene citrate in women
Bibliographic Source(s)
- Use of clomiphene citrate in women. Fertil Steril 2003 Nov;80(5):1302-8. [71 references] PubMed
Guideline Status
This is the current release of the guideline.
Guideline Category
Diagnosis
Evaluation
Treatment
Intended Users
Physicians
Guideline Objective(s)
- To describe the pharmacology mode of action and indications for clomiphene citrate (CC) treatment
- To outline the pretreatment evaluation standard and combination treatment regimens and alternative strategies for the CC-resistant patient
- To summarize the methods for monitoring therapy and review the results side effects and risks of CC treatment
Target Population
Women with ovulatory dysfunction (anovulation and luteal phase deficiency)
Interventions and Practices Considered
Diagnosis/Evaluation
- Pretreatment evaluation including
- Basal body temperature recordings
- Timed serum progesterone determinations
- Monitoring urinary luteinizing hormone (LH) excretion
- Timed endometrial biopsy
- Serial transvaginal ultrasound
- Detailed medical history
- Physical examination
- Screening for hypothyroidism (serum thyroid stimulating hormone [TSH]) and hyperprolactinemia (serum prolactin)
- Semen analysis in male partner
- Hysterosalpingography
Treatment
- Standard therapy using oral clomiphene citrate (CC)
- Alternative and combination treatment regimens
- Insulin sensitizing agents (metformin)*
- Clomiphene and human chorionic gonadotropin (hCG)
- Clomiphene and glucocorticoids (e.g. dexamethasone or prednisone)
- Clomiphene and gonadotropins (e.g. menotropins [hMG] or purified or recombinant follicle stimulating hormone [FSH])
- Ovarian drilling
*Not currently approved by the Food and Drug Administration (FDA) for this indication
- Treatment monitoring including basal body temperature midcycle luteinizing surge endometrial biopsy serial transvaginal ultrasound
Major Outcomes Considered
Ovulation conception and pregnancy rates
Methods Used to Collect/Select Evidence
Searches of Electronic Databases
Description of Methods used to Collect/Select the Evidence
Not stated
Number of Source Documents
Not stated
Methods Used to Assess the Quality and Strength of the Evidence
Not stated
Rating Scheme for the Strength of the Evidence
Not applicable
Methods Used to Analyze the Evidence
Review
Description of the Methods Used to Analyze the Evidence
Not stated
Methods Used to Formulate the Recommendations
Not stated
Rating Scheme for the Strength of the Recommendations
Not applicable
Cost Analysis
A formal cost analysis was not performed and published cost analyses were not reviewed.
Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation
This bulletin was approved by the Practice Committee of the American Society for Reproductive Medicine and the Board of Directors of the American Society for Reproductive Medicine.
Major Recommendations
- Clomiphene citrate (CC) is the best initial treatment for the majority of women whose infertility is associated with ovulatory dysfunction (anovulation luteal phase deficiency). Combined with appropriately timed intrauterine insemination (IUI) CC treatment also increases cycle fecundity in couples with unexplained infertility.
- CC treatment generally should be limited to the minimum effective dose and to no more than six ovulatory cycles. Failure to conceive after successful CC-induced ovulation is indication for further evaluation to exclude other contributing causes of infertility.
- Combination therapies involving CC and other agents (metformin glucocorticoids exogenous gonadotropins) may be effective when treatment with CC alone fails to induce ovulation. Alternative strategies for the CC-resistant woman include treatment with aromatase inhibitors or exogenous gonadotropins and in selected patients ovarian drilling.
- CC treatment should be monitored (basal body temperature [BBT] serum progesterone concentration urinary luteinizing hormone [LH] excretion) to ensure its effectiveness in ovulation induction.
- Side effects of CC treatment are generally mild and well tolerated. The principal risk of CC treatment is an increased incidence of multifetal gestation (<10%).< li>
Clinical Algorithm(s)
None provided
Type of Evidence supporting the Recommendations
The type of supporting evidence is not specifically stated for each recommendation.
Potential Benefits
Clomiphene citrate (CC) is generally very well tolerated. Some side effects are relatively common but rarely are they persistent or severe enough to threaten completion of the usual 5-day course or next cycle of treatment. Although CC treatment does have intrinsic risks they are typically modest and manageable.
