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Cervical
Mucus Quality, Clomid and Sperm Transport?
Q: I
have read information about the maximum amount of time
that sperm can survive in fertile cervical mucus (CM).
Can you tell me the maximum amount of time sperm can
survive in non-fertile CM, like sticky or creamy? Is it
only a problem in the vagina and once the sperm makes it
into the uterus it can survive for several days? Or, is
it that sperm can only make it from the vagina into the
cervix if there is fertile CM?
A: After
ejaculation, sperm have to be able to swim through the
cervix to reach the Fallopian Tube where fertilization
of the egg occurs. The sperm that can fertilize the egg
begin leaving the ejaculate within 1 min after
deposition, and no sperm that get to the Fallopian Tube
have ever been proven to do so after 30 min of
ejaculation. The "cervical reservoir" of sperm is not an
actual pool of fertilizing sperm.
Sperm have to get thru CM to get to the Fallopian tube
where they are then stored for hours to days until the
egg comes. However, the interactions of sperm and
cervical mucus that allow this migration are often
disrupted in fertility patients. It is thought that at
least a third (if not more) of subfertile couples have
some disruption of sperm-cervical mucus interactions
that limit sperm transport to the tubes.
The importance of normal CM in natural reproduction is
widely recognized. For most of a woman’s cycle the CM is
a thick gel and hostile to sperm, with a low pH and a
structure that stops sperm transport by the presence of
closely spaced microfibers. During ovulation, however,
the CM becomes more alkaline (higher pH), and the fibers
align in parallel with an expanded distance between
them. This allows the sperm to swim through the mucus.
Normally, the volume of daily CM also increases 5 fold
at ovulation. CM is a hydrogel of 90% water, and its
primary function appears to be bathing sperm in a fluid
medium to protect them during transport . The presence
of sugar-proteins in the gel that hold the water is
controlled by hormone changes at ovulation (especially
the presence of estrogen). These sugars increase the
mucus gel’s capacity to hold water, expand fiber
spacing, & allow sperm migration. Taken together, these
changes permit sperm to rapidly swim through the cervix
and proceed to the Fallopian tube for fertilization.
In women with poor sperm-CM interaction there is a
reduction in CM fiber spacing making sperm migration
difficult, a primary cause of which in many women may be
inadequate water in the gel. This may be caused by
advancing age (with low grade hormonal disruptions); and
following the use fertility medication such as
clomiphene citrate (CC or clomid). CC is a widely
prescribed fertility drug. In fact, it has become
increasingly used as a first line therapy for couples
with fertility issues. With easy internet access, many
women are also taking CC without doctor oversight.
Estimates are that 40% of couples with fertility
problems utilize CC at some point for the woman.
Although it’s wide spread use has helped many couples
conceive, it does cause significant problems with
vaginal dryness and CM production and function.
Specifically, numerous studies have shown that CC causes
decreases in: volumes of CM; quality of CM (“egg-white
like appearance”); and sperm penetration into CM. In
fact, women on CC are seven times more likely to have
“hostile” CM that is difficult for sperm to penetrate
than are women not on the medication.
Women on CC also have an increased prevalence of vaginal
dryness, which can cause pain at intercourse and
decrease enjoyment for the man (which can decrease sperm
counts). Many women on CC (which is already making them
prone to poor sperm-cervical mucus penetration) are
therefore also using lubricants that can harm sperm such
as KY, Astroglide and Replens. These women may be
creating a vaginal environment that limits sperm
transport. Pre~Seed “sperm-friendly” Intimate
Moisturizer can replenish vaginal moisture without
harming sperm. A clinical trial is also planned to
evaluate the effect of Pre~Seed on sperm and cervical
mucus interactions, especially for women on Clomid.
Dr. E
Declining Fertility
with Age in Men
Declining fertility with age-- Not just a female issue.
We all know about the increased risks of infertility or
birth defects in older women who want to have a child.
