The clinical characteristics of HP were listed in Table 1. The mean age of the 40 patients was 30.4 ± 4.9 (range 21–45) years, the mean body mass index (BMI) was 21.7 ± 2.7 (range 17.3–29.6) kg/m2. About the surgical history, 12 (30.0%) patients had undergone uni/bilateral tuboplasty to treat fallopian tube obstruction, and seven (17.5%) patients bilateral salpingectomy/tubal ligation because of severe hydrosalpinx. Five (12.5%) patients had received unilateral salpingectomy due to tubal ectopic pregnancy, and sixteen patients had no history of tubal surgery. Fifteen (37.5%) patients had a history of primary infertility, and twenty-five patients reported a history of pregnancy. All patients have two embryos transferred. Of these women, 15 patients had pregnancies via fresh non-donor embryo transfer cycles, and 25 patients conceived after frozen-thawed embryo transfer.
Table 1
Variables
|
No. (%) of patients
|
Age, mean ± SD (range), yr
|
30.4 ± 4.9(21-45)
|
BMI, mean ± SD (range), kg/m2
|
21.7 ± 2.7 (17.3–29.6)
|
History of abortion, n (%)
|
|
0
|
15 (37.5)
|
1-2
|
12 (30.0)
|
≥3
|
13 (32.5)
|
History of tubal surgery, n (%)
|
|
Salpingotomy
|
0
|
Uni/bilateral tuboplasty
|
12 (30.0)
|
Unilateral salpingectomy
|
5 (12.5)
|
Bilateral salpingectomy/tubal ligation
|
7 (17.5)
|
No
|
16 (40.0)
|
Type of infertility, n (%)
|
|
Primary
|
15 (37.5)
|
Secondary
|
25 (62.5)
|
Method of pregnancy, n (%)
|
|
Frozen-thawed embryo
|
15(37.5)
|
Fresh non-donor embryo
|
25(62.5)
|
SD Standard deviation, BMI body mass index |
The symptoms of HP were reported as abdominal pain, irregular vaginal bleeding, rectal tenesmus and sometimes nausea or dizzy in cases (listed on Table 2). The most frequent manifestations before diagnosis were vaginal bleeding (30.0%), 9 patients (22.5%) had abdominal pain, but 7 patients (17.5%) had no symptoms and were found by routine ultrasound examination. We reviewed previous abortion, previous ectopic pregnancy, and pelvic surgery history in HP, 37.5% (15/40) of HP had no abortion before; and 12.5% (5/40) of HP had ectopic pregnancy before. HP could constantly occur at fallopian tubes, and occasionally happen at ovary or at tubal stump (the distribution of EP location was shown in Table 2). Most of ectopic lesion in HP occurred at fallopian tubes, taking up 67.5% (27/40); and 17.5% (7/40) of ectopic lesion occurred at interstitial fallopian. States of ectopic embryos was confirmed by surgery, nine patients were diagnosed with rupture of EP, two of them had suffered hypovolemic shock, fortunately with no maternal death.
