Proton Pump Inhibitors (PPI’s)
Proton pump inhibitors are used primarily in the treatment of acid reflux or gastro-oesophageal reflux disease. They are commonly prescribed in general practice, with omeprazole being the only PPI licensed for use in pregnancy. However, the use of PPIs in women undergoing ART is unclear and even though use in pregnancy is generally considered safe, there is insufficient data on associated miscarriage and stillbirth rates (22). One nationwide study in Iceland found increasing rates of PPI use with age and especially amongst women therefore more information on the use of PPIs in females undergoing ART is required (23).
A cross-sectional study of nearly 22,000 people in Denmark found a roughly equal prevalence of PPI usage amongst men and women and also found that those on PPI’s had higher incidences of obesity and smoking, both important factors in fertility (24). Another study found that men who had PPI treatment in the 12 to six-month period prior to ART had a 3-fold higher risk of low total mobile sperm count than those who did not, however there was no significant effect if treatment was limited to less than 6 months prior to ART (25). This study did adjust for age and other medications, however, did not take other factors into consideration such as obesity and smoking status. One theory to explain the 6-month delay is that PPI use increases gastric pH and impairs gastrointestinal absorption resulting in vitamin B deficiency. Vitamin B is essential for spermatogenesis and after 4-6 months, the resources of vitamin B become exhausted hence semen quality becomes impaired. A more recent retrospective study looked at the effect of PPI’s on subfertile men and found no significant impact on semen parameters on men who were already known to have male factor subfertility (26).