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Male Fertility Evaluations: What to Expect

Couple in hug watching sunrise togetherIf you are seeking to start a family, but are encountering problems, you are not alone. As many as 15% of couples struggle with conception, with male infertility accounting for or contributing to up to 60% of cases1. If you and your partner are part of this 15% of couples, you should both seek a professional fertility evaluation, as factors contributing to conception, or the lack thereof, are unique to each individual and couple. For men, a thorough male fertility evaluation usually involves examination of the following aspects:

 

Reproductive History

Your doctor will need to know a little more about you and your attempts at conception. You will need to provide information on things like:

  • when and how frequently you and your partner have sex
  • how long you have been having difficulty conceiving
  • childhood illnesses and developmental history
  • medical conditions, medications, and allergies
  • sexual history and STDs
  • exposure to toxins

Semen Analysis

In addition to knowing your history, the doctor will also want to understand where things stand today—with your semen. Analysis of a semen sample provides the doctor with information about sperm concentration, motility, and morphology, as well as overall semen volume. If the semen analysis raises any red flags, or if no abnormalities are identified that can account for infertility, additional information gathering and testing might be in order.

Medical History and Physical Examination

If further information is needed, the next step is to complete a medical history and physical examination. Your medical history can identify and risk factors that can contribute to infertility, including elements of your family history or lifestyle. The physical examination focuses largely on the reproductive organs, determining if any physical factors contribute to infertility.

Other Tests

Many causes of male infertility can be identified by the previous steps, but sometimes further testing is required. Each patient is unique, and a medical professional will work with you to determine which steps you need to take to determine the cause of infertility. For example, you may undergo an endocrine evaluation to determine if a hormonal abnormality plays a part, or your doctor may recommend ultrasonography to image your reproductive tract. These and many other specialized tests and procedures are available to aid your doctor in discovering the source of infertility. A thorough fertility evaluation performed by a caring medical professional will help you identify any obstacles to starting your family. Since many conditions that affect fertility can be treated, this evaluation may be the first step in opening doors to solutions.

  1. The Practice Committee of the American Society for Reproductive Medicine (2012). Diagnostic evaluation of the infertile male: a committee opinion. Fertility and Sterility, 98(2), 294–301. Retrieved from http://www.asrm.org/uploadedFiles/ASRM_Content/News_and_Publications/Practice_Guidelines/Committee_Opinions/optimal_evaluation_of_the_infertile_male(1).pdf
  2. Our practice websites:
    1. http://brucegilbertmd.com
    2. https://nycryo.com
    3. http://vasectomyreversalmd.com

 

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Antioxidants and Male Fertility

BlueberrySome diets recommend eating ‘Superfoods’—foods that contain antioxidants and have supplemental health benefits. These foods are supposed to be good for your overall wellness, with the potential to help treat certain conditions or symptoms. But what you don’t normally hear is how these antioxidant-rich foods can help your reproductive health.

Antioxidant Basics

When molecules in your body become oxidized, free radicals are released. These free radicals roam the body and cause chain reactions that end up damaging and killing cells. Antioxidants are the antidote. Not only can they stop these harmful chain reactions in their tracks, they can also prevent molecules from becoming oxidized in the first place1.

Antioxidants and Fertility

Free radicals aren’t all bad. A certain level of free radicals is normal, and even necessary, in the body. For men, normal sperm function requires the presence of free radicals. But an excess of these molecules can negatively impact sperm function and subsequent fertilization. In fact, some data suggests that high levels of free radicals contribute to 30-80% of cases of male infertility2. And not only can these free radicals make conception challenging, but the damage they do to sperm can result in birth defects, disease, pregnancy loss, and other complications if your partner does get pregnant3. Antioxidants reduce the levels of free radicals in your body, in turn reducing the damage they do to your sperm’s DNA and improving sperm motility.