Table 2
Variables
|
No. (%) of patients
|
Clinical manifestations, n (%)
|
|
Asymptomatic
|
7(17.5)
|
Abdominal pain
|
9(22.5)
|
Vaginal bleeding
|
12(30.0)
|
Abdominal pain and vaginal bleeding
|
9(22.5)
|
Rectal tenesmus
|
3(7.5)
|
Location of EP, n
|
|
Tubal (right vs. left)
|
27 (13 vs. 14)
|
Interstitial (right vs. left)
|
7 (5 vs. 2)
|
Cornual (right vs. left)
|
6 (3 vs. 3)
|
Gestational age at symptom onset, mean ± SD (range), d
|
44.8 ± 8.6 (27–68)
|
Gestational age on first TVS, mean ± SD (range), d
|
46.3 ± 7.6 (29–68)
|
Gestational age at diagnosis, mean ± SD (range), d
|
49.4 ± 7.6 (29–68)
|
First TVS suspected HP, n (%)
|
|
Yes
|
29(72.5)
|
No
|
11(27.5)
|
Diameters of gestational mass, mean ± SD (range), mm
|
24.1 ± 11.5 (11.3–56.3)
|
EP Ectopic pregnancy, TVS transvaginal sonography, HP heterotopic pregnancy, IUP Intrauterine pregnancy |
Thirty-five patients (83.3%) had symptoms appearing before first TVS, and the other 5 patients after TVS, the mean gestational age at symptom onset was 44.8 ± 8.6 (range, 27-68) days. The gestational age at the time of diagnosis was 49.4 ± 7.6 (range, 29-68) days. The time of diagnosis by TVS ranged from 15 and 54 days after ET, and the mean gestational age on first TVS was 46.3 ± 7.6 (range, 29–68) days. The mean gestational mass diameter of the EP was 24.1 ± 11.5 (range, 11.3-56.3) mm. Twenty-nine (85.5%) patients had suspected HP when they received first TVS. Among these cases, 23 patients were present as inhomogeneous masses, 3 patients were extrauterine empty gestational sacs, 3 patients were gestational sacs with yolk, and 11 patients were feta poles with cardiac activity. Moreover, patients who found no sign of ectopic embryos on first TVS had received repeated TVS before they were admitted to inpatient department. Hence, the sensitivity of TVS for detecting HP was72.5% (29/40).
In order to monitor the changing situation of HP, patients were admitted to receive repeated TVS. The last TVS before surgery showed that 30 patients (75.0%) were detected the fetal cardiac activity in intrauterine conception (Table 3). Eleven patients received expectant management, 29 patients underwent laparotomy (13/29) or laparoscopy (16/29) without anesthetic complications, and no patients received ultrasound-guided embryo aspiration. The mean gestational age at surgery day was 51.0 ± 8.6 (range 33–67) days. In the expectant group, no patients suffered rupture of ectopic pregnancy and 3 miscarriages occurred during the period of strict observation. In the surgical group, 9 patients had EP ruptures, 3 of whom required blood transfusions. The total miscarriage rate in the surgical group was 37.9% (11/29). Furthermore, there was no significant difference between perinatal outcome in the expectant management vs. surgical groups (P=0.169).
Table 3
Surgical information and clinical outcomes
Variables
|
No. (%) of patients
|
Management of HP, n (%)
|
|
Expectant management
|
11(27.5)
|
Surgical management
|
29(72.5)
|
Embryo aspiration management
|
0
|
TVS before surgery
|
|
IUP, n (%)
|
|
Gestational sac
|
10(25.0)
|
Fetal cardiac activity
|
30(75.0)
|
HP, n (%)
|
|
Inhomogeneous/hyperechoic mass
|
23(57.5)
|
Gestational sac
|
6(15.0)
|
Fetal cardiac activity
|
11(27.5)
|
Gestational age at surgery day, mean ± SD (range), d
|
51.0±8.6 (33–67)
|
Clinical outcomes, n (%)
|
|
Term delivery
|
22(55.0)
|
Preterm delivery
|
4(10.0)
|
Abortion
|
14(35.0)
|
Mode of delivery, n (%)
|
|
Vaginal delivery
|
5(19.2)
|
Cesarean section
|
21(80.8)
|
IUP Intrauterine pregnancy |
TVS at HP diagnosis revealed that a gestational sac of an IUP without fetal cardiac activity was found in 10 patients, while with fetal cardiac activity was found in 30 patients. Moreover, both 3 patients with empty gestational sac and 4 patients with yolk sac for the IUP were ended in early miscarriage. The miscarriage rate was 16.7% (5/30) for patients with IUP cardiac activity at HP diagnosis, and 90.0% (9/10) for patients without IUP cardiac activity; a significant correlation was identified (χ2 = 18.857, P < 0.001) (Table 4). Additionally, the abortion rate of patients after frozen-thawed embryo was lower than patients following fresh non-donor embryo (P<0.05). Further logistic regression models indicated that patients following an IUP with fetal cardiac activity at HP diagnosis were identified as an independent factor of perinatal outcome (P<0.001) (Table 5). However, the rate of miscarriage exhibited no significant association with other factors, such as patients’ age, first TVS-suspected HP, gestational age at diagnosis, HP positions, ectopic gestational mass diameter, EP fetal heartbeat, pelvic hemorrhage volume (Table 5).
