Sperm Morphology: The Most Important Parameter in the Semen Analysis:

• Kruger Morphology Strict Criteria is widely accepted as the best predictor of male fertility potential, better than concentration or motility

• Low Kruger morphology has been associated with poor outcome in spontaneous conception, IUI cycles and traditional IVF. IVF/ICSI is considered to be the treatment of choice when there is poor morphology as assessed by the Kruger strict criteria

• With IVF/ICSI, poor sperm morphology has been associated with normal fertilization rates but higher rates of spontaneous abortion (Soderlund 1994; Janny and Menezo 1994; Oehninger 1988)

• Delayed fertilization and lower embryo cleavage rates have been associated with morphologically abnormal sperm (Ron-El et al. 1991)

• Sperm with abnormal morphology result in higher incidence of embryos with poor cleavage, fragmentation and overall poorer embryo morphology

• Abnormal morphology of sperm correlates with the DNA/chromatin quality; higher rates of abnormal morphology correlate with higher rates of DNA damage. DNA damage, in turn effects, embryo development, cleavage of the embryos, blastocyst formation and subsequent ability to implant successfully.

• Poor morphology of the sperm is linked to abnormal embryo development and poor implantation with subsequent early repeated pregnancy loss (S. Hammah et al. 1997, Hum Rep Update)

• Specific sperm structures, like the centrosome housed in the sperm midpiece, have been closely associated with poor embryo cleavage (von Berklom, 1995 Hum Rep Up)

• As good as the Kruger strict criteria system is, relative to other established semen assessment standards, it is imprecise in predicting live birth outcome. This is partly due to the fact that at the time of ICSI, clearly abnormal sperm (at 250x magnification) are de-selected by the embryologist prior to injection of any single sperm into the egg.

• The Kruger assessment is done at 1000x magnification thus some more subtle abnormalities seen at the time of the semen analysis are not visible that at the time of ICSI (250x magnification).

• Thus, our ability to select the morphologically best sperm is limited by the system of sperm preparation and magnification. However we now have an improved way of doing this whole process, allowing us to isolate and use the most normal appearing sperm in a sample. In this way we can take full advantage of the eggs that are ‘normal’, we are doing the best we can to not compromise the eggs with morphologically poor sperm.

• We have now instituted this process of sperm selection at SIRM St Louis. Our ability to see the amount of morphologically ‘textbook appearing sperm’ is now optimized with what we call the MSA. This is a high resolution semen analysis that tells us the most we can learn about morphology of the sperm and how we can optimize treatment with IVF/ICSI.
  
  

DNA Fragmentation: Why Advanced Semen Analysis is Vital

Time to conception (in natural circumstances) is increased when DNA fragmentation is present. With DNA fragmentation (DNAF) of the sperm, there is an increased chance of early pregnancy loss and biochemical pregnancy associated with other abnormalities in the semen analysis, but not always.

• DNAF can often be associated with normal semen analysis
• DNAF can be improved with antioxidant vitamin regimen in some cases
• DNAF can often be associated with varicocele and most often it is improved after varicocele surgery
• DNAF can be associated with exposure to toxic chemicals, smoking and excessive alcohol intake
• DNAF can be improved with hormone treatment in some cases.
• DNAF is often present in couples with 'unexplained infertility', thus actually explaining the problem
• The worse the semen parameters on the traditional semen analysis, the more likely DNA fragmentation is present also.
• DNAF can be measured in specific labs only, but all evaluations of the semen can be done through our office on a single sample in the majority of cases.
• DNAF of the sperm can affect the outcome of IVF procedures such as poor fertilization, poor embyro development, and early pregnancy loss/negative pregnancy test.
• DNAF Is associated with lower chances of success with IUI cycles also.
• When there are problems with the traditional semen analysis and DNA fragmentation, the best treatment is most likely IVF and ICSI to optimize success.
• DNAF can be affected by increasing male age.
• DNAF is associated with exposure to 'heavy metals' like lead, mercury, cadmium, etc.
  