Antioxidant Sources

Antioxidants are relatively easy to come by. Your body makes some of its own, but you can boost your internal supply. Many dietary supplements contain antioxidants, but it is ideal if you go right to the source: fresh foods. Examples of antioxidant-rich foods include:

  • berries and red grapes
  • broccoli, spinach, and artichokes
  • beans and legumes
  • whole grains, nuts, and seeds

 References

1. Sies, H. (1997). Oxidative stress: Oxidants and antioxidants. Experimental Physiology, 82 (2),  291–295. Retrieved from http://ep.physoc.org/content/82/2/291.long

2. Agarwal, A. & Allamaneni, S. S. (2011). Free radicals and male reproduction. Journal of the Indian Medical Association, 109(3), 184–187. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22010591

3. Gharagozloo1,P & Aitken, R. J. (2011). The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Human Reproduction, 26(7), 1628–1640. Retrieved from http://humrep.oxfordjournals.org/content/26/7/1628.long

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Why Your Heart Health is Important in the Bedroom

Young couple sleeping in a bedSex is an emotional, physical, and sensory experience, but sexual performance is dependent on physical processes. If you want to improve your performance in the bedroom, you would do well to begin by focusing on your heart. Why the heart? Because the heart is what pumps your blood, and erections are caused by increased blood flow to the penis. If you want to improve your vascular health (and your sexual performance along with it), it’s good to remember that “whatever’s good for the heart is also good for the penis”1.  The arteries in the penis are three times smaller than the arteries supplying the muscles of the heart. Therefore, many common diseases such as high blood pressure, high cholesterol, diabetes and obesity will often affect the smaller vessels in the penis first making erectile dysfunction and early indicator of vascular health.

High Blood Pressure

Individuals with high blood pressure often blame their medication for negative sexual side effects. While these medications can decrease sexual function, high blood pressure itself can also be the cause. High blood pressure can change patterns of circulation in the body, even damaging the inner lining of arteries—both of these effects can decrease blood flow to the penis and impact sexual performance2.

High Cholesterol

While your body needs a certain level of cholesterol to function properly, too much cholesterol can be bad for your heart, as well as your performance in the bedroom. An overabundance of cholesterol clogs arteries and restricts blood flow. Without proper blood flow throughout your body (and to your penis), reaching and maintaining an erection can be more difficult.

Food

What you eat plays a big role in your heart health, impacting your blood pressure and cholesterol level. But in addition to eating right to avoid or treat these conditions, there are foods you can eat to improve your sexual function and drive. See our earlier blog on the Mediterranean Diet (http://bit.ly/1l8sfHC). For example, spinach contains magnesium, which helps dilate blood vessels and improve blood flow. Spinach and other green vegetables also contain folate, which can help rid your body of homocysteine. This harmful substance encourages plaque buildup in arteries and puts you at risk for peripheral arterial disease3, so eating your veggies is good for your heart health and your sexual health.

References

1. Men’s Journal. 6 things that hurt sexual performance. Retrieved from http://www.mensjournal.com/expert-advice/6-things-that-hurt-sexual-performance-20140210

2. Harvard Health Publications (2004). High blood pressure can affect your sex life, says the Harvard Heart Letter. Retrieved from http://www.health.harvard.edu/press_releases/high_blood_pressure_and_sex

3. Men’s Health (2013). How to eat for better sex. Retrieved from http://www.menshealth.com/sex-md/better-sex-diet

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Acupuncture for Men’s Health

Man Undergoing Acupuncture Treatment In SpaAcupuncture is a popular form of complementary medicine. According to the National Center for Complementary and Alternative Medicine (NCCAM),a s of 2007, 3.1 million Americans1 were using acupuncture to assist with a variety of conditions. Acupuncture practitioners insert thin needles through the skin to stimulate specific muscles and nerves in the body, promoting healing and reducing pain. If you’re interested in learning more about this healing practice, here’s a look at how acupuncture may be able to help you.

Headaches and Pain

Acupuncture can be used to treat pain in many areas of the body. While most patients seek acupuncture for back pain, the practice is also commonly used for joint pain, neck pain, and headaches2. Science doesn’t always agree about the efficacy of acupuncture treatment for all types of pain, but some studies have shown that acupuncture used in conjunction with traditional medical care can be more effective at reducing pain than conventional treatment alone2. This goes for everything from chronic lower back pain to osteoarthritis knee pain to tennis elbow.

For tension headaches, acupuncture does more than encourage your tense muscles to relax.  A contributing factor to tension headaches is an imbalance of neurochemicals like serotonin. Acupuncture appears to send signals to the brain3 to adjust the levels of these brain chemicals, resulting in reduced headache pain.

