The International Council on Infertility Information Dissemination, Inc

Aytu BioScience Demonstrates Expanded Clinical Utility of MiOXSYS™ for Assessing Oxidative Stress as a Marker for Male Infertility with New Study

ENGLEWOOD, Colo., May 10, 2016 /PRNewswire/ -- Aytu BioScience, Inc. (OTCQX: AYTU), a specialty pharmaceutical company focused on global commercialization of novel products in the field of urology, today announced new clinical findings that further validate and expand the potential utility of its MiOXSYS System as an advanced tool for assessing oxidative stress in human semen, which is broadly implicated as a major cause of male infertility. The results demonstrate that the level of oxidative stress reported by MiOXSYS from semen samples that had been frozen and thawed did not differ significantly from readings taken before freezing. This is significant, as it eliminates the need for fresh sampling and enables MiOXSYS to be used by regional or national reference laboratories that can receive and store shipped frozen samples, in addition to rapid, on-site testing by local urologists' offices, hospital, and fertility clinical laboratories.

The poster, titled, "Validation of oxidation-reduction potential in fresh and frozen semen samples with MiOXSYS™ System," was presented yesterday by the study's principal investigator, Ashok Agarwal, Ph.D., Director of the Glickman Urological & Kidney Institute's Andrology Center at Cleveland Clinic and Director of the American Center for Reproductive Medicine, at the 111th American Urological Society Annual Meeting in San Diego, CA.

Josh Disbrow, Chief Executive Officer of Aytu BioScience, stated, "These latest clinical findings add robustness to our MiOXSYS System, which we've already demonstrated to be a uniquely dynamic tool for assessing oxidative stress levels in semen as it relates to male infertility, offering substantial clinical benefit beyond the complicated and highly time-sensitive methods used today.  Being able to use MiOXSYS to analyze frozen then thawed semen samples is another key differentiator for our product that further reduces the burden and increases efficiency for routine oxidative stress testing. It also enables Aytu to potentially engage with large laboratory networks to offer MiOXSYS testing through their current frozen sample collection channels. As we continue to pursue FDA clearance of MiOXSYS in the U.S. by conducting larger, multicenter studies, these commercial implications may add significantly greater value to the product upon potential launch."

In the study, semen samples were collected from 20 healthy normospermic men and oxidative stress was induced using varying concentrations of cumene hydroperoxide (CH). Using MiOXSYS, the differences in oxidative stress readings between pre-freeze and post-thaw samples were not significant, either for controls or samples exposed to CH, indicating that MiOXSYS can measure real-time oxidative stress levels accurately in both fresh and frozen semen samples. Furthermore, MiOXSYS was sensitive enough to detect CH-induced changes when compared with control (Mean ± standard error of mean) in oxidative stress as measured by static ORP (millivolts (mV)/106 sperm/mL) both prior to freezing (0.52 + 0.24; 95 % confidence interval (0.03, 1.01); p=0.04) and after post-thaw change (0.75 + 0.31; 95 % confidence interval (0.10, 1.39); p=.025), as an indicator of strong test performance under both conditions. There was also a dose-dependent decrease in sperm motility in samples upon exposure to CH, confirming a decline in sperm quality as a result of oxidative stress. 

The MiOXSYS System received CE Marking in the European Union in January 2016 and approval from Health Canada in March 2016, and it is currently being commercialized in Europe and the Middle East. Aytu has established and will continue to seek additional partnerships with prominent hospitals, academic centers, and other early MiOXSYS users in order to develop these markets.

About Aytu BioScience, Inc. 
Aytu BioScience is a commercial-stage specialty pharmaceutical company focused on global commercialization of novel products in the field of urology. The company currently markets two products: ProstaScint® (capromab pendetide), the only FDA-approved imaging agent specific to prostate cancer, and Primsol® (trimethoprim hydrochloride), the only FDA-approved trimethoprim-only oral solution for urinary tract infections. Aytu recently acquired exclusive U.S. rights to Natesto®, the first and only FDA-approved nasal formulation of testosterone for men with hypogonadism (low testosterone, or "Low T"), which the company plans to launch in July 2016. Additionally, Aytu is developing MiOXSYS™, a novel, rapid semen analysis system with the potential to become a standard of care for the diagnosis and management of male infertility caused by oxidative stress. MiOXSYS is commercialized outside the U.S. where it is a CE Marked, Health Canada cleared product, and Aytu is conducting U.S.-based clinical trials in pursuit of 510k de novo medical device clearance by the FDA. Aytu's strategy is to continue building its portfolio of revenue-generating urology products, leveraging its focused commercial team and expertise to build leading brands within well-established markets.

Investors & Media: 
Tiberend Strategic Advisors, Inc. 
Joshua Drumm, Ph.D.: jdrumm@tiberend.com; (212) 375-2664  
Janine McCargo: jmccargo@tiberend.com; (646) 604-5150

Forward Looking Statement 
This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, or the Exchange Act. All statements other than statements of historical facts contained in this presentation, including statements regarding our anticipated future clinical and regulatory events, future financial position, business strategy and plans and objectives of management for future operations, are forward-looking statements. Forward looking statements are generally written in the future tense and/or are preceded by words such as "may," "will," "should," "forecast," "could," "expect," "suggest," "believe," "estimate," "continue," "anticipate," "intend," "plan," or similar words, or the negatives of such terms or other variations on such terms or comparable terminology. These statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: risks related to our planned launch and commercialization of Natesto and the integration of Natesto into our existing operations; our plans for product growth, expansion and acquisition; the anticipated start dates, durations and completion dates, as well as the potential future results, of our ongoing and future clinical trials; risks relating to gaining market acceptance of our products; obtaining reimbursement by third-party payors; the potential future commercialization of our product candidates; the anticipated designs of our future clinical trials; anticipated future regulatory submissions and events; our anticipated future cash position; and future events under our current and potential future collaborations. We also refer you to the risks described in "Risk Factors" in Part I, Item 1A of Aytu BioScience, Inc.'s Annual Report on Form 10-K and in the other reports and documents we file with the Securities and Exchange Commission from time to time.

 

SOURCE Aytu BioScience, Inc.

Changes in Fertility after Exposure of Sperm to Exogenous PAF

By Julia Robison, Slee Yi, and William E. Roudebush
PAF Audio File
 

In order to understand the concept of male fertility, a basic understanding of two processes is required. Sperm must undergo a series of steps toward maturation. The next to last step in this series is called capacitation. This typically occurs in the female’s uterus after the sperm has been ejaculated, and prepares sperm for binding with the female egg.1 Once sperm reaches the egg, it must then be able to penetrate its outer membrane – the zona pellucida2 The acrosome (a structure found around the head of the sperm) releases enzymes that break down the zona pellucida and facilitate penetration.1 This process is called the acrosome reaction. In males, fertility requires that an appropriate number of normal sperm be produced, and that these sperm be capable of undergoing both capacitation and the acrosome reaction in order to fertilize the egg and produce a pregnancy.2 Additionally, sperm motility has been identified as a principal factor in sperm function and potential for achieving fertilization.3 Infertility can result from a number of different abnormalities. However, abnormalities occurring in sperm can prevent either or both of the processes afore mentioned.

