CASE REPORT

Spontaneous ovarian hyperstimulation in a pregnant

woman with hypothyroidism
Sedigheh Borna, M.D.,a and Azita Nasery, M.D.a
a
Department of Perinatology, Vali-asr Hospital, Tehran University of Medical Sciences, Tehran, Iran

Objective: This report describes an unusual case in which a naturally conceived pregnancy is associated with spon-
taneous ovarian hyperstimulation and hypothyroidism.
Design: Case report.
Setting: University medical center.
Patient(s): A 30-year-old pregnant woman with abdominal pain and distension caused by ovarian hyperstimula-
tion.
Intervention(s): Medical management and laparotomy.
Main Outcome Measure(s): Incomplete regression after 3 months.
Result(s): Thyroid-stimulating hormone level was elevated. Hormonal studies confirmed hypothyroidism with
spontaneous ovarian hyperstimulation. She was given levothyroxine 200 mg/d. Results of the hormonal tests for
thyroid function were normal 3 months after treatment, but in this case the ovarian cysts did not regress completely
until delivery. Laparotomy and cesarean section were done for both diagnosis and treatment. Ten weeks after de-
livery ovarian cysts regressed completely.
Conclusion(s): Thyroid hormone replacement seems to be the best therapeutic approach in some patients, but, in
some, complete resolution of the ovarian cysts does not occur after 3 months. (Fertil Steril 2007;88:705.e1–3.
2007 by American Society for Reproductive Medicine.)
Key Words: Hypothyroidism, spontaneous ovarian hyperstimulation, pregnancy

The ovarian hyperstimulation syndrome (OHSS) has been
described extensively in patients after treatment with exoge-
nous gonadotropins, clomiphene citrate, and GnRH. Ovarian
hyperstimulation syndrome not related to ovulation induction
is rare. Spontaneous hyperactive stimulation syndrome had
been reported in women with hypothyroidism, polycystic
ovary syndrome and pregnancy, gonadotropin pituitary ade-
noma, and normal pregnancy (1–4). This report describes
a case in which a naturally conceived pregnancy is associated
with OHSS and hypothyroidism.
CASE REPORT
A 30-year-old woman, gravida 1, was admitted at 20 weeks
gestation because of abdominal pain and distension. The cur-
rent gestation started spontaneously, and the patient had
taken no medications during the preceding months. Physical
examination on admission detected mild tenderness and dis-
tension of the lower abdomen. Pelvic examination found
bilaterally enlarged cystic ovaries and a pregnant uterus of
Received June 1, 2006; revised December 5, 2006; accepted December
20, 2006.
Reprint requests: Sedigheh Borna, M.D., Department of Perinatology, Va-
li-asr Hospital, Tehran University of Medical Sciences, Keshavarz Blvd.,
Tehran 14194, Iran (FAX: 98-21-8718062; E-mail: s_borna@hotmail.
com).
20 weeks gestation. Abdominal ultrasound showed a single-
ton normal pregnancy at 20 weeks and bilateral multilobu-
lated ovarian cysts with diameters of 20  16 cm (right
ovary) and 16  10 cm (left ovary) and mild ascites; the pla-
cental appearance was normal (Fig. 1). Doppler ultrasono-
graphic study results were normal. Laboratory testing
revealed normal platelet and leukocyte count and normal
levels of hemoglobin, hematocrit, blood urea nitrogen, and
creatinine. Ovarian tumor markers were negative. The serum
levels of b-hCG, antithyroglobulin, and antiperoxidase were
normal.
Thyroid-stimulating hormone concentration was increased
(400 mU/mL). Table 1 summarizes the results of the hor-
monal tests performed. With these findings, the diagnosis
was made of mild spontaneous OHSS associated with a sin-
gleton intrauterine pregnancy and hypothyroidism.
Treatment consisted of bed rest and close monitoring
(blood pressure, pulse rate, urine output, hematocrit, electro-
lytes, coagulation profile, and fluid therapy). On the basis of
the diagnosis of hypothyroidism, associated with OHSS,
treatment with levothyroxine 100 mg/d was instituted, which
progressively reached the dose of 200 mg/d. Within 2 weeks,
remarkable improvement was observed, with resolution of
ascites and gradual reduction of ovarian size. The patient
was discharged after 2 weeks.

