Fertility Issues Associated With
DES-exposure
A majority of DES-exposed men and women are currently in their later
reproductive years and may be seeking therapy for fertility problems.
A review of existing medical literature suggests that approximately
82% of DES-exposed women will achieve pregnancy without medical
intervention. The mean conception time may be delayed however and
a small number of DES-exposed women may have primay or
secondary infertility problems that interfere with unassisted attempts to
become pregnant.
Virtually the entire female reproductive tract has been
affected by DES-exposure in utero. Adverse pregnancy
outcomes attributable to DES-exposure that have been
confirmed by a number of controlled and uncontrolled studies
include : early spontaneous abortion, a significantly higher
rate of ectopic tubal pregnancy, and more frequent stillbirth
preterm delivery. 63,36,5,8,15,44,55,56
Studies of DES and actual conception rates are conflicting.
Some studies have found no difference in actual infertility
rates (defined as pregnancy achieved after 12 months of
intercourse). 15,5 Other studies have found increased infertility
rates in DES-exposed patients. 35,44,56,8,7,9 With the increased
risk of miscarriage, ectopic pregnancy, and stillbirth among
the DES-exposed population, it is necessary to emphasize
that successful pregnancy outcome for the DES-exposed
population must be determined by the actual live birth rate
instead of pregnancy rates achieved.
Etiologic factors which may affect fertility in
DES-exposed women
UTERINE
MALFORMATION
Structural changes include T-shaped uterus, constriction bands,
hypoplastic uteri, irregularity of endometrium, diminished
endometrial cavity, and narrowed endocervical canal which may
interfere with successful implantation. 40,29 Uterine surgery to
correct anatomic abnormalities has not been shown to improve
live birth rates. 51
MENSTRUAL
IRREGULARITIES
Oligomenorrhea and amenorrhea have been documented. 9,15,56,5
Some DES-exposed women have been observed with elevated
serum levels of testosterone, a condition which frequently occurs
in unexposed women with chronic anovulation.68
TUBAL
IRREGULARITIES
Tubal factor infertility may result from DES-related anatomic
abnormalities of the tubes which include "withered''
(foreshortened) fallopian tubes 17,52,45 and the presence Of
parafimbrial paratubal cysts. 28 Higher frequencies of ectopic
gestation is evidence of tubal dysfunction in DES-exposed
women. 64
ENDOMETRIOSIS
Significant association between DES exposure and
endometriosis has been found in patients with primary infertility.
16,62,7
Structural changes such as cervical stenosis, dilated lower
uterine segment and a T-shaped uterus may predispose DESexposed women to endometriosis via retrograde menstruation
and contribute to subjectivity and infertility. 64
POOR CERVICAL
MUCUS
Anecdotally reported qualitative and/or quantitative changes
may be the result of insufficient mucus-secreting cells in the
endocervical canal. Surgical treatment of the cervix (conization,
cryosurgery, or cauterization) may cause scar tissue which
covers or replaces mucus-secreting cells. The use of estrogens
either topically or systematically to improve the cervical mucus
has not been proven effective to date in clinical studies
evaluating the quantity and quality of cervical mucus. 27
OVARIAN CYSTS
Increased numbers of paraovarian cysts in DES-exposed women
may interfere with conception. 28 Some of these have an unusual
histiology consisting of pseudostratified columnar epithelium
which has been stimulated in utero. 30
Pregnancy Complications
SPONTANEOUS
FIRST TRIMESTER
ABORTION
Virtually all available studies have noted an increase in the
spontaneous first trimester abortion rate in women exposed to
DES prenatally. 5,56,55,44 Irregular endometrial contour and the
overall hypoplastic appearance of the uterus is the likely
explanation. 30 An increase in the rate of premature labour in
woman with prenatal DES exposure is manifested by a decrease
in term deliveries and higher perinatal morbidity and mortality.