A number of endogenous factors have been attributed to regulate the fertility potential and motility of the spermatozoa, for example platelet-activating factor. Platelet-activating factor (PAF) is a unique and novel signaling phospholipid that has many different and varying biological properties in addition to platelet activation. Since its discovery in the early 1970's this novel compound has been implicated in a variety of reproductive functions including fertilization, implantation and parturition.4,5

Platelet Activating Factor

Platelet-activating factor, or PAF, is a phospholipid. In other words, it is a molecule that has a fat component and a phosphate group and makes up cell membranes. PAF was discovered around 30 years ago; it is found in many mammalian species, including in humans. This phospholipid is present in many cell types and has been shown to have a diversity of effects in addition to platelet activation.2 The name of PAF is a misleading because it causes people to associate the molecule with blood platelets. In reality, it was first observed in platelets and that is where its name comes from. PAF is of  great interest in the study of reproduction due to its important effects on fertility and pregnancy, and more specifically, its effects on sperm in respect to motility, capacitation, and the acrosome reaction. One of the places in which PAF is produced is human sperm. Although its exact mechanism of action is yet unclear, PAF is shown to positively correlate with sperm motility and ability to fertilize the female egg.2

Studies indicate that sperm contain PAF receptors in their membrane.  The distribution of these receptors throughout the sperm membrane is not uniform, and different binding sites are shown to produce different results.6 For instance, binding of PAF to receptors at the sperm cell’s midpiece will increase motility. The binding of PAF to its receptor at yet another location results in an increase of intracellular levels of calcium, triggering the acrosome reaction.7 It is further understood that PAF receptors can equally bind to PAF antagonists. When PAF successfully binds to its midpiece receptor, it increases sperm motility. Conversely, when PAF antagonists bind to these receptors, preventing PAF itself from binding, sperm motility is negatively affected. The suggestion that sperm have PAF receptors allows for the assumption that a receptor-related type of subfertility or infertility exists when receptors are abnormally distributed or absent.2 PAF and its interactions with sperm membrane receptors are worthy of review and further research.  This leads us to the hypothesis that adding exogenous/synthetic/artificial PAF to sperm sample will improve sperm function, resulting in higher pregnancy rates.

Exogenous exposure to PAF

Sperm can be treated with exogenous PAF for improved outcomes in intrauterine insemination (IUI) as well as in-vitro fertilization (IVF).  Wild and Roudebush conducted the original PAF-IUI study comparing 60 men with normal semen specimens, who were preparing to undergo IUI. Half of the men had their semen exposed to PAF for 15 minutes while the other half was not exposed. The PAF-exposed group exhibited a 46.7% pregnancy rate compared with the unexposed group, which had only a 16.7% pregnancy rate.8  Sperm treatments with PAF have produced similar results in other studies.9,10 Treatment with exogenous PAF causes sperm motility to rise, thus improving the quality of the sperm.  However, it is important to note that PAF treatment is shown to improve the performance of normal, motile sperm only.11,12 As explained above, PAF must bind to receptors on the sperm membrane in order to produce effects. Those sperm that have defective receptors will not respond to PAF treatment. This eliminates the concern that abnormal sperm cells might penetrate the egg as a result of PAF-induced motility.  Although the PAF treatment of sperm has been used and shown to be successful in human IUI procedures, there is a great potential for the use of this treatment in human IVF procedures. PAF treatment in IVF procedures has been studied in animals, where success was noted and even the quality of the embryos was improved.13,14

 

 

Summary

PAF plays an important role in human reproduction. It is produced in human sperm and acts on sperm cell membranes, causing several effects. One of the major effects is the marked increase in sperm motility. Treatment of sperm with exogenous PAF is shown to increase success rates of IUI procedures. There is great potential for the use of PAF treatment in IVF. Further research should be conducted in order to explore the potential use of PAF in other clinical applications including IVF.

INCIID gratefully thanks and acknowledges the:

1University of South Carolina School of Medicine Greenville, 2Fertility Center of the Carolinas, and

Department of Obstetrics & Gynecology, Greenville Health System, Greenville, South Carolina

 

 

 

References

  1. Davis BK. Timing of fertilization in mammals: Sperm cholesterol/phospholipid radio as a determinant of the capacitation interval. PNAS(USA) 1981;78:7560-7564.
  2. Roudebush WE. Seminal platelet-activating factor. Sem Thromb Hemost 2007;33:69-74.
  3. Roudebush WE, Purnell ET. Platelet-activating factor content in human spermatozoa and pregnancy outcome. Fertil Steril 2000;74:257-260.
  4. Harper MJK. Platelet activating factor: a paracrine factor in 
preimplantation stages of development. Biol Reprod 1989;40: 907–913
  5. Roudebush WE, Diehl JR. Platelet-activating factor content in boar spermatozoa correlates with fertility. Therio 2001;55:1633–1638.
  6. Sathananthan AH, Ratnam SS, Ng SC, et al. The sperm centriole: Its inheritance, replication and perpetuation in early human embryos. Hum Reprod 1996;11:345-356.
  7. Benoff N. Modeling human-sperm interactions in vitro: Signal transduction pathways regulating the acrosome reaction. Mol Hum Reprod 1998;4:453-471.
  8. Wild MD, Roudebush WE. Platelet-activating factor improves intrauterine insemination success. Amer J Obstet Gynecol 2001;184:1064-1065.
  9. Roudebush WE, Massey JB, Toledo AA, et al. Platelet-activating factor significantly enhances intrauterine insemination pregnancy rates. Fertil Steril 2004;82:52-56.
  10. Grigoriou O, Makrais E, Konidaris S, et al. Effect of sperm treatment with exogenous platelet-activating factor on the outcome of intrauterine insemination. Fertil Steril 2005;83: 618-621
  11. Stavroula B, Odysseas G, Dimitris H, et al. Treatment of sperm with platelet-activating factor does not improve intrauterine insemination outcomes in unselected cases of mild male factor infertility: A prospective double-blind randomized crossover study. Urology 2009;74:1025-1028.
  12. Wang R, Sikka SC, Veeraragavan K. Platelet activating factor and pentoxifylline as human sperm cryoprotectants. Fertil Steril 1993;56:768-770.
  13.  Roudebush WE, Minhas BS, Ricker DD, Palmer TV, Dodson /SN>MG. Platelet activating factor enhances in vitro fertilization of rabbit oocytes. Am J Obstet Gynecol 1990;163:1670–1673
  14. Roudebush WE, Fukuda AI, Minhas BS. Enhanced embryo development of rabbit oocytes fertilized in vitro with platelet- activating factor (PAF) treated sperm. J Assist Reprod Genet 1993;10:91–94

 

 

Additional Resources

Briton-Jones C, Yeung QS, Tjer GC. The effects of follicular fluid and platelet-activating factor on motion characteristics of poor-quality cryopreserved human sperm. J Assisted Reprod Genet 2001;183:165-170.

