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Mack - December 6th, 2006 1:38 AM

My husband has been on an (ARB) for 6 years due to high blood pressure. About 8 months ago we went to a RE and he was informed my husband was on Micardis for his blood pressure. No changes were recommended. My labs and his sperm test were both very good. We tried 4 IUI's with Letrazole then 3 more with the addition of Follistim. Nothing. Then I decided to pursue IVF and read again that BP medication can affect sperm. I did my own research and found an article in the Journal of Reproduction and Fertility that discussed how my husband's class of medication inhibited the acrosome reaction (in other words the sperm could not penetrate the egg). I brought this up to my RE and he hadn't heard of the study (eventhough this article was 6 years old) and he asked ME for a copy. I had my husband's physician put him on an alternate medication and we proceeded with IVF. To my dismay I was told I responded poorly and they canceled my cycle. 45 days and no period - then, strangely, I could tell I was ovulating again. At this point my husband had been off the medication about 3 months (the time it takes for new sperm to completely regenerate) and we gave it a shot. My RE doubted I had ovulated , however an ultrasound confirmed that I had started a new cycle, and had in fact ovulated. A couple weeks later my pregnancy test came back positive! The first time we tried (after he had been off the medication) we got pregnant after years of trying! I have no doubt it was the medication. They had told me I had a narrow cervix, possible endometriosis, possible partially blocked tube, my eggs might be old, etc. I hope that anyone who reads this re-examines any medication their partner might be on. I find it astonishing that none of the primary care physicians are aware of this, yet they are prescribing blood pressure medication to younger and younger individuals (more aggresive goals) not to mention couples are waiting until they are older to have children, thus increasing the odds that they will be on a blood pressure medication.


Dr Smith - December 6th, 2006 1:35 PM

Scientific stuff:

Angiotensin II type 1 receptors were found in human sperm, but they were restricted to the specific regions of the tail (not the acrosomal region). Exposure to angiotensin II was found to stimulate motility. In contrast, an angiotensin II type 1 receptor antagonist/blocker (ARB) was found to inhibit angiotensis II type 1 stimulation of motility. In this particular study, angiotensin II receptors were not found on the anterior region of the sperm head overlying the acrosome. Hence, the authors concluded that, in [i]human[/i] sperm, the effect of angiotensin II was restricted to stimulating motility. There was no mention of its effect on the acrosome reaction (the release of enzymes that disolve the protein coat surrounding the egg) in human sperm.

Reference: J Endocrinol. 1995 Feb;144(2):369-78.
Type 1 angiotensin II receptors in rat and human sperm. Vinson GP, et al.

In a subsequent study of bovine (cow) sperm, angiotensin II receptors were found in both the sperm head and tail and angiotensin II had a stimulatory effect on both motility and the acrosome reaction. This effect was inhibited by Losartan, an ARB. This suggested that angiotensin may play a role in the induction of the acrosome reaction in bovine sperm.

Am J Physiol. 1998 Jul;275(1 Pt 1):E87-93.
Angiotensin II induces acrosomal exocytosis in bovine spermatozoa. Gur Y, et al.

In a similar study, angiotensin II was found to stimulate the acrosome reaction of equine (horse) sperm. THis was also inhibited by the ARB Losartan. The authors concluded that angiotensin II may play a role in the induction of the acrosome reaction.

J Reprod Fertil. 2000 Sep;120(1):135-42.
Effects of angiotensin II on the acrosome reaction in equine spermatozoa. Sabeur K, et al.

I am unaware of any scientific studies directly linking ARBs to the inhibition of the acrosome reaction in [i]human[/i] sperm. Although it is possible that angiotensin II receptor blockers may inhibit the acrosome reaction in human sperm, the direct evidence is just not there. It is important to recognize the dangers of making cross-species jumps. In reproduction, there are significant differences between species and what is found to be true in one specieis may not necessarily be true for another species.

Opinion stuff:

It is not surprising that your RE was unaware of the angiotensin II receptor blocker studies on cow and horse sperm. It is difficult enough to keep up with human reproductive studies, let alone farm animals.

All this being said, I think you have a valid point. Patients should be more proactive in asking their physicians about the possible reproductive side effects of the medications they are on and REs need to be more aware of the negative effect of certain medfications on SPERM. Although ARBs are contra-indicated in pregnant women (they may cause birth defects), there is no mention of the potential side effects of ARBs on sperm function. And its not just ARBs. Reproductive toxicity studies are not required by pharmacuetical companies (in the US) before bringing a drug to market. There are some prescription medications that affect sperm funtion (i.e. ACE inhibitors), but you won't find that written in the product insert. Personally, I think the FDA should require more extensive reproductive studies before approving a drug. Yeah right. Like that's gonna happen.

Thanks for making your point.

Ryley - December 8th, 2006 6:37 PM

Can you tell me what blood pressure medications should be avoided for husbands? We have been trying for along time to get pregnant and now I have found this information and asked the doctors about this. Any information you could share would be helpful.

Thanks,
Ryley

Dr Smith - December 11th, 2006 10:19 AM

ACE inhibitors were once considered detrimental to sperm motility, but subsequent studies were unable to verify this finding. The problem with all studies whereby the effect of a particular medication on sperm function is that they are in vitro studies. The pharmacological agent is added to the culture medium in which the sperm are swimming and the effect is observed. That's not the way it happens in real life. When a drug in absorbed into the body, it may be converted to a completely different compound which then, in turn, has the desired systemic effect. For this reason, in vitro studies must be interpreted with caution.

I am not aware of any blood pressure medications that have been shown to have a detrimental after being absorbed by the body.


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