Many of us who became pregnant in our 40’s have had to
decide what level of testing we will undergo in order to
conceive a child, and once pregnant, to find out the
health of our unborn baby. We are all aware that these
risks are due to chromosome changes in the egg that
occur as women age.
However, as with most things reproductive, the medical
community has lagged far behind in evaluating the effect
of aging in men on sperm quality. Several recent studies
have begun to paint a picture of aging of the male
reproductive tract which is very similar to that seen in
women.
Specifically, in a study of 2,000 couples published in
2003(Hassan & Killick, Fertility & Sterility; June,
2003), men that were over 45 years of age had a five
fold increase in time to pregnancy (how long it took to
become pregnant) as compared to younger men. This effect
was seen even after taking into account the variables of
their wife’s age, how often they had intercourse and
whether or not they had fertility adverse life styles
(smoking, drinking etc..). Even older men who had very
young wives (<25 yrs of age) had a 4 fold increase in
time to pregnancy.
In this study, 57% of these 2,000 unselected couples
became pregnant within 3 months of trying to conceive,
and 81% after 1 year. The average time to pregnancy
increased from 7 months in men that were 25 years of age
or younger, to 37 months in men that were over 45 years
of age.
Other work suggests that similar to the changes seen in
women, these delays in fertility may be due to DNA or
chromosomal abnormalities in the sperm of older men.
Singh et al (Fertility & Sterility, Dec 2003) found that
the DNA of sperm in men ages 36-57 had far more breakage
in the strands than did sperm from men ages 20-35. These
strand breaks have been associated with infertility,
early embryo losses, miscarriages and even birth defects
or cancer in children.
Another study (Sloter et al., Fertility & Sterility
April, 2004) also showed age related increases in the
number of sperm with broken or damaged DNA for men,
especially sperm with structural chromosomal
abnormalities. This study suggested that these changes
may be due to environmental toxin damage, or a loss of
antioxidant effectiveness in aging individuals.
Unfortunately, there are not studies yet to confirm if
taking antioxidant vitamins can help sperm quality in
older men that desire to father children. However, there
is a growing body of evidence that vitamins with
antioxidants help men with sperm damage in general.
Visit the www.helpconceive.com Reference Library to see these
studies.
What can be done to help the chances of conceiving for
older men? Be sure and have a sperm chromatin assay done
in addition to a normal semen analysis (visit
www.scsadiagnostics.com to learn more), so that you
know what you are working with. His~Seed Moisturizer for
men, can help make semen sample collection feel better,
and the more fun ejaculation is, the more sperm a man
can produce for these samples. Talk to your doctor about
supplementing with a vitamin containing antioxidants,
especially one formulated for fertility issues. Finally,
make sure you have well timed intercourse with ovulation
to optimize the chances of sperm and egg meeting.
Vaginal dryness issues that occur with daily intercourse
around ovulation can be relieved with Pre~Seed, a
sperm-friendly Intimate Moisturizer that does not harm
sperm, as do vaginal lubricants.
Dr. E
Final Pre~Seed User
Survey Report
Final Pre~Seed User Survey Results 7.1.05
The following data is from 100 self-reporting Pre~Seed
Users, responding to an internet request for information
in May and June, 2005. This is a self responding survey,
and there are no controls for comparison (i.e. couples
not using Pre~Seed) so it is NOT in any way a scientific
study. But it has some interesting information!
These self reported findings include:
31% of respondents became pregnant using Pre~Seed. This
broke down into pregnancies in: 30% of couples who had
been trying for 0- 2 months;
40% of couples trying for 3-6 months;
23% of couples trying for 7-12 months; and
31% of couples trying for one year or more.
This is in comparison to population studies suggesting a
maximum pregnancy rate per cycle of 30% in presumed
“fertile” couples over the first 2 cycles which then
declines over the following cycles (Zinaman et al. Fert
Ster 1996).
65% of these became pregnant in the first two cycles of
use, and 35% became pregnant after 3 or more cycles of
use.
