The International Council on Infertility Information Dissemination, Inc

Non-Surgical Alternatives for Men Desiring Children Following a Vasectomy

Non-Surgical Alternatives for Men Desiring Children Following a Vasectomy

by Michael Feinman, M.D., F.A.C.O.G.

In the late 1980’s, Dr. Sherman Silber in St. Louis, proved that sperm obtained directly from the scrotum could be used to successfully fertilize eggs and achieve viable pregnancies. While this procedure was originally intended for men who are born with an obstruction in the genital tract (congenital absence of the vas deferens), it has become clear over the past decade that men with previous vasectomies can benefit from similar procedures as well.
 

The development and maturation of sperm occurs in the testes. The testes also produce most of the testosterone in men. The sperm begins its trip through the male ducts in an enlarged portion of the ducts called the epididymis. This duct eventually becomes the vas deferens (vas). Along the route of the vas, the prostate and seminal vesicles add the fluid portion of the ejaculated semen. When a vasectomy has been performed, the vas deferens is blocked before the area where the seminal vesicles add the fluid. That is why these men still produce semen, but no sperm. Dr. Silber microsurgically removed sperm from the epididymis and achieved viable pregnancies through assisted reproductive procedures, thus proving that sperm do not have to make the trip through the ducts to achieve fertilizing potential.
 

Vasectomies represent an important and effective method of “permanent” birth control. For a variety of reasons, a small percentage of men who have a vasectomy later desire more children. Until recently, if semen was not frozen at the time of the surgery, microsurgical reversal of the vasectomy has been the only option for these men. Vasectomy reversal has several disadvantages, however. Vasectomy reversal represents major surgery of the scrotum. Most men with longstanding vasectomies develop sperm antibodies that may inhibit fertilization, even if the reversal procedure is surgically successful. Finally, reversals done more than seven years from the original procedure are associated with very poor pregnancy rates.  Unfortunately, many men seeking fertility after a vasectomy fall into this last category.
 

Removing sperm directly from the scrotum, combined with in-vitro fertilization (IVF), represents an excellent alternative to vasectomy reversal.  The original microsurgical approach is known as “microsurgical epididymal sperm aspiration,” or “MESA.” This procedure produces enough sperm to freeze for future use. However, like vasectomy reversal itself, the procedure involves major surgery of the scrotum, is relatively expensive, and can often only be performed once on each side because scar tissue hinders the ability to find the duct on subsequent attempts.
 

Over the past few years, HRC doctors have developed two non-surgical alternatives to MESA. The first approach is called, “percutaneous epididymal sperm aspiration,” or, “PESA.” The second alternative is called, “testicular sperm extraction,” or, “TESE.” Both procedures can be done using local anesthesia.  With PESA, a small needle is guided through the skin into the epididymis, and a small amount of fluid containing sperm is aspirated. In contrast, with TESE, a small amount of tissue is directly removed from the testis using a small biopsy needle. In either case, relatively small numbers of sperm are obtained, and these can fertilize the female partner’s eggs through intracytoplasmic sperm injection (ICSI), where individual sperm are actually injected into the eggs. None of these procedures produce enough mobile sperm for simple artificial inseminations.
 

Potential complications of the non-surgical procedures include infection and bleeding. Bleeding under the scrotal skin can theoretically cause the formation of a painful blood clot known as a hematoma. In over 5 years of performing these procedures, we have not seen either of these complications.
 

Before proceeding with any of these treatments, the male partner should be evaluated by the person who will perform the procedure. An appropriate history and physical examination should be performed, focusing on potential factors that could impact on likely successful aspiration of sperm. The physical exam can identify potential problems that might be encountered and can help the physician estimate the likelihood of finding adequate amounts of viable sperm. We measure serum levels of testosterone and FSH in the men to make sure they are producing enough hormones to sustain normal sperm development.
 

As with routine IVF cycles, the female partner uses injectable hormones to both stimulate multiple egg production and to control the timing of ovulation. The egg retrieval is done vaginally, using an ultrasound probe to guide a needle into the ovaries. This procedure can be done with local anesthesia, or with conscious sedation. The PESA or TESE is done on the same day, and the eggs are inseminated shortly after the conclusion of both procedures. Three days later, a small number of embryos are inserted through the cervix into the uterus. The number of embryos transferred depends on the age of the woman and the quality of the embryos. Extra embryos can be frozen for future use. Over the past year, the doctors at HRC have been addressing the issue of multiple births by transferring lower numbers of embryos in younger patients. We can do this, in part, because of the quality of our freezing program, giving couples a realistic second chance.
 

The choice of procedure is largely dependent on physician preference. All three variations of the male procedure are available at HRC. Over the past several years, we have experienced a 20-30% ongoing pregnancy rate with non-surgical sperm extraction procedures. The success rates vary, based on numerous factors, maternal age being one of the most important. We believe, for couples in whom the male partner has a vasectomy more than seven years old, these success rates following single procedures are greater than the overall success rates with vasectomy reversal. For younger women, the overall success rate following the initial combination of PESA/ TESE and IVF, is enhanced if there are frozen embryos available for another embryo transfer.
 
 

INCIID Insights is sponsored by Sher Institutes for Reproductive Medicine.

Fordham Study - Emotional Impact of Multiple Miscarriages on Men

This article is part of the June 2006 INCIID Insights Newsletter

 
Multiple Miscarriage Study- Participants Needed

 
An Investigation of the Emotional Effects of Multiple Miscarriages on Men

 

Fordham University

 

 
Ms. Erica Tennenbaum, a Doctoral Candidate at Fordham University’s Counseling Psychology Department is currently working on her dissertation research, which focuses on multiple miscarriages (i.e. three or more miscarriages). She is investigating men's psychological and emotional experiences following their partner's multiple miscarriages. Although there is some research that exists focusing on the effects of miscarriage, none focus on men's experience with multiple miscarriages.  She hopes to add new insights on men's experiences and perspective during and after multiple miscarriages.
 

