Content uploaded by Kuo-Chung Lan
Author content
All content in this area was uploaded by Kuo-Chung Lan on Nov 05, 2015
Content may be subject to copyright.
Original Article
Ectopic pregnancy following in vitro fertilization with embryo
transfer: A single-center experience during 15 years
Ling-Yun Cheng
a
, Pin-Yao Lin
b
, Fu-Jen Huang
b
, Fu-Tsai Kung
b
, Hsin-Ju Chiang
b
,
Yu-Ju Lin
a
, Kuo-Chung Lan
b
,
*
a
Department of Obstetrics and Gynecology, Chiayi Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Chiayi, Taiwan
b
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
article info
Article history:
Accepted 18 March 2015
Keywords:
bladder distention
ectopic pregnancy
embryo transfer
in vitro fertilization
abstract
Objective: Ectopic pregnancy is an obstetrical disease that is potentially associated with maternal death
in the first trimester. It is one of the well-known complications following in vitro fertilization (IVF) with
embryo transfer (ET). The incidence of ectopic pregnancy is estimated to be 2.1e8.6% of clinical preg-
nancy after IVF-ET, which is higher than natural conceptions (incidence rate 2%). This study aimed to re-
evaluate the ectopic pregnancy rate in patients undergoing IVF-ET and to investigate the effects of
embryo stage and frozenethawed blastocyst transfer and ET during full bladder distention on ectopic
pregnancy rate.
Materials and methods: This retrospective study reviewed women who achieved a clinical pregnancy
after IVF-ET at the Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital
between 1999 and 2013. We compared ectopic pregnancy rate following Day 3 ET with Day 5 ET, and
after fresh ET with thawed ET. Besides, multivariate analysis was used to clarify the factors affecting
ectopic pregnancy after IVF-ET.
Results: Of the total 1213 clinical pregnancies after fresh ET, 18 (1.5%) were verified as ectopic, which is
similar to the rate following natural conception. The ectopic pregnancy rates were similar for Day 3 (1.2%)
and Day 5 (1.7%) ETs. The incidence of ectopic pregnancy in thawed ET cycles (0.6%) was not significantly
reduced than fresh ET cycles (1.5%). Tubal ET (TET) and ET under full bladder distention had a significant
effect on ectopic pregnancy.
Conclusion: Thawed ET was not associated with a lower incidence of ectopic pregnancy than fresh ET,
and embryo stage did not affect the rate of ectopic pregnancy. In addition, TET and ET under conditions of
full bladder distention may increase the ectopic pregnancy rate.
Copyright ©2015, Taiwan Association of Obstetrics &Gynecology. Published by Elsevier Taiwan LLC. All
rights reserved.
Introduction
In vitro fertilization (IVF) with embryo transfer (ET) has been
reported to result in a higher rate of ectopic pregnancies than
spontaneous pregnancies. Approximately 2.1e8.6% of all clinical
pregnancies after IVF-ET have been reported to be ectopic [1e3],
compared with an ectopic pregnancy rate of 2% after natural
conception [4]. Several hypotheses have been advanced to explain
this difference, including different hormonal milieu, the repro-
ductive health characteristics of infertile women, technical aspects
of IVF procedures, and the estimated embryo implantation poten-
tial [2]. Because of the low incidence of ectopic pregnancy, the
definite risk factors for ectopic pregnancy after IVF-ET remain
inconclusive. Nonetheless, several studies have assessed the risk
factors for ectopic pregnancy after IVF-ET with a view to improving
IVF-ET outcomes and reducing ectopic pregnancy rates. Although a
review of various technical aspects of ET procedures suggested an
optimal method of ET [5], no direct relationships between ET
techniques and ectopic pregnancy rates have been observed to
date.
Over the last few decades, marked improvements in IVF-ET
technologies have made treatment courses more similar to
*Corresponding author. Department of Obstetrics and Gynecology, Kaohsiung
Chang Gung Memorial Hospital and Chang Gung University College of Medicine,
Number 123, Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan.
E-mail address: lankuochung@gmail.com (K.-C. Lan).