Fertility and ED

ED has many causes and contributing factors, ranging from hormone imbalances to physical damage. Emotional or psychological factors can play a role, too. Acupuncture can be used to help treat the psychological contributors to ED, and studies4 have shown that, for many man, this treatment alone is enough to completely resolve their ED.

Other studies have shown that acupuncture helps with fertility, as well. According to researchers5, acupuncture improves fertility in three ways: it increases the percentage of healthy sperm found in ejaculate, it increases sperm motility, and it improves the quality of sperm structure.

Whether you are looking to ease pain of the body or mind or improve your body’s function, there just may be an acupuncture technique to help you. Acupuncture is a nearly-painless procedure, and since it is a popular and ever-growing practice, chances are that you can easily find an experienced practitioner in your area. Please visit our webpage for additional information http://bit.ly/1mh5rsa and contact us if you have questions.

References

1. NCCAM (2012). Acupuncture: An introduction. Retrieved from http://nccam.nih.gov/health/acupuncture/introduction.htm#ususe

2. NCCAM (2010). Acupuncture for pain. Retrieved from http://nccam.nih.gov/health/acupuncture/acupuncture-for-pain.htm

3. Matlack, J. 5 ways acupuncture can fix your health problems. Retrieved from http://www.menshealth.com/mhlists/acupuncture_benefits/acupuncture_for_headaches.php

4. WebMD (2000). Impotence Gets ‘Needled’ in Acupuncture Study. Retrieved from http://www.webmd.com/erectile-dysfunction/news/20000505/impotence-gets-needled-in-acupuncture-study

5. Pei, J., Strehler, E., Noss, U., Abt, M., Piomboni, P., Baccetti, B. & Sterzik, K. (2005). Quantitative evaluation of spermatozoa ultrastructure after acupuncture treatment for idiopathic male infertility. Fertility and Sterility84(1), 141–147. Retrieved from http://www.acupuncturist.nl/wp-content/uploads/Quantitative-Evaluation-of-Spermatozoa-Ultrastructure-After-Acupuncture-Treatment-for-Idiopathic-Male-Infertility.pdf

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The Mediterranean Diet and Erectile Function

Ikarian Diet: Vegetables, legumes and greens, and olive oil.

Ikarian Diet: Vegetables, legumes and greens, and olive oil.

With the New Year comes New Year’s resolutions, and a common resolution for both women and men revolve around losing weight or improving fitness and heath. In fact, the #1 resolution for 2014 was “Lose Weight,” and #5 was “Staying Fit and Healthy”1. But, while more than 40% of Americans make a resolution in the New Year, only about 8% actually keep them, according to Forbes2. If you were one of the many individuals who made a health-focused goal this year (with the aid of a diet), and you have fallen off the wagon, you might just want to get back on—and not just for the sake of swimsuit season. Studies have shown that going on a diet can improve erectile function.

The Mediterranean Diet

Numerous news articles have lauded the effects of the Mediterranean Diet on women’s health, but what about men’s health? It turns out that men who follow the Mediterranean diet experience significant improvement of erectile function3, meaning that this diet can be used to treat ED.

The sexual performance benefits of the Mediterranean Diet are demonstrated by a group of Greeks on the island of Icaria. One-third of the residents of that island live to be over 90, and according to AARP, most Ikarians over 90 are sexually active4.

How to Eat Like an Ikarian

If this diet sounds like your dream come true, it is relatively easy to adopt. The Mediterranean Diet focuses on nuts, fish, veggies, and beans. Here are a few examples of Mediterranean Diet foods to incorporate into your diet:

  • Nuts
  • Legumes (beans, lentils, chickpeas)
  • Whole grains
  • Fruits and vegetables
  • Olive oil (instead of butter)
  • Herbs and spices (instead of salt)
  • Fish and poultry (instead of red meat)

References

1. Statistic Brain (2041). New Year’s resolution statistics. Retrieved from http://www.statisticbrain.com/new-years-resolution-statistics/

2. Diamond, D. (2013). Just 8% of people achieve their new year’s resolutions. Here’s how they do it. Retrieved from http://www.forbes.com/sites/dandiamond/2013/01/01/just-8-of-people-achieve-their-new-years-resolutions-heres-how-they-did-it/?_ga=1.31932087.82904362.1398303739