5,8,15,44,55
PREMATURE
LABOUR
Premature labour has been observed at any point in gestation and
can be treated similarly to non- exposed women at high risk for
premature labour (ie. redress and tocolytics). The use of
prophylactic cerclage has been advocated with tocolysis but the
effectiveness of this procedure remains controversial. 30
CERVICAL
INCOMPETENCE
Cervical incompetence among the DES-exposed population has
been identified in case reports. 25,44 The cervix exhibits an
unusual structure in DES-exposed pregnant women, specifically
with regard to length and effacement. Second trimester abortion
in DES daughters can be caused by an incompetent cervix or
appear as the earliest form of premature labour. 31
Treatment Considerations
The risks and benefits of Gamete Intrafallopian Transfer and in vitro fertilization have not
been evaluated for the DES-exposed population. 49 Inherent risk factors associated with
DES-exposure warrant careful consideration of these procedures. There are also current
concerns about the malignant effects of hormonal treatments on hormone-responsive tissues
which may be further compounded by DES-exposure. Caution is advised concerning the
administration of any form of hormonal agents to the DES-exposed. Some physicians
counsel DES daughters against the use of birth control pills because of their increased
potential sensitivity to chemical estrogens. 27
A similar warning concerning the use of ovulation inductors may also be in order. Studies
which suggest a link between the use of ovulation inductors and increased incidences of
ovarian cancer have recently been published. 67 The long-term effects of ovulation inductors
on the fetus and mother need to be assessed with properly controlled long-term studies.
The Effects of DES on Male Fertility
Approximately one-half of offspring exposed in utero to DES
were male. Increasing incidence of reproductive abnormalities in
men may be related to prenatal exposure to DES.
ANATOMICAL
ABNORMALITIES
Recognized anatomical abnormalities attributable to DES
include: epididymal cysts, microphallus hypotropic testes,
hypoplasia, cryptochordism, capsular induration and varicocele.
22,2,61,58
DECREASED
FERTILITY
Decreased fertility in males is suspected. Diminished Eliasson
scores have been reported among DES-exposed males. 24 DESexposed males have also been diagnosed with azoospermia. 24,34
Altered semen analyses have been reported in DES-exposed
males which include: decreased sperm concentration, decreased
sperm count, lower motility grade, poor sperm penetration (using
the zona-free hamster egg sperm penetration assay) and
decreased normal morphology. 22,58,61,66 Other studies have
challenged these data. 2,42 True infertility studies for men
exposed to DES, which include evaluation of the female partner,
need to be performed.
TESTICULAR
CANCER
The association between in utero DES exposure and testicular
cancer is controversial. Several cases of testicular cancer have
been reported in DES-exposed men. 23,13,65,3 Subsequent Case
Control studies have failed to show significant association. 10,48,21
A recent study suggests that increasing incidences of
reproductive abnormalities in the human male may be related to
exposure to exogenous estrogen in utero, specifically DES. 57
Because of the well-known reproductive tract teratogenicity of
exogenous estrogens and steroids on males, further studies are
certainly warranted.
Treatment Considerations
Seeking evidence of in utero DES-exposure of the male as well as the female as part of an
assessment of various factors which may decrease fertility potential is suggested. Careful
semen evaluation, perhaps including sperm penetrating assay and hemizona assays may also
be warranted for DES-exposed males. 49
DES Fertility Issues
References and Selected Bibliography
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2.
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3.
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4.
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9.
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38. Horne, H.W.; Kundsin, R.B., "Results of Infertility Studies on 1001 DES-expose and
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39. Karande, V.C. et a1., "Are Implantation and Pregnancy Outcome Impaired in
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What is DES ACTION?
DES ACTION CANADA is a national non-profit consumer organization whose purpose is
to identify, educate, provide support to, and advocate for people exposed to the drug DES.
The organization also works toward the prevention of similar public health problems,
particularily in the field of reproductive health care. DES ACTION offers:
INFORMATION
pamphlets, posters, a documentation centre, web site, toll-free info line
PUBLICATIONS
DES Action Canada Newsletter
Beyond Early Detection: A New Look at Breast Cancer
A Guide to Coping with Gynecological Cancer
PHYSICIAN REFERRALS
________________________________________________________________
DES ACTION regional chapters are located in:
British Columbia Ontario Newfoundland Nova Scotia
Manitoba Quebec Saskatchewan Prince Edward Island
For more information contact:
DES ACTION CANADA
107-5890 Monkland Avenue
Montreal, QC H4A 1G2
Tel: (514) 482-3204
Toll-free: 1-800-482-1-DES
E-mail: desact@web.net
Website: www.web.net/~desact
________________________________________________________________
Fertility Issues Associated With DES Exposure
written by Dawn Kiddell
published by DES Action Canada
layout and typesetting by LA PRESSE WYSIWYG
printed October 1993