Contents lists available at ScienceDirect
Taiwanese Journal of Obstetrics & Gynecology
journal homepage: www.tjog-online.com
http://dx.doi.org/10.1016/j.tjog.2015.08.004
1028-4559/Copyright ©2015, Taiwan Association of Obstetrics &Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 541e545
natural processes. The Society for Assisted Reproductive Technol-
ogy (SART) reported that the incidence of ectopic pregnancy
following IVF-ET declined from 2.1%/clinical pregnancy in 2000 to
1.8%/clinical pregnancy in 2001 [6,7], suggesting that the risk of
ectopic pregnancy is no higher after IVF-ET than after natural
conception.
Theoretically, blastocyst ET, which is more similar to the natural
cycle than cleavage-stage ET, has a higher implantation potential
[8]. Previous studies have shown that decreased uterine contrac-
tility during the later luteal phase [9] and the larger sizes of blas-
tocysts would prevent the retrograde passage of embryos [10],
which imply that blastocyst ET reduces the rate of ectopic preg-
nancy compared with cleavage-stage ET. In practice, however, the
ectopic pregnancy rate was found to be significantly higher after
blastocyst ET [11,12]. These results support Chang and Suh's
observation that transfer of three or more embryos with higher
estimated embryo implantation potential was reported to be
associated with an increased risk of ectopic pregnancy [2]. More-
over, two studies suggested that the rate of ectopic pregnancy was
not reduced after blastocyst ET compared with cleavage-stage ET
[13,14].
This retrospective cohort study was designed to analyze the
incidence of ectopic pregnancy after IVF-ET over the past 15 years in
our institution. Rates of ectopic pregnancy were compared
following fresh versus frozen ET and following cleavage-stage
versus blastocyst transfer. Furthermore, the annual incidence of
ectopic pregnancy was determined, as well as whether full bladder
distention during ET was associated with ectopic pregnancy risk. To
address this issue, multivariate analyses were conducted.
Materials and methods
Study population
This retrospective cohort study included all clinical pregnancies
conceived after IVF-ET in the Department of Obstetrics and Gyne-
cology, Kaohsiung Chang Gung Memorial Hospital, Taiwan, be-
tween January 1999 and December 2013. A clinical pregnancy was
defined as the presence of an intrauterine gestational sac on
transvaginal ultrasound or the diagnosis of an ectopic pregnancy.
Patients' baseline demographic and clinical characteristics were
obtained from their medical records. This study excluded oocyte-
recipient cycles. The study was approved by the Institutional Re-
view Board of the Ethics Committee of Chang Gung Memorial
Hospital, Kaohsiung, Taiwan.
Clinical and laboratory procedures
During the study period, patients underwent ovarian stimula-
tion, which was achieved by gonadotropins, as well as pituitary
suppression by either gonadotropin-releasing hormone (GnRH)
agonist or GnRH antagonist. After triggering ovulation, oocyte
retrieval was followed 34e36 hours later. Oocytes were insemi-
nated conventionally or by intracytoplasmic sperm injection, and
embryos were cultured for 3e6 days, depending on their
morphological score on Day 2, which was determined by the
number of blastomeres and the degree of fragmentation. For fro-
zenethawed cycles, blastocysts were cryopreserved on Day 5. All
women received natural cycle IVF or clomiphene citrate-stimulated
cycle ovarian stimulation (Clomid; Sinphar Pharmaceuticals, Yilan,
Taiwan) to prepare the endometrium for thawed ET. Our protocols
for controlled ovarian hyperstimulation and laboratory procedures
have been described elsewhere [15e18]. During ET, the patient was
placed in a lithotomy position and the cervix was exposed using a
speculum. ET catheter sets (Labotect, GmbH, Germany) were used
for all transvaginal ETs, with a standard transfer volume of
20e30
m
L. Several patients underwent tubal ET (TET) between 1999
and 2001. Before the first half of 2010, ET was performed without
bladder distention; since 2011, all patients underwent ET with full
bladder distention without ultrasound guidance. One year later, ET
was performed under transabdominal ultrasound guidance, with or
without full bladder distention depending on the uterine position.