3. Esposito, K., Ciotola, M., Giugliano, F., De Sio, M., Giugliano, G., D’armiento, M. & Giugliano, D. (2006). Mediterranean diet improves erectile function in subjects with the metabolic syndrome. International Journal of Impotence Research18, 405–410. doi:10.1038/sj.ijir.3901447

4. Buettner, D. (2009). Live more good years. Retrieved from http://www.aarp.org/health/longevity/info-09-2009/more_good_years.2.html

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I Changed My Mind After a Vasectomy—Can I Still Have a Baby?

Father Kissing Baby Girl As They Lie In Bed TogetherYou may have thought you never wanted to have kids, or that you were done growing your family. You were sure of your decision—so sure that you got a vasectomy. But what if your situation has changed? What if you and your partner decide that you want to get pregnant, after all? Luckily, a vasectomy does not need to be the end of the line for your family. There are options you can pursue to make your pregnancy dream a reality.

Sperm Banking

Before your vasectomy, you may have had the opportunity to preserve a sample of your sperm. If you participate in sperm banking, your cryopreserved sperm can be used to impregnate your partner via intrauterine insemination or in vitro fertilization. Even though you’ve had a vasectomy, your genetic material is available for your use, and it can be withdrawn from your sperm bank in a timely manner so that you can begin the process.

Vasectomy Reversal

A vasectomy reversal is a surgical procedure to repair and reconnect the tubes that carry sperm from the testicles into the semen. While this is a complex procedure, the surgery is usually performed as an out-patient procedure, taking between 2 to 4 hours. Patients can return to desk work within three or four days, but they should wait about a month before engaging in sports or strenuous physical activity.

The success of vasectomy reversals is impacted by the type of procedure performed, as well as the length of time that has elapsed since the original vasectomy. Generally, pregnancy success rates after a vasectomy reversal reach over 75%1. If it’s been many years since your vasectomy, it does decrease the likelihood that a vasectomy reversal will successfully restore fertility. Generally, vasectomy reversals are more successful during the first 10 years after the original vasectomy procedure.

Sperm Retrieval

Another option is sperm retrieval. This procedure is the surgical extraction of sperm from the vas deferens, epididymis, or testicular tissue. There are several different methods for sperm retrieval. Sperm extracted through the scrotal skin called percutaneous  sperm retrieval, from an open testis biopsy, or microsurgical sperm retrieval from the epididymal tubules or vas deferens. All these methods are used in conjunction with In Vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). For patients with very poor sperm production microTESE  (microsurgical testicular sperm extraction) is an option. Unfortunately, too little sperm as well as non-moving sperm are obtained by these methods and therefore cannot be used with intrauterine insemination (IUI).

So if you’ve had a vasectomy, but you see kids in your future, you may still have a few opportunities for impregnating your partner. Check out your options. You might be surprised by just how attainable your family goal can be. For additional information please visit http://vasectomyreversalmd.com

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Testicular Self-Exam: It can save your life!

 

April is Testicular Cancer Awareness Month!

April is Testicular Cancer Awareness Month!

Testicular cancer is one of the most frequently occurring cancers in men ages 18–35, with teens as young as 15 at risk. Testicular self-exams should be a regular part of a man’s wellness routine for early detection.

Why

According to the American Cancer Society1, in the United States in 2014 there will be more cases of testicular cancer than ever:

  • about 8,820 new cases of testicular cancer will be diagnosed.
  • about 380 men will die of testicular cancer

Most of these cases (87%) will occur in young and middle-aged men most often between the ages of 15 and 35. That equals a lifetime chance of developing testicular cancer of roughly 1 in 270. While this cancer is not as common as other types of cancer, it is still a matter of concern for many men. And as with most cancers, early detection can have a significant effect on survival rates. For example, if testicular cancer is identified when it is still localized (the cancer is still only in the testicle), the survival rate is 99%. But if the cancer has a chance to spread, the survival rate is only 74%2. That is why early detection, through testicular self-exam, is so important.  The disease, is able to be found by the patient early, assuring the best prognosis.

How

testicular-cancer-selfexaminationLuckily, performing a self-exam for testicular cancer is easy….and painless!