Table 4
The clinical outcomes of patients with HP
Variables
|
No. of patients
|
Abortion
|
Premature birth
|
Full-term birth
|
χ2
|
P value
|
IUP without cardiac activity
|
|
|
|
|
18.857
|
<0.00011
|
Empty gestational sac
|
3
|
3
|
0
|
0
|
|
|
Yolk sac
|
4
|
4
|
0
|
0
|
|
|
Yolk sac and fetal pole
|
3
|
2
|
0
|
1
|
|
|
IUP with cardiac activity
|
30
|
5
|
4
|
21
|
|
|
1 The abortion rate of patients without IUP cardiac activity group was higher than patients with IUP cardiac activity group at HP diagnosis, and the difference was significant (χ2 = 18.857, P< 0.001). |
Table 5
Uni- and Multi-variable logistic regression of predictive factors associated with pregnancy outcomes in HP patients
Variables
|
Univariate analyses
|
Multivariate analyses
|
N
|
P
|
Regression coeffificient (SE)
|
P
|
95%CI
|
Age (years)
|
|
|
|
|
|
<34
|
29
|
0.406
|
0.144(0.172)
|
0.846
|
-0.286~0.347
|
≥34
|
11
|
|
|
|
|
Method of IVF-ET, n (%)
|
|
|
|
|
|
Frozen-thawed embryo
|
15
|
0.130
|
0.240(0.155)
|
0.412
|
-0.175~0.416
|
Fresh non-donor embryo
|
25
|
|
|
|
|
Gestational age at diagnosis, d
|
|
|
|
|
|
<52
|
24
|
0.694
|
-0.062(0.158)
|
0.870
|
-0.288~0.338
|
≥52
|
16
|
|
|
|
|
Suspected HP at the initial TVS, n
|
|
|
|
|
|
Yes
|
29
|
0.406
|
0.144(0.172)
|
0.805
|
-0.470~0.368
|
No
|
11
|
|
|
|
|
Gestational mass diameter (mm)
|
|
|
|
|
|
<30
|
30
|
0.262
|
0.200(0.176)
|
0.151
|
-0.084~0.520
|
≥30
|
10
|
|
|
|
|
EP fetal heartbeat
|
|
|
|
|
|
Yes
|
11
|
0.914
|
-0.019(0.173)
|
0.267
|
-0.600~0.173
|
No
|
29
|
|
|
|
|
IUP fetal heartbeat
|
|
|
|
|
|
Yes
|
30
|
<0.001
|
0.733(0.133)
|
<0.001
|
0.474-1.119
|
No
|
10
|
|
|
|
|
HP positions
|
|
|
|
|
|
Adnexal regions
|
27
|
0.758
|
0.051(0.165)
|
0.655
|
-0.390~0.249
|
Other regions
|
13
|
|
|
|
|
Pelvic hemorrhage volume, n
|
|
|
|
|
|
<400ml
|
32
|
0.540
|
-0.107(0.172)
|
0.669
|
-0.504~0.328
|
≥400ml
|
8
|
|
|
|
|
Ruptured EP, n
|
|
|
|
|
|
Yes
|
9
|
0.333
|
0.188(0.191)
|
0.499
|
-0.645~1.294
|
No
|
31
|
|
|
|
|
Treatment modality, n
|
|
|
|
|
|
Surgical managements
|
29
|
0.512
|
-0.122(0.184)
|
0.634
|
-0.646~1.043
|
Other managements
|
11
|
|
|
|
|