Yoram Sorokin, M.D.
Mark P. Johnson, M.D.
David A. Richardson, M.D.
Mark L Evans, M.D.
From the Section of Antenatal Fetal Diagnosis and Therapy,
Departments of Obstetrics and Gynecology, and the Section of Molecular
Biology, Wayne State University/Hutzel Hospital, Detroit, Michigan, and
the Ehlers-Danlos National Foundation, Southgate, Michigan.
This article is reprinted with the permissionof the
Journal of Reproductive Medicine; Volume 39, Number 4, April 1994: pages281 â€“ 284
Women members of the newly formed Ehlers-Danlos National Foundation
(EDNF) were surveyed with a very detailed questionnaire with 50
questions concerning family history and inheritance, past medical
history, and obstetric and gynecologic problems, They entailed the
largest extant database on Ehlers-Danlos syndrome (EDS) patients. The
mean age of the 68 women who responded to the survey was 42 years, most
had EDS types I, III, IV and unknown. Forty-three women had 138
pregnancies, 13 women never married, The stillbirth rate was 3.15%
(3/95); the preterm delivery rate was 23.1% (22/95); and the
spontaneous abortion rate was 28.9% (40/138). There was a cesarean
delivery rate of 8.4% with 14.7% having perinatal bleeding problems.
One woman (EDS type IV) had congestive heart failure. Common
gynecologic problems were recurrent anovulation (41.3%), recurrent
vaginal infections (53%), abnormal cytologic smears (19%); and sexual
dysfunction (61%), irregular menses (28%), endometriosis (15.8%);
vaginal dryness (25%); and a need for hysterectomy (19.1%)- In this
largest series of pregnancies with EDS, we found relatively high rates
of abortion, preterm delivery, pregnancy-related bleeding and
stillbirth. Women with EDS also seem to have high frequency of
anovulation, vaginal infections, abnormal cytologic smears and
The Ehlers-Danlos syndrome (EDS) is a heterogeneous collection of at
least 10 connective tissue disorders causing abnormal production or
secretion of collagens (Table I). Early reports on EDS emphasized joint
laxity and skin hyperextensibility in the disorders. The classification
of EDS is based on phenotype manifestations, specific biochemical
abnormalities and mode of inheritance. The main clinical features are
fragility of the skin and of the dermal blood vessels, characteristic
"papyraceous" scars, hyperextensible and transparent skin, and
hypermobile joints. Most reports in the obstetric and gynecologic
literature have been anecdotal and were published before the various
types of Ehlers-Danlos syndrome were recognized. There are several case
reports that emphasize type IV EDS as distinct in carrying a high risk
of major complications and maternal death due to ruptured blood
vessels. The maternal mortality rate in type IV EDS has been estimated
to be 25%.
It has been suggested for many years that during pregnancy, women
with EDS are at increased risk of vascular complications, including
varicose veins, aneurysm of blood vessels, cerebrovascular accidents,
increased bruising, antepartum and postpartum hemorrhage, separation of
the symphysia pubis, hematoma formation, increasing joint laxity,
premature rupture of the membranes and prematurity. In nonpregnant
women, menometrorrhagia, recurrent pelvic floor relaxation and uterine
prolapse have been reported. However, because of the low incidence and
multiple types of EDS, there are no recent large series from which one
can draw any conclusions regarding obstetric and gynecologic symptoms,
signs, morbidity or mortality. Recently, the Ehlers-Danlos National
Foundation (EDNF) brought together enough patients with EDS to ask some
meaningful questions. Below we report on any obstetrics and gynecologic
aspects and complications in the largest extant group of women with EDS.
MATERIALS AND METHODS
A detailed questionnaire was mailed to women members of the EDNF. Fifty
questions inquired about family history and inheritance, past medical
and surgical problems and complications, obstetric and gynecologic
history and issues of sexuality. Sixty-eight questionnaires that were
completed and returned formed that database from which this report was
generated. There were several cases in which no specific EDS type had
been clinically assigned to the patient, and they are referred to below
The women surveyed had a mean age of 42 years. Of the 68 women, at
least 30 had some relatives affected by EDS. The diagnosis was made
clinically in two-thirds of the women. Very few women used alcohol (2
women, more than six drinks per week) or drugs; only 6 women smoked +\-
O.5 packs per day. Eleven women were unemployed, and 30 had a
professional career. Of the 68 surveyed, 42 had had 138 pregnancies
(3.2 per woman). Thirteen women (19%) were never married.
