Improvements in semen parameters in men treated with clomiphene citrate—A retrospective analysis

Abstract

Clomiphene citrate (CC) is commonly used off‐label for the treatment of male infertility, yet there is limited data to guide patient selection. To identify a subset of patients more likely to benefit from CC, we aimed to define predictors of improvement in semen parameters among men receiving CC. We retrospectively analysed 151 men treated with at least 25 mg CC daily for male infertility and/or hypogonadism at two institutions between 2004 and 2014. Men previously on testosterone were excluded. The primary outcome was change in semen parameters. Variables included baseline patient characteristics, pre‐treatment hormone profiles and pre‐treatment semen analyses. A total of 77 men met inclusion criteria. Median length of therapy was 2.8 months. There was significant improvement in sperm concentration (14–21 million/ml; p = 0.002) and total motile count (TMC; 13–28 million; p = 0.04). One third of patients who began with fewer than 5 million motile spermatozoon improved to a TMC > 5 million, increasing reproductive options to include intrauterine insemination. Patient characteristics, pre‐treatment hormone profile and degree of oligozoospermia did not predict treatment response. While no predictors of improvement were identified, clinically useful response rates are described for use in shared decision‐making.

Evaluation of a serum 17-hydroxyprogesterone as predictor of semen parameter(s) improvement in men undergoing medical treatment for infertility

“…A p-value < 0.05 was considered statistically significant. Based on a statistical power calculation using ClinCalc software (https://clincalc.com/stats/samplesize.aspx), and a study published on changes in sperm concentration after CC therapy, 14 we needed at least 30 men to achieve acceptable statistical power of 80% and α = 0.05.…”

“…Our current study focuses on the response of infertile men with testosterone deficiency to targeted therapy with CC and CC combined with hCG. The current gap in knowledge is determining predictors of semen parameter[s] improvement following medical therapy using CC 14 and hCG. We hypothesized that men with lower baseline 17-OHP will experience a more…”

Should empiric therapies be used for male factor infertility?

“…In contradistinction to the poor evidence for scattershot empiric therapy with CC, targeted therapy with anastrozole, 21 million/mL) and total motile sperm count (mean 13 million to 28 million) (3). A meta-analysis of 11 randomized controlled trials by Chua et al (4) examined the evidence to support the treatment of idiopathic male infertility with estrogen antagonists.…”

Empirical medical therapy for idiopathic male infertility

“…Its effects on improving testosterone and symptoms of hypogonadism, with minimal side-effects, is well established (6)(7)(8). Sperm concentration and total motile count have also been confirmed to improve in some studies (9)(10)(11)(12)(13). Work from Helo et al, however, did not confirm these findings.…”