We are learning constantly about the problem and how DNAF affects fertility. However, there are some obvious things that we can do to improve the fertility potential and increase the success of treatments like IUI and IVF. The first important thing to do is to evaluate whether DNAF is present with the simple tests recommended. Then we can deal with it as best as possible to enhance the chances of success.

Please contact me if we can discuss or provide further information.

Peter Ahlering MD
SIRM St Louis
pahlering@sherinstitute.com
314-983-9000
http://www.haveababy.com/

Male Infertility Article in St. Louis Women's Journal

CLICK HERE to read the article on male infertility I wrote recently for St. Louis Women's Journal:

DNA FRAGMENTATION ASSESSMENT ON SPERM

Sperm Chromatin Structure Assay (SCSA) is a tool for measuring clinically important properties of sperm nuclear chromatin integrity. The results correlate well with the potential of sperm from a given male to produce embryos that would be sufficiently “competent to produce a live birth. The SDIA utilizes the metachromatic features of acridine orange (AO), a DNA probe, and the principles of flow cytometry (FCM).
SCSA data are not well correlated with classical sperm quality parameters and have been solidly shown to predict sub/infertility and poor reproductive performance. The SCSA measures DNA damage. The degree of abnormalities in the genetic material of the sperm is expressed numerically as the DNA Fragmentation Index (DFI). DNA damage may be present in sperm from both fertile and infertile men. Therefore, this sperm DNA damage analysis may reveal a hidden abnormality of sperm DNA in infertile men classified as unexplained based on apparently normal standard sperm parameters. Infertile men with abnormal sperm characteristics exhibit increased levels of DNA damage in their sperm. Sperm from infertile men with normal-appearing sperm may have DNA damage to a degree comparable to that of infertile men with abnormal-appearing sperm. The data suggests that an abnormal SDI assay is more likely to occur in cases of abnormal semen parameters. Thus the assay is ideally suited to fertility clinics to assess male sperm DNA integrity as related to fertility potential and embryo development as well as effects of reproductive toxicants. Since SCSA assay parameters are independent of conventional semen parameters, results may allow physicians to identify male patients for whom IVF or intracytoplasmic sperm injection ( ICSI) are necessary.

Cancer treatments are well known to adversely affect male fertility. Reduction of sperm output arises from the cytotoxic effects of chemo-or radiotherapy upon the spermatogenic epithelium. However, even if the epithelium survives there is a hazard to reproduction as the transgenerational in expression and present with effects ranging from “infertility" to miscarriage and there is an association with infertility and reproductive performance. Optimal sperm chromatin packaging seems necessary for full expression of the male fertility potential. SDI assays emerge as predictors of the probability to conceive and carry the pregnancy to viability
The improvement seen in sperm motility after sperm separation and sperm washing with IUI processing is not associated with a similar improvement in sperm DNA integrity. These data suggest that sperm processing techniques will not minimize sperm DNA damage and the potential transmission of genetic mutations in assisted reproductive cycles.

Data suggests the following :

• The viable (>12 weeks) IVF pregnancy rate (and thus presumably also the birth rate) could be as much as 2 times lower in women under 33yrs of age, whose husbands have abnormal SCSA assays ( with a DFI of <30%).>
• Although it is possible for abnormal SCSA results to sometimes spontaneously revert back to normal, this probably occurs quite infrequently.
• Although abnormal SCSA results are detected in men with apparently normal semen analyses, abnormal results are more commonly seen in cases of men who have abnormal sperm parameters (abnormal sperm count, motility and/or morphology)
• There is some suggestion that the use of antioxidant therapy ( Pycnogenol 200mg daily, L-Carnitine 3 grams per day, acetyl carnitine 500mg per day, Vitamin C 1,000mg per day and Vitamin E 800IU per day) taken for 6-8 weeks , can causes the SCSA assay to revert to normal in many cases. There is some suggestion that men who have varicoceles ( a collection of distended veins in the scrotum) associated with an abnormal SDI assay may experience a reversion of the SDI assay back to normal, 3-6 months following surgical or radiological ablation of the varicocele.