Stavroula B, Odysseas G, Dimitris H, et al. Treatment of sperm with platelet-activating factor does not improve intrauterine insemination outcomes in unselected cases of mild male factor infertility: A prospective double-blind randomized crossover study. Urology 2009;74:1025-1028.

Roudebush WE, Fukuda AI, Minhas BS. Enhanced embryo development of rabbit oocytes fertilized in vitro with platelet-activating factor (PAF) treated spermatozoa. J Assisted Reprod Genet 1993;10:91-94.

Sengoku K, Ishikawa M, Tamate K, et al. Effects of platelet activating factor on mouse sperm function. J Assisted Reprod Genet 1992;9:447-453.

Zhu J, Massey M, Mitchell-Leef D, et al. Platelet-activating factor acetylhydrolase activity affects sperm motility and serves as a decapacitation factor. Fertil Steril 2006;85:391-394.

Jarvey K, Langlais J, Gagnon C. Platelet-activating factor acetylhydrolase in the male reproductive tract: Origin and properties. Internat J Androl 1993;16:121-127.

Hellstrom WJG, Wang R, Sikka SC. Platelet-activating factor stimulates motion parameters of cryopreserved human sperm. Fertil Steril 1991;56:768-770.

 

Infertility Humor

If you've been going through treatment for a long time - have you ever felt like this?

 

 

What do men, directions and infertility have in common?

 

Have a cartoon, joke or other bits of humor that will make us laugh?  Send it our way!

Micromanipulation techniques offer new hope for couples with male factor infertility By Marc Goldstein, M.D., Zev Rosenwaks, M.D., and Linda F. Davey

    
A tiny pipette is used to inject a single sperm into the awaiting egg in the revolutionary new procedure: Intracytoplasmic Sperm Injection

In any field of medical research, success is often measured in minute degrees, the impact of which may only be known to those whose careers are spent in the laboratories. Occasionally, however, there comes a discovery so astounding that it revolutionizes medical procedure. Such is the case with Intracytoplasmic Sperm Injection, or ICSI, a new infertility treatment utilizing micromanipulation technology that specifically addresses male factor infertility issues. ICSI is so remarkable, in fact, that most treatments previously used have been abandoned in its favor.

 

MALE FACTOR INFERTILITY - A DEFINITION

Male factor infertility can include any of the following problems: low sperm counts, poor motility or movement of the sperm, poor sperm quality, or sperm that lack the ability to penetrate an egg.

 

MICROMANIPULATION TECHNIQUES - AN OVERVIEW

The first process used to address the problems of male factor infertility was called Partial Zona Dissection (PZD). Using PZD, the zona pellucida, or shell, surrounding a woman's egg was opened, using either chemical dissolution or a sharp instrument to file through the shell. This process, while certainly a step forward in the relatively new field of micromanipulation, was considered rather passive because even with the zona opened there was no guarantee the sperm would enter and fertilize the egg. With PZD, frequently too many sperm would enter the egg causing genetic abnormalities and arrested development of the zygote. With any of those problems, a couple was not helped to achieve pregnancy through the PZD process.
    
This Metaphase II Oocyte has extruded its first polar body and displays a sunburst array of cumulus-corona cells. The cumulus cells must be removed before the ICSI procedure can take place.

 

A logical next step was a process called Sub-Zonal Insertion (SUZI), which was similar to PZD, but more aggressive. With SUZI, once the shell was punctured the sperm was then injected into the area between the zona and the egg, rather than left to find its own way. The sperm still had to enter the egg, but its chances were greatly increased with this specific placement. This process dramatically increased the success rate of in vitro fertilization (IVF), and could partially overcome poor motility and low sperm count. However, polyspermy (more than one sperm entering egg) was still a problem. It was still not possible to control the number of sperm entering the egg with the SUZI process. Few could have imagined how dramatically the ICSI process would change all that.

 

ICSI - WHAT IS IT?

While at a clinic in Belgium, Gianpiero D. Palermo, M.D., currently assistant professor of embryology, the Center for Reproductive Medicine & Infertility, The New York Hospital-Cornell Medical Center, pioneered the ICSI process.
When a single sperm was injected directly into the egg, it virtually eliminated the problems and limitations found with previous treatments. Palermo and others studying ICSI found that not only did it address the issues of poor sperm motility and low count, but it was also successful with sperm that were considered less than ideal for an IVF process. In addition to normal sperm, with the ICSI process, Dr. Palermo has successfully used round-headed sperm, those collected directly from the epididymis and those previously cryopreserved.

 

ICSI - HOW IS IT DONE?

The ICSI process takes place following a cycle during which fertility drugs are administered to the female partner to aid in the production of multiple eggs. The eggs are then surgically removed. In normal circumstances, the egg is surrounded by a cluster of cells known as the cumulus-corona cells, all of which must be removed before the sperm injection takes place. If cumulus were not removed, it could create a shadow that may impair viewing and jeopardize the injection. This removal also allows the embryologist to assess the maturity of the egg. Sperm is collected from the male partner, usually through masturbation.

Once eggs and sperm are collected, the actual process of injecting a single sperm into the egg is carried out in a laboratory using a petri dish or a glass slide with a well in the center. Though some tools used in the injection process are available commercially most embryologists prefer to make their own. Quality tools are essential to the overall success of an ICSI program. A glass holding pipette 40-50 microns in diameter is used to secure the egg, usually on the left side. An injection needle with an outer diameter of roughly five to six microns and an inner diameter of three to four microns, is used to pierce the egg membrane on the right side at about 3:00 o'clock. The injection needle has an extremely sharp or beveled end, one that will most easily pierce the egg membrane. For embryologists using a glass slide, the arm of the injecting needle can be straight or only slightly bent at the end. For those using a petri dish, the arm of the needle must be angled about 40 degrees to ensure manipulation can occur without interference from the lip or side of the petri dish.

Active sperm are chosen and placed in a drop of polyvinyl pyrrolidone solution, or PVP. This solution is dropped onto a viscous medium such as mineral oil and is used to slow down the activity of the sperm and also serves as a cleanser. It is necessary that active sperm be slowed so they may be properly viewed and so they are not damaged once drawn into the injecting needle. Though active sperm are chosen prior to being placed in the PVP, once in the solution, the sperm with the least amount of activity are the best candidates for injection. In fact, those that stick to the bottom of the well by their heads are often the best choices. The reason for this choice is that an actively moving sperm tail can whip around inside an egg and cause damage or even destroy it. In fact, before putting the sperm in the egg, the tail is pinched to immobilize it.

