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01.12.2017 | Case report | Ausgabe 1/2017 Open Access

BMC Pregnancy and Childbirth 1/2017

An abdominal ectopic pregnancy following a frozen-thawed ART cycle: a case report and review of the literature

Zeitschrift:
BMC Pregnancy and Childbirth > Ausgabe 1/2017
Autoren:
Atsushi Yanaihara, Shirei Ohgi, Kenichirou Motomura, Yuko Hagiwara, Tae Mogami, Keisuke Saito, Takumi Yanaihara
Abbreviations
AEP
Abdominal ectopic pregnancy
EP
Ectopic pregnancy
GS
Gestational sac
HCG
Human chorionic gonadotropin
ICSI
Intracytoplasmic sperm injection
IUI
Intrauterine inseminations
IVF
Conventional in vitro fertilization
T-ET
Thawed embryo transfer

Background

Ectopic pregnancies (EP) occur in approximately 1% of all pregnancies, although traditionally the incidence is thought to be significantly higher in pregnancies resulting from in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment [1, 2]. This has particularly been reported to be the case for women with tubal rather than non-tubal infertility [3, 4]. Multivariable logistic regression analyses have also accordingly demonstrated that the major risk factor for EP is the presence of tubal infertility, followed by an increased number of embryos transferred. On the other hand, extended embryo culture, such as blastocyst transfer, has shown to significantly reduce the risk of EP, while frozen-thawed embryo transfer (T-ET) has shown no effect on the risk of EP following IVF/ICSI [57].
As over 90% of EP are tubal pregnancies, abdominal ectopic pregnancies (AEP) constitute a rare form of EP, with increasing morbidity and difficulty in diagnosis [5, 8]. In this article a case of AEP is presented, which occurred following a single T-ET cycle of ICSI in a woman with non-tubal infertility. The beta-human chorionic gonadotropin (HCG) level was very low at 4 weeks 0 days of gestation, highlighting the difficulty such cases can pose for diagnosis and management.

Case presentation

A 37-year-old primipara who had had three previous intrauterine inseminations (IUI) at another clinic was referred to our clinic for a second opinion. She had been undergoing infertility treatment for five years. Clinical information forwarded from the previous clinic included: semen analysis, within normal limits; hysterosalpingography, patent Fallopian tubes; serum hormone levels, within normal limits (Day 3, follicle-stimulating hormone 11.3 IU/L, luteinizing hormone 2.4 IU/L, prolactin 11.3 ng/ml; Day 20, estradiol 113 pg/ml, progesterone 15.6 ng/ml). The clinical findings at out clinic were: transvaginal ultrasound, uterine myoma (2.7 cm) in the muscular layer; endometrium, no irregularity; postcoital test, negative; and antisperm antibody, negative.
The patient underwent one IUI in our clinic; subsequently, she and her husband agreed to undergo IVF for infertility of unknown origin. The IVF process entailed ovarian stimulation with clomiphene plus human menopausal gonadotropin injections for two cycles [9]. Four ova were harvested, and three were fertilized via ICSI. Although semen analysis was previously reported as normal, ICSI was performed during the IVF/ICSI cycle due to a low motility (<10%) found during that cycle. In the next cycle, intrauterine T-ET of one blastocyst (5BA grade; Gardner criteria) was done with a hormone replacement cycle under ultrasound guidance with a soft-tipped catheter by a board-certified member of the Japan Society for Reproductive Medicine. The endometrial thickness was 10.5 mm, and the embryo was expelled into the uterine cavity approximately 1 cm from the uterine fundus with good visualization. A subsequent pregnancy test was negative, and the serum β-HCG was 3.4 IU/L at 4 weeks 0 days of gestation from T-ET (post-transfer 9 days). A re-examination was planned for day 3 of the menstrual cycle or one week if menses did not occur. Four days later, the patient called and informed us that menstruation had begun, but she was unable to come to the clinic because of her business schedule; therefore, we advised her to present at the clinic 12 days after menstruation began. At that time (post-transfer 24 days), a transvaginal ultrasound imaged a follicle-like circle with low echogenicity near the Pouch of Douglas; thus, we advised her that, based on her menstrual cycle, it was a good date for sexual intercourse. She was not able to present for her next examination for ovulation because of other commitments. Twenty-seven days after her menses began (post-transfer 40 days), she informed us that her urinary pregnancy test was positive. She presented at our clinic the following day, and a second urinary pregnancy test was also positive (post-transfer 46 day, 9 weeks 3 days of gestation).
Transvaginal ultrasound was performed and a gestational sac (GS) could not be located in the uterus, but there was a GS containing a fetus consistent with 8 weeks 6 days of gestation (crown rump length: 18.8 mm) near the pouch of Douglas. (Fig. 1) An EP was diagnosed, and the patient was transported to another hospital because our clinic does not have an operating room suitable for laparoscopy. The laparoscopic diagnosis was an unruptured AEP of the pouch of Douglas. (Fig. 2). The gestational tissue was removed by forceps, and electrocauterization was used for hemostasis under laparoscopic surgery. The serum β-HCG was less than 0.5 IU/L 33 days after surgery.