In summary, an abnormal SCSA assay augurs poorly for the outcome of non IVF (IUI or natural conception) fertility treatment in general but not IVF/ICSI in specific. In such cases, the fertilization rate and pregnancy rates are reduced and the chance of early pregnancy loss appears to be increased significantly. An abnormal SCSA result of course does not totally preclude a successful pregnancy. The prognosis worsens progressively as other factors come into play like female age.

The SDIA or the SCSA has become regarded as required baseline tests (to performed, regardless of their basic traditional semen analysis parameters (count, motility and sperm morphology) as the results are independently predictive of non IVF treatment outcomes. This obviously is important in decision making for the couple on what treatments to do and what expectations should then be on success.

Unexplained IVF Failure: Caused by Thrombophilia?

Hereditary thrombophilia is defined as the genetic predisposition to develop intravascular thrombosis. It affects as many as one in five people in the United States and at least 60% of women who experience recurrent pregnancy loss (RPL) and/or recurrent IVF failures (RIF). It is due to hypercoagulability of the blood leading to impairment of initial vascularization that takes place during implantation.

Aside from increasing the risk of RPL and RIF, hereditary thrombophilia is also associated with late pregnancy-induced complications such as preeclampsia, premature separation of the placenta (abruptio placenta), placental insufficiency with intrauterine growth retardation and in still birth. This having been said, it is a fact that most women with a thrombophilia experience healthy pregnancies.Thrombophilia occurs in association with one or more of the following risk factors:

• Mutational defect involving methylenetetrahydrofolate reductase (MTHFR), which occurs in at least 20% of affected cases. Homozygosity for a common C677T mutation in the MTHFR gene that is associated with hyperhomocysteinemia is the most common form of hereditary thrombophilia leading to a 3-fold increase in risk of complications.
• Mutation of factor V Leiden (FVL), which increases the risk of recurrent early pregnancy loss, 3-4 fold
• A mutation of prothrombin G20210A, which reportedly increases the risk of early pregnancy loss 2-4 fold
• Deficiency of antithrombin III
• Deficiency of protein C
• Deficiency of protein S
• Increase in antiphospholipid antibodies (APA), i.e. “APA Syndrome”

All pregnant women with a history of having had a blood clot should be offered testing for hereditary thrombophilias. Also women with a family history of blood clots, pulmonary embolism (blood clot in the lung), strokes, or a history of the pregnancy complications referred to above should be tested.Low-dose aspirin with the B vitamins folic acid, B6 and B12 can be given to women who have milder thrombophilias and no history of pregnancy complications. Women found to have severe varieties (e.g. homozygous MTHFR mutations. Protein C deficiency or prothrombin G20210A mutation) and those who have experienced one or more of the thrombophilia-related complications mentioned above , are best treated , with low-molecular weight heparin (LMWH), begining with the chemical diagnosis of pregnancy and continuing for at least 6 weeks following delivery.

Read Dr. Geoffrey Sher's article on the same topic here: Unexplained IVF Failure: Can it be Caused by a Hereditary Clotting Defect (Thrombophilia)?