0015-0282/07/$32.00 Fertility and Sterility Vol. 88, No. 3, September 2007 705.e1
doi:10.1016/j.fertnstert.2006.12.003 Copyright ª2007 American Society for Reproductive Medicine, Published by Elsevier Inc.
 FIGURE 1
Sonogram showing enlarged ovaries (20  16 cm,
right ovary, and 16  10 cm, left ovary).
Borna. Ovarian hyperstimulation and hypothyroidism. Fertil Steril 2007.
The patient’s condition was monitored with weekly exam-
inations for 1 month. After 1 month, her progress was fol-
lowed at normal antenatal checkup intervals. Fetal growth
rate and amniotic fluid were normal, and no morphologic
fetal abnormalities were seen.
By 34 weeks, TSH was normal (4 mU/mL), and on transab-
dominal ultrasound examination the ovarian cysts had
decreased in size to 15  8 cm and 13  8 cm (in right and
left ovaries, respectively). Treatment with levothyroxine
was never discontinued, and clinical and laboratory follow-
up control were periodically carried out up to 38 weeks.
Eighteen weeks after starting levothyroxine treatment, fol-
low-up ultrasonography did not show marked reduction in the
size of her ovaries. At 38 weeks, the size of ovarian cysts was
unchanged, and the fetus was in breech presentation. It was
decided to do laparotomy and cesarean section, both for diag-
nosis and treatment. The patient gave birth to a healthy, nor-
mal girl of 3,200 g at 38 weeks gestation.
705.e2 Borna and Nasery Ovarian hyperstimulation and hypothyroidism
TABLE 1
Results of hormonal tests
Biochemical
tests Results Normal range
TSH (mU/mL) >400 0.47–5
T3 (ng/mL) 0.28 80–200
T4 (mg/dL) 0.6 9.1–23.8
Free T3 (pg/mL) 1.1 2.2–5
Free T4 (ng/dL) 0.4 0.7–1/8
CA-125 (U/mL) 39 %35
Note: T3 ¼ triiodothyronine.
Spontaneous hyperstimulation syndrome had been re-
ported in women with hypothyroidism, polycystic
ovary syndrome, and pregnancy. This report de-
scribes a case in which a naturally conceived preg-
nancy is associated with spontaneous ovarian
hyperstimulation and hypothyroidism. In this case
the ovarian cysts did not regress completely after 4
months of thyroid replacement therapy. Ten weeks
after delivery the ovarian cysts regressed completely.
Thyroid hormone replacement seems to be the best
therapeutic approach, but in some patients the com-
plete resolution of the ovarian cysts does not occur
after 3 months.
Borna. Ovarian hyperstimulation and hypothyroidism. Fertil Steril 2007.
Aspiration of a large superficial ovarian cyst and wedge
biopsy were done by laparotomy. Intraoperative histologic
examination of frozen sections from the ovaries revealed
benign cysts. The final histologic diagnosis was follicular
cyst. Ten weeks after delivery, serial follow-up sonography
showed her ovaries to be of normal size.
DISCUSSION
Our patient was seen initially with abdominal pain and was
found to have bilateral large ovarian cyst masses, mimicking
hyperstimulation syndrome. In our case, hypothyroidism was
diagnosed at 20 weeks gestation of a pregnancy that had been
conceived spontaneously. This case suggests a possible rela-
tionship between spontaneous ovarian hyperstimulation and
primary hypothyroidism.
Ovarian hyperstimulation syndrome usually occurs in
association with ovulation induction, polycystic ovary syn-
drome, Down syndrome, hypothyroidism, and multiple preg-
nancies (1–4), but the physiopathologic mechanisms are
poorly understood. Spontaneous OHSS usually associated
with hypothyroidism was described in three case reports
(1–3). The causal relationship between hypothyroidism and
ovarian hyperstimulation is suggested by the consistent
regression of the ovarian cysts after the institution of thyroid
hormone replacement therapy. In these studies, results of
the hormonal tests for thyroid function and ovarian size
were normal 3 months after treatment. However, this did
not happen in our patient. The cysts did not resolve until 10
Vol. 88, No. 3, September 2007
weeks after delivery. The exact mechanism by which ovarian
hyperstimulation might occur in patients with hypothyroid-
ism is not understood clearly. In women with hypothyroid-
ism, the elevated concentrations of TSH may mediate
ovarian hyperstimulation because of the presence of nuclear
thyroid receptors (TR and TRb) in the granulosa cells. Be-
cause the exact pathogenesis of OHSS is unknown, treatment
relies on an empirical and symptomatic approach (1). In cases
treated by medical management, the complete resolution of
the ovarian cysts takes almost 3 months. Thyroid hormone re-
placement seems to be the best therapeutic approach in these
patients (1, 5). In our case, results of the hormonal tests for
thyroid function were normal 3 months after treatment, but
the ovarian cysts did not regress completely after 4 months
of thyroid replacement therapy. Surgical management of
spontaneous OHSS increases the risk of abortion; however,
it simultaneously shortens the period in which most serious
complications develop. Surgical management is advocated
only for cases of follicular rupture, hemorrhage, or torsion
of the ovarian cyst (6). Because in our case the ovarian cysts
did not resolve significantly after 4 months of thyroid re-
placement therapy, it was decided to proceed with an
exploratory laparotomy during cesarean section. Aspiration
of the large ovarian cysts was done to avoid the probable
serious complications of remaining cysts. Cyst aspiration is
recommended during pregnancy by a group of clinicians
and should be judged against the risk of bleeding of fragile
ovaries that could lead to oophorectomy (6). Abu-Louz
et al. reported one case of hyperstimulation syndrome associ-
ated with pregnancy; aspiration of a large superficial ovarian
Fertility and Sterility
cyst was done under ultrasonographic guidance, and laparot-
omy was avoided (6).
Thyroid hormone replacement seems to be the best thera-
peutic approach, but in some patients, the complete resolu-
tion of the ovarian cysts does not occur after 3 months. In
cases of spontaneous OHSS associated with pregnancy and
hypothyroidism, conservative surgery should be the first ap-
proach when the ovarian cysts remain in spite of adequate
medical treatment. It is suggested to consider longer observa-
tional management without surgical intervention in some
specific cases of OHSS if there is no other indication for
laparotomy.
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