Starting the day after oocyte retrieval and throughout the luteal
phase, all patients received either Crinone 8% gel (90 mg daily; Fleet
Laboratories Ltd., Watford, UK) or Utrogestan vaginal capsules
(200 mg 4 times daily; Piette International Laboratories, Dro-
genbos, Belgium) [19]. As part of the controlled ovarian hyper-
stimulation protocol in our center, urinary concentration of beta
subunit of human chorionic gonadotropin was measured 2 weeks
after ET, and transvaginal ultrasound was performed at 3e5weeks
to confirm the clinical diagnosis of pregnancy.
Ectopic pregnancies
Ectopic pregnancies after IVF-ET were classified as clinical or
verified ectopic pregnancies. A verified ectopic pregnancy was
defined as the presence of an extrauterine gestational sac on ul-
trasound or following surgical intervention, whereas a clinical
ectopic pregnancy was defined as the absence of an intrauterine
gestational sac with abnormally increased serum human chorionic
gonadotropin concentrations.
Statistical analysis
All statistical analyses were performed using SPSS for Windows,
version 20.0 (SPSS Inc., Chicago, IL, USA). Data were expressed as
mean ±standard deviation, median with interquartile range, or n
(%). Continuous variables were compared using the Man-
neWhitney Utest, whereas categorical variables were compared
using the Chi-square test or Fisher exact test depending on sample
size. A multiple logistic regression analysis was performed to assess
risk factors of ectopic pregnancy following IVF-ET. All tests for
significance were two-tailed, with statistical significance defined as
ap<0.05. Transfers of fresh and frozenethawed embryos were
analyzed separately. The incidence of ectopic pregnancy was
compared after the transfer of fresh Day 3 and Day 5 embryos and
after the transfer of fresh and thawed embryos. Annual incidence of
ectopic pregnancy in women undergoing IVF-ET in our center and
in Taiwan from 1999 to 2013 was analyzed.
Results
A total 3006 IVF cycles following fresh ETs were studied,
including 1711 (56.9%) Day 3 and 1295 (43.1%) Day 5 transfers. Of
the 1213 clinical pregnancies, 574 (47.3%) resulted from Day 3 and
639 (52.7%) from Day 5 transfers. The characteristics of these
clinical pregnancies are presented in Table 1.
During the study period, there were 22 clinical ectopic preg-
nancies following fresh IVF-ET, among which 18 were verified
sonographically or surgically. Thus, the overall rates of clinical and
verified ectopic pregnancy for each clinical pregnancy were 1.8%
and 1.5%, respectively. Of the 18 verified ectopic pregnancies, 17
were tubal pregnancies (of these, 2 were heterotopic pregnancies, 1
each after Day 3 and Day 5 transfers) and one was a cesarean scar
pregnancy. Two of the tubal ETs resulted in verified ectopic preg-
nancies in 1999. The ectopic pregnancy rates relative to the number
of clinical pregnancies and number of transfer cycles are presented
in Table 2.
A total of 154 clinical pregnancies resulted from frozenethawed
ET, with three being verified ectopic pregnancies (1.9%), including
L.-Y. Cheng et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 541e545542
two cervical pregnancies. Both cervical pregnancies occurred due
to difficulties in performing ET, requiring either Hegar dilators or
extensive manipulation with a second catheter. After the exclusion
of these confounders, the verified ectopic pregnancy rate after
frozenethawed ET was 0.6%, which was not significantly reduced
than the rate following fresh cycle ET (p¼0.71).
Table 3 shows details of the rates of ectopic pregnancy following
Day 3 and Day 5 ETs. Clinical ectopic pregnancies were observed
after 10 of 574 (1.7%) Day 3 and 12 of 639 (1.9%) Day 5 ETs (p¼0.86),
and verified ectopic pregnancies after seven of 574 (1.2%) Day 3 and
11 of 639 (1.7%) Day 5 transfers (p¼0.34). Among the verified
ectopic pregnancies, the mean patient age and mean number of
embryos transferred were similar after Day 3 and Day 5 ETs.
Because the ET techniques used in our center changed over time,
the multivariate analysis was conducted to clarify the factors
affecting ectopic pregnancy following fresh IVF-ET. The result
showed that TET (p¼0.005) and full bladder distention during ET
(p¼0.010) had a significant effect on ectopic pregnancy after IVF-
ET (Table 4). The annual incidence of verified ectopic pregnancy
from 1999 to 2013 is shown in Figure 1. The incidence was signif-
icantly higher in 2011 than in the previous years, with four verified
ectopic pregnancies occurring during that year. This increase may
be due to changes in ET techniques, specifically from ET without
bladder distention to ET with full bladder distention.
