ArticlePDF Available

Ectopic pregnancy following in vitro fertilization with embryo transfer: A single-center experience during 15 years

Authors:

Abstract and Figures

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 2.1–8.6% of clinical pregnancy 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 frozen–thawed 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.
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 rst 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 veried 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 signicantly
reduced than fresh ET cycles (1.5%). Tubal ET (TET) and ET under full bladder distention had a signicant
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
denite 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 signicantly 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
dened 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 rst 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 conrm the clinical diagnosis of pregnancy.
Ectopic pregnancies
Ectopic pregnancies after IVF-ET were classied as clinical or
veried ectopic pregnancies. A veried ectopic pregnancy was
dened as the presence of an extrauterine gestational sac on ul-
trasound or following surgical intervention, whereas a clinical
ectopic pregnancy was dened 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
signicance were two-tailed, with statistical signicance dened 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 veried
sonographically or surgically. Thus, the overall rates of clinical and
veried ectopic pregnancy for each clinical pregnancy were 1.8%
and 1.5%, respectively. Of the 18 veried 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 veried 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 veried 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 difculties in performing ET, requiring either Hegar dilators or
extensive manipulation with a second catheter. After the exclusion
of these confounders, the veried ectopic pregnancy rate after
frozenethawed ET was 0.6%, which was not signicantly 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 veried ectopic pregnancies after seven of 574 (1.2%) Day 3 and
11 of 639 (1.7%) Day 5 transfers (p¼0.34). Among the veried
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 signicant effect on ectopic pregnancy after IVF-
ET (Table 4). The annual incidence of veried 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 veried
ectopic pregnancies occurring during that year. This increase may
be due to changes in ET techniques, specically from ET without
bladder distention to ET with full bladder distention.
Discussion
Since Steptoe and Edwards [20] rst 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 uid during ET, and transferring frozenethawed em-
bryos [22,23]. Over the past 15 years, the veried 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 ndings
conrm that ectopic pregnancy is no longer a complication spe-
cically 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 difculties in performing
ET, we found no signicant 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 nding 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)
Veried EP/cycle 18/3006 (0.6)
Veried EP/clinical pregnancy 18/1213 (1.5)
Tubal pregnancy 17
Heterotopic pregnancy 2
Cesarean scar pregnancy 1
Thawed transfer
Veried EP/cycle 3/498 (0.6)
Veried 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
Veried 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
signicant 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 nal step of IVF cycles. Since uterine straightening
by bladder distention was rst shown to be benecial [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
rst half of 2010, the ET techniques in our center were modied,
from ET without bladder distention to ET with full bladder
distention. This was accompanied by a signicant increase in the
ectopic pregnancy rate in 2010 and 2011. These ndings 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 ndings are worth summarizing. First, with the
signicant improvements in IVF technology, ectopic pregnancy is
no longer a complication specically 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. Specically, 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.
Conicts of interest
The authors have no conicts 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
B¼coefcient; 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 vitrication-thawed blastocyst transfer.
Fertil Steril 2009;92:1764e6.
[19] Wang LJ, Huang FJ, Kung FT, Lin PY, Chang SY, Lan KC. Comparison of the
efcacy 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. Inuence 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 signicantly 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 simplies
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
... Ishihara et al. reported that there was no ectopic pregnancy in treatment outcomes of registered fresh cycles in assisted reproductive technology in Japan in 2017 [18]. In vitro fertilization (IVF) with embryo transfer (ET) has been reported to result in a higher rate of ectopic pregnancies than spontaneous pregnancies [19,20]. However, our findings and the report by Ishihara et al [18] does not support this as the ectopic pregnancy rate after natural conception is about 2% [21]. ...
... The relatively lower ectopic pregnancy rates we found, may be because about 9 in 10 embryo transferred in our study center were done with day-5 embryo. Some studies have shown that decreased uterine contractility during the later luteal phase [22,23] and blastocyst embryo transfer are associated with reduced rate of ectopic pregnancy compared with cleavage-stage embryo transfer [19,23]. The low rate (0.3%) of frozen embryo used in this study is because facilities for freezing embryos were not available in the study centre until mid-2022. ...
Article
Full-text available