51% of our users started using Pre~Seed after they had
been trying to conceive for 7 or more months, and 54% of
all folks who became pregnant had been trying to
conceive for 7 or more months before they started using
Pre~Seed.
The pregnancies reported resulted in:
17% a boy,
19% a girl,
35% reported no gender,
29% had a lost pregnancy (miscarriage), including early
“chemical” losses.
The gender difference is likely not significant. The
miscarriage rate is very consistent with pregnancy
losses reported in other studies (31% - Wilcox et al,
NEJM, 1988; 33% - Wang et al Fert Ster, 2003.
25% of all couples using Pre~Seed had undiagnosed
infertility, 26% had diagnosed male factor issues, and
34% had diagnosed female factor issues. Further, 25%
were taking Clomid, and 16% other fertility medications.
For couples that became pregnant, this was 15%
undiagnosed, 19% male factor, 23% female factor, with
21% on Clomid, and 21% on other fertility medications.
45% mentioned no infertility diagnosis.
84% of users liked “the way Pre~Seed feels” well enough
to want to use it as their regular lubricant, if a more
cost effective version were available for non-fertile
times.
65% of users disliked the cost- this of course varied on
if the couple had become pregnant or not!!! And 50%
disliked that it wasn’t in a regular drugstore chain.
70% of you liked 6 or more applicators in a box;
however, about 25% of you wanted a new “intro pack” size
for people trying the product for the first time.
Dr. E
How Long
to Abstain for a Sperm Test/Analysis
Recent studies suggest that abstaining for a
sperm test or a procedure such as IUI/IVF should be
limited to no more than 1- 2 days. The first study
looked at men with abnormal sperm (oligospermic) and
found the best sperm quality occurred at 1 day of
waiting or abstaining prior to production. For men with
normal sperm waiting more than 10 days between
productions resulted in abnormal sperm quality.
In the second study that looked at functional quality
(i.e. “did the sperm result in an artificial
insemination IUI pregnancy”, they found:
”Abstinence correlated positively with inseminate sperm
count but negatively with motility.”
meaning that abstinence increased sperm count but
lowered motility... who cares the number of sperm if
they can't swim!
”Variations in inseminate parameters did not correlate
with pregnancy rates”.
How the sperm looked on testing did not relate to
pregnancy outcomes - discussed in the FAQ on doing sperm
analysis.
However, abstinence intervals significantly affected
pregnancy rates.
”The time of abstinence impacted outcome. Couples that
had 10 or more days of waiting had only a 3% pregnancy
rate!
Based on these studies 1-2 days wait before production
is probably best.
References:
Fertil Steril. 2005 Jun;83(6):1680-6.
Relationship between the duration of sexual abstinence
and semen quality: analysis of 9,489 semen samples.
Fertil Steril. 2005 Sep;84(3):678-81.
Related Articles, Links:
Effect of ejaculatory abstinence period on the pregnancy
rate after intrauterine insemination.
Dr. E
Parabens
Q. I have heard that
parabens can cause infertility and cancer, why do you
have them in Pre~Seed?
A. A preservative, such as methylparaben (in
Pre~Seed) is required to
keep products from growing bacteria, and
other preservatives can
cause much more sperm
damage (acids, EDTA
etc…). Additionally,
bacterial byproducts
called endotoxins can
damage sperm and the
female reproductive
tract (Fallopian tube).
We pride ourselves on
the low level of
endotoxin that we
tolerate in Pre~Seed.
Other lubricants,
especially natural
productones, can have
much higher endotoxins
levels, some as high as
700 EU/ml! So this is
why we have a
preservative.
Does the preservative
harm fertility? The
studies as to Pre~Seed’s
effect on sperm and
embryos have been done
by several third party
Universities, and
include
no effect of the product
on human sperm motility,
fertilization of embryos
in vitro (animal model)
or subsequent embryo
development even at 50%
concentrations of the
Pre~Seed in
the dish at the time of
fertilization. In fact,
Pre~Seed maintained
sperm DNA quality in the
laboratory versus other
lubricants that damaged
sperm DNA. You can see
reviews of these studies
at our
Science page.