Potential Harms
Side Effects of Clomiphene Citrate (CC)
- Vasomotor flushes (hot flashes) occur in approximately 10% of CC-treated women but typically abate soon after treatment ends. Mood swings are also common. Visual disturbances including blurred or double vision scotomata and light sensitivity are generally uncommon (<2% prevalence) and reversible although there are isolated reports of persistent symptoms and more severe complications such as optic neuropathy. whenever visual disturbances are identified it is prudent to stop treatment and consider alternative methods of ovulation induction. less specific side effects include breast tenderness pelvic discomfort and nausea all observed in 2% to 5% of cc-treated li>
Multiple Gestation
- Multi-follicular development is relatively common during CC treatment and the risk of multiple gestation is clearly increased to approximately 8% overall. The overwhelming majority of multiple pregnancies that result from CC treatment are twin gestations; triplet and higher order pregnancies are rare but may occur.
Spontaneous Abortion
- Early studies suggested that the incidence of spontaneous abortion in pregnancies resulting from CC treatment was increased over that observed in spontaneous pregnancies. However a number of more recent studies have described abortion rates that are not different from those observed in spontaneous pregnancies (10% to 15%).
Ovarian Cancer
- Two epidemiologic studies published early in the last decade suggested that the risk of ovarian cancer might be significantly increased in women exposed to ovulation inducing drugs but subsequent studies have failed to corroborate those findings.
Ovarian Drilling
- A reasonable option for clomiphene-resistant anovulatory women but the temporary effects of treatment and the risks of postoperative adhesions or diminished ovarian reserve should be carefully considered.
Qualifying Statements
While this document reflects appropriate management of a problem encountered in the practice of reproductive medicine it is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate taking into account the needs of the individual patient available resources and institutional or clinical practice limitations.
Description of Implementation Strategy
An implementation strategy was not provided.
IOM Care Need
Getting Better
IOM Domain
Effectiveness
Bibliographic Source(s)
- Use of clomiphene citrate in women. Fertil Steril 2003 Nov;80(5):1302-8. [71 references] PubMed
Adaptation
Not applicable: The guideline was not adapted from another source.
Source(s) of Funding
American Society for Reproductive Medicine
Guideline Committee
The Practice Committee of the American Society for Reproductive Medicine
Composition of Group that Authored the Guideline
Not stated
Financial Disclosures/Conflicts of Interest
Not stated
Guideline Status
This is the current release of the guideline.
Guideline Availability
Electronic copies: Available from the American Society for Reproductive Medicine Web site.
Print copies: Available from American Society for Reproductive Medicine 1209 Montgomery Highway Birmingham Alabama 35216-2809; Phone: (205) 978-5000; Fax: (205) 978-5005; E-mail: asrm@asrm.org; Web site: www.asrm.org.
Availability of Companion Documents
None available
Patient Resources
None available
NGC STATUS
This NGC summary was completed by ECRI on August 23 2004.
COPYRIGHT STATEMENT
This NGC summary is based on the original guideline which is subject to the guideline developer's copyright restrictions.
NGC Disclaimer
The National Guideline Clearinghouse™ (NGC) does not develop produce approve or endorse the guidelines represented on this site.
All guidelines summarized by NGC and hosted on our site are produced under the auspices of medical specialty societies relevant professional associations public or private organizations other government agencies health care organizations or plans and similar entities.
Guidelines represented on the NGC Web site are submitted by guideline developers and are screened solely to determine that they meet the NGC Inclusion Criteria which may be found at http://www.guideline.gov/about/inclusion.aspx .
NGC AHRQ and its contractor ECRI Institute make no warranties concerning the content or clinical efficacy or effectiveness of the clinical practice guidelines and related materials represented on this site. Moreover the views and opinions of developers or authors of guidelines represented on this site do not necessarily state or reflect those of NGC AHRQ or its contractor ECRI Institute and inclusion or hosting of guidelines in NGC may not be used for advertising or commercial endorsement purposes.
Readers with questions regarding guideline content are directed to contact the guideline developer.
Tools
No Quick Reference tools have been developed.