Discussion
Since Steptoe and Edwards [20] first reported ectopic pregnancy
following IVF, the epidemiology of and risk factors for ectopic
pregnancy after IVF have been widely investigated. In the past,
ectopic pregnancy was thought to be a well-known risk following
IVF. Differences between natural conception and IVF-ET may affect
the incidence of ectopic pregnancy. Despite the health character-
istics of infertile women, improvements in IVF-ET technology have
made this process more similar to natural conception in the recent
decades. Rates of ectopic pregnancy following IVF-ET have been
reduced by restricting the number of embryos transferred [1,2],
avoiding deep fundal transfer [21], and TET [2], injecting a smaller
volume of fluid during ET, and transferring frozenethawed em-
bryos [22,23]. Over the past 15 years, the verified ectopic pregnancy
rate following fresh cycle ET in our center was 1.5% of clinical
pregnancies, which is in good agreement with the rate of 1.8% re-
ported by SART in 2001 (1.8%) [6] and similar to the 2% rate
observed following natural conception [4]. Thus, our findings
confirm that ectopic pregnancy is no longer a complication spe-
cifically associated with IVF-ET.
In general, there has been a belief that higher progesterone
concentrations in the luteal phase may reduce uterine contractility
during fresh ET, which may prevent the embryo from migrating
into the fallopian tubes [24]. However, a growing number of studies
are now available to shed some light on lower ectopic pregnancy
rate following frozenethawed ET [22,23]. The clinical pregnancy
rate was found to be higher following frozenethawed than fresh ET
[25], suggesting impairment of endometrial receptivity after
ovarian stimulation in fresh ET. The lower ectopic pregnancy rate
after frozenethawed ET than fresh ET may be due to the negative
effect of ovarian stimulation on endometrial receptivity in the
latter. However, some studies reported no reduced ectopic preg-
nancy rates with thawed ET [26,27]. After excluding the two cer-
vical pregnancies, which occurred due to difficulties in performing
ET, we found no significant difference in ectopic pregnancy rate
between frozenethawed and fresh ET. Although low incidence of
ectopic pregnancy and relative small sample size of frozenethawed
ET may affect the result in our study, our finding was not able to
Table 1
Characteristics of women with clinical pregnancies after fresh embryo transfer on Day 3 and Day 5.
Characteristic Full cohort Day 3 (n¼574) Day 5 (n¼639)
Age (y) 32.9 ±4.3 33.4 ±4.3 32.3 ±4.3
No. of oocytes retrieved 7.5 (4.5e10) 5.5 (3e7) 9.4 (7e11)
No. of oocytes transferred 2.8 (2e3) 2.9 (2e3) 2.7 (2e3)
EM thickness (cm) 1.3 ±0.3 1.3 ±0.32 1.3 ±0.32
E2 on hCG day (
m
g/mL) 1977.2 (978e2644) 1588.2 (756e2084) 2314.8 (1303e3017)
Infertility diagnosis
a
Tubal factor 331 (27.3) 165 (28.7) 166 (26.0)
Uterine factor 192 (15.8) 93 (16.2) 99 (15.5)
Male factor 395 (32.6) 185 (32.2) 210 (32.9)
Ovulation factor 169 (13.9) 71 (12.4) 98 (15.3)
Unexplained 188 (15.5) 81 (14.1) 107 (16.7)
Others 42 (3.5) 21 (3.7) 21 (3.3)
Values are mean ±standard deviation, n(%), or median (interquartile range).
E2 ¼estradiol; EM ¼endometrial; hCG ¼human chorionic gonadotropin.
a
Sum may be greater than 100% because some patients had more than one infertility diagnosis.
Table 2
Rates of ectopic pregnancy after fresh and frozenethawed embryo transfers.
n(%)
Fresh transfer
Clinical EP/cycle 22/3006 (0.7)
Clinical EP/clinical pregnancy 22/1213 (1.8)
Verified EP/cycle 18/3006 (0.6)
Verified EP/clinical pregnancy 18/1213 (1.5)
Tubal pregnancy 17
Heterotopic pregnancy 2
Cesarean scar pregnancy 1
Thawed transfer
Verified EP/cycle 3/498 (0.6)
Verified EP/clinical pregnancy 3/154 (1.9)
Excluding cervical pregnancy/clinical pregnancy 1/154 (0.6)
Values are n(rate).