We chose to use
methylparaben (single
use products) and
propylparaben (multi-use
products) in our
isotonic vaginal dryness
relief products (Pre~Seed
& Pre’) because they
have very long histories
of use and safety data.
Other parabens (such as
butylparaben) have been
shown to be mildly
estrogenic at high
doses, although some of
the studies on this have
since been refuted. I am
an Andrologist and I
study sperm physiology.
You can read about my
work at this link
http://preseed.com/PDF/wsmEllington.pdf,
including my concerns
about environmental
estrogens, and my Award
for my research in this
area.
A recent toxicology
review (first article
below) states that it
does not appear possible
to intake enough
parabens through product
use to surpass any
estrogenic activity from
dietary estrogens,
although I do believe
you want to limit your
overall load. Most
importantly, this should
include not eating
commercial meat (with
the hormone injections),
and I can see a case for
avoiding the higher
order parabens such as
butyl (based on other
studies). Of course you
should use products that
fit in your overall
lifestyle choices.
Methyl and propyl
paraben are low active
parabens (see the second
article with NO activity
on the sperm production-
one of the most
sensitive indicators).
Further, in a study
where they cultured
parabens directly with
sperm in a dish (no body
metabolism or dilution)
methylparaben had no
adverse effect on sperm
until it reached high levels. Our products
have 1.5 mg/ml methylparaben, so the
concentration is far
below any adverse level,
even in this extreme
condition of direct
culture contact. The
active level in this
study for the
propylparaben was 3
mg/ml. Our products
have 0.15 mg/ml
The
studies can be reviewed
below:
Crit Rev Toxicol. 2005
Jun;35(5):435-58.
A review of the
endocrine activity of
parabens and
implications for
potential risks to human
health.
·
Golden R,
·
Gandy J,
·
Vollmer G.
ToxLogic LC, Potomac,
Maryland 20854, USA.
RGolden124@aol.com
Parabens are a group of
the alkyl esters of p-hydroxybenzoic
acid and typically
include methylparaben,
ethylparaben,
propylparaben,
butylparaben,
isobutylparaben,
isopropylparaben, and
benzylparaben. Parabens
(or their salts) are
widely used as
preservatives in
cosmetics, toiletries,
and pharmaceuticals due
to their relatively low
toxicity profile and a
long history of safe
use. Testing of parabens
has revealed to varying
degrees that individual
paraben compounds have
weakly estrogenic
activity in some in
vitro screening tests,
such as ligand binding
to the estrogen
receptor, regulation of
CAT gene expression, and
proliferation of MCF-7
cells. Reported in vivo
effects include
increased uterine weight
(i.e., butyl-,
isobutyl-, and
benzylparaben) and male
reproductive-tract
effects (i.e., butyl-
and propylparaben).
However, in relation to
estrogen as a control
during in vivo studies,
the parabens with
activity are many orders
of magnitude less active
than estrogen. While
exposure to sufficient
doses of exogenous
estrogen can increase
the risk of certain
adverse effects, the
presumption that similar
risks might also result
from exposure to
endocrine-active
chemicals (EACs) with
far weaker activity is
still speculative. In
assessing the likelihood
that exposure to weakly
active EACs might be
etiologically associated
with adverse effects due
to an endocrine-mediated
mode of action, it is
paramount to consider
both the doses and the
potency of such
compounds in comparison
with estrogen. In this
review, a comparative
approach involving both
dose and potency is used
to assess whether in
utero or adult exposure
to parabens might be
associated with adverse
effects mediated via an
estrogen-modulating mode
of action. In utilizing
this approach, the
paraben doses required
to produce estrogenic
effects in vivo are
compared with the doses
of either
17beta-estradiol or
diethylstilbestrol (DES)
that are well
established in their
ability to affect
endocrine activity.
