Dear Robert,
Firstly, I would like to say how much I appreciate the opportunity to ask you a question and also for sharing such helpful and stories on your website. I have recently had my first cycle of IVF(ICSI) which was unsuccessul. A brief summary of our cycle: I am 33 years old next month and have an AMH of 9.4 My husband is 38 and has low sperm count and motility. We managed 7 eggs at egg retrieval stage however only 1 egg fertilised and was subsequently transferred, unfortunately failing to result in pregnancy. The doctor treating my husband and I had initially advised me about taking DHEA to possibly help improve the quality of my eggs, however for this first cycle, we decided not to do this as we had questions marks over the use and possible side effects of DHEA. We are hoping to start another cycle and I was wondering if you might be able to give us your thoughts on the benefits of DHEA in our case? Also, I would like to know your thoughts on whether IVF or ICSI might be a better option for us? My husband’s sperm count is 13.6 x 10 6 /ml and motility is 27%. It has been suggested to us that we get the comet test done. Do you think this would be beneficial to inform us of which type of treatment might be best? I would be extremely grateful for any advice you might have on this, Many thanks in advance, N

Reply…

Dear N,

Thank you for your enquiry.

The use of a drug in the form of DHEA (dehydroepiandrosterone – a steroid hormone which normally leads to the formation [a precursor] of both testosterone and estradiol – i.e. male and female steroid hormones), particularly for so-called poor responders was recommended by colleagues in Chicago at least ten years ago. The precise reason for this has never been entirely clear to me except that this hormone is involved at the onset of puberty and its manufacture by the body gradually falls during and after the menopause. A number of respected scientists have postulated various possible mechanisms for a possible effect on improving ovarian function when that is failing. In particular, there is considerable evidence that its use is associated with an increase in the number of antral follicles in the ovaries (in which of course, mature eggs eventually develop and from which they ovulate). Since then there has been fairly extensive experience with its use in IVF clinics in many parts of the world and a substantial number of scientific publications (I have counted some 60 in different journals) about its effects in human IVF treatment. Most recently there have been some good randomised controlled trials (the gold standard test for drug trials) and the most prominent one is by Dr Kara and colleagues in Turkey. They treated 104 IVF patients with DHEA, comparing them with another group of 104 women who were (randomly selected) not treated with the drug. The pregnancy rate was actually higher in the untreated group (34 compared with 33). They conclude that although patients on DHEA yield slightly more eggs, this does not improve the pregnancy rate. This finding has just been confirmed by another group in the University of Athens, headed by Dr Nikos Vlahos. They found that AMH levels increased slightly and that FSH levels fell slightly, but the pregnancy rate was actually better in the untreated women.

Most importantly, an entirely independent assessment of the world literature has just been published by the British Fertility Society. The lead author of this important paper is Dr Luciano Nardo, and a number of other excellent physicians contributed to this paper. They have no vested interests. They conclude that there is insufficient evidence to justify the use of DHEA at the present time and do not recommend it.

With regard to the use of the comet test to evaluate DNA damage of sperm, I think this is certainly worthwhile. There is no doubt that DNA damage is associated with decreased fertilisation rates in IVF. Comet evaluates breaks in the DNA chains and only uses a few thousand sperm so the test can usually be done on a sample which is simultaneously being used for fertilisation. If the damage is severe, a clinic may rightly recommend ICSI, rather than routine IVF. Pregnancy rates fall considerably when the level of damage is greater than 50% – when generally ICSI is recommended. Incidentally, comet seems to be more reliable as a predictor than mere sperm motility. Other tests for DNA damage include tests on the chromatin structure, or more simply a test called the halo test which is relatively inexpensive. There is also a test called TUNEL (much used as a research tool in my lab to evaluate DNA damage in cells, including cells from embryos) which may be offered by some clinics – but comet is a very useful and is now quite a well-tried evaluation.

Happy New Year,

I hope this is helpful,
Robert Winston

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