EP ¼ectopic pregnancy.
Table 3
Comparison of ectopic pregnancy rates after Day 3 and Day 5 fresh embryo transfers.
Day 3 Day 5 p
Clinical EP (%) 10 (1.7) 12 (1.9) 0.86
Verified EP (%) 7 (1.2) 11 (1.7) 0.34
Age (y) 29.1 ±4.5 31.8 ±6.2 0.47
No. of oocytes transferred 3.0 (2e4) 2.5 (2e3) 0.24
Values are presented as n(incidence), mean ±standard deviation, or median
(interquartile range).
EP ¼ectopic pregnancy.
L.-Y. Cheng et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 541e545 543
indicate no difference in the risk of ectopic pregnancy among fresh
ET compared with frozenethawed ET.
There may be a concern for a lower ectopic pregnancy rate
following blastocyst transfer as speculated by decreased uterine
contractility in the later luteal phase and larger embryo diameter.
When not restricted by patient history or number of embryos
transferred, however, we found that ectopic pregnancy rates were
similar following Day 3 and Day 5 ETs. Another large study, which
adjusted for the number of fertilized embryos, found no statistically
significant difference in ectopic pregnancy rates between Day 3 and
Day 5 ETs [14]. These results support previous research, which
suggests that the higher implantation potential at the blastocyst
stage may increase the risk of ectopic pregnancies except when
only one or two embryos are transferred [2].
Although embryo quality and endometrial receptivity are fac-
tors associated with pregnancy rate, ET is regarded as the critical
element in the final step of IVF cycles. Since uterine straightening
by bladder distention was first shown to be beneficial [28], several
studies have investigated the correlations between pregnancy
outcomes and full bladder distention during ET. A full bladder helps
to straighten the uterocervical angle and facilitates entry of the
catheter, especially for the anteverted uterus. A systematic review
summarized that passive full bladder distention during ET catheter
placement may optimize the outcomes of ET without having direct
adverse effects, including multiple pregnancies and miscarriages
[29]. To date, however, no study has analyzed the relationship be-
tween full bladder distention and ectopic pregnancy rates. In the
first half of 2010, the ET techniques in our center were modified,
from ET without bladder distention to ET with full bladder
distention. This was accompanied by a significant increase in the
ectopic pregnancy rate in 2010 and 2011. These findings suggested
that a full bladder may straighten not only the uterocervical angle
but also the utero-fallopian angle. The utero-fallopian angle in the
patient with anteverted uterus had larger angles under no bladder
distention compared with full bladder distention. This indicated
that full bladder distension makes the uterus and the fallopian
tubes lie nearly on the same plane, allowing embryos to more easily
migrate into the fallopian tubes. After the introduction of
ultrasound-guided ET in 2012, ectopic pregnancy rates have
decreased. ET under ultrasound guidance helps physicians evaluate
the uterocervical angle and decide whether their patients have full
bladder distention or not. Furthermore, it avoids deep fundal
transfer. Despite the impact of new strategy with ultrasound-
guided ET, the result of our study suggests that changing from no
to full bladder extension may have increased the ectopic pregnancy
rate. However, this proposal is an intuitive hypothesis, requiring
more empirical investigation.
This study is unique in competitive case numbers of Day 3 and
Day 5 ETs in our center, thus reducing possible statistical bias.
However, this study had limitations, including its retrospective
design and the relatively low rate of ectopic pregnancy. There were
also several potential confounders, including tubal disease;
numbers of oocytes retrieved, embryos fertilized, and embryos
transferred/cycle; and ET strategies. Moreover, this retrospective
study covers a long period, and may thus pose the risk of bias if the
IVF protocol changes over this interval.