As with the selection of tools, the method used to stage the process is a matter of preference of the embryologist or technician. Commonly, the sperm are placed in a drop in the middle of the dish or slide, then surrounded by eggs that have also been placed in a viscous medium. In some cases, only one egg is placed in a droplet around the sperm in order to preserve their individuality , or some technicians prefer all sperm in one drop and all eggs in another. Both methods have been used successfully.

Once the egg is secured by the holding pipette, it takes less than 60 seconds for the sperm to be injected directly into the center of the egg. There are many factors that must be mastered to ensure success of the ICSI process, chief among them is successful penetration of the egg membrane, ensuring the sperm is not redrawn back into the pipette upon removal from the egg, and guarding against injecting too much medium into the egg along with the sperm. The skill of the technician is a critical factor in the success of the ICSI process. Remarkably, once the injecting pipette is withdrawn, the egg will close and assume its original shape within 60 seconds.

Once the egg is injected with a single sperm, it is observed approximately 14 hours later to see if fertilization has taken place, and 24 hours later to ensure that the egg has cleaved. In some cases, assisted hatching, or removal of anucleated fragments located between the cell divisions, is performed to ensure proper cleavage. If each step has occurred as planned, implantation of the fertilized egg into the female patient can occur within 72 hours of the ICSI process. In most cases, the number of embryos implanted into the patient depends upon her age. The following chart indicates a usual number.

 

ICSI - WHAT'S IN THE FUTURE

The future for the ICSI process is very promising. Researchers expect that the current fertilization rate of 65 percent will continue to improve. As stated previously, sperm selection for the ICSI process focuses on available motile sperm, but it is only a matter of time until the ability to select living, but non-motile sperm will help up the odds even more for couples seeking to have a baby. Currently, results are poor with sperm that don't move as it is not known whether they are alive or dead The staining method currently used for determining whether non-motile sperm are dead or alive kills living sperm. In the future, a technique will be developed which will help determine which sperm are alive and viable for the ICSI process without killing them with the stain.

Another exciting breakthrough in the field of male factor infertility and micromanipulation is a process called Round Spermatid Nucleus Injection or ROSNI that specifically targets men who are not manufacturing sperm and have zero sperm counts. The ROSNI process involves taking immature cells (round spermatids) directly from the testicle, removing the nucleus containing the genetic material and injecting the nucleus into the female partner's eggs, which are removed during an in vitro fertilization cycle. While this process has yet to produce a live birth, researchers believe it will eventually become a successful technique that will allow men who previous had no hope, to father a biological child.

Clearly, there continues to be much hope and promising news for couples facing infertility.

 

Dr. Marc Goldstein is a professor of urology and director, Male Reproduction and Microsurgery, and Dr. Zev Rosenwaks is a professor of obstetrics and director of the Center for Reproductive Medicine and Infertility. Both are at The New York Hospital-Cornell Medical Center. Linda Davey was an INCIID cofounder and holds a journalism degree from North Texas State University.

Donor Insemination: Sperm Banks Offer Many Choices by Brent Hazelrigg

Donor Insemination: Sperm Banks Offer Many Choices 
by Brent Hazelrigg

 

"A couple has been trying to conceive a pregnancy for a longtime. Their doctor recommends testing on both the woman and the man. A semen analysis reveals a low sperm count. Treatment options include using donor sperm with intrauterine insemination (IUI)."

"A woman has yet to find Mr. Right and feels the biological clock ticking. One choice is to consider having a child on her own, using donor sperm."

Couples and individuals facing reproductive choices have exciting options available to them today. Just a few decades ago, if a patient needed donor sperm their physician made all the choices for them and had little information to share about the donor. Now the world of selecting a donor has been revolutionized. Couples can choose a donor based on not only physical and medical attributes, but audio interviews, personality profiles, essays, advanced degrees, and childhood photos. Someone would know more about the donor they select then they do about their own spouse.

 

What to expect from a Sperm Bank

  • Extensive medical screening of the donors should be standard. Only three percent of the donors who apply are actually accepted into the program at the Fairfax Cryobank. This makes this sperm bank three times harder to get into than Harvard. Prospective donors must pass rigorous standards for the semen analysis, family history, medical history, infectious disease testing, and genetic testing and evaluation. Not all sperm banks test to the same level---compare which tests are done by each sperm bank. Couples have told us that the most important factor in making a selection of which sperm bank to use is the level of testing performed on the donor. Infectious disease testing is the most critical to these couples. How a test is done can be different between sperm banks, as well. For example a test which detects infectious agents by PCR (by finding the genetic copy of the virus in the cells) is the most accurate type of detection. This is cutting edge technology and should be what you look for in donor testing.
  • All specimens must be quarantined to allow adequate testing for HIV and other infectious agents.
  • A guarantee on specimen quality should be provided. When the sample arrives and is thawed by the doctor's office, a minimum standard is assured.
  • There should be a large selection of donors with wide variability of characteristics and traits. Physical traits, educational backgrounds including doctorate degrees, ethnic background, profession, and hobbies are examples of information available on donors. On line search engine registries help the prospective patient find a match. You can narrow down your search by using the most important selection criteria for you. On line access to information makes the process easy for individuals to use in the privacy of their own home.
  • Information beyond the basics. Personality profiles, audio interviews (Sample audio clip MP3 format) essays written by the donors themselves, childhood photos and extensive medical and personal profiles provide even more details.
  • Exceptional customer service to help with the final selection. There should be someone to answer your unique questions and help you through the process. Is there a person you want the donor to look like? (consider photo matching) Do you want to have more than one child with the same donor? Do you want to find a compatible donor to your personality type? (take the test yourself at www.keirsey.com and see who is compatible with you-it's fun) You just want to talk about the process with someone who knows.

 

Once you've made a choice and are ready to move ahead---what next? 

You must have a physician working with you that feels comfortable accepting the frozen semen sample in his office, thawing and processing the sample as required and performing the intrauterine insemination (IUI). In an IUI, this specially prepared semen sample is gently placed in the uterus using a catheter carefully maneuvered through the cervix.

An IUI should be preformed at the optimal time for conception to occur, at ovulation. The exact time of ovulation can be predicted by certain hormonal changes that can be monitored by laboratory tests and/or home ovulation predictor kits. Additional ultrasound monitoring of the ovary can identify when to expect the egg(s) to rupture (ovulate) from the follicle(s). Women who plan to use IUI can potentially enhance the number of eggs expected at ovulation from the normal number of one up to three or four. Medications such as clomid are used for this purpose.

The likelihood that a pregnancy will result from one IUI cycle is usually about 15-20%. Even with fertile couples the chance of pregnancy in any one cycle is about the same. Yet factors such as age of the woman and other health issues can dramatically effect the chance of pregnancy. The likelihood of pregnancy with IUI for any one couple is best discussed with their own physician who knows their history the best.

 

Is donor insemination right for you? 