Currently, she is in the early phases of the study and is starting to recruit participants.  Thus, if you or someone you know has suffered at least three miscarriages, does not have any living children, and is interested in participating in the study please contact Ms. Tennenbaun via e-mail at tennenbaum@fordham.edu.
 

Both men and women will be asked to participate in the study.  Women will be asked to complete a short written questionnaire.  Men will be asked to partake in an in-person or phone interview with the primary research investigator. Each couple will receive $100 after they have completed their participation. All information provided would be kept confidential and the couple would not be identified as participants in any publication that results from the study.

 
INCIID Insights is sponsored by Sher Institutes for Reproductive Medicine.

Sperm Donor Anonymity

This article is part of the June 2006 INCIID Insights Newsletter

 
The Importance of Sperm Donor Anonymity
 
by Betsy Cairo, PhD, HCLD

 
While the advent of recent FDA regulations for United States (US) sperm banks may be complicating their lives and raising the cost of doing business, another looming issue may have greater implications for sperm banks and their donors and recipients alike.  In the United Kingdom (UK), The Department of Health announced that sperm donors could no longer remain anonymous and that all sperm donors would have to register with the Human Fertilisation and Embryology Authority (HFEA) as an identity-release donor.  After April 1st, no UK fertility center can use donor sperm unless the donor has been registered with identifying information.
 

What this means to the donor is this—any child born to these donors can have access to his information once (the child) has turned 18.  The first year this information may be accessed by offspring for new donors entering the program after April 1st, 2005 will be the year 2023.  The rationale behind identity release is that offspring have the right to know their biological background and have the opportunity to meet and interact with such individuals.  This is not a bad rationale but unfortunately it has led to undesirable results.
 

The UK is now scrambling to meet its donor sperm demand.  Since the announcement of this change in standards for the sperm donors, there has been a steady decrease in the number of sperm donors that have applied to programs, with the sharpest decline being after 2000.  For example, the number of donor applicants in 1994 was reported as 175. The number of applicants in 2003 was 25.  A decline of this magnitude makes for a huge deficit in donor specimens.  To combat this problem, the UK is appealing to other countries to supply them with donors that are willing to have their identification released in their county.  What this ultimately means to the recipient is a possible waiting list for donor sperm and a marked increase in the price.  The patient is hit twice:  money and time.
 

It is important to pay attention to what has happened in the U.K. as it might apply in the U.S., perhaps sooner than we’d like.  The donors available in the United States have the option of having their ID released.  A majority of donors decline.  We have found that our donors are willing to have their identification released in the U.K. but not in the United States. Not now and not ever.  However, this does not mean that donors are unwilling to cooperate in the event of a medical situation involving an offspring.  We have to pay our donors more to have their ID released in the U.K., which of course results in higher prices for the recipients there.
 

This could happen in the United States.  Unfortunately, because of competition, sperm banks try to out do each other by offering something new, different and leading edge to their clientele.  This has led to an increase in talk among patients about ID release donors, and sperm banks are attempting to respond to this line of thinking.  I do not think that recipients understand the potential downfall of forcing this issue.   It is time to remind ourselves, and perhaps our clients as well, that the sperm donor is simply that - a genetic donor.  He is not a daddy, a buddy, a father or a friend.  He is not going to pay child support or attend soccer games.  We need to be honest with our patients and gently remind them of the exact role a genetic donor plays.  This does not make the job of the donor any less important.  A wonderful thing these men do for others is offering people the chance at a family in this manner.  Besides, in our program and in most others, recipients have access to a wide range of information on the donor.  A complete family and personal health history, genetic review and even an essay section where a recipient can view the donor’s personal answers and see their handwriting.
 

What about the donor’s freedom?  If donors are required to relinquish their anonymity, do they have the right to know who utilized their specimens and whether or not a live birth resulted?  And if so, are they free to contact these people and have contact with the child?  Perhaps we should also keep in mind the importance of anonymity when thinking of the recipients who do not want to know the identity of their donor.  Sometimes the concern of using donor sperm is the concern that the donor will obtain information about them and seek them out and try to infiltrate their life and that of the child. Where do we draw the line?  It appears that in the interest of fairness it should go both ways.
 

The FDA has already gained a foothold on regulating sperm banks.  Such regulations are tedious and have increased our cost of operation.   I am concerned that they may add to their regulation of sperm banks the requirement of identity release for all donors due to the undercurrent that is spreading across the US.   If this happens, where will anyone get sperm and at what cost?
 

Betsy Cairo, PhD, HCLD, founded CryoGam Colorado, LLC in 1990.  She is currently one of its owners and is its director.  CryoGam offers all aspects of cryopreservation including: anonymous and personal sperm freezing and storage. Additionally CryoGam does long term embryo storage.
 

FDA inspected in February of 2006, CryoGam was given a report of no deficiencies. CryoGam is also licensed by the New York State Dept. of Health and is also regulated and inspected by CLIA.
 
To learn more about CryoGam please visit our website at www.cryogam.com or by phone at 800-473-9601.  Dr. Cairo also answers questions on a special discussion board at www.haveababy.com,  CryoGam’s  address is :

CryoGam Colorado, LLC
2216 Hoffman Dr
Loveland, CO 80538 
 

INCIID Insights is sponsored by Sher Institutes for Reproductive Medicine.

Updated Views and Data on Sperm DNA Fragmentation and Pregnancy Outcomes

Updated Views and Data on Sperm DNA Fragmentation and Pregnancy Outcomes

 
Donald Evenson, Ph.D.