The Biological Clock and Fertility Evaluations

There are few individuals, male or
female, that don't think at some point in
their lives about having children and
raising a family. It's hardwired in the
human genetic code. However, it's
become increasingly common to get
"distracted" in life from these thoughts of
procreation and family, pushing them out
of our minds while we occupy ourselves
with career and other various activities.
Invariably, however, the idea of childbearing
comes back.
The problem is that nature doesn't get
distracted from its incessant negative
effects on reproductive potential. The
"Biological Clock" does not stop ticking
for anyone, and for some individuals, it
ticks much faster than they would hope
or expect.
This sounds horribly ominous!
Nevertheless, it's true. The good news is
that there are ways to preemptively
address this reproductive aging process.
The first crucial step for anyone in understanding
the effect on the clock on them
at any given point in time is a fertility
assessment.
For females, this 'snapshot'
assessment is simple
and easy to perform
with routine blood work
and an ultrasound. It's
usually covered by insurance,
and if not, can all be
done for a few hundred
dollars.
Here's the background
for women: Even before
birth, you're losing eggs
from your ovaries. (See
Table 1) At birth, a woman
has about two million
eggs. By the time the first
menses occurs at around
age 11, she has about 400,000. In her
mid-thirties, the rate of loss increases,
such that by around age 50, there aren't
any left. This is the onset of menopause.
Adding insult to injury, egg quality also
declines as a woman ages. That is, the
chance that any one egg will make a
baby decreases as "the Clock" ticks. So
with age comes fewer eggs - and poorer
quality ones at that. Though I think that
most people instinctively understand the
concept of age-related fertility decline,
I've found that very few of them understand
that the decline starts a lot
younger than is commonly thought - on
average around age 27. (See Table 2)
As a reproductive specialist, the first
thing that I do when evaluating a
patient/couple that is having problems
achieving pregnancy is assess the
impact of the Biologic Clock in that individual
woman. This means assessing
ovarian reserve - finding out "how many
eggs are left." If the reserve is low, time
is not that patient's friend. She may
decide to pursue pregnancy sooner
rather than later, before the reserve
declines further or is completely depleted.
If reserve is high, she can plan her
childbearing path accordingly.
Ovarian reserve and egg quality are
undeniably the most important aspects
to achieving a pregnancy. Knowing
these things is a relatively simple matter
of undergoing the basic screening tests
and discussing the results with your
physician.
Fertility screening can empower a
woman by providing critical information
about her fertility that she can use to
make informed decisions that impact her
life, such as:
- Do I want a family?
- If so, how soon?
- What do I want to do with my career?
- Does the knowledge gained from fertility
screening alter how I look at that?
Some misconceptions I hear frequently
are:
- "I'm young. I should have no problems
getting pregnant when I'm ready."
- "I know someone that had a baby at
age 42. I'll be OK."
- "I'm healthy, eat right and exercise,
so I should have great fertility."
- "My Mom was 55
before she hit menopause,
so I'll be fertile for a long
time."
These thoughts often
give people false hope.
Don't make assumptions.
The only way to know is to
do the simple blood tests
and ultrasound - so simple,
yet so valuable. Then talk
to your doctor or reproductive
specialist about what it
means to you. Ask them to
put it in the context of your
particular situation. This is
easy to do and it can change your thinking
and your life.
In the field of Reproductive Medicine,
there are viable emerging techniques
and technologies for egg freezing or
"cryopreservation" (sperm cryopreservation
has been available for decades).
These technologies have recently
undergone significant advances that
dramatically improve live birth rates. We
can now cryopreserve eggs for patients
that are undergoing potentially damaging
ovarian surgery and cancer
chemotherapy (both which can negatively
impact ovarian reserve and thus fertility
future). These techniques also make
it possible to freeze and store eggs for
those that wish to preserve fertility or
postpone childbearing for other personal
reasons.
I strongly encourage women who are
considering having children now or in the
future to undergo a fertility evaluation.
The information is too easily obtained
and too valuable to neglect.
SIRM™ - St. Louis
456 N. New Ballas, Suite 101
Creve Coeur, MO 63141
(314)983-9000
www.haveababy.com stlouis@haveababy.com
Table 1
Table 2
By: Peter Ahlering MD
Medical Director,
Sher Institutes for Reproductive
Medicine - St. Louis
Fertility Screening and Preservation: Planning for the Future

Male Infertility

Welcome to the Male Factor Infertility blog. This site is a "sister" (or maybe more appropriately a "brother") site to my main blog - PeterAhleringMD.com

I am the Medical Director for the Sher Institute for Reproductive Medicine in St. Louis, which also is home to our specialized facility, The Center for Male Infertility. I have a special interest in the diagnosis and treatment of male factor issues, and have dedicated a portion of my practice to this purpose.

It is a fairly well known fact that men in the Midwest have an inordinately high incidence of sperm quality issues. This is due largely to the prevalence of various pesticides used in farming throughout the region. Fortunately, there are a number of steps that can be taken to help offset this problem. In upcoming posts, I will address this issue specifically, as well as a wide spectrum of other male infertility factors.

I will probably alternate posts between this blog and my home blog, so please bookmark both sites.

www.PeterAhleringMD.com