  • When to examine: You should perform a testicular self-exam (TSE) once a month, right after a warm bath or shower. The heat from the shower or bath relaxes the skin of the scrotum, making it easier to examine the testicles.
  • How to examine: Place pads of your fingers behind testicles, with your thumbs on top of your testicle. Using slight pressure, gently roll your testicle between your fingers. Check each testicle separately.
  • What to look for: As you roll each testicle between your fingers, check for bumps or lumps along the sides or front. Lumps can range in size, from as small as a grain of rice to a size larger than a marble. Examine the entire surface of the testicle. It should feel completely smooth, without tenderness. In addition to lumps, also look for swelling, discoloration, or changes in testicle size. Note if you experience any pain or ache in your groin or lower abdomen.
  • What is normal: During your examination, you will be able to feel where your epididymis (the tube that caries sperm) connects to the testicle, at the top back part of each testicle. This is normal. You may also notice that one of your testicles is slightly larger than the other, but this is also normal.

Testicular cancer is one of the most curable kinds of cancer. Regular TSEs increase your odds of early detection and successful treatment. If you encounter any testicular irregularities (lumps, tenderness, enlargement, etc.) during a TSE, talk to your Physician immediately.

References

1. American Cancer Society. (2014). What are the key statistics about testicular cancer? Retrieved from http://www.cancer.org/cancer/testicularcancer/detailedguide/testicular-cancer-key-statistics

2. American Cancer Society. (2014). Testicular cancer survival rates. Retrieved from http://www.cancer.org/cancer/testicularcancer/detailedguide/testicular-cancer-survival-rates

3. American Cancer Society. (2014).  Testicular Self Exam

http://www.cancer.org/cancer/testicularcancer/moreinformation/doihavetesticularcancer/do-i-have-testicular-cancer-self-exam

4. National Cancer Institute. (2014). Surveillance, Epidemiology, and End Results Program

http://seer.cancer.gov/statfacts/html/testis.html

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Fertility Preservation in Children: Testicular Stem Cells

An early stage of a zygoteMany of our sperm bank patients are young men recently diagnosed with cancer. Chemotherapy and radiation therapy put these men at risk for permanent infertility as both treatments kill off sperm cells along with cancer cells. Some of these men will eventually regain the ability to produce sperm after the cessation of treatment, but many unfortunately will not. Cryopreserving sperm prior to starting treatment provides adult male cancer patients with a way to preserve their fertility and father their own biological children in the event their sperm production does not rebound after treatment.

However, not all male cancer patients are old enough to produce sperm, so sperm cryopreservation is not an option for fertility preservation.  As a matter of fact, right now there are no proven options available for pre-pubertal males to preserve their fertility, which can be very distressing for their families. Fortunately researchers are working hard to end this dilemma. They are using cutting edge stem cell technologies to develop fertility preservation options for pre-pubertal boys. Our facility, in fact, is one of only a few reproductive tissue banks in the country that has an approved research protocol that allows banking of testicular tissue from pre-pubertal boys for potential use in the future……read on.

The cells of the human body are highly specialized depending on their designated function. This means they have developed specialized structures that enable them to carry out a specific function in the organ system to which they belong. A nerve cell (neuron) has dendrites and an axon to enable it to transmit nerve impulses. A sperm cell has a flagellum (tail) and a lot of mitochondria (energy production) to enable it to move through the male and female reproductive tracts. A stem cell is a cell that has not yet undergone this process of specialization (cell differentiation). Mature sperm start out as spermatogonial stem cells (SSCs) in the basement membrane of seminiferous tubules in the testes. Men of all ages, newborn to ninety, have spermatogonial stem cells (SSCs).

Researchers are developing several techniques for generating mature sperm from spermatogonial stem cells (SSCs). This would mean that testis tissue containing SSCs could be surgically extracted from a pre-pubescent male cancer patient prior to the start of his treatment. The tissue would be cryopreserved and stored. At a later point in his life, the tissue would be thawed and the appropriate stem cell therapy would be used to generate mature sperm cells from the SSCs, thus enabling the patient to achieve a pregnancy with his partner. Our approved protocol allows us, after obtaining an informed consent from the patient and/or patient’s parents, to store testicular tissue for potential use of their own stem cells that may be present in the stored tissue.