 
Lisa and Jim were happily celebrating their two years of marriage.  This was the second marriage for Jim, age 48, and the first for Lisa, age 32.  Jim has two children, ages 22 and 24, by his previous marriage. Shortly after Jim and Lisa were married they looked forward to having children together and had non-protected sex in hopes of a successful pregnancy.  Six months later their dream appeared to become true with the good news that Lisa was pregnant.  Two weeks later however, that dream chilled with a spontaneous miscarriage. Lisa’s OB/GYN physician calmed Lisa and Jim’s disappointment saying that miscarriages are a part of the human fertility experience and that they should simply continue their quest for a successful pregnancy by natural means.

 

A year later after their miscarriage, Lisa kept having her timely menstrual periods but no known pregnancy.  Becoming concerned, Lisa and Jim decided to go to a comprehensive infertility center staffed with doctors of varied specialties for a comprehensive evaluation of their fertility health.  Jim’s exam by a urologist found no abnormalities of his urogenital system, except for one small varicocele (enlarged testicular region where blood vessels may cause detrimental heat to the testis) that his doctor did not consider to be a problem.  Jim had a routine semen analysis where trained personnel exam the sperm under a light microscope for sperm concentration, motility and morphology. 
 

Jim’s semen analysis test came back with all parameters normal according to the standard World Health Organization guidelines.  Jim’s doctor emphasized the point that since Jim had fathered two normal pregnancies with his first wife that he was considered a normal fertile man.  Since Lisa’s examinations also came back as totally normal, this left the couple with the uncomforting diagnosis as having “idiopathic infertility” or, more simply stated, there was no known explanation for their lack of a timely, normal pregnancy.
 

Emotions began building with Jim and Lisa to search out possible answers to their dream of having children. A recommendation was made to begin with assisted reproductive technologies (ART).  Since Jim and Lisa had only limited financial resources, they opted for the least expensive method, namely, intrauterine insemination (IUI).  Further disappointment followed the lack of pregnancy with their first IUI attempt.  Two months later their clinic performed a second IUI procedure again only to be met with the same disappointment.
 

Jim and Lisa felt compelled to seek additional counsel and information.  They turned to the Internet and typed into various search engines the logical words of infertility, male infertility, female infertility, idiopathic infertility and others.  They ordered half dozen books written by medical personnel on the general topic of “how to achieve a normal pregnancy”. 
 

Armed with new knowledge and insights, they visited a well known infertility specialist who had recently attended an international infertility conference.  The specialist noted two presentations on the role of sperm DNA damage as a cause for male factor infertility; the presenters:  Donald Evenson, Ph.D., HCLD and the other Mona Bungum, M.D.  Dr. Evenson outlined his laboratory’s 25 year effort in pioneering a high tech method of detecting DNA damage in sperm. Dr. Evenson’s project began while he was on faculty at the Memorial Sloan Kettering Cancer Center in New York researching potential damage done to sperm DNA by chemotherapy medications.   Obviously, the integrity of the DNA comprising the male genome is of critical importance for the man’s contribution of his half of genetic input for a child. 
 

The discovery of this new protocol, now known as the Sperm Chromatin Structure Assay, (SCSA), was due to the invention of a scientific instrument called a flow cytometer.  Sperm cells are stained with a fluorescent dye and then forced though a glass channel of the flow cytometer that is illuminated with a laser beam.  The sperm that stain green have a zero to low level of DNA fragmentation and those that stain red have various levels of fragmented DNA.  Dr. Evenson and his Sloan Kettering colleagues announced to the scientific world the SCSA invention on the cover issue of the prestigious journal Science in December, 1980.  That 1980 publication had the summarizing statement: “We expect this assay to have application in animal husbandry, human infertility and environmental and public health”.
 

Now, fast forward a quarter century to Lisa and Jim in 2005.  Could it be that this promising speculation could be of help to Jim and Lisa 25 years later? The answer is “yes” as envisioned.  Then the obvious question: why has it taken so many years to arrive at the conclusion that the SCSA should be available for male factor infertility diagnosis and prognosis including the problem faced by Jim and Lisa? 
 

That answer lies in the testing plan developed by Dr. Evenson who was very concerned that the SCSA test would provide meaningful information to the sperm analysis laboratory.  First, extensive testing and validation was needed to determine just what the SCSA was measuring and what it meant biologically for the human infertility clinic.  Thus, Dr. Evenson, together with many national and international colleagues, spent almost two decades of research, generously funded by federal health agencies, to determine the use of the SCSA for human and livestock animal fertility as well as determining the negative effects of environmental chemicals and other reproductive toxicants on sperm DNA integrity.
 

Over two million semen analyses are done annually in the United States. he classical measurements are sperm count, morphology, viability and motility. Consensus of world wide experts has suggested levels for each of these parameters that are considered to be in the normal range or abnormal range.  While these may be the best consensus by experts, the real problem is lack of accuracy and recognizing that men who have an abnormal value may be fertile and those with normal values may be infertile.
 

The important point for Jim and Lisa was that Jim’s sperm had normal morphology values. However, in sharp contrast to looking at the “outside” of the sperm with a light microscope, the SCSA looks inside the sperm at the most important part of the sperm, namely, the integrity of the sperm DNA. Especially in this era of ICSI where sperm of various abnormalities from outside appearances can be injected into eggs and cause fertilization, nothing is as important as the quality of the DNA which is the object of measurement by the SCSA.   
 

Since the SCSA measurements of DNA integrity have generally shown very little relationship to the classical light microscope measurements of sperm count, motility and morphology, the SCSA can be considered an independent measurement that provides valuable new information to both the physician and patient.
 

All sperm quality tests, including the SCSA, provide information on the probability of infertility and not fertility.  Thus, a man’s sperm count, motility and viability value of zero would suggest that the man is infertile. But even if all the tests had good scores, this is not a guarantee for pregnancy to occur.
 

What is the consistency of semen analysis tests and DNA fragmentation tests?  The reason that most infertility clinics tell male patients to obtain at least two semen analyses spaced 1-3 months apart is that the various values of sperm count, motility and morphology can change quite dramatically over a short period of time.  The time to produce a sperm from the testis to ejaculated semen takes about three months.  Since various factors that potentially affect the numbers of sperm produced or the quality of the sperm during this three months can change, it is obviously important to check the status two or three times. 
 