Conclusions
Three of our findings are worth summarizing. First, with the
significant improvements in IVF technology, ectopic pregnancy is
no longer a complication specifically associated with IVF-ET. Sec-
ond, the embryo stage on the day of transfer did not affect the
ectopic pregnancy rate. Finally, the strategy used for ET may affect
the incidence of ectopic pregnancy. Specifically, in addition to TET,
we found that the ectopic pregnancy rate was associated with the
extent of bladder distention. The relationship between ectopic
pregnancy and bladder distention requires further investigation.
Conflicts of interest
The authors have no conflicts of interest relevant to this article.
Acknowledgments
The authors would like to thank Dr Scott Butler, PhD, for English
editing and Yun-Fang Chiang, RN, of the Department of Obstetrics
and Gynecology at Chang Gung Memorial Hospital for assistance in
patient registration and data collection.
Table 4
Multivariate analysis of variables in relation to ectopic pregnancy.
Variable B SEM Wald test p
Physician difference ddd 0.114
TET 3.200 1.128 8.045 0.005
No. of embryo transfer ddd 0.313
Embryo stage on transfer day (Day 3/Day 5) ddd 0.111
Age of female partners (y) ddd 0.052
EM thickness (cm) ddd 0.058
E2 on hCG day (
m
g/mL) ddd 0.147
Tubal factor infertility ddd 0.138
Ultrasound guidance ddd 0.460
Full bladder distention during embryo transfer 3.295 1.273 6.697 0.010
B¼coefficient; EM ¼endometrial; E2 ¼estradiol; hCG ¼human chorionic gonadotropin; SEM ¼structural equation modeling; TET ¼tubal embryo transfer.
Figure 1. Annual incidence of ectopic pregnancy in women undergoing in vitro
fertilization with embryo transfer in our center and in Taiwan from 1999 to 2013.
EP ¼ectopic pregnancy; HPA ¼Health Promotion Administration;
KCGMH ¼Kaohsiung Chang Gung Memorial Hospital.
L.-Y. Cheng et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 541e545544
References
[1] Clayton HB, Schieve LA, Peterson HB, Jamieson DJ, Reynolds MA, Wright VC.
Ectopic pregnancy risk with assisted reproductive technology procedures.
Obstet Gynecol 2006;107:595e604.
[2] Chang HJ, Suh CS. Ectopic pregnancy after assisted reproductive technology:
what are the risk factors? Curr Opin Obstet Gynecol 2010;22:202e7.
[3] Nazari A, Askari HA, Check JH, O'Shaughnessy A. Embryo transfer technique as a
cause of ectopic pregnancy in in vitro fertilization. Fertil Steril 1993;60:919e21.
[4] Centers for Disease C, Prevention. Ectopic pregnancydUnited States,
1990e1992. MMWR Morb Mortal Wkly Rep 1995;44:46e8.
[5] Mains L, Van Voorhis BJ. Optimizing the technique of embryo transfer. Fertil
Steril 2010;94:785e90.
[6] Society for Assisted Reproductive Technology, American Society for Repro-
ductive Medicine. Assisted reproductive technology in the United States: 2001
results generated from the American Society for Reproductive Medicine/So-
ciety for Assisted Reproductive Technology registry. Fertil Steril 2007;87:
1253e66.
[7] Society for Assisted Reproductive Technology, American Society for Repro-
ductive Medicine. Assisted reproductive technology in the United States: 2000
results generated from the American Society for Reproductive Medicine/So-
ciety for Assisted Reproductive Technology Registry. Fertil Steril 2004;81:
1207e20.
[8] Glujovsky D, Blake D, Farquhar C, Bardach A. Cleavage stage versus blastocyst
stage embryo transfer in assisted reproductive technology. Cochrane Database
Syst Rev 2012;7:CD002118.
[9] Fanchin R, Ayoubi JM, Righini C, Olivennes F, Schonauer LM, Frydman R.
Uterine contractility decreases at the time of blastocyst transfers. Hum Reprod
2001;16:1115e9.
[10] Schoolcraft WB, Surrey ES, Gardner DK. Embryo transfer: techniques and
variables affecting success. Fertil Steril 2001;76:863e70.
[11] Keegan DA, Morelli SS, Noyes N, Flisser ED, Berkeley AS, Grifo JA. Low ectopic
pregnancy rates after in vitro fertilization: do practice habits matter? Fertil
Steril 2007;88:734e6.