Only you can know for sure. Natural conception is not always able to provide children to those who very much want them. Hence, using technology to assist in the process becomes a consideration. IUI with donor sperm is one of those options. Feeling comfortable with your choice in sperm banks and ultimately the donor you have selected to become the biological father of your child is critically important. It can take time and some emotional reserves to make these important decisions. Only the couple or individuals themselves can make those choices.

 

Editor's note: Brent Hazelrigg, M.S., is the Program Director/COO of Fairfax Cryobank. He holds Master of Science degree in reproductive biology, and has more than 15 years experience in sperm and embryo cryobiology.

ICSI and SCSA Sperm Diagnostics by Donald P Evenson, Ph.D., HCLD and Kjersten Larson-Cook, Ph.D.

ICSI and SCSA Sperm Diagnositics 
by Donald P. Evenson, Ph.D., HCLD 
and Kjersten Larson-Cook, Ph.D.

 

Amy and Todd have been trying to conceive for 2 years. Initially, when they decided to start a family, Todd was certain they would become pregnant very quickly. In his previous marriage, Todd had conceived each of his two children, now 20 and 22 years old, within 3 months. However, on Amy's 35th birthday, the couple realized they could no longer explain away their problem and decided to consult a fertility specialist.

Even with Todd's previous fertility, their physician informed them that Todd should have a semen analysis. Todd questioned if this was necessary remembering a physician saying "Men just get better with age, like a fine wine." But, not wanting to seem uncooperative, Todd made an appointment for his semen analysis, which measures the concentration, motility and morphology (shape) of his sperm. He was not worried but was pleased to learn that, as a 55 year old man, his results came back completely normal.

Meanwhile, Amy's test results also were normal. It seemed that there was no identifiable cause for their struggle with infertility. This made the situation more complicated. If there was some identifiable cause like Todd's sperm count being extremely low, or Amy's fallopian tubes being blocked, it seemed it would have been easier to determine the appropriate treatment. Without a known cause, Todd and Amy were diagnosed as having idiopathic infertility. They felt more frustrated than ever in their failure to conceive.

Due to the length of their infertility and Amy's advancing age, their physician recommended that the couple begin in vitro fertilization. Their physician explained that as a general protocol Amy's eggs would be fertilized using a technique called intracytoplasmic sperm injection (ICSI), where individual sperm from Todd would be injected into each of Amy's eggs. Todd questioned the use of this technique since he believed that it only was used in cases where men had severe and irreversible sperm problems. However, the doctor explained they used this technique to increase fertilization rates and the odds that there would be high quality embryos to transfer to Amy.

The couple proceeded though one ICSI cycle. They were optimistic learning that all of Amy's 20 eggs had fertilized normally, and that the embryos were developing beautifully. The embryos were allowed to mature in culture media for 3 days at which time 4 were transferred to Amy's uterus. The couple waited anxiously to take a pregnancy test but were devastated to find that Amy had a negative BhCG. What happened? Everything seemed perfect at the time of transfer. The couple continued through 2 frozen embryo transfers - and still no pregnancies.

Amy and Todd were frustrated and saddened by their experience, but wished to try again. Their physician recommended that in this ICSI cycle they should culture the embryos for 5 days before transferring them to Amy. In this way, she said they would be more able to identify the embryos that were most healthy and would have the best chance to implant and develop into a healthy baby. Ten eggs were harvested and again all fertilized beautifully and developed nicely through day 3. Yet, on day 4, many of the embryos were beginning to show signs of abnormal development and by day 5 only 2 embryos of poor quality remained viable for transfer. Todd and Amy again faced a negative BhCG.

 

What was happening?

Why had everything looked so promising and without explanation seemingly crashed at Day 4 of embryo development?
ICSI bypasses all requirements of normal sperm motility and sperm/oocyte oolemma interaction. The only requirement for fertilization and early embryonic development is oocyte activation and adequate DNA integrity. Surprising to many, the male genome (sperm DNA) is silent in the first 3 days of embryo development. The oocyte drives the development and cleavage of the early embryo. On Day 4, a critical switch occurs, and the male genome is turned on. At this time, the maternal and paternal genomes begin to work in concert to orchestrate the activities of the newly developing embryo.

It is at this time - Day 4 - when abnormalities in the paternal genome may begin to have what can be profoundly devastating effects on embryo development. Therefore, using sperm with abnormal DNA for ICSI may lead to normal fertilization and early embryo development yet be followed by embryo death expressed as a failure to implant (no chemical pregnancy) or early pregnancy loss (prior to an ultrasound-confirmed heartbeat.)

Abnormalities in the paternal genome (sperm DNA) are weakly related to sperm concentration, motility, and morphology. Therefore, men like Todd with excellent sperm quality may still harbor sperm with poor DNA quality that contribute to infertility. Thus, a test of DNA integrity is very helpful in deciding which couple would most likely benefit from ICSI and which couple would be at greater risk for failed cycles. Table I lists conditions when DNA fragmentation testing could potentially benefit a couple.

An international consensus group stated that "practical and reliable tests to detect damaged DNA in sperm are needed in order to optimize adverse developmental defects in the embryos." Furthermore, this group agreed that "the remarkable consistency of the methodology makes the SCSA® [sperm chromatin structure assay] an ideal technique to detect sperm cell damage" and "that the SCSA® is a good predictor, relative to other sperm measures, for clinical diagnosis of male infertility."

SCSA® Diagnostics, Inc.'s team of scientists invented and patented the Sperm Chromatin Structure Assay (SCSA®) test and has over 30 years of experience studying how disease, environmental toxicants and age affect chromatin (DNA and protein) structure and function. These studies have included researchers from around the world and resulted in over 125 peer-reviewed journal articles. During that time, the ability of the SCSA® test to identify men at risk for infertility has been validated and is now offered by SCSA® Diagnostics, Inc. to physicians and patients around the world.

The SCSA® test measures the percent of sperm in a semen sample that has fragmented DNA as well as the extent of that DNA fragmentation. In the SCSA® test, sperm with very low levels of fragmentation fluoresce green, while sperm with moderate to high levels of fragmentation fluoresce red. A flow cytometer measures the ratio of red to green fluorescence in each of 5000 sperm. The percent of sperm with DNA fragmentation (red fluorescence) is expressed as the DNA Fragmentation Index (DFI).
The SCSA® test is practical for clinical evaluations of sperm DNA quality due to the speed of analysis and the consistency of results. The clinical report includes two SCSA® test measurements of the same ejaculate to ensure accuracy. Typically, these two measurements yield nearly identical results. SCSA® test results also are extremely consistent among samples collected from an individual man over time. Indeed, the SCSA® test provides much greater consistency both within a single sample and between samples collected over time than is provided by standard measures of semen quality such as concentration, motility and morphology. This highly accurate SCSA® test analysis and Clinical Report can be completed and made available to physicians and patients located across the country within a week. In addition to the speed and reliability of the SCSA® test, the large numbers of sperm that are evaluated make the test statistically robust, providing consistent evidence for the relationship between sperm DNA fragmentation and function. The first large scale human fertility study using the SCSA® test identified sperm DNA Fragmentation Index (DFI) thresholds of 0-15%, 16-29%, ?30% that related to high, moderate and very low natural fertility potential, respectively. Specifically, if ?30% of the sperm in a sample had SCSA®-detected DNA fragmentation, the risk for infertility was significantly higher.