It is of interest that a comprehensive study comparing routine semen quality tests with the SCSA DNA fragmentation test indicated that the SCSA results were much more consistent over time.  Even so, there are various factors that will cause a dramatic shift in sperm DNA integrity also.  An example is seen on the Internet (www.SCSAdiagnostics) where the male partner of a couple had very poor SCSA measures for two successive months with no pregnancy followed by an excellent measurement and a successful pregnancy that month.
 

Jim and Lisa’s physician who heard Drs. Evenson and Bungum speak saw the possible reason why pregnancy was not happening after a year and a half of trying for a natural pregnancy, a spontaneous abortion and two failed attempts with IUI.  Dr. Evenson showed results from two large studies, one done at the Georgetown Medical Center, Washington, DC and the second at the Danish National Hospital in Copenhagen. 
 

In the first study, 170 couples who sought to become pregnant were counseled by fertility personnel on the best methods to obtain pregnancy by natural intercourse.  Each man had a semen analysis, including a SCSA DNA fragmentation test, several days after the prime time for conception.  The women had hCG testing to determine if a biochemical pregnancy had occurred that month.  A manuscript published by Dr. Evenson and colleagues showed that the level of sperm DNA damage was low (less than 30% of the  sperm showed fragmented DNA)  in the couples that became pregnant in any of the first three months of that study.  Thus, the DNA Fragmentation Index (DFI) was less than 30% (DFI < 30%). 
 

While the SCSA was measured only during the first three months, some couples with greater than 30% sperm with fragmented DNA (>30% DFI) in the first three months became pregnant in months 4-12 of the study while others did not achieve pregnancy within the one year study.
 

The second study was done on 215 couples trying to start a family in Denmark by natural intercourse.  Likewise in this study, the statistical odds showed that these couples were ten times less probable to become pregnant when the DFI was less than 40% (considered about the same as the Evenson threshold of 30% since very few pregnancies occurred above 30%).
 

Now enter the important study of Dr. Mona Bungum in Norway. Dr. Bungum and colleagues enrolled one thousand patients in a comparative ART study.  One third of the patients had IUI, one third routine IVF and one third used ICSI fertilization of the retrieved eggs.   What captured Jim and Lisa’s physician attention was the fact that Lisa had two failed IUIs and Dr. Bungum’s large study showed that if the DFI was greater than 27%, there was 8.7 fold decreased probability of a pregnancy by IUI than when the DFI was less than 27%.   
 

Jim and Lisa’s physician decided to order a SCSA test for Jim.  Upon calling SCSA Diagnostics, it was learned that a semen sample could be collected and shipped to this diagnostic lab in two different ways.  First, Jim could go to the clinic, produce a semen sample and the clinic would freeze the sample and send it by overnight courier to SCSA Diagnostics lab.  Alternatively, since Jim and Lisa lived an hour’s drive from the clinic and Jim did not want to take off a day’s work to go to the clinic, they had SCSA Diagnostics send (Federal Express) a custom shipper to their home.  Jim was instructed to have two ejaculations prior to an abstinence period of two days when he then produced a semen sample into a collection jar that was part of a collection kit sent with the shipping container. Following the simple instructions provided, a small amount of semen was placed into a special tube and that tube was simply placed into the shipping container that was prechilled to a freezing temperature. Federal Express picked up the pre-paid shipping container for delivery the next morning at SCSA Diagnostics in Brookings, SD. This sample was then thawed and subjected to the SCSA protocol. The results were then faxed to the doctor’s office. 
 

The results showed that 41% of Jim’s sperm had DNA fragmentation.  These results placed Jim into the group of men that, statistically speaking, took a longer time to initiate a successful pregnancy, had an increased risk of spontaneous miscarriage or did not have a successful pregnancy.

 

Thus, it appeared to Jim and Lisa’s physician that no further attempts with IUI should be done, but go into routine IVF or for even better probabilities go to ICSI. This approach to the management of Lisa and Jim’s pregnancy quest was made clearer by Dr. Evenson’s results of a statistical analysis of SCSA DNA fragmentation studies on ~2000 clinical patients which indicated that ICSI fertilization appears to provide the best odds for a pregnancy when the man’s DFI is above 30%.  However, it is also the most costly and this was a major factor for Jim and Lisa with their limited finances. Even so, they went ahead with ICSI and were told the day after the procedure that 8 of 10 eggs fertilized, and five of the embryos looked “beautiful”.  The physician explained however, that although the majority of the embryos looked beautiful, that Jim’s sperm DNA would not contribute genetic information until day 3 and that development up to that time was maternal contribution to the embryo.  So the important question was:  Did ICSI process select sperm with mostly normal or damaged DNA?
 

Two of the best looking embryos were transferred to Lisa and then the waiting started again.  They accepted the possibility of twins, but as desperate as their feelings were for wanting a child, they decided not to run the risk of triplets with three embryos implanted.  And finally, good news!  Lisa received a phone call to say that her hCG was elevated and that pregnancy had occurred.  Furthermore, after some anxious wondering whether, once again, that only a biochemical pregnancy had occurred, more good news arrived at six weeks to confirm a clinical pregnancy.
 

Knowing that Jim had a level of sperm DNA fragmentation that put him into a statistical group of men that took  a longer time to conception and increased odds of a spontaneous abortion, they discussed with their doctor what the odds were of a normal baby with their situation.  Despite the possibility of some increased odds for spontaneous abortion, their doctor told them to relax and fully enjoy the pregnancy since the probability was very high of giving birth to a completely normal child. Jim and Lisa are waiting for their expected delivery date, and to this point, all is well.
 

