Human Reproduction vol.13 no.2 pp.468-470, 1998
CASE REPORT
A woman with three ectopic pregnancies after in-vitro
fertilization and embryo transfer
T.Oki 1, T.Douchi, S.Nakamura, K.Maruta, H.ljuin
and Y.Nagata
Department of Obstetrics and Gynecology, Faculty of Medicine,
Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan
1To
whom correspondence should be addressed
Although a higher incidence of ectopic pregnancy has
been reported after in-vitro fertilization (IVF) and embryo
transfer, three ectopic pregnancies in the same woman is
very rare. A patient of 32 years underwent IVF-embryo
transfer six times within 3 years. Three of four conceptions
resulted in ectopic pregnancies. The first involved
simultaneous intrauterine and left tubal pregnancy, the
second was a right tubal pregnancy, and the third was
a right interstitial pregnancy. In IVF-embryo transfer,
bilateral salpingectomy does not remove the risk of
interstitial or cornual pregnancy.
Key words: ectopic pregnancy/embryo transfer/in-vitro
fertilization
Introduction
The development of in-vitro fertilization (IVF) and embryo
transfer has increased the chances of conception for infertile
couples. However, IVF-embryo transfer has increased the
incidence of ectopic pregnancy (Lancaster, 1985; Varma et al.,
1987; Dimitry et al., 1990; Molloy et al., 1990). In particular,
unusual types of ectopic pregnancy may occur, including
heterotopic (simultaneous intrauterine and tubal pregnancy)
(Dimitry et al., 1990; Molloy et al., 1990; Marcus et al.,
1995a), cornual and interstitial pregnancy (Beck et al., 1990;
Hamilton et al., 1992; Sharif et al., 1994; Agarwal et al.,
1996). In the present study, we report a patient who had
the very rare condition of three ectopic pregnancies after
IVF-embryo transfer, and discuss the implications.
Case report
The patient was a 32 year old woman. She had been married
for 8 years, but had never conceived prior to her attendance
at the out-patient clinic of our hospital at age 28. Basal
body temperature and endocrinological findings indicated the
occurrence of ovulation. Semen analysis showed normaspermia. On hystero-salpingography, however, stenosis of the
left oviduct and occlusion of the right oviduct were found.
468
Eventually, tubal infertility was diagnosed, and IVF-embryo
transfer was indicated.
Superovulation was induced by the short protocol from the
first to the fifth IVF-embryo transfer attempt, and by the long
protocol for the sixth attempt. The results of these attempts
during 3 years from 1994 to 1996 are summarized in Table I.
Four pregnancies were achieved. However, only one baby was
successfully delivered; at 37 weeks, a boy weighing 2684 g
(appropriate for gestational age) was delivered by elective
Caesarean section because of breech presentation. The other
three pregnancies were ectopic and are described below.
First ectopic pregnancy
At age 29, two embryos at the 4-cell stage were transferred.
A urinary pregnancy test was positive on the 15th day after
embryo transfer. An intrauterine gestational sac was confirmed
by transvaginal ultrasonography on the 30th day after embryo
transfer. On the night of the 50th day after embryo transfer
(9 weeks and 1 day of gestation), however, the patient suddenly
complained of abdominal pain and was brought to our hospital
immediately. On arrival, she was in shock with blood pressure
of 80/30 mmHg. A massive intra-abdominal haemorrhage was
strongly suspected. Emergency laparotomy was performed
under a diagnosis of suspected rupture of tubal pregnancy.
Laparotomy revealed rupture of the oviduct due to pregnancy
in the isthmus portion of the left oviduct, and the left oviduct
was resected. The amount of intra-abdominal haemorrhage
was 3000 g. Postoperatively, some irregular vaginal bleeding
persisted and intrauterine fetal death was diagnosed at 9 weeks
and 6 days of gestation.
Second ectopic pregnancy
At 32 years of age, two embryos at the 2-cell stage and the
4-cell stage, respectively, were transferred. Pregnancy was
confirmed on the 17th day after embryo transfer. However, the
patient complained of a mild lower abdominal pain and
was diagnosed \s having pregnancy in the right oviduct by
transvaginal ultrasonography at 5 weeks and 6 days of gestation.
Laparotomy revealed pregnancy in the isthmus portion of the
right oviduct, and the right oviduct was removed.
Third ectopic pregnancy
At 32 years of age, two embryos at the 4-cell stage and one
embryo at the 8-cell stage were transferred. The patient had
irregular vaginal bleeding for 5 days beginning the 11th day
after embryo transfer. On the 20th day after embryo transfer,
© European Society for Human Reproduction and Embryology
Ectopic pregnancies after IVF
Table I. Outcomes of in-vitro fertilization (IVF)-embryo transfer
Attempts of IVF-embryo transfer
1st
2nd
3rd
4tb
5tb
6tb
Total doses of HMG (IU)
Day of HCG administration
Serum oestradiol concentrations• (pg/ml)
Diameter of leading follicle• (mm)
Developing follicles• (n)
Recovered oocytes (n)
Fertilized oocytes (n)
Transferred embryos (n)
Volume of culture medium (J.ll)
Pregnancies (n)
Pregnancy outcome
Site of tubal pregnancy
2100
II
ND
17.5
2
2
2
2
40
2
heterotopic
left tube
3450
16
390
17.0
5
5
3
2
40
4800
16
305
17.5
1
3600
18
961
16.0
3
3
3
2
40
1
EP
right tube
3300
13
622
17.0
3
3
3
3
40
0
5100
26
274
19.0
3
3
3
3
40
1
40
0
I
term
I
EP
right interstitial
n = number; ND = not done; HMG = human menopausal gonadotrophin; HCG
term delivery; heterotopic = simultaneous intrauterine and tubal pregnancy.
