DMB Sept-Oct 2008 Feature Article

Current  First-Line Infertility Treatments Were No Better Than Couples Who Did Nothing

By Dr. Carol Lin

In light of a recent published study in the British Medical Journal (BMJ), commonly used first-line treatments for unexplained infertility do not seem to enhance fertility.1 

The diagnosis of unexplained infertility is warranted when no abnormalities were detected through standard infertility investigations including semen analysis, tubal patency, and ovulation testing.  It is estimated that one in seven couples in the United Kingdom experience infertility and a quarter of these couples are affected by unexplained infertility.      

A total of 580 women experiencing unexplained infertility for more than two years were recruited for for a multi-centered randomised controlled study.  These women were randomly assigned to three different groups: (1) the expectant management group (n=193) received only general advice about natural pregnancy but no medical intervention; (2) the clomifene citrate group (n=194) received a 50 mg daily oral dose of the pituitary stimulating medication to promote ovulation between day 2 to day 6 of each cycle; and (3) the unstimulated intrauterine insemination group (n=193) received no medication, but a single insemination procedure when a surge of the mid-morning urine luteinizing hormone is detected.  

Number of live births is the main study outcome measure.  The researchers reported that the no medical intervention group had a live birth rate of 17%, the group with clomifene citrate had a live birth rate of 14%, and the group with unstimulated intrauterine insemination had a live birth rate of 23%.  

The comparable outcomes in all three treatment groups lead the researchers calling for the need to weight the risks and benefits of clomifene treatment.  Women in the clomifene citrate group experienced more side effects such as abdominal pain, bloating, hot flashes, nausea, and headaches (13-24%) than those in the other groups (0-7%).  Women from the no treatment group reported the process and the outcome less acceptable, while all three groups experienced parallel levels of anxiety and depression.  

Commentary:  I believe both the outcome and satisfaction rate would have been improved in the expectant management group if the women were reassured with simple dietary and lifestyle modifications; “doing nothing’ was probably the main reason for the lower level of satisfaction in this group.  Researches have shown that advancing age, psychological stress, history of STD and pelvic inflammatory diseases, environmental pollutant, caffeine consumption, tobacco use, alcohol ingestion, and extreme body weight (both under and over-weight) have potential implications on fertility. 2, 3.  Furthermore, a pilot study on a nutritional supplement containing Vitex agnus-castus (chasteberry), green tea extract, L-arginine, vitamins and minerals have been shown to improve fertility as measured by the increased mid-luteal progesterone level and increased number of days of basal body temperature above 37°C in the luteal phase. 4

I truly hope that one day wholistic treatment would be considered and included as a treatment arm in most outcome-based clinical studies, which would allow the doctor to implement the fundamental practices of naturopathic medicine including the diet, lifestyle, nutritional supplements, botanicals, homeopathics to each patient.  All treatment arms then should be evaluated according to the outcomes, costs, and side effects. I believe that is the true “evidence based medicine.” 


1. Bhattacharya S., Harrild K., Mollison J., Wordsworth S., Tay C., Harrold A. et al.  Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial.  BMJ . 2008; 337:a716.  doi: 10.1136/bmj.a716

2. Homan G.F., Davis M., Norman R. The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review.  Hum Reprod Update. 2007 May-Jun;13(3):209-23. 

3. Kelly-Weeder S., O'Connor A.  Modifiable risk factors for impaired fertility in women: what nurse practitioners need to know.  J Am Acad Nurse Pract. 2006 Jun;18(6):268-76.

4.  Westphal L.M., Polan M.L., Trant A.S., Mooney S.B.  A nutritional supplement for improving fertility in women: a pilot study.  J. Reprod Med. 2004 Apr;49(4):289-93.