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CASE STUDY: Prolonged Clomiphene Citrate Therapy can in Some cases reverse Male Factor Infertility and Avoid the need for IVF/ICSI

by Dr. Geoffrey Sher on February 8, 2016

About 2 years ago, I consulted with a couple who presented with many years of infertility due exclusively to severe male factor (sperm count= 1.0 million/ml; sperm motility= <10% and <1% normal sperm forms. I had a sperm chromatin structure assay (SCSA) performed and this revealed a sperm DNA fragmentation index (DFI) of >60%2% elevated/abnormal). The female partner, who had never been pregnant before, was 30y of age, had patent fallopian tubes and had been ovulating normally and regularly.

I sent the male partner’s blood for off for FSH, LH and testosterone measurement. His FSH and LH levels came back at 3.2 and 4.3 mIU/ml respectively and his blood testosterone level was in the normal range. Both a physical and ultrasound examination excluded a varicocele and other testicular lesions.  An ultrasound of his scrotum and culture of his semen came back normal.

I suggested to the couple that it might be possible to reverse husband’s sperm parameters through the administration of low dosage clomiphene citrate for about 90 days and that the chance of this working was about 50%. I went on to say that if it did not work, in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) would be needed. PR commenced taking clomiphene citrate immediately. About 3 months later his sperm count had increased to 65 million/ml, motility to 56% and morphology to within the normal range. His FSH level had increased to 5.5MIU/ml and his LH to 6.1MIU/ml.  We collected several masturbation specimens of his semen and cryobanked these in case they were needed down the oline and stopped the clomiphene.

Approximately 2 months later I got a call to inform me that the couple had conceived on their own.

Discussion:  This case illustrates the value of testing FSH/LH/testosterone in men with unexplained low sperm counts oligospermia. The reason is that When FSH is low, the administration of clomiphene will in a significant percentage of cases result in a rapid return to normal and it is the FSH which is primarily responsible for sperm production. LH, in turn drives testicular testosterone production.

I use an FSH of 7.0 mIU/ml as a cutoff to determine who will and who will not be treated with clomiphene.  If the blood FSH concentration falls below this level I treat, and if it is higher in concentration, I’m reluctant to do so.  In some cases (as in this instance) the improvement is rapid and dramatic while in others the treatment is unsuccessful and as I informed PR, such cases will require ICSI.

In my experience, a reduction of sperm count (oligospermia) is rarely if ever attributable to  a varicocele (a collection of varicose veins in the scrotum) where the commonest presentation is a high sperm count with low motility and many immature sperm forms (a so called “stress reaction”).

In many such cases, the man will in addition to a low sperm count, also have a low blood testosterone level with resultant effects such as lethargy, muscle weakness, low sex drive and even erectile dysfunction.   Since the administration of low dosage clomiphene usually causes an elevation in both FSH and LH levels and the rise in LH results in reciprocal elevation in testosterone, these symptoms often disappear on clomiphene therapy.

Finally, when low dosage clomiphene reverses oligospermia, it is always advisable to collect and freeze-store (cryobank) several specimens of sperm for later dispensation, as it is not advisable to administer clomiphene citrate to the male partner for longer than a period of 6 months.

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