Researchers are exploring several different methods of using spermatogonial stem cells (SSCs) to generate mature sperm. The first is to transplant the SSCs back into the testes when the patient is past puberty. “For this approach, an injection needle is simply inserted under ultrasound guidance through the scrotal skin and testicular parenchyma (working tissue) into the rete testis space”. The transplanted SSCs would regenerate spermatogenesis, producing mature sperm and restoring fertility. This method has been successfully tried on rhesus monkeys. The downside to this technique is it potentially runs the risk of reintroducing cancer cells into the patient, and testis tissue samples typically contain a very small number of SSCs.

The second method being developed by researchers involves culturing spermatogonial stem cells (SSCs) before transplanting them into the testes. Culturing means growing cells or tissue under controlled conditions in a laboratory. Culturing SSCs enables researchers to increase the number of SSCs that are transplanted. It also allows researchers to determine whether or not cancer cells are present. Further work is needed to develop the best culturing media and techniques, and to evaluate if the resulting stem cells function properly.

Rather than isolating spermatogonial stem cells (SSCs) for transplantation, some researchers are working with grafting testicular tissue under the skin of mice. The SSCs in the grafted tissue mature into sperm that can be retrieved and used in IVF/ICSI. This technique has been successfully tested using fresh testis tissue from newborn pigs, mice, and goats. Trials using cryopreserved tissue have been unsuccessful in producing mature sperm – maturation is arrested at an early stage of sperm development. Obviously this glitch needs to be addressed before testicular tissue grafting is to be a fertility preservation option for pre-pubescent male cancer patients.

Researchers have been able to generate mature sperm from testicular tissue organ culture. Testis tissue from baby mice containing only SSCs has been cultured, generating mature sperm that have been used in ICSI resulting in normal offspring. Cryopreserved and thawed tissue has been successfully cultured to produce mature sperm. Sperm generated from cryopreserved and thawed tissue however has not yet been tested to determine fertility potential (ie can it achieve pregnancy).

I know for some readers, the concept of using stem cell therapies to generate mature sperm may seem “off in the distant future”, but many in the scientific and medical communities would firmly disagree. As discussed earlier, or facility has applied for, and obtained, Institutional Review Board (IRB) approval to cryopreserve and store testis tissue from pre-pubescent male cancer patients, as our director believes that stem cell therapies will exist to enable these patients to use this tissue to father their own biological children, should the need arise.  The future is truly almost here, and the families of pre-pubertal male cancer patients should be informed of the potential fertility preserving benefit of cryopreserving and storing testis tissue prior to starting chemotherapy or radiation treatment.

References:

Valli H, Philips BT, et al. Germline stem cells: toward the regeneration of spermatogenesis. Fertil Steril, Jan 2014; 101 (1): 3-13.

Stem Cell Information, from http://stemcells.nih.gov/info/basics/Pages/Default.aspx

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New Study about the Likelihood of Fatherhood for Cancer Survivors who used Cryopreservation

Lovely family sitting together on the bedSperm production can be impacted by cancer and its treatment, permanently altering the male body’s reproductive capacity. These treatments are referred to as potentially gonadotoxic treatments. Sperm production can be impaired by both radiation and chemotherapy, and these treatments may alter the DNA of sperm that is produced. Cryopreservation is science’s answer to safeguard male fertility during cancer treatments.

Recently, researchers1 for the European Society of Human Reproduction and Embryology asked the following question:

  • How does the successful cryopreservation of semen affect the odds of post-treatment fatherhood among Hodgkin lymphoma survivors?

The researchers knew that cryopreservation of semen is the safest and easiest way to ensure that male patients facing cancer treatment can preserve their fertility. But they did not know how many patients are using this option with success.

Using a survey, the researchers polled Hodgkin’s Lymphoma survivors who were treated between 1974 and 2004. Of the 902 respondents, only 334 indicated that they desired to conceive children after treatment, while a total of 363 men opted to preserve their semen prior to treatment.  The decision to preserve semen was reportedly influenced by the patient’s age, treatment period, disease stage, treatment modality, and education level. Of the 363 who preserved their semen, only 78 men chose to use their cryopreserved semen in an attempt to convince children. 48 were successful, a 62% rate of conception using cryopreserved sperm. Many of the survivors (210 men) were able to conceive children after treatment without the aid of cryopreservation.