A pilot study including 27 men showed that the percentage of sperm with DNA damage was significantly greater in men with no pregnancy (31.1 % DFI ? 3.2) than in men that initiated pregnancy following IVF or ICSI (15.4 % DFI ? 4.6). In addition, the study identified a DFI threshold (?27%) for infertility following IVF and ICSI indicating the potential value of the SCSA® test in predicting negative ART outcomes (Larson et al., 2000). Larger studies including hundreds of infertile couples have validated that ?30% DFI places men at a significantly greater risk for infertility. Although this risk is influenced by a myriad of potential sources (age of maternal partner, clinical techniques etc.), exceeding this DFI threshold appears to decrease pregnancy rates by 50% or more.

Therefore, exceeding the 30% DFI threshold is telling of problems within the entire sperm population. Otherwise, the other 70% of the sperm in the population without elevated levels of DNA fragmentation would support normal pregnancies. As a possible explanation, Dr. Evenson, innovator and developer of the SCSA® test, describes the "tip of the iceberg" phenomenon. When the physical stress of the SCSA® test is enough to draw out and detect 30% of the sperm as abnormal, the damage within the entire sperm population is sufficient to increase the risk of infertility.

Because the SCSA® test is not representative of WHO parameters, it is a predictor of infertility, not fertility potential. Fertility may be affected by many other factors (e.g., poor motility, acrosome deficiency) even when the DNA quality is excellent. In contrast, DNA quality may be very poor in men with normal semen parameters that would otherwise be diagnosed with idiopathic infertility. A number of cases have been documented where a man with normal conventional semen parameters had multiple failed IVF/ICSI attempts, even using donor eggs. Twelve couples with multiple failed ART cycles and no known male factors progressed to sperm donor following discussion of their abnormal SCSA® test results (>30% DFI). Nine of these couples conceived within 3 sperm donor cycles after years of infertility.

Estimating the risk of infertility based on DNA fragmentation also may be valuable to men diagnosed with cancer. These men must decide prior to treatment if they wish to cryopreserve their semen for future ART. The DNA quality in cancer patients ranges from excellent to very poor prior to any treatment. Those men who have excellent sperm DNA quality may wish to cryopreseve their sample, while those with very poor DNA quality may wish to begin cancer treatment immediately, avoiding the delay and expense required for semen cryopreservation and storage.

A man's age, long periods of abstinence, high fever (>103°F) and the presence of leucocytes (indicating infection) appear to be related to a significant increase in sperm DNA damage. Data also show that exposure to environmental stresses, pollutants, as well as cigarette smoking, may have a negative effect on sperm DNA quality.

DNA fragmentation by the SCSA® test reflects the quality of sperm that have just undergone maturation in the male reproductive tract. While an excellent-quality sample is likely reflective of previous and future quality, poor DNA quality may be transient due to high fever, medications, physical or mental stress, or other unidentified conditions. Therefore, if SCSA® test results are poor, it is necessary to question the patient as to whether he has been exposed to conditions that may negatively affect sperm quality, correct these conditions if possible, and repeat the SCSA® test in 2 to 3 months.

The SCSA® test provides a rapid, unbiased, quantitative assessment of sperm DNA fragmentation that is an independent predictor of natural as well as in vitro infertility. This prognostic information provides invaluable information to couples who may consider donor insemination or discontinuing ART when sperm DNA quality is very poor putting them at a significantly greater risk for not achieving a pregnancy or early miscarriage. This prognostic information provides a significant medical, emotional, and financial benefit to couples considering ART, donor sperm or adoption.

Because Todd's standard semen analysis was normal, their medical team felt certain the failed cycles were associated with female factors. Amy underwent a myriad of tests, but no problem was identified. After two failed ICSI cycles, Todd and Amy did not know which way to turn. Should they continue with another cycle or begin looking into egg donation? During this time, Todd and Amy's physician learned about the SCSA® test and felt that sperm DNA fragmentation may have contributed to the poor embryo development and ultimately the couple's failure to conceive naturally and through IVF. She suggested they check the sperm DNA fragmentation levels - just as a precaution - before undergoing more costly and invasive procedures. She explained that the test was $200 plus shipping ($150) and that this was a small price for the information it could provide.

Certain it was a female factor, Amy and Todd were hesitant, but at the urging of their physician, they decided to have the SCSA® test completed. Todd had a high level of DNA fragmentation ~ 48% DFI (well above the 30% DFI threshold that places couples at risk for infertility.) Recognizing their low odds for success with Todd's sperm, they decided to go ahead with donor sperm. Amy became pregnant on her first cycle, and the couple is now awaiting the birth of their baby, which is expected in just 2 months.
The experience of the couple outlined above demonstrates the importance of the diagnostic and prognostic information provided by the SCSA® test. They may have made different decisions going into ART had they known of Todd's increased risk for infertility. They could have saved time, money and emotional costs associated with failed ART and proceeded more quickly to the treatment that allowed them to successfully begin building their family.

Table I. Conditions Indicating SCSA® Testing

  • abnormal Semen Analysis
  • Unexplained Infertility
  • Persistent Infertility after Treatment of Female
  • Recurrent Miscarriage
  • Prior to Assisted Reproductive Technologies
  • Cancer in Male: Before and after Treatment
  • Advancing Male Age

 

Commonly asked questions about the SCSA® test.

Important questions are raised by couples similar to the one described above and are outlined here.

 

Q: My physician requested that I have the SCSA test and gave me your telephone number. What do I need to do?
A: We are able to send the sperm shipping container to your physician's office or directly to your home. We will send all of the necessary supplies to the address you request. The sample collection, packaging and shipping procedures are simple and completely explained on our Web site as well as in the instructions provided. In our experience, people have very few questions and do not make mistakes.

Q: What is the cost of the SCSA test?
A. The test costs $200, which includes pre-cooling the shipping container, packaging all of the materials and instructions, preparing the Federal Express paperwork for shipping and return, and measuring and analyzing the sample for DNA fragmentation. All of the paperwork for the return shipping is included so you need only call your Federal Express station for pick-up. When the sample arrives at SCSA Diagnostics, the sample is then thawed and treated by a very precise procedure. Of importance, two independent measurements are made for each sample to be absolutely certain that the results are correct. The results are then processed by a special computer program, and the clinical report prepared.

Q: What is the cost of the Federal Express overnight shipping?
A: For round trip shipping in the US, the cost is $150. The reason for this amount is due to the fact that the shipping container is fairly large (2 ft. tall) so that the tank liner can absorb enough liquid nitrogen to keep your sample frozen and safe on the trip back to our laboratory.

