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The ovarian causes for an ovulatory dysfunction include
* (1) the woman's age (ovarian reserve)
Females are born with all of their eggs and they will use these
eggs throughout their life. At menopause, few to no remaining
maturable eggs are thought to exist in the ovaries.
The decrease in fertility with maternal age is gradual rather
than sudden and usually is thought to occur slowly after about
the age of 30, then more rapidly after about 35 and much more
rapidly after about 40 years of age.
The basis for the age related decline in fertility is not well
characterized. It is widely believed that the best (most fertile)
eggs undergo recruitment and maturation in the earlier portion
of the reproductive lifespan and that those "left" in
later years represent less ovulation and fertilization capable
eggs.
A woman's fertility appears to be directly related to the number
of follicles (ovarian cysts containing maturable eggs) in her
ovaries (that is, the "ovarian reserve").
The ovarian reserve is continually decreasing with maternal age
due to the loss of many follicles each month.
There is also an age dependent increase in the miscarriage rate.
The reason for this is believed to be due to a greater number
of errors in the final assortment of the egg's chromosomes just
prior to ovulation or at fertilization. These errors lead to an
increased number of lethal chromosomal mutations in embryos. On
the one hand it is unfortunate that there are so many chromosomal
accidents and on the other hand it is fortunate that humans will
quickly reject (abort) almost any chromosomal abnormality. The
0.6% rate of chromosomal anomalies in human liveborns is quite
low compared to other animal species.
* (2) ovarian surgery,
Surgery involving partial or complete removal of an ovary will
result in fewer remaining eggs. Reports suggest that as little
as one tenth of one ovary may be sufficient for fertility in the
presence of an otherwise completely normal reproductive system.
Certainly all other things being equal, the more eggs present
in the ovary the greater the fertility.
* (3) pelvic radiation or chemotherapy
Alkylating agents and/or higher cumulative dosages of any chemotherapy
can destroy developing ovarian follicles. This may result in months
to years of anovulation and amenorrhea. Generally, if the ovary
does recover from the radiation or chemotherapy at a later date,
the quality of the eggs that are matured is not compromised and
therefore may result in normal pregnancies. There are no tests
currently available to "check the remaining eggs" for
"any genetic problem" following these treatments.
* (4) ovarian failure
When ovarian failure with amenorrhea occurs prior to 40 y/o this
is called "premature ovarian failure" (POF). POF occurs
in about 1 in 100 women. In the USA, a normal reproductive lifespan
generally is from 14 to 44 y/o, and menopause occurs typically
at about 52 y/o.
POF may be caused by a genetic abnormality. A normal duration
reproductive life requires the presence of 2 fully functioning
X chromosomes. If one X chromosome is completely lacking (resulting
in "Turner's syndrome") then all the eggs that are present
(in normal amount) during the female's development within her
mother's uterus will have degenerated by the time of her birth.
When a less severe abnormality exists on one of the X chromosomes,
the only identified problem with the female may be POF due to
the rapid depletion of her eggs. There are genetic tests (probes)
available for some of these X chromosome abnormalities. Specific
X testing may be useful for women with otherwise unexplained POF,
if she has a female relative who might also carry the abnormality
(who could then to use the information for her own family planning).
POF may be due to an immunologic abnormality. Autoimmune disease
occurs when a woman's immune system attacks her own organs. If
this attack is directed against the ovary, ovarian failure is
thought to be possible. I do not recommend these tests since anti-ovarian antibody testing
can be expensive. Up to 30% of normally ovulating women have antiovarian
antibodies, and there is no known effective treatment for the antibodies
if present.
Uncommon forms of POF exist. The "resistant ovary syndrome"
(where numerous early stage follicles can be found but do not
respond to FSH) and some "steroid hormone enzyme deficiencies"
(where the enzymes required for hormone production are decreased
or absent) possibly present as amenorrhea after a few spontaneous
menses at puberty.
* (5) cigarette smoking
Cigarettes are associated with fertility problems. Research consistently
demonstrates a significant decrease in fertility (up to 30-50%)
when comparing smokers to nonsmokers.
Cigarette smoking can interfere with the communication between
the brain and the ovary such that a smaller sized follicle develops.
Cigarettes can limit the secretion of pituitary LH during the
preovulatory LH surge which might interfere with ovulation. Cigarettes
can also directly reduce the number of eggs remaining in the ovary,
with more than 13 studies showing that smokers go through menopause
(ovarian failure due to egg depletion) 1-2 years prior to nonsmokers.
Cigarettes can also result in tubal function abnormalities. Reports
demonstrate that smokers have a 2-4 fold increase in ectopic pregnancy
rate.
Cigarettes can also result in implantation abnormalities. Reports
demonstrate that smokers have up to 2 times as many miscarriages.
Cigarettes may result in male factor fertility abnormalities.
Reports demonstrate decreases in semen analysis parameters in
smokers.
* (6) infections
When infection involves the reproductive organs the damage to
those tissues can be extensive. If the ovary is involved, especially
when there is an abscess involving the ovaries and tubes, the
infection and inflammation can destroy the ovary to the point
where a surgeon cannot even establish the presence of normal ovarian
tissue. The woman can experience amenorrhea either immediately
or within a year or so of treatment.
* (7) compromised blood supply
An abundant blood supply is required for the survival of the ovary,
and if compromised either following surgery (uncommon) or due
to blood clots developing in the vessels to the ovary (rare) deterioration
of ovarian function may occur.
* (8) endometriosis
Endometriosis is associated with infertility but the mechanism
is not clear. It is widely accepted that it is more difficult
to stimulate ovulation with fertility medications in women with
endometriosis. The nature of the effect that endometriosis seems
to have on the ovary is not clear.
* (9) medications
Nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit ovulation.
The physical release of the egg from the ovary seems to be partly
dependent upon a class of molecules called prostaglandins. Medication
that inhibits the production or function of prostaglandins (such
as NSAIDs like Motrin or Alleve) may interfere with ovulation.
NSAIDs have been shown to disrupt ovulation in rabbits and rodents
and therefore peri-ovulatory use is discouraged in women trying
to get pregnant.
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