According to the researchers, “the availability of cryopreserved semen doubled the odds of post-treatment fatherhood.”

While the researchers focused their study on survivors of Hodgkin’s Lymphoma, these results illustrate the benefits that cryopreservation of semen can have for patients facing potentially gonadotoxic treatments for any type of cancer. If you are scheduled for treatment that may impact fertility, you can double your chances of post-treatment fatherhood by cryopreserving your sperm prior to treatment.

References

1) van der Kaaij, M.A.E., van Echten-Arends, J., Heutte, N., Meijnders, P., Abeilard-Lemoisson, E., Spina, M. & Kluin-Nelemans, J.C. (2014). Cryopreservation, semen use and the likelihood of fatherhood in male Hodgkin lymphoma survivors: an EORTC-GELA Lymphoma Group cohort study. Human Reproduction, 29(3), 525–533.

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Categories:

Bruce Gilbert

I am a Urologist/Andrologist practicing in Great Neck, New York for the past 30 years. I am also the Medical and Laboratory Director of New York Cryo, an andrology laboratory and long-term reproductive tissue bank on Long Island. Please send ideas and comments to me at bgilbert@nycryo.com

Looks Can Be Deceiving: Sperm DNA Fragmentation and Male Fertility

FecundationMany of our new male fertility patients are perplexed about their inability to conceive. They have been told that it is not a female factor and that their semen quality is excellent. Their sperm have perfectly shaped oval heads, normal-sized mid-pieces, and straight well aligned tails, and they demonstrate great motility (i.e. sperm movement) and forward progression. On visual inspection, one would assume that their sperm could fertilize an egg with ease producing a normal embryo that would develop into a beautiful baby.  Unfortunately, in spite of their good looks, their sperm may never be baby-makers. The integrity of their DNA might be impaired. Even if a sperm is able to fertilize an egg, DNA fragmentation will most likely prevent normal development of an embryo, resulting in a failed pregnancy or miscarriage.

It’s a growing concern amongst fertility specialists that sperm DNA fragmentation might be the cause of many couples’ inability to achieve a pregnancy naturally or through an assisted reproductive technology protocol using IUI, IVF, or ICSI.  Many medical practices specializing in fertility have added sperm DNA fragmentation testing to the battery of tests they typically perform to evaluate a man’s fertility potential. Our practice recently started screening male fertility patients with known association for higher levels of DNA fragmentation such as advanced male age, presence of large varicoceles, history of miscarriages. We have found greater than 40% of these men have abnormal levels of fragmentation. This has resulted in many questions from patients anxious to know what it means, how it happens, and what options are available to enable them to achieve a pregnancy. We hope to answer many of these questions here. We have provided links for those wanting additional information.

Genetic engineerring

The Nobel Prize in Physiology or Medicine 1962 was awarded jointly to Francis Harry Compton Crick, James Dewey Watson and Maurice Hugh Frederick Wilkins for their discovery of the molecular structure of DNA – the double helix shown here.

DNA is an organic molecule that consists of two strands (Double Helix) of repeating building blocks called nucleotides. Each nucleotide consists of a sugar, a phosphate group, and a nitrogen base. The nucleotides in each strand are tightly bonded. The two strands however are loosely held together by weaker bonds. DNA fragmentation occurs when separations and breaks occur in these bonds. Our chromosomes are composed primarily of DNA, and segments of that DNA form genes, whose specific sequence of nitrogen bases constitutes genetic code. DNA fragmentation can impair the transmission of this genetic code, disrupting a cell’s ability to function. For a sperm cell, DNA fragmentation can prevent fertilization or proper development of an embryo if fertilization occurs.

Scientists have identified several factors that contribute to an increase in sperm DNA fragmentation. Oxidative stress is a major cause of DNA damage. Oxidative stress is the damage caused by free radicals reacting with molecules like DNA and thus disrupting their bonds. Physical and environmental changes can increase the level of free radicals to which sperm DNA is exposed. Recent studies have linked environmental toxins in certain chemical air pollutants, pesticides, and plastics to elevated oxidative stress and sperm DNA fragmentation. Obesity, alcohol consumption, and tobacco have also been associated with DNA damage from increased oxidative stress.