Q: How often do male-factors contribute to infertility?
A: In about 50% of infertile couples, male-factors play a significant role in infertility.

Q: How often is DNA fragmentation a significant source of infertility? 

A: In couples that seek a male infertility evaluation, up to one out of four male partners are identified by the SCSA® test as having levels of DNA fragmentation known to put them at risk for infertility..

Q: What exactly is the sperm chromatin structure assay (SCSA®)?
A: The Sperm Chromatin Structure Assay (SCSA®) is an assessment of sperm DNA fragmentation that identifies men with a highly reduced probability of initiating and supporting a successful pregnancy. The percentage of sperm in a semen sample with fragmented DNA is reported as the DNA Fragmentation Index (% DFI). More detailed information may be found on SCSA Diagnostics Web page, www.SCSAdiagnostics.com.

Q: What is sperm chromatin?
A: The 23 chromosomes in the sperm head are made up of chromatin, which consists of DNA and proteins.

Q: Semen analysis showed that my sperm concentration, motility and morphology are normal. Can I still have high levels of DNA fragmentation?
A: Yes. Sperm that appear to be completely normal by all the standard measurements may have high levels of DNA fragmentation.

Q: I fathered two children, now 16 and 18 yrs old, with my previous wife. Isn't this proof that my sperm are fertile?
A: Although some older men are highly fertile, the natural aging process appears to be associated with increasing levels of sperm DNA fragmentation. Like many men, aging may have decreased your fertility potential.
Q: Are there medications that may influence my SCSA® test results?

A: Preliminary results indicate that some medications may influence SCSA® test results. Therefore, we recommend if you are on medication, consult with your doctor about temporarily reducing or discontinuing your medication for 2-3 months to have the SCSA® test. If a significant improvement has occurred your doctor may suggest either that you proceed with attempts for fertility at that time, or that you freeze the sperm so that you can go back on medication and use the sperm when your wife cycles.

Q: I was recently sick with a high fever. Could this influence my test results?
A: Yes. A high fever (>103°F) has been shown to impact SCSA® test results, and you should wait 2-3 months to have the test.

Q: Is there a required abstinence period required before collecting semen for the test? 
A: Yes, there is an important window of time. Abstinence time should not be less than 2 days or greater than 3 days.
Q: What SCSA® test results would indicate that we are at high risk for infertility? 

A: When ?30% of the sperm in your sample contain high levels of DNA fragmentation (?30% DFI, DNA Fragmentation Index), your sample results are similar to men that, as a group, have a significantly reduced probability of initiating a pregnancy that will go to term.

Q: Have you ever seen pregnancies in men with ?30% DFI? 
A: Yes, but in studies of hundreds of patients from very highly respected clinics, we have seen that pregnancy rates drop by 50% to 100%. Therefore, poor results do not mean that you will not initiate a pregnancy, but that your chances for success are less. 

Q: Can assisted reproductive techniques (ART) like in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) overcome high levels of DNA fragmentation? 
A: Men with high levels of fragmentation also are at high risk for failed ART cycles.

Q: If a semen sample has a high percentage of sperm with fragmented DNA, is this percentage permanent or might it improve over time?
A: SCSA® test results are significantly more stable over time than results obtained by conventional semen analysis (sperm concentration, motility and shape). However, some men bordering on infertility may have relatively unstable DNA quality as assessed by the SCSA® test. Therefore, if the SCSA® test indicates a high level of DNA fragmentation in one month, it is recommended that a second SCSA® test be done two to three months later.

Q: What causes sperm DNA fragmentation? 
A: DNA fragmentation in sperm may be the result of many factors including, but not limited to, disease, diet, drug use, high fever, elevated testicular temperature, air pollution, cigarette smoking and advanced age.

Q: How long will it take to receive our SCSA® test results? 
A: We are typically able to provide results to your physician within one week of receiving your sample.
Q: What do SCSA® test results indicate? 

A: A man's SCSA® test results place him in one of three statistical categories of fertility potential. These categories were derived from a comprehensive study of male fertility without assisted reproductive techniques. Excellent fertility potential ~ <15% DFI, Good to fair fertility potential ~ 15-29.9% DFI, Poor fertility potential ~ ?30% DFI.

 

Dr. Evenson is a Distinguished Professor of Biochemistry at South Dakota State University and President and Director of SCSA® Diagnostics, Inc. a private corporation that is dedicated to using the SCSA® test to determine the relationship between infertility and DNA fragmentation in sperm. Dr. Evenson invented and developed the SCSA® test and has over 20 years experience measuring thousands of animal and human sperm samples. He has published more than 125 peer reviewed research papers and has presented many invited lectures around the world. His research on the SCSA® test has been continuously supported over the past two decades by competitive, federally funded grants.

Thatcher's Thoughts on Aspirin, Endometrium and Paternal Aging

1. Aspirin and infertility

2. Uterine responsiveness and reproductive aging

3. Paternal age

Aspirin and infertility
Title: Low-dose aspirin for infertile women with thick endometrium receiving intrauterine insemination: A prospective, randomized study
Author: Y. Hsieh
Address: Taichung, Taiwan
Source: Journal of Assisted reproduction and Genetics 17:174-178 (March) 2000
Summary: To evaluate the effect of aspirin on infertile women with thin endometrium, 114 women were placed into an aspirin group and 122 women into a nonaspirin group. These subjects had an endometrium £ 8mm and intrauterine insemination. Endometrial pattern and thickness, the pulsatility index and resistance index of the uterine artery, spiral artery, and ovarian dominant follicles, and pregnancy rates of both groups were measured. Significantly higher percentages of trilaminar endometrium (46.5% vs. 26.2%) and pregnancy rate (18.4% vs. 9.0%) after aspirin therapy were noted. Researchers concluded that higher pregnancy rates and better endometrial pattern were achieved in patients with thin endometrium after aspirin administration. However, aspirin therapy could not significantly add to the endometrial thickness and the resistance of uterine and ovarian flow.
Comment: Use of aspirin to improve implantation or prevent miscarriage has been bantered about for a number of years. Theoretically, aspirin could improve circulation by its action on prostacyclin/thromboxane pathways, but its anti-inflammatory action could equally blunt the prerequisite inflammatory response necessary for implantation. The mere fact that most do not use it can be taken as an indication of its lack of effectiveness. I wish someone would perform a definitive well-designed and controlled study to put this issue to rest. 

Uterine responsiveness and reproductive aging
Title: Pregnancy after embolization of uterine myoma: report of 12 cases
Author: J. H. Check, et al.
Address: Camden, New Jersey
Source: Human Reproduction 15: 1679-1684 (August) 2000
Summary: The purpose of this study was to determine if uterine vascular impedance escalates with aging in women experiencing ovarian stimulation for IVF. Women (n=162) who had undergone standard IVF and embryo transfer were divided into three subgroups according to age: 30-34 years (n=49), 35-39 years (n=79), and 40-44 years (n=34). Pulsatility index (PI) and resistance index (RI) of the right and left uterine arteries were measured at baseline, the day of oocyte retrieval, and at mid-luteal phase. The luteal phase values of PI and RI were lower than those observed earlier in the cycle for all groups. Ovarian response, as measured by mean number of oocytes retrieved, declined significantly with age. Researchers concluded that reduced pregnancy rates in older women undergoing ovarian stimulation are more likely to occur because of oocyte quality and quantity rather than uterine senescence. 
Comment: More support for the issue of fertility rests more with egg and therefore, embryo quality than that of the uterus. 