Discussion and Conclusions

Recently, the diagnosis of EP has been possible before rupture because of a new technique for improving ultrasound diagnosis and improving early sensitive serum HCG measurements [10]. It is difficult to discover an EP during a spontaneous pregnancy, but, for a patient who presents regularly at a hospital during early gestation, early diagnosis is facilitated. It is sometimes still difficult to discriminate between an EP and a miscarriage during early gestation. However, the literature contains a number of reports addressing the association between EP and a frozen-thawed IVF/ICSI cycle. Many reports have suggested that frozen embryo transfer has no effect on the risk of EP [5, 1113]. In addition, frozen-thawed day 5 blastocyst transfer is associated with a lower risk of EP than either day 3 transfer or fresh transfer [14]. A peritoneal pregnancy is rarer, and the incidence of EP has been reported to be 0.9%. It has also been reported that the mortality rate is 7.7 times higher than other types of EP [15]. It is thought that this is because intra-abdominal hemorrhage is more common in an EP than a tubal pregnancy, and the symptoms have an abrupt onset and progression. It was fortunate that an intra-abdominal pregnancy was avoided in the present case, but the risk is ever-present.
This case illustrates the following points:
1.
This case was very likely to be misdiagnosed as a miscarriage because the serum β-HCG at 4 weeks 0 days from T-ET was quite low (3.4 IU/L). However, the literature contains a report of a ruptured EP with an HCG level of <10 IU/L [16]. Thus, we must keep the possibility of an EP in mind at all times, even if the HCG titer is very low.
 
2.
The bleeding 4 days after the diagnosis of pregnancy was misdiagnosed as menstruation via a telephone conversation; however, it was actually dysfunctional uterine bleeding. This situation can often occur during a normal pregnancy.
 
3.
A gestational sac or follicle was not detected when the patient presented at our clinic 12 days after the onset of menses. Based on the day of transfer, a yolk sac should have been observed within the echogenic area, and it should have been determined that the echogenic area was not a follicle.
 
