The most severe forms of male infertility are non-obstructive azoospermia and severe oligospermia (or cryptozoospermia), where men have very rare sperm in the ejaculate. It is important to remember that standard semen analyses do not evaluate the entire semen specimen. What? How can that be true? Let me review the details of how a semen analysis is done.
A standard semen analysis evaluates the ejaculated fluid for the number, motility, and morphology (shape) of sperm as well as some other characteristics. If no sperm are initially seen, then the sample is centrifuged (spun at high speed) to concentrate the cells, including sperm, that may be present in the specimen.
The centrifuged specimen typically has a volume of 200 to 400 microliters. The specimen typically has 5 to 20 microliters of that sample taken and examined under an operating microscope for analysis. The report that you receive is therefore on a very small part, possibly as little as 1% of the total concentrated sample. So, it is not a complete evaluation of the semen specimen. More complete evaluation of a semen specimen is only done by a limited number of laboratories, and is typically called an Extended Sperm Preparation (ESP) or Extended Prep, and requires much more work on the part of the laboratory (as the second part of this analysis can take hours.) Early reports describing this “ESP” are provided here ( https://pubmed.ncbi.nlm.nih.gov/9222005/ ) A relevant brief video is https://youtu.be/0WaTfxB6IeA?list=TLPQMjEwOTIwMjP1bcMbSy7Ktw
Additional management of both cryptozoospermia as well as non-obstructive azoospermia are provided below.
Infertility affects 10-15% of couples, approximately 10% of infertile men have no sperm in their ejaculate, also known as azoospermia. In men with NOA, non-obstructive azoospermia, many patients can be effectively treated with surgery to extract sperm from the testes and assisted reproduction (IVF) to use those sperm. If unsuccessful, especially if the condition within the testes is maturation arrest, then there are limited treatment options. Maturation arrest is a condition where sperm-making cells are present inside the testicle, but they are not developing as they should. Although hormone treatments can help sperm to be produced more efficiently if there is a low testosterone level, there has not been a treatment to improve sperm development for men with normal testosterone levels. Therefore, new approaches to the treatment of male infertility due to azoospermia are being studied.
Retinoids (Vitamin A derivatives) have a role in spermatogenesis, and men with Vitamin A deficiency can have sperm production improved with treatment. Isotretinoin (brand name, Accutane) is a vitamin A derivative that has been used to treat a certain type of severe acne that has not responded to other treatments. Basic studies have suggested that men with severely impaired sperm production may have low levels of retinoic acid within the testis and in preliminary studies, it has been suggested that men with low sperm production (Amory et al., 2017) as well as unselected men (Cinar et al., 2016) may have improved sperm production, even when other conditions that affect sperm production, such as varicocele, are present (Gurel et al., 2023.)
Only preliminary, limited studies have been done with isotretinoin therapy in men with severe male infertility, including azoospermia. Therefore, we offer consideration of isotretinoin therapy for men with a previously failed TESE and evidence of maturation arrest. Treatment with this drug may require 3-6 months of administration, since sperm production takes 2.5 months, and the drug appears to act at some of the earlier stages of sperm development. Repeated semen tests are needed to assess whether the drug may be helping you. Since isotretinoin does not act through hormonal pathways, routine hormone blood tests are not needed unless you are taking other hormonally active drugs.
Please feel free to contact us with any questions. This is an experimental drug that is not FDA-approved for use in male infertility, but treatment of patients for a “nonFDA-approved indication” is common medical practice, when multiple studies have suggested the potential for benefit.
Isotretinoin Warnings and Side Effects:
Isotretinoin is known to cause birth defects in women who are pregnant and are taking the drug, so avoidance of any exposure of a woman who may become pregnant is important. Fortunately, the FDA and NHS report that isotretinoin is present in semen at levels too low to harm an unborn baby, and men can safely take Accutane even if their partner is pregnant or they are trying to conceive. Responders had sperm in the ejaculate at all time points; after 3 months of treatment, 6 and 9 months of treatment.
Isotretinoin has been widely prescribed for the treatment of acne since 1982 and has a well described safety profile (Bauer et al., 2016).
However, all drugs can have side effects, and the most common reported adverse effects of isotretinoin are listed below. Please stop the medication and notify office if you have any of these side effects that bother you:
Your skin may be very sensitive to light from the sun and devices that give off similar light, such as sunlamps and tanning beds, while you are taking certain drugs, including isotretinoin. This is called photosensitivity. Use sunscreen and wear a hat and clothes that cover your skin if you need to be in the sunlight. Exposing your skin to this kind of light, even for a short time, can cause your skin to be severely sunburned, blistered, or swollen.
Isotretinoin may cause suicidal thoughts or actions in a small number of people. Notify the office if you have any of the following symptoms.
Isotretinoin should be stored at room temperature, between 68 F to 77 F (20 C to 25 C). It can be exposed to temperatures between 59 F to 86 F (15 C to 30 C), for shorter periods of time, such as when transporting it. Store in a cool, dry place.
Take the first step towards better health and schedule a consultation with Dr. Schlegel today to discuss your specific concerns and explore personalized medical solutions.
New York Men’s Health Medical
Dr. Peter N. Schlegel
983 Park Ave, 1C
New York, NY 10028
(833) 746-5491
International: +1-646-661-5877
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