[12] Rosman ER, Keegan DA, Krey L, Liu M, Licciardi F, Grifo JA. Ectopic pregnancy
rates after in vitro fertilization: a look at the donor egg population. Fertil Steril
2009;92:1791e3.
[13] Milki AA, Jun SH. Ectopic pregnancy rates with day 3 versus day 5 embryo
transfer: a retrospective analysis. BMC Pregnancy Childbirth 2003;3:7.
[14] Smith LP, Oskowitz SP, Dodge LE, Hacker MR. Risk of ectopic pregnancy
following day-5 embryo transfer compared with day-3 transfer. Reprod Bio-
med Online 2013;27:407e13.
[15] Ou YC, Lan KC, Huang FJ, Kung FT, Lan TH, Chang SY. Comparison of in vitro
fertilization versus intracytoplasmic sperm injection in extremely low oocyte
retrieval cycles. Fertil Steril 2010;93:96e100.
[16] Lan KC, Hseh CY, Lu SY, Chang SY, Shyr CR, Chen YT, et al. Expression of
androgen receptor co-regulators in the testes of men with azoospermia. Fertil
Steril 2008;89:1397e405.
[17] Lan KC, Huang FJ, Lin YC, Kung FT, Hsieh CH, Huang HW, et al. The
predictive value of using a combined Z-score and day 3 embryo morphology
score in the assessment of embryo survival on day 5. Hum Reprod 2003;18:
1299e306.
[18] Lin P-Y, Huang F-J, Kung F-T, Wang L-J, Chang SY, Lan K-C. Comparison of the
offspring sex ratio between fresh and vitrification-thawed blastocyst transfer.
Fertil Steril 2009;92:1764e6.
[19] Wang LJ, Huang FJ, Kung FT, Lin PY, Chang SY, Lan KC. Comparison of the
efficacy of two vaginal progesterone formulations, Crinone 8% gel and Utro-
gestan capsules, used for luteal support in blastocyst stage embryo transfers.
Taiwan J Obstet Gynecol 2009;48:375e9.
[20] Steptoe PC, Edwards RG. Reimplantation of a human embryo with subsequent
tubal pregnancy. Lancet 1976;1:880e2.
[21] Pope CS, Cook EK, Arny M, Novak A, Grow DR. Influence of embryo transfer
depth on in vitro fertilization and embryo transfer outcomes. Fertil Steril
2004;81:51e8.
[22] Ishihara O, Kuwahara A, Saitoh H. Frozen-thawed blastocyst transfer reduces
ectopic pregnancy risk: an analysis of single embryo transfer cycles in Japan.
Fertil Steril 2011;95:1966e9.
[23] Shapiro BS, Daneshmand ST, De Leon L, Garner FC, Aguirre M, Hudson C.
Frozen-thawed embryo transfer is associated with a significantly reduced
incidence of ectopic pregnancy. Fertil Steril 2012;98:1490e4.
[24] Pyrgiotis E, Sultan KM, Neal GS, Liu HC, Grifo JA, Rosenwaks Z. Ectopic preg-
nancies after in vitro fertilization and embryo transfer. J Assist Reprod Genet
1994;11:79e84.
[25] Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Ev-
idence of impaired endometrial receptivity after ovarian stimulation for
in vitro fertilization: a prospective randomized trial comparing fresh and
frozen-thawed embryo transfer in normal responders. Fertil Steril 2011;96:
344e8.
[26] Check JH, Choe JK, Katsoff B, Krotec JW, Nazari A. Ectopic pregnancy is not
more likely following fresh vs frozen embryo transfer. Clin Exp Obstet
Gynecol 2005;32:95e6.
[27] Jun SH, Milki AA. Ectopic pregnancy rates with frozen compared with fresh
blastocyst transfer. Fertil Steril 2007;88:629e31.
[28] Sundstrom P, Wramsby H, Persson PH, Liedholm P. Filled bladder simplifies
human embryo transfer. Br J Obstet Gynaecol 1984;91:506e7.
[29] Abou-Setta AM. Effect of passive uterine straightening during embryo trans-
fer: a systematic review and meta-analysis. Acta Obstet Gynecol Scand
2007;86:516e22.
L.-Y. Cheng et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 541e545 545