It was fortunate in this case that a rupture did not occur. The pouch of Douglas might be an area where minimal friction between the EP.
There are some previous reports of EP, and many have undergone surgery or diagnostic examination laparoscopically.
Author (year)
Age
Infertility
Fresh
NET
SET
Operation
Outcome
diagnosis
/Frozen ET
/diagnosis
Oehniger (1988) [17]
35
endometriosis
Fresh
4
2
Laparotomy
Removal of pregnancy tissue
Bassil (1991) [18]
33
male factor
Fresh
4
unknown
Laparotomy
Delivery of viable twins at 34 weeks
Ferland (1991) [19]
32
tubal factor
Fresh
3
2
Laparotomy
Removal of pregnancy tissue
Ragni (1991) [20]
32
pelvic disease
Fresh
3
2
Laparotomy
Removal of pregnancy tissue
Balmaceda (1993) [21]
33
tubal factor
Fresh
4
4
Laparoscopy
Removal of pregnancy tissue
Fisch (1995) [22]
32
tubal factor
Fresh
3
unknown
Laparotomy
Removal of pregnancy tissue
DelRosario (1996) [23]
33
tubal factor
Frozen
4
unknown
Laparoscopy
Removal of pregnancy tissue
Fisch (1996) [24]
38
tubal factor
Fresh
4
3
Laparotomy
Removal of pregnancy tissue
Moonen-Delarue (1996) [25]
23
pelvic disease
Fresh
unknown
unknown
Laparotomy
Removal of pregnancy tissue
Pisarska (1998) [26]
35
unexplained
Fresh
6
unknown
Laparoscopy
Removal of pregnancy tissue
Deshpande (1999) [27]
33
endometriosis
Fresh
2
3
Laparotomy
Removal of pregnancy tissue
Scheiber (1999) [28]
37
tubal factor
Frozen
2
3
Chemical
KCL
Dmowski (2002) [29]
34
tubal factor
Fresh
3
3
Laparotomy
Removal of pregnancy tissue
Jain (2002) [30]
29
unexplained
unknown
2
unknown
Laparotomy
Removal of pregnancy tissue
Cormio (2003) [31]
30
tubal factor
Fresh
4
3
Laparotomy
Removal of pregnancy tissue
Reid (2003) [32]
28
tubal factor
unknown
3
unkown
Laparotomy
Removal of pregnancy tissue
Kitade (2005) [33]
37
unexplained
Fresh
3
3
Laparoscopy
Removal of pregnancy tissue
Ali (2006) [15]
35
tubal factor
Fresh
1
unkown
Laparoscopy
Removal of pregnancy tissue
Apantaku (2006) [34]
33
tubal factor
Fresh
2
unkown
Laparoscopy
Removal of pregnancy tissue
Knopman (2007) [35]
37
unexplained
Fresh
2
5
Laparoscopy
Removal of pregnancy tissue
Shih (2007) [36]
33
male factor
Fresh
unkown
unkown
Laparoscopy
Removal of pregnancy tissue
Shojai (2007) [37]
35
structural
unknown
3
unkown
Laparotomy
Delivery of viable twins at 32 weeks
Iwama (2008) [38]
31
tubal factor
Fresh
3
3
Laparotomy
Removal of pregnancy tissue
Hyvarinen (2009) [39]
unknown
unknown
unknown
unknown
unknown
Laparotomy
30 weeks delivery
Zacche (2011) [40]
36
tubal factor
Fresh
2
unknown
Laparotomy
Delivery of viable twins at 30 weeks
Angelova (2015) [41]
33
male factor
Fresh
2
3
Laparoscopy
Removal of pregnancy tissue
Yoder (2016) [8]
30
male factor
Fresh
1
5
Laparoscopy
Removal of pregnancy tissue
NET Number of embryo(s) transferred, SET Stage of embryo transferred
Among the EP cases, some have been reported to continue to term [42, 43], and in EP after IVF/ICSI, there have been cases that were delivered [18].
Yoder et al. have recently reported a systematic review of 29 cases (including their case) of AEP after IVF/ICSI. According to their review, several trends of AEP were identified. The majority of cases (61%) had a history of anatomic/structural infertility with a history of tubal factor infertility (46%). This was consistent with tubal factor infertility being a known risk factor for ectopic pregnancy following IVF/ICSI. In addition, a history of tubal EP was particularly common, being reported in 37% of the abdominal ectopic cases. A history of prior tubal surgery was also particularly common (50%) among abdominal ectopic cases in their systematic review. Fresh embryo transfer was far more common in abdominal ectopic cases than frozen embryo transfer (11% of cases) [8].
The risk of EP after IVF/ICSI is increased by the number of embryos [6, 7]. As a mechanism for AEP by IVF/ICSI, aspects of the transfer that may increase the risk of EP include a large volume of transfer media, induction of abnormal uterine contractions, and the location of the embryo transfer in relation to the uterine fundus [10]. Bu et al. reported that the rate of EP was positively associated with ovarian stimulation for fresh IVF/ICSI cycles [6]. The endometrial combined thickness was also linked to an increased risk of EP [44]. Thus, it may be that EP may occur when some factors are present at the same time.
The present case was a rare occurrence, and AEP can occur even in cases where the index of suspicion would be theoretically low. The cause of AEP is unknown at present, and it is difficult to prevent. Technical improvement of IVF/ICSI may lower its incidence if IVF/ICSI is hypothesized to be one cause of EP. Further study is necessary to avoid this rare IVF/ICSI complication.

Acknowledgements

The authors would like to thank Dr.Luba Wolchuk who provided medical writing services on behalf of Forte Inc.

Funding

Not applicable.

Availability of data and materials

All data of this case report are available in this manuscript.

Authors’ contributions

AY and SO drafted the manuscript. YH, TM, and KS performed laparoscopic surgery. TY and KM helped draft the manuscript. All authors read and approved the final manuscript.

Competing interests

The authors report no conflict of interest concerning the materials or methods used in this case report or the findings specified in this paper. The authors have no competing financial interests related to this case report.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Ethics approval and consent to participate

This case report was conducted with the approval of the Ethics Committee of Yanaihara Women’s Clinic and with patient consent (ERBY/3, 2016).

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
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