The outcomes of pregnancies by EDS type are displayed in Table II.
The incidence of bleeding problems during pregnancy was 14.7%; there
were 40 miscarriages (29%), 3 stillbirths (3.15%) and 13 pregnancies
with an antepartu m and/or intrapartum hemorrhage. There was one
pregnancy with heart failure (EDS type IV), I with hip pains, I with
preeclampsia and I with separation of the symphysis. Difficult or
prolonged Iabor was reported for 5 (5.2%) pregnancies and precipitous
labor for 2. Forceps delivery, breech delivery and retained placenta
occurred in I pregnancy each. The preterm delivery rate was 23.l%
(22/95), and there were 15 (15.7%) small for gestational age infants,
The cesarean delivery rate was 8.4%.
Recurrent anovulation, frequent and recurrent vaginal infections,
abnormal cytologic smear and sexual dysfunction due to dyspareunia were
relatively common, with incidences of 41.3%, 53%, 19% and 61%
respectively (Table III). Gynecologic problems included irregular
menses (16/57), with most women having periods every 15-40 days.
Menorrhagia (longer than seven days) was found in eight (13.7%) women.
Pubarche and thelarche were in the normal range. Endometriosis was
common (10/63, 15.8%), with seven women having severe cases; however,
in five women, the diagnosis was made on the basis of the history and
physical examination alone. Five of 10 women with endometriosis had EDS
type IV. Hysterectomy was the most common gynecologic operation. Three
women had a uterine prolapse, and two had cystocele and rectocele
repair. Most of the women used contraceptives and had sexual activity
with one male partner, however, many expressed having unsatisfactory
sexual activity (15/58, 25.8%), dyspareunia (I2/58, 20.7%), sexual
dysfunction (7/59, 11.8%), postcoital bleeding (5/59, 8.5%) and vaginal
dryness (15/60, 25%).
EDS is a heterogeneous collection of connective tissue disorders. The
incidence of complications varies with the different types. The precise
underlying biochemical nature of the complications in several EDS types
is known. However, in most clinical complications, the precise
mechanisms are still a matter of speculation. In this series we
attempted to look at several clinical obstetric and gynecologic
symptoms, signs and complications in a large group of women with EDS.
This was the first attempt to create an EDS obstetric and
gynecologic database, The need for such a database was obvious at the
first meeting of the EDNF. This type of database has the limitation of
selection bias and dependence on retrospective patient reporting.
In this series, we found suggested associations between
miscarriages, antepartum hemorrhages, stillbirth and EDS. Previous
series had similar findings as well as increased frequencies of
backache, varicose veins and straie gravidarum, In 1966, Barabas
reported on 39 pregnancies with 14 premature deliveries (defined as
< 5.5 lb.), of which 13 started with premature rupture of the
membranes. All the deliveries occurred between 32 and 35 weeks of
pregnancy. The other reports were published earlier, had smaller
numbers, did not contain information on EDS typing or defined
prematurity as a neonatal weight < 2.5 kg. Beighton reported a 350%,
(9/32) premature delivery rate in EDS type I (gravis). In the present
series, we found a high preterm delivery rate, 23.1% (22/95); however,
most women having preterm deliveries did not have premature rupture of
the membranes. When the 95 deliveries are classified according to EDS
type, there are still too few pregnancies in each type for meaningful
Lethal complications of EDS (especially EDS type IV) have been
reported extensively. The present series was biased toward women with
survival and very low rate of serious complications (dissecting
aneurysms, arterial rupture, vascular complications). We did not find
high rates of postpartum hemorrhages or surgical interventions, as
found in some earlier series. None of the patients in the present
series had serious bleeding problems during pregnancy.
The literature on gynecologic problems in women with EDS is much
scantier than that on obstetrics problems. Most of the clinical
gynecologic problems could be easily explained by the skin and
supportive tissue fragility in women with EDS. In our series very few
women had surgery for symptoms of pelvic relaxation; however, recurrent
vaginal infections, sexual dysfunction, vaginal dryness and dyspareunia
were very common complaints. A more extensive gynecologic and
urogynecologic evaluation in women with EDS is planned.
Obstetricians and gynecologists should be aware of the clinical
symptoms and signs that reveal the possible presence of EDS and should
understand that today many of the disorders can be confirmed by
biochemical examination. Diagnosis should entail the patients'
obstetric and gynecologic risks as well as the risk of transmitting the
disease to their children.
Editor's Note: References available upon request.