Scrotal varicoceles have been shown to exacerbate sperm DNA fragmentation. Varicoceles elevate the temperature inside the testes to levels that disrupt the bonds of DNA molecules, resulting in fragmentation. Excess fat around the scrotum from being overweight will also elevate testicular temperatures to unfavorable levels that damage the DNA bonds.

Chemotherapy and radiation therapy have been linked to sperm DNA fragmentation, and further investigation is needed to determine if this is a long-term or even permanent side-effect of some cancer treatments. Reproductive aged men who have been diagnosed with cancer should be encouraged to cryopreserve sperm prior to starting treatment as a means of preserving their fertility. Post treatment fertility evaluations should include an assessment of sperm DNA fragmentation, especially since men with normal semen analyses can have high levels of sperm DNA fragmentation.

Glitches in the process of sperm maturation can cause sperm DNA fragmentation. The structure of the human sperm cell makes it more susceptible to DNA fragmentation than any other cell in the body. Its nucleus has 40% less space compared to most other cells, so sperm DNA has to be highly compacted and coiled to enable it to fit in the nucleus. This highly compacted and structured arrangement protects the sperm cell’s genetic material (DNA) as it travels through the male and female reproductive tracts, and it enables the proper fusion of DNA from both sperm and egg at fertilization. Sperm maturation is a process that transforms a round germ cell into an elongated mature sperm cell with a head, acrosome, midpiece, and a tail. During this process DNA is uncoiled, transcribed (which is the process of reading the DNA’s genetic code) and recoiled a couple of times. Intentional nicks and breaks are made in sperm DNA to enable it to be tightly compacted and recoiled. These nicks are supposed to be repaired when the DNA is being transcribed, but external factors, such as oxidative stress and advanced paternal age, often prevent this and hence result in sperm DNA fragmentation.

Sertoli cells which function to support and nourish developing sperm cells in the testes also screen sperm cells and mark defective ones for elimination. Sometimes external factors disrupt this process and marked sperm cells are not eliminated, or apoptosis (cell death) is initiated but not completed. These sperm cells have a much higher incidence of DNA fragmentation.

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Sperm with normal DNA fluoresces green and can be quantified with a flow cytometer which can identify these sperm and count the number of them present

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Sperm with fragmented DNA fluoresces orange and can be counted with a flow cytometer which can identify these sperm and count the number of them present

Sperm DNA fragmentation can occur during the movement of sperm from the seminiferous tubules through the vas deferens, an event that allows immature and mature sperm to be tightly packed together.  Immature sperm produce a high level of reactive oxygen species (a type of free radical), which often react with and damage the DNA of mature sperm.  Reactive oxygen species also activate enzymes called caspases and endonucleases that are part of the process of apoptosis, further damaging sperm DNA. This is the primary reason that sperm retrieved from the testes has less DNA damage than sperm from ejaculate.

If you are reading this blog because your doctor has recommended you be tested for sperm DNA fragmentation or you recently had testing that indicated a high level of DNA damage, your situation is not hopeless. For many men, simple lifestyle changes can improve sperm DNA fragmentation. Weight loss, healthy diet, cessation of smoking, reduced consumption of alcohol, and antioxidants have all been shown to improve DNA integrity. For older men, who typically experience DNA damage because the mechanisms of sperm maturation function less efficiently, and men who have undergone treatment for cancer, it may not be possible to reduce sperm DNA damage. However, sperm can be surgically retrieved from the testis and used in IVF/ICSI, as the incidence of DNA fragmentation is usually much lower in sperm from the testes than from ejaculate.

References:

 Sakkas D, Alvarez J. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril, Mar 2010; 90(4): 1027-1036.

Ribas-Maynou J, Garcia-Peiro A, et al. Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral Comet assay. Andrology, 2013; 1: 715-722.

Erenpreiss J, Spano M, et al. Sperm chromatin structure and male fertility: biological and clinical aspects. Asian J Androl, 2006; 8(1): 11-29.

Agarwal A, Said T. Sperm chromatin assessment. From http://www.clevelandclinic.org/reproductiveresearchcenter/docs/agrach016.pdf

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