Jim asked their doctor what might have caused his sperm DNA to be fragmented to the point that his DFI was above the statistical threshold of 30%.  He pointed out that a number of factors may cause a temporary increase of sperm DNA fragmentation.  These included use of very warm hot tubs or saunas, a fever in the range of 103-104oF, exposure to toxic chemicals including pesticides and herbicides, some medications like cortisone, urogenital infections, and others (examples of how these factors affect sperm DNA fragmentation can be seen on the Internet at www.SCSAdiagnostics.com). 
 

Since Jim was not aware that he was exposed to these factors, the physician thought that the most likely cause for a long term elevated DFI was Jim’s age of 48.  A study on sperm quality and age was conducted at the Lawrence Livermore National Laboratory (LLNL)  and the University of California, San Francisco, where about 100 men ranging  in age from 21 to 80 who were working or had worked at the LLNL provided a semen sample to help answer the question whether sperm quality decreased with age.  Previous thought in the medical world was that age made little or no difference and that once the sperm fertilized an egg that its work was done. 
 

Not so from current research!  Sperm quality does decrease with age, but it varies much more with men than women where there is a sharp decline after about age 36.  Dr. Evenson showed that men in their early 20’s had a DFI of approximately 5%.  In their thirties this level increased into a DFI in the range of 13-19% and in their forties into a DFI greater than 20%.  The data suggested that Jim, at age 48, had approximately a one out of three chance that his DFI would be above 30% which is the current suggested level to put Jim at risk for a reduced pregnancy outcome.  Therefore, the picture became clearer why he had easily fathered children when in his early 20’s and now that he was age 48 with a DFI of 41%, his age was likely the major contributor to the diagnosis of unexplained infertility.  The SCSA had detected a problem that was not detectable by light microscopy.  The idiopathic infertility was now explained.
 

Great progress has been made in the past quarter century for overcoming couple infertility.  The great breakthrough of in vitro fertilization is now a routine procedure in many clinics around the world.  The second major breakthrough celebrated its 10th anniversary last year, namely, ICSI, where sperm of lower quality can be injected into an egg.     With this accomplishment, many thought that any man’s sperm would be sufficient for fertilization and normal embryo development; this has not proven to be true.  While fertilization can occur even for sperm with high levels of DNA damage, ongoing genetic support of the growing embryo is dependent on a high level of DNA integrity.
 

As can be seen from the story of Lisa and Jim, there are many couples with idiopathic infertility that could be spared unnecessary tests and treatments by a simple DNA fragmentation test.  The information gained could be of significant help to both physicians and patients alike to better manage cases of couple infertility.
 
 
Contact information:

Donald Evenson Ph.D.
SCSA Diagnostics Corporation
Multiplex Research & Technology Center
807 32nd Aveue
Brookings, SD 57006
Phone:  605-692-5938
Fax:  605-692-9730
Email:  scsadon@brookings.net
 
Website:  http://www.scsadiagnostics.com
 
INCIID member profile:  http://www.inciid.org/members/member.php?cust_id=10286
 

Breakthroughs in Andrology (Abstract)

Journal of Andrology, Vol. 27, No. 1, January/February 2006
Copyright © American Society of Andrology
DOI: 10.2164/jandrol.05121

 

Reduced Seminal Parameters Associated With Environmental DDT Exposure and p,p'-DDE 
Concentrations in Men in Chiapas, Mexico: A Cross-Sectional Study

 

CHRISTIAAN DE JAGER*,, PAULINA FARIAS, ALBINO BARRAZA-VILLARREAL, MAURICIO HERNANDEZ AVILA, PIERRE AYOTTE, ERIC DEWAILLY, CHRISTIAN DOMBROWSKI||, FRANÇOIS ROUSSEAU||, VICENTE DIAZ SANCHEZ¶ AND JANICE L. BAILEY* 

 

From the * Centre de Recherche en Biologie de la Reproduction, Département des Sciences Animales, Université Laval, Québec City, Québec, Canada;  Environmental Health, School of Health Systems & Public Health, University of Pretoria, Pretoria, South Africa;  Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca Morelos, México;  Unité de Recherche en Santé Publique, Centre de Recherche du Centre Hospitalier de l'Université Laval-Centre Hospitalier Universitaire de Québec, Université Laval et Direction de la Toxicologie Humaine-Institut de la Recherche en Santé Publique du Québec, Sainte Foy, Québec, Canada; || Unité de Recherche en Génétique Humaine et Moléculaire, Services de Biochimie Médicale et de Génétique de Laboratoire, Centre Hospitalier Universitaire de Québec, Pavillon St-François d'Assise, Québec, City, Québec, Canada; and the ¶ Departmento de Biología de la Reproducción, Instituto Nacional de Nutrición, México DF, México.

 

Correspondence to: Dr Janice L. Bailey, Centre de Recherche en Biologie de la Reproduction, Département des Sciences Animales, Université Laval, Québec City, Québec, Canada, G1K 7P4 (e-mail: janice.bailey@crbr.ulaval.ca ). 

 

