Clomiphene Citrate in Combination with Vitamin E Enhances Sperm Count and Motility in Idiopathic Male Infertility
March 17, 2009
Clomiphene citrate, a selective estrogen receptor modulator, is commonly used for treating female infertility, especially in ovulatory dysfunction that includes anovulation and luteal phase deficiency. Previous studies have shown that the antioxidant property of vitamin E improves fertility in both men and women. Now, researchers have demonstrated that the concomitant administration of clomiphene citrate and vitamin E substantially helps increase sperm count, progressive sperm motility, and thereby pregnancy rate in idiopathic oligoasthenozoospermia. The findings of the prospective study have been published in the recent issue of the journal, Fertility and Sterility.
Hussein Ghanem, Professor at the Department of Andrology, Cairo University, Egypt, and colleagues, conducted the randomized trial to determine the efficacy of clomiphene citrate as an antiestrogen and vitamin E as an antioxidant in the treatment of idiopathic oligoasthenozoospermia and male infertility. The placebo-controlled study involved 60 infertile men, divided into 2 equal groups; group 1 receiving 25 mg/day of clomiphene citrate and 400 mg/day of vitamin E, and group 2 administered with placebo. The primary outcomes measured were the incidence of pregnancy, and alterations in sperm parameters such as sperm count and motility.
Results showed a substantial enhancement in sperm count and progressive sperm motility in the subjects receiving combination treatment, compared to the controls. However, no significant variations were observed in total sperm motility, percentage of abnormal forms and semen volume. The investigators noted a 36.7% pregnancy rate (odds ratio=3.76; 95% confidence interval=1.03-13.64) in group 1 compared to 13.3% in the placebo group. Considering the findings, it was concluded that the combination of clomiphene citrate and vitamin E has the potential to improve fertility in men with idiopathic oligoasthenozoospermia.
Clomiphene raises intratesticular testosterone levels by the secretion of endogenous gonadotropin-releasing hormone from hypothalamus and gonadotropin hormone from pituitary. Hussein, et al. (Journal of Andrology, 2005) conducted a study on 42 men with nonobstructive azoospermia to analyze if sufficient number of sperms is produced for ICSI with the administration of clomiphene citrate. The effect of the drug was determined by either identifying sperms in the ejaculate or the improvement noted in the outcomes of surgical testicular sperm extraction. Routine history, physical examination, hormonal evaluation was performed along with testicular biopsy, which showed that 42.9% and 57.1% of the participants had maturation arrest and hypospermatogenesis, respectively. The analyses of semen were done at periodic intervals, following the administration of clomiphene citrate to attain serum testosterone levels of 600 to 800 ng/dL. Surgical testicular biopsy and sperm extraction were carried out in those who remained azoospermic on semen analysis.
Semen analyses showed that the sperms were in the range of 1 to 16 million/mL (mean sperm density=3.8 million/mL) post clomiphene citrate treatment in 64.3% of the participants. Although 35.7% were azoospermic, testicular sperm extraction in all patients resulted in the retrieval of adequate sperms for performing ICSI. Also, a considerable improvement in testis biopsy patterns, linked to higher chances of sperm retrieval by surgical extraction was observed following clomiphene therapy. Based on the positive results of the therapy, the scientists suggested the administration of clomiphene citrate before surgically extracting the sperms in men with nonobstructive azoospermia.
Although various therapies for infertility due to specific causes are available and effective, the treatment for idiopathic male infertility is still tough and challenging. ARTs are generally used for treating idiopathic male infertility; however, the techniques are expensive and involve the treatment of the female partner for a problem related to the male.
The identification of the usefulness of clomiphene citrate administration with vitamin E in improving the fertility outcomes, such as sperm count, progressive sperm motility, and pregnancy rate, may pave the way for the development of specific therapeutic regimen for idiopathic oligoasthenozoospermia. This may be further considered as an option prior to the selection of ART procedures to treat men with idiopathic infertility.
References
1. Ghanem H, Shaeer O, El-Segini A. Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: a randomized controlled trial. Fertil Steril. 2009 Mar 5. [Epub ahead of print].
2. Hussein A, Ozgok Y, Ross L, Niederberger C. Clomiphene administration for cases of nonobstructive azoospermia: a multicenter study. J Androl. 2005 Nov-Dec;26(6):787-91; discussion 792-3.
3. Siddiq FM, Sigman M. A new look at the medical management of infertility. Urol Clin North Am. 2002 Nov;29(4):949-63.
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