•nata were obtained on tbe day of HCG administration.
=
she consulted our clinic because of mild lower abdominal
pain. The urinary pregnancy test was positive, and she was
diagnosed as being at 4 weeks and 6 days of gestation. On the
second visit at 28 days after embryo transfer, the transvaginal
ultrasonography revealed an extrauterine gestational sac. She
was hospitalized immediately under a diagnosis of ectopic
pregnancy. Ultrasonographic examination revealed a gestational sac 3 em in diameter at the region of the right cornu at
the fundus, and fetal heartbeat was also confirmed. The
endometrium was thin at 3 mm, and there was no evidence of
intrauterine pregnancy. The ostium of the right oviduct was
confirmed by hysteroscopy, and interstitial pregnancy in the
right oviduct was diagnosed. Surgical findings, when the region
of implantation was examined, showed that the gestational sac
had ruptured. After removal of the villous tissue, the interstitial
portion of the right oviduct was resected in a V-shape. The
interstitial portion of the left oviduct was also resected in the
shape of a V to prevent further ectopic pregnancy. Trophoblast
was detected microscopically in the interstitial portion of the
right oviduct.
who demonstrated that the aetiology of ectopic pregnancy after
IVF-embryo transfer is multifactorial, with tubal damage as
the main factor. Predisposing factors for ectopic pregnancy in
IVF-embryo transfer are similar to those for ectopic pregnancy
occurring following normal fertilization (Jibodu and Dame,
1997).
In this series, we transferred one to three embryos with
40 Jll of culture medium. When 40 Jll of radiopaque dye was
injected into the uterine cavity under the same conditions as
used for embryo transfer, the partial or whole volume of dye
was found to enter the oviduct in 38.2% of cases (Knutzen
et al., 1992). In fact, the number of embryos migrating into
the oviduct increased, when a high volume of transfer medium
was used (Zouves et al., 1991). In addition, it is likely that
the number of embryos migrating into the oviduct is increased
when many embryos are transferred. Considering these findings, tubal damage, the number of embryos transferred, and
the volume of culture medium may contribute to the occurrence
of ectopic pregnancy in IVF-embryo transfer.
The incidence of interstitial pregnancy among ectopic
pregnancies occurring after IVF-embryo transfer is reported
to be ~26.9% (Agarwal et al., 1996), which is higher than
the incidence of natural interstitial pregnancy (Burgener and
Strickler, 1978). It would be of great interest to elucidate why
the incidence of interstitial pregnancy is higher after IVFembryo transfer. The patient in the present study had undergone
bilateral salpingectomy due to recurrent tubal pregnancies. In
fact, many patients with interstitial or cornual pregnancy after
IVF-embryo transfer have undergone bilateral salpingectomy
(Becket al., 1990; Hamilton et al., 1992; Sharif et al., 1994;
Agarwal et al., 1996). Agarwal et al. (1996) reported that of
26 ectopic pregnancies detected after embryo transfer during
a 7 year period, seven were located in the cornua or tubal
stump after prior salpingectomy. Their report indicates that
interstitial or cornual pregnancy is not uncommon after IVFembryo transfer and furthermore that cornual or interstitial
pregnancy may be specifically related to salpingectomy. Thus,
the absence of a Fallopian tube does not remove the risk of
interstitial or cornual pregnancy (Sharif et al., 1994).
In the majority of IVF patients, tubal damage has been
caused by clinical and/or subclinical salpingitis, leading to
Discussion
The incidence of ectopic pregnancy following IVF-embryo
transfer is higher than that following spontaneous conception
(Lancaster, 1985; Varma et al., 1987; Molloy et al., 1990).
The occurrence of ectopic pregnancy after IVF-embryo transfer
involves certain prerequisite conditions; the transferred embryo
passes back from the uterine cavity into the oviduct, while
transport of the embryo in the oviduct back to the uterine
cavity is disturbed. Based on this concept, we suggest that
tubal dysfunction is likely to exist in patients with ectopic
pregnancy after IVF-embryo transfer. Chang et al. (1996)
found that a majority of IVF candidates had tubal damage. In
the patient in the present study, tubal damage appeared to be
the causative factor for infertility. Martinez and Trounson
(1986) speculated that prior tubal damage, the presence of
infection introduced during transfer, or some other cause of
tubal dysfunction could be potential predisposing factors
toward ectopic pregnancy following IVF-embryo transfer. This
was supported by the recent study of Marcus et al. (1995a),
human chorionic gonadotrophin; EP
=
ectopic pregnancy; term
=
full
469
T.Oid et
trimester
transfer should be followed
of
until the
addition, lower
up after the
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Recei1'e{i on
9, /997; accepted on October 3, 1997