Abstract

In response to mounting concerns about the endocrine-disrupting influence of environmental chemicals on human health, this epidemiological study was initiated to test the hypothesis that nonoccupational exposure to the estrogenic pesticide 1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane (DDT) affects male reproductive parameters. One hundred and sixteen men aged 27 years (SD = 8.2) living in malaria endemic-areas in Chiapas (Mexico), where DDT was sprayed until 2000, participated in a cross-sectional study. Semen analyses were conducted according to World Health Organization methods and a quality control program was followed. DDT exposure was defined as the level of blood plasma p,p'-dichlorodiphenyl dichloroethylene (DDE), the major metabolite of DDT. The p,p'-DDE concentration adjusted for total lipids was 100 times higher than that reported for nonexposed populations at 45 plus or minus 32 µg/g (mean ± SD). Crude regression analysis showed that several sperm motion parameters, including the percentage of motile sperm, decreased with higher p,p'-DDE concentrations (ß = -8.38; P = .05 for squared motility), and the percentage of sperm with morphological tail defects increased with higher plasma p,p'-DDE concentration (ß = 0.003; P = .017). Insufficient sperm chromatin condensation was observed in 46.6% of participants, and the most severe category of incomplete DNA condensation was also positively correlated with p,p'-DDE concentration (r = .223; P = .044). Therefore, nonoccupational exposure to DDT, as assessed by plasma p,p'-DDE concentrations, is associated with poorer semen parameters in men, indicating adverse effects on testicular function and/or the regulation of reproductive hormones. Previously, a causal role of environmental toxicants in human male infertility has been lacking because observed effects have been the result of unusually high exposures, either occupationally or as a result of industrial accidents, resulting in unprecedented controversy (reviewed by Cheek & McLachlan, Environmental hormones and the male reproductive system. J Androl. 1998;19:5). This is the first epidemiological study demonstrating effects after nonoccupational exposures to DDT. Based on these findings, the effect of DDT on male reproductive health should not be ignored.

Microsurgical Management of Male Infertility by Jonathan Schiff, M.D.

Microsurgical Management of Male Infertility 
by Jonathan Schiff, M.D.  

 

The surgical management of male infertility is one of the most exciting topics in all of medicine.  Over the last 25 years, the application of advanced microsurgical techniques has made the treatment of the infertile male one of the great success stories in medicine.  We can now offer successful treatment options to thousands of couples affected by male factor infertility whose only options in the past were donor sperm or adoption.
 
The most common correctable conditions that are associated with male infertility are varicoceles, vasal obstruction or severe testicular sperm production defects.  Microsurgical ligation of a varicocele or surgical reconstruction of the vas deferens can correct these two states.  With severe sperm production problems, microsurgical testicular sperm extraction is the most successful means of retrieving sperm for IVF.

 
Varicoceles:

Varicoceles are found in 35-40% of men with primary infertility (never had a pregnancy).  The presence of a varicocele is even more likely among couples who have had a child in the past and now can not (secondary infertility) and is found in 75-80% of these men.  Ligation of a varicocele may prevent infertility and low testosterone levels after repair.
 
The microsurgical, subinguinal approach is the preferred technique to fix varicoceles.  This approach with optical magnification produces the best results in terms of removing all of the veins that may contribute to the formation of a varicocele.  Furthermore, the microsurgical approach minimizes the complications associated with fixing varicoceles.  We can precisely identify the testicular artery and prevent damage to this important structure.  We also preserve any cremasteric arteries and lymphatic channels to prevent the formation of hydroceles.

 
Vasal Obstruction:

Obstruction to the vas and epididymis represents the most treatable causes of male infertility.  In these states, the testis functions normally and the problem is strictly a transport problem.  In the United States, the most common cause of obstruction of the vas deferens is vasectomy.  Up to 500,000 vasectomies are done annually and up to 5% ultimately are reversed.  Injury to the vas is another common cause of obstruction, most often the result of childhood hernia repair or testis surgery.  Several conditions including congenital bilateral absence of the vas deferens also result in variable lengths of vasal or epididymal obstruction.  Microsurgical techniques have vastly improved the success rate of surgery to repair vasal or epididymal obstruction.  Vasovasostomy is successful in up to 99% of cases, while vasoepididymostomy has a success rate of up to 90%.
 
 
Vasectomy Reversal - Vasovasostomy:

Overall patency rates of 86% and pregnancy rate of 51.6% were reported with the results for men with obstruction less than 3 years of 97% patency with a 76% pregnancy rate.  Others have reported similarly good results with a microsurgical approach to vasectomy reversal.  Several recent innovations have improved vasovasostomy outcomes.  The use of the microdot technique represented an important technical point in terms of planning for optimal suture placement.  Using this technique allows the surgeon to precisely target where to place sutures to achieve a water-tight anaastomosis and can result in up to a 99.5% rate of return of sperm to the ejaculate.

 
Vasectomy Reversal - Vasoepididymostomy:

Vasovasostomy is not always a feasible option to restore vasal patency.  If epididymal obstruction is present, whether primary or secondary to chronic vasal obstruction, a vasoepididymostomy is required proximal to the obstruction in order to restore continuity for sperm transport. In the situation of epididymal obstruction, the decision to perform a vasovasotomy or vasoepididymostomy is made intraoperatively and is based on the microscopic examination of the vas fluid and the time of obstruction. To provide optimal outcomes, surgeons should be skilled at performing a microsurgical vasoepidymostomy if they perform vasectomy reversals.
 
Results comparing the four main techniques of vasoepididymostomy were recently published.  The newer intussusception techniques which provide a more water-tight anastomosis have comparable patency rates with lower late failure rates than the older techniques.  This very important finding suggests that men undergoing the intussusception techniques have a much lower failure rate after reconstruction, and will remain potentially fertile longer.

 
Sperm Retrieval Techniques
 
Not infrequently, men will have severe impairments in sperm production, with or without female factors.  In these cases, sperm retrieval for assisted reproductive techniques may be the most appropriate option.  Most couples prefer natural conception, and we make every effort to enable couples to conceive on their own.  However, we evaluate each couple’s best reproductive options on a case by case basis, and when needed, microsurgical sperm retrieval is the surest path to success.
 
Several genetic and acquired problems cause men with obstructive azoospermia to be unreconstructable.  Some patients with congenital bilateral absence of the vas deferens have defects in the sperm transport system.  Many of these men are not candidates for reconstruction.  Non-obstructive azoospermia occurs when men without obstruction have no sperm in their ejaculation.  This is caused by either genetic or environmental problems -such as chemotherapy- that results in severe depression in spermatogenesis to the point that no sperm are present in the ejaculate.  However, sperm retrieval is still possible in the majority of cases.  Sperm production within the testicle is very variable.  We believe that a technique that exposes the entire testis is critical to find sperm in these difficult cases.
 
