Ovarian pregnancy occurs when a fertilized
ovum implants in or on the ovary. This entity is
a rare variant of extrauterine pregnancy and represents 1.1-3% of all ectopic pregnancies or one
ovarian pregnancy per 7000-90000 live births (
Serous cyst adenoma is a cystic ovarian tumor
containing serous fluid and solid- tissue component. This tumor is benign form, presenting as
cystic unilocular or multilocular ovarian mass with
thin wall and minimal papillary projections (
Polycystic ovarian syndrome (PCOS) is the most
common endocrinopathy among subfertile women
Infertility and subfertility managements including induction of ovulation seem to be responsible
causes in the occurrence of the ectopic pregnancies (
In some retrospective studies, an association has
been found between fertility drugs use and ovarian
neoplasia risk in infertile patients (
The case presented here is interesting in term of the rarity of ovarian pregnancy and coincidence with serous cyst ovarian tumor, and also occurring after ovulation induction by metformin.
In January 2013, a 28-year-old primigravida
woman with sever lower abdominal pain presented to the emergency room of our hospital (Tehran Women General Hospital, Tehran,
Iran). She suffered from vaginal spotting and lower abdominal pain for 5-6 consecutive days.
She revealed a history of primary infertility
with 3 years duration. Because of clinical and
paraclinical manifestations of polycystic ovarian syndrome, metformin (1500 mg/day) has
been prescribed for induction of ovulation since
8 months ago. After starting this medication,
she developed regular menstruation pattern.
Her last menstrual period was 25 days prior to
admission date. She had no previous history of
pelvic inflammatory disease, abdominal surgery, abortion, or use of any intrauterine contraceptive device (IUCD). Her hysterosalpingography (HSG) demonstrated an otherwise
normal image without uteroovarian fistula. On
general examination, she was pale. Abdominal
examination showed abdominal distention and
guarding. On vaginal examination, the uterus
was normal in size and the cervix was tender
in motion. There was a tenderous mass in deep
palpation of right fornix. Clinical investigation
showed hematocrit level of 25.2%, and betahuman chorionic gonadotropin (β-hCG) titer of
3569 m IU/mL. Vaginal ultrasonography demonstrated empty uterus with 6 mm endometrial
thickness, free fluid in the peritoneal cavity,
and a right sided heterogeneous adnexal mass
(52×61 mm) beside the uterus. These findings
were suggestive of ruptured ectopic gestation.
Based on the above findings, the patient underwent emergency laparotomy in which demonstrated an enlarged and bluish right ovary with
a 4 cm hemorrhagic and ruptured ovarian mass
and a leaking hematoma on its surface. A 3×3
cm multicystic structure was identified in the
other side of right ovary and was presumed to
be a tumorous lesion. The uterus, both tubes
and the left ovary appeared to be normal in appearance. The right tube had normal fimbriated
end without dilation. There was no obvious
evidence of endometriosis, metastatic lesions,
pelvic inflammation, or adhesion. We found
1500 mL bloody fluid in abdominal cavity.
The diagnosis of ovarian pregnancy was made.
Therefore, surgical resection of hemorrhagic
mass with conservation of the right ovary was
done carefully. Because of bad looking appearance of the concurrent cyst in the right ovary,
ovarian cystectomy and endometrial curetting
were performed, respectively. The final pathologic analysis revealed vascularized chorionic
villi and trophoblastic cells within ovarian paranchymal tissue (Figes
Photomicrograph identified trophoblastic cells within the ovarian parenchyma (H&E); ×200.
Photomicrograph identified chorionic villi (H&E); ×100.
Photomicrograph identified serous cyst adenoma (H&E); ×400.
Ovarian pregnancy is a rare variant of ectopic
Its true incidence is underestimated. Some
of the suspected tubal pregnancies that are approached with conservative managements, without laparoscopic validation, are in fact ovarian
The exact etiologic factors of increased risk of
ovarian pregnancy after ART programs are unclear, but the most likely mechanisms are as follows: reverse migration of embryo after deep deposition, the use of large volumes of culture fluid
during embryo transfer (ET) procedures, difficult
ET, and tubal pathologies (
The risk of ovarian pregnancy in patients with
endometriosis or using IUCDs is controversial (
Preoperative diagnosis is a challenge to the clinician due to its rarity and lack of typical presenting
symptoms or documented risk factors (
The ultrasound features are ovarian enlargement with or without containing a double hyperechogenic ring along with yolk sac, fetal part, or
fetal heart beat within ovary; fluid collection surrounding the ovary; and an empty uterus (
In recent years, accurate and earlier diagnosis
has been performed by the application of vaginal
ultrasound scanning and quantitative hCG measurement (
Serous cyst adenoma is the most common benign epithelial cell tumor of ovary (
In the other hand, a high frequency of hyperplasia and metaplasia in the ovarian epithelial surface and 2.5-fold increased risk of ovarian cancer
have been showed in women with PCOS (
In some cohort studies, ovulation-inducing
drugs were related to an elevated risk of border
line serous tumors (
Fertility experts frequently use metformin, an
insulin-sensitizing agent, as an ovulation-inducing
medication in PCOS (
However, to the best of our knowledge, this
study is the first case report of coexistence of an
ovarian pregnancy and a serous cyst adenoma
in the same ovary following ovulation induction
with metformin. Review of the literature showed
only a few reports presenting the coincidence of
a serous cyst adenoma with an ectopic pregnancy.
They have been cases involving tubal or abdominal pregnancy coinciding with serous cyst adenoma (
In our case, the presenting signs and symptoms were severe abdominal pain with vaginal spotting, elevated β-hCG, ovarian mass and empty uterus. She fulfilled the criteria for ovarian pregnancy, as by Spiegelberg’s outlines. She had a concurrent benign serous cyst adenoma in the same ovary. Our patient was previously labeled with PCOS. Pregnancy happened following induction of ovulation with metformin. In term of risk factors, infertility and the use of ovulation inducing drugs might be the possible predisposing factors for the ovarian pregnancy. The relationship between metformin and serous cyst adenoma is not clear.
Ovarian pregnancy is uncommon entity, which is difficult to diagnose. The microinvasive surgical procedures and medical managements are effective therapeutic options in the treatment of unruptured ovarian pregnancies, especially in young patients. Although the current findings are not strong to support a link between fertility drugs and ovarian cancer, it seems to be an association between reduced fertility and increased neoplasia risk. Careful inspection of the ovaries at surgery indicated the high risk of ovarian tumors for patients with long-standing history of infertility or fertility agents use in order to exclude the presence of a neoplasm. Moreover, further prospective, multicenter, and long follow-up studies considering all confounding factors are necessary to improve our ability for diagnosis and treatment of ovarian pregnancy, and to determine the patho-physiological mechanisms underlying the possible link between infertility or the use of ovulation inducing drugs and ovarian tumors.