 

Paternal Age
Title: Increasing paternal age is associated with delayed conception in a large population of fertile couples: Evidence of declining fecundity in older men
Author: W. C. Ford, et al. 
Address: Bristol, UK
Source: Human Reproduction 15:1703-1708 (August) 2000
Summary: Because controversy continues to surround the issue of aging and male fertility, researchers conducted this study to determine the effect of male age on the length of time it takes to conceive. This study is based on pregnancies that resulted in the birth of a baby. Both the male and female partners completed questionnaires at 18 weeks gestation. The questions were related to such topics as parity, paternity, cohabitation, oral contraception, education, smoking and obesity. Out of 8515 planned pregnancies, 74% were conceived in £6 months, 14% in the second 6 months and 12% after more than a year. After adjustment for 9 different variables, including the age of the woman, the likelihood of conception within 6 or 12 months was lower in older men. Compared to men less than 25 years old, the adjusted odds ratios for conception £12 months were 0.62 in men aged 30-34, 0.50 in men 35-39, and 0.51 in men >40 years of age. 
Comment: Still not too bad for the old men. 

Normal Ranges for a Semen Analysis

Normal Ranges for a Semen Analysis*

Parameter

Normal Ranges

Color

Gray/Transluscent

Coagulate?

Yes

Liquify?

Yes

  If yes, time in minutes

Less than or equal to 30

Volume (mL)

2 to 6

Viscosity (1,2,3,4)

1

pH

7.5 to 8.1

% Motility

Greater than or equal to 50%

% of 3-4 + Forward Motile Sperm

Greater than or equal to 50%

Sperm Concentration (x 1 Million per mL)

20-200

Total Sperm Count (x 1 Million per mL)

Greater than or equal to 40

Total Motile Sperm (x 1 Million per mL)

Greater than or equal to 20

White Blood Cells (x 1 Million per mL)

Less than or equal to 1

Agglutination (0,1,2,3)

 

  Clumping of sperm to sperm

0

  Clumping of sperm to round cells

0

% Normal Morphology

Greater than or equal to 30%

Penetrak Score (mm)

Greater than or equal to 30

 

mL = milliliter

mm=millimeter

   

Based on World Heath Organization criteria, 1992. Table excerpted from Berger, G.S., Goldstein, M., and Fuerst, M. (1995). The Couple's Guide to Fertility. New York: Doubleday.

Platlet Activating Factor and Intrauterine Inseminations by William E. Roudebush, PhD

William E. Roudebush, Ph.D., HCLD
Clinical Associate Professor, Physiology
University of South Carolina
T 864.455.9842
F 864.455.5267

Dr. Roudebush’s work involving PAF and fertility has received many awards and honors. He has published over 160 articles, book chapters and abstracts relating to research in the field of infertility.

In many centers drug induced ovulation induction (OI) followed by intrauterine insemination (IUI) have become standard therapy for non-tubal factor related infertility. As the initial treatment for infertile couples, IUI is commonly used and is a cost effective procedure. The success of IUI is dependent on the ovulation induction regimen as well as seminal parameters. Commonly, because of lower patient costs, complexity and risks of high order multiple pregnancy, clomiphene citrate (CC) is initially used. At Reproductive Biology Associates (RBA), Atlanta, GA the typical treatment regimen involves three CC/IUI cycles followed by GT/IUI for up to three cycles. Failed IUI therapy subsequently results in consideration of in vitro fertilization therapy.
 

Male fertility requires production of an adequate number of normal sperm with sufficient motility for fertilization. Poor production of quality sperm may lead to subfertility or infertility. A number of endogenous biochemical factors have been attributed to regulate the fertility potential of spermatozoa, for example platelet-activating factor.  Platelet-activating factor (PAF) is present in human spermatozoa, and its content has a significant and positive relationship with motility and pregnancy rate. In a recently published paper (Fertility & Sterility 2004;82:52-56), we reported on the benefit of washing sperm with PAF for intrauterine insemination.
 

Since February 10, 2003 RBA has been routinely adding PAF to the IUI sperm wash protocol.  The average pregnancy rate for PAF-IUI cycles is >40% (see graph below), nearly twice the rate of non-PAF treated IUI cycles (~29%). Additionally, we are finding a tremendous improvement in first-cycle IUI pregnancy rates. Patients are finding less time (a 1 in 3 chance with PAF compared to a less than 1 in 5 chance without PAF) required to become pregnant with PAF-IUI, thereby resulting in reduced cost for infertility treatment.
 

PAF is a potent phospholipid that is naturally found in sperm and whose content has a positive correlation with pregnancy outcome. From our studies on PAF, we have found that morphologically abnormal sperm do not respond to PAF as do normal-motile sperm, with improvements in overall sperm motility (numbers and grade). We believe PAF has a sperm-selective capacity that results in the improved pregnancy outcomes. PAF is a safe and efficacious treatment for patients undergoing IUI therapy for infertility.

William E. Roudebush, Ph.D., HCLD
Clinical Associate Professor, Physiology
T 864.455.9842
F 864.455.5267

Dr. Roudebush’s work involving PAF and fertility has received many awards and honors. He has published over 160 articles, book chapters and abstracts relating to research in the field of infertility.

Male Infertility Webinar

Webinars or Educational Modules are audio visual and virtual presentations which provide solid content, information and a great deal of support for individuals and couples experiencing the struggle to build a family. They are a teaching tool to help educate you on specific topics of interest in your quest to build or add to your familiy.

 

Live webinars presentations differ from in-person workshops only in method by which the information is delivered. The webinar programs augment and enhance other patient education experiences. It is INCIID’s desire to expand the reach of consumers in order to make education and support much more accessible. That's why INCIID Webinar Programs provides resources for learning regardless of time and place. They are interactive, auditory and visual presentations which provide opportunities to learn while maintaining a more private and intimate setting for the consumer. The format allows the presenter to speak and also interact with comments and questions from the comfort of their own home setting. Once a live presentation is complete we archive these modules to be utilized over and over again by our community members.

 

Dr. Mark Perloe presents an AUDIO VISUAL educational primer on Male Infertility; its physiology, anatomy and current treatments. This module was made possible by an unrestricted and generous donation by Sigma-tau Pharmaceuticals, Makers of ProXeed.

You'll need to give the audio a few minutes to start. Although you can jump from slide to slide, the program will progress automatically.

 

If you have a problem with the module, please email us HERE

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