Where possible and
appropriate, emphasis is
placed on direct
comparisons with human
data with either
17beta-estradiol or DES,
since this does not
require extrapolation
from animal data with
the uncertainties
inherent in such
comparisons. Based on
these comparisons using
worst-case assumptions
pertaining to total
daily exposures to
parabens and
dose/potency comparisons
with both human and
animal
no-observed-effect
levels (NOELs) and
lowest-observed-effect
levels (LOELs) for
estrogen or DES,
it is biologically
implausible that
parabens could increase
the risk of any
estrogen-mediated
endpoint, including
effects on the male
reproductive tract or
breast cancer.
Additional analysis
based on the concept of
a hygiene-based margin
of safety (HBMOS), a
comparative approach for
assessing the estrogen
activities of weakly
active EACs,
demonstrates that
worst-case daily
exposure to parabens
would present
substantially less risk
relative to exposure to
naturally occurring EACs
in the diet such as the
phytoestrogen daidzein.
Food Chem Toxicol.
2002 Dec;40(12):1807-13
Effects of propyl
paraben on the male
reproductive system.
Oishi S.
Department of
Toxicology, Tokyo
Metropolitan Research
Laboratory of Public
Health, 3-24-1,
Hyakunin-cho,
Shinjuku-ku, Japan.
oishi@tokyo-eiken.go.jp
Parabens are p-hydroxybenzoic
acid ester compounds
widely used as
preservatives in foods,
cosmetics, toiletries
and pharmaceuticals.
These compounds exert a
weak estrogenic activity
as determined by in
vitro estrogen receptor
assay and in vivo
uterotrophic assay. In a
previous study, it was
demonstrated by the
present author that
exposure of post-weaning
mammals to butyl paraben
adversely affects the
secretion of
testosterone and the
function of the male
reproductive system. In
the present study, it is
shown that propyl
paraben also adversely
affects the hormonal
secretion and the male
reproductive functions.
Propyl paraben was
administered to
3-week-old rats which
were divided into four
groups of eight animals
each, at doses of 0.00,
0.01, 0.10 and 1.00%
with the AIN93G modified
diet. At the end of 4
weeks, the rats were
sacrificed by
decapitation and the
weights of testes,
epididymides, prostates,
seminal vesicles and
preputial glands were
determined. There were
no treatment-related
effects of propyl
paraben on the organ
weights in any of the
study groups. The cauda
epididymal sperm
reserves and
concentrations decreased
in a dose-dependent
manner and the
difference was
significant at
dose of 0.10%
and above. Daily sperm
production and its
efficiency in the testis
of all groups receiving
propyl paraben
significantly decreased.
The serum testosterone
concentration decreased
in a dose-dependent
manner and the decrease
was significant in the
group that received the
highest dose. The
exposure level at which
this effect was observed
is the same as the
upper-limit acceptable
daily intake (10 mg/kg
body weight/day) of
parabens in the European
Community and Japan.
Contraception.
1989 Mar;39(3):331-5.
In vitro spermicidal
activity of parabens
against human
spermatozoa.
Song BL,
Li HY,
Peng DR.
Tianjin Family Planning
Research Institute,
People's Republic of
China.
Potent in vitro
spermicidal activity of
parabens against human
spermatozoa was
demonstrated in this
study. The "pass" point
concentration of the
four
parabens--methylparaben,
ethylparaben,
propylparaben, and
butylparaben, at which
all spermatozoa were
immobilized and no
immobilized spermatozoon
revived after 30 min
incubation in phosphate
buffered glucose
solution, was 6, 8, 3,
and 1 mg/ml,
respectively, as tested
by Harris' method. These
parabens are used as
food and pharmaceutic
preservatives; less
toxicity and side
effects were expected
for the development of
parabens as vaginal
contraceptive agents.
Dr. E
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