Many patients 40 years of age and older will be asked to perform a clomiphene citrate challenge test (CCCT) as part of their evaluation. The original design of the test was to predict ovarian reserve and prognosis for future pregnancy. Most insurance companies now require an annual “passing” score on the CCCT to permit coverage for treatment cycles.
The CCCT involves a cycle day 3 blood test measuring follicle stimulating hormone (FSH) and estrogen followed by two clomiphene pills per day (cycle days 5-9) and finally a repeat measurement of FSH on cycle day 10. A high FSH may indicate decreased ovarian reserve or fewer remaining quality eggs. Women 40-41 typically require an FSH < 15 on either cycle day 3 or 10 to pass the CCCT. Women 42 and older, dependent on their specific insurance provider, require an FSH < 12-15.
Despite its requirement by many insurance companies, the CCCT is not absolutely predictive of ovarian reserve. It is a piece of the puzzle but not the only piece. A systematic review of 12 different CCCT medical studies (Fertil Steril 86(4):807-18) report the sensitivity and specificity of the CCCT in predicting poor response varied significantly from 35% to 93% and 47% to 98%, respectively. If a test was absolutely predictive, it would have a sensitivity and specificity of 100%. An FSH value may also vary month to month in the same patient.
In the patient with unexplained infertility, it can be diagnostically useful to assess by ultrasound the growth of ovarian follicles and endometrium at a time near ovulation. If that same patient is also taking clomiphene during the same evaluation, it may be difficult to assess whether the findings are indicative of a patient’s typical natural cycle or whether the findings are attributed to a side-effect of clomiphene. As an example, clomiphene may thin the endometrium in some patients due to its anti-estrogenic effects. Is a thin endometrium due to prior scarring or is this a side-effect of the clomiphene in that cycle?
A consortium of medical directors from each fertility center in New England requested that insurance providers abolish the use of CCCT as a gatekeeper to infertility treatment. Despite the unanimous support and evidence presented, the CCCT remains today. Patients are made aware of its utility and well as its limitations.