Men with Klinefelter’s syndrome have a very severe form of genetic infertility associated with an abnormal karyotype of 47 XXY.  Prior to modern assisted reproductive techniques, men with this problem were sterile.  Today, a technique of sperm retrieval with intra-cytoplasmic sperm injection (ICSI), is the preferred treatment modality in those desiring paternity. Even in this severely impacted group of men, sperm can be retrieved in over 70% of cases and pregnancies are now routinely reported.
 
The technique of microsurgical epididymal sperm aspiration is used to obtain sperm in men with an intact epididymis.  In men with non-obstructive azoospermia, the micro-dissection testicular sperm extraction technique provides the highest yield in terms of sperm retrieval while preserving as much testicular parenchyma as possible.  Even in men with severe genetic causes of infertility such as Klinefelter’s syndrome, successful retrieval of sperm is possible in up to 70% of men.    After chemotherapy, sperm can be found in nearly half of retrieval attempts in men with azoospermia.
 
Microsurgical testicular sperm extraction is the most successful technique to retrieve sperm in men with non-obstructive azoospermia and it results in the least damage to the testis.  Post-operative scarring is substantially lower with this technique compared to open biopsy.  The disadvantages of any microsurgical technique are the need for experience and the acquisition of microsurgical skills.

 
Conclusion:

Most men with infertility are treatable using either medical therapy or via surgical techniques. The advances of microsurgery in the past 20 years have enabled thousands of men who would otherwise have been unable to father their own genetic children to help create life. Some obstacles remain, but each day brings new advances that allow us to help couples conceive.
 
Jonathan Schiff, M.D.
Assistant Clinical Professor, Urology, Mount Sinai School of Medicine, New York, NY
212-996-6660
 
 
Selected References:

 

Gorelick, J. and Goldstein, M.  Loss of fertility in men with variocele.  Fertil. Steril., 59:  613-616, 1993.

Kim, E.D., Leibman, B.B., Brinblat, D.I, Lipshultz, L.I.  Varicocele repair improves semen parameters in axoospermic men with spermatogenic failure.  J. Urol., 162:  737-740, 1999.
 

Russell, J.K.  Varicocele, age, and fertility.  Lancet, 2:  222-230, 1957.
 
Cheval MJ, Purcell MH.  Deterioration of semen parameters over time in men with untreated varicocele: evidence of progressive testicular damage.  Fertil. Steril., 57: 174-177, 1992.
 
Su, L.M., Goldstein, M., Schlegel, P.  The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles.  J. Urol., 154: 1752-1756, 1995.
 
Dubin, L., Amelar, R.D..  Etiologic factors in 1294 consecutive cases of male infertility.  Fertil. Steril., 22: 469-474, 1971
 
Zorgniotti, A.W., MacLeod, J.  Studies in temperature human sperm quality and varicocele.  Fertil. Steril., 24: 854-863, 1973
 
Goldstein, M. Eid, J.F.  Elevation of intratesticular and scrotal skin surface temperature in men with varicocele.  J. Urol., 142: 743-747, 1989

Younes, AK.  Improvement of sexual activity, pregnancy rate, and low plasma testosterone after bilateral varicocelectomy in impotence and male infertility patients.  Arch. Androl., 49: 219-228, 2003.
 
Shah, J.B., et. al.  Is there an association between varicoceles and hypogonadism in infertile men?  J. Urol., 173: 449, 2005.

Takihara, M., Ichikawa, T., Shiseki, Y., Nakamura, T., Shimazaki, J..  Relationship between grade of varicocele and the resonse to varicocelectomy.  Int. J. Urol., 3: 282-285, 1996
 
Goldstein M, Gilbert BR, Dicker AP, Dwosh J, Gnecco C.  Microsurgical inguinal varicocelectomy with delivery of the testis: an artery and lymphatic sparing technique.  J Urol., 148:  1808-11, 1992.
 

Marmar, J. L, and Kim Y.  Subinguinal microsurgical varicocelectomy:  a technical critique and statistical analysis of semen and pregnancy data.  J. Urol., 152: 1127-1132, 1994.
 
Hassan JM, Adams MC, Pope JC 4th, Demarco RT, Brock JW 3rd.  Hydrocele formation following laparoscopic varicocelectomy.  J Urol. 2006 Mar;175(3 Pt 1):1076-9.
 
Wright, E.J., Young, G.P.H., Goldstein, M.  Reduction in testicular temperatrue after varicocelectomy in infertile men.  Urology, 50: 257-260, 1997 
 
Steckel, J., Dicker, A., Goldstein, M.  Relationship between varicocele size and response to varicocelectomy.  J. Urol., 149: 769-771, 1993.
 
Jarow, J., Ogle, S., Eskew, L.A..  Seminal improvement following repair of ultrasound detected subclinical varicoceles.  J. Urol., 155: 1287-1290, 1996
 
McClure R.D, Hricak H.  Scrotal ultrasound in the infertile man:  detection of subclinical unilateral and bilateral varicoceles.  J. Urol. 135: 711-715, 1986
 
Pierik, F.H., Vreeburg, J.T., Stijnen, T., van Roijen, J.H., Dohle, G.R., Lameris, J.S., Timmers, T., Weber, R.F.  Improvement of sperm count and motility after ligation of varicoceles detected with colour Doppler ultrasonography.  Int.  J. Androl., 21: 256-260, 1998  
 
Schiff, J., Li, P, Goldstein, M. Correlation of ultrasound-measured venous size and reversal of flow with Valsalva with improvement in semen-analysis parameters after varicocelectomy.  Fertil Steril. 2006 Jul;86(1):250-2.
 
Shenkyin, Y.R. et. al.  Microsurgical repair of iatrofenic injury to the vas deferens.  J. Urol., 159: 139-141, 1998.

Silber, S.J.  Microscopic vasectomy reversal.  Fertil. Steril., 28: 1191, 1977.
 
Belker, AM, Thomas Jr., AJ, Fuchs, EF, Konnak, JW, and Sharlip, ID.  Results of 1,469 microsurgical vasectomy reversals by the vasovasostomy study group.  J. Urol, 1991; 145: 505-511.    
 
Goldstein M, Li PS, Matthews GJ. Microsurgical vasovasostomy: the microdot technique of precision suture placement. J Urol. 1998 Jan;159(1):188-90. 
 
Schiff, J., et. al.  Outcome and late failures compared in 4 techniques of microsurgical vasoepididymostomy in 153 consecutive men.  J. Urol., 174: 651-655, 2005.
 
Owen, ER.  Microsurgical vasovasostomy: a reliable vasectomy reversal.
Aust N Z J Surg. 1977 Jun;47(3):305-9.
 
Silber, SJ, Pregnancy after vasovasostomy for vasectomy reversal:  a study of factors affecting log-term return of fertility in 282 patients followed for 10 years.  Hum. Reprod., 4: 318, 1989. 
 
Mathews, G.J., et. al.  Patency following microsurgical vasoepididymostomy and vasovasostomy :  temporal considerations.  J. Urol., 154: 2070-2073, 1995.
 
Berger RE. Triangulation end-to-side vasoepididymostomy.  J Urol. Jun;159(6):1951-3,1998
 
McCallum S, Li PS, Sheynkin Y, Su LM, Chan P, Goldstein M. Comparison of intussusception pull-through end-to-side and conventional end-to-side microsurgical vasoepididymostomy: prospective randomized controlled study in male wistar rats.  J Urol.;167(5):2284-8. 2002 

Marmar JL. Modified vasoepididymostomy with simultaneous double needle placement, tubulotomy and tubular invagination.  J Urol.;163(2):483-6. 2000 
 
Chan PT, Li PS, Goldstein M. Microsurgical vasoepididymostomy: a prospective randomized study of 3 intussusception techniques in rats.  J Urol.,169(5):1924-9. 2003
 
Palermo, G.D., et. al.  Fertilization and pregnancy outcome with intracytoplasmic sperm injection for azoospermic men.  Hum. Reprod., 14: 741-748, 1999.
 
Schiff, J., et. al.  Success of testicular sperm injection and intracytoplasmic sperm injection in men with Klinefelter syndrome. J Clin Endocrinol Metab,.90:6263-7, 2005.
 
Ramasamy, R., et. al., Structural and functional changes to the testis after conventional versus microdissection testicular sperm extraction.  Urology, 65: 1190-1194, 2005.
 
Chan PT, Palermo GD, Veeck LL, Rosenwaks Z, Schlegel PN. Testicular sperm extraction combined with intracytoplasmic sperm injection in the treatment of men with persistent azoospermia postchemotherapy.  Cancer. 2001 Sep 15;92(6):1632-7
 

High Resolution Sperm Selection by Peter Ahlering, MD

HIGH-RESOLUTION SPERM SELECTION (HRSS)

A Fact Sheet by Peter M. Ahlering, M.D., F.A.C.O.G.

 

With the process of in-vitro fertilization through ICSI, sperm are hand-selected at about a magnification of 500x. The sperm are selected based upon two criteria.

1. Motility, clearly we prefer to select sperm that are viable.

2. Morphology. Morphology is a description of size, shape, and physical assessment of the sperm based upon what we know to be “normal” or “textbook” appearance. When the sperm has a normal appearance according to what is referred to as the Kruger standard, then this correlates with sperm quality. In essence, “textbook” sperm is more likely to have chromosomal normality (euploidy) as well as to have less fragmented DNA. So, of course,morphology is the single most important factor that we use to select sperm.

 

Once the sperm are selected at 500 magnification, they were then set aside and subsequently injected into the egg through the process of ICSI. Thus, in essence, the process of ICSI involves two steps:

1. Selection.

2. Injection.

 

The process of sperm selection under magnification allows us to optimize sperm quality for the process of fertilization. In essence, also selecting the “best” sperm for subsequent injection minimizes the negative impact that sperm can have on an otherwise normal egg. This is in large part what we are trying to achieve through the process of ICSI: to remove the negative influence male factor can have on fertilization and subsequent embryo development in the process of IVF/ICSI.

 

Thus, of course, it stands to reason that improved ability to select sperm would translate into improved fertilization and subsequent embryo development. Then, of course, it stands to reason that improved embryo development would translate into improved implantation potential of an embryo and subsequent improved pregnancy rate/pregnancy outcome.
 
As such, optimizing sperm selection is crucial in the process of ICSI. Along this line, we have developed a system that is referred to HRSS (high-resolution sperm selection). With this technique, we are able to visualize the sperm under higher magnification at about 6000x. Utilizing this high magnification system, we optimize visualization of the sperm for the selection phase of ICSI. As noted, with this technique we were able to see fine morphologic details of the sperm that otherwise may go unnoticed in a lower magnification setting as done with traditional ICSI. In turn, we are able to more easily select “textbook” sperm, thus truly minimizing the negative impact that sperm can potentially have on otherwise normal eggs.

Indeed, the increased use of HRSS over the past three years in SIRM, St. Louis has shown to enhance positive pregnancy tests,  ongoing pregnancy rates and implantation rates versus the traditional process of ICSI. Early on, we focused on treating patients with multiple failed IVFs, multiple failed prior traditional ICSI procedures, and male factor couples. In this “high-risk” group of patients, we have seen an improved pregnancy rate, implantation, and ongoing pregnancy rate

(see data below). We believe that with continued use of this technique and broadening the application to a variety of clinical circumstances, we will continue to see improved pregnancy rates. The technique has unquestionably been shown to be safe and effective, in essence similar to traditional ICSI.

 

____________________________________

Peter M. Ahlering, M.D., F.A.C.O.G.

 

Semen Analysis: Normal Ranges

 

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.

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