Background: The World Health Organization recommends that Assisted Reproductive Technology be complementary to other ethically acceptable solutions to infertility. Whereas fertility centres are increasing in number in urban regions of Africa, published reports of their performance are sparse. We present a 10-year review of assisted reproductive technology performed in a public tertiary centre in Lagos, Nigeria. Methods: This was a hospital-based, retrospective, cross-sectional review of 604 women, over a 10-year period that had in-vitro fertilization or in-vitro fertilization with intra-cytoplasmic sperm injection at the Institute of Fertility Medicine, Lagos State University Teaching Hospital. Data obtained were expressed in descriptive statistics and Pearson correlation was used to determine the strength of linear relationship between two continuous variables at a significance level of p < 0.05. Results: The mean age of the women was of 37.7 ± 6.2 years and 89.7% had no previous parous experience. About 27.2% of the male partners had normal seminal fluid parameters while 4.6% had azoospermia. Median serum follicle stimulating hormone of the women was 8.1 IU/L and median serum anti-mullerian hormone was 6.3 pmol/L. There was weak positive correlation between age and serum follicle stimulating hormone (r = 0.306, p < 0.001); weak negative correlation between age and serum anti-mullerian hormone (r = -0.48, p < 0.001) and very weak correlation between body mass index and serum follicle stimulating hormone (r = 0.173, p = 0.011). In-vitro fertilization and intra-cytoplasmic sperm injection was the method of fertilization used in 97.4% of the cases and 81.8% of embryos formed were of good quality. Most women (94.5%) had 2 embryos transferred and 89.9% had day-5 embryo transfer done. About 1 in 4 of the women (143/604, 23.7%) had clinical pregnancy and 49.7% of women who got pregnant had delivery of a live baby at term while 11.9% had preterm delivery of a live baby. Conclusion: Despite increasing use and success of assisted reproductive technology in south-western Nigeria, there is room for improvement in clinical pregnancy rates and live birth rates post- assisted reproductive technology. Complication rates are desirably low.
... However, surgery may be an additional option for high-risk, chemoresistant, or unsuitable cases (7,8) . EP refers to the implantation of the embryo in any site rather than the endometrial cavity (9) . Tubal pregnancy is the most common type of EP and is associated with the highest mortality rate (10) . ...
Article
Full-text available
High-intensity focused ultrasound (HIFU) is a non-surgical and noninvasive treatment modality that depends on external ultrasound energy sources that induce focused mass ablation and protein degeneration in the treatment area via thermal energy penetration under the intact skin. We aim in our study to collectively evaluate the safety of HIFU for the treatment of different obstetric and gynecological diseases in the literature. We searched PubMed, Scopus, and Science Direct databases, without restriction on date or language, from the inception of these databases until January 20, 2024. We also examined the references of the included studies in the Mendeley archive for eligible articles. We found a total of 706 studies. After the screening and selection process, 56 participants were included. Our dichotomous outcomes were pooled in our single-arm meta-analysis as risk ratio (RR) and with 95% confidence interval (CI) while our continuous outcomes were pooled as mean change and 95% CIs. Fixed- or random-effects models were applied depending on the heterogeneity detected. Our systematic review and meta-analysis included 56 studies including 11.740 patients. Depending on the Society of Interventional Radiology (SIR) classification for adverse effects. The results of this meta-analysis for the type A category that did not require clinical intervention found that pain in the treatment site estimated RR with 95% CI: 0.61 (0.33, 0.89), abnormal vaginal discharge 0.16 (0.073, 0.24), low-grade fever (<38 °C) 0.005 (0.002, 0.009). Sensory abnormalities of the lower limbs were examined in 3390 individuals and observed in only 19 patients who experienced gradual relief of symptoms within one month after treatment. Regarding SIR type B, 99 of a total of 6.437 patients had small vesicles and superficial burns with pooled RR and 95% CI: 0.012 (0.007, 0.018). In terms of groin or perianal and lower abdominal pain, our RRs with 95% CIs were 0.1 (0.067, 0.13) and 0.38 (0.25, 0.51). However, vaginal bleeding was detected in only 32 out of a total of 3.017. Major adverse events like lumber disc herniation, thrombocytopenia, and renal failure, were unmentionable. Additionally, our included studies did not record any deaths. HIFU, either alone or in combination with oxytocin or any other enhancing agent, is safe for patients with different gynecological and obstetric diseases. In terms of efficacy, it showed promising results compared with traditional treatment lines. To our knowledge, we are the first and most comprehensive meta-analysis in the literature that has studied the different safety outcomes related to HIFU as a treatment modality for different obstetric and gynecological diseases with a very large sample size, making our evidence strong and less attributed to errors. Keywords: HIFU, ectopic pregnancy, endometriosis, gestational trophoblastic diseases, adenomyosis Address for Correspondence/Yazışma Adresi: Mostafa Maged Ali, MD, Egyptian Ministry of Health and Population, Fayoum General Hospital, Department of Obstetrics and Gynecology, Fayoum, Egypt
... 4 The rate of EP among IVF pregnancies ranged from 2.1% to 8.6% following embryo transfer, compared to 2% in natural conceptions. 5 When women are in a clinically stable condition, systemic and local methotrexate (MTX) injections, a viable treatment option, should be considered. 6 Strategic management approaches are particularly essential in the context of ART, as patients frequently express a strong desire for future fertility. ...
Article
Full-text available
The incidence of ectopic pregnancy (EP) has increased in recent years, owing to causes such as pelvic inflammatory diseases and assisted reproductive technologies (ART). The present study reported a case of a 33-year-old nulliparous woman with a history of previous ectopic pregnancies, who underwent pelvic ultrasound in August 2022, which revealed a double EP including a cervical pregnancy and a tubal stump pregnancy. Despite known risk factors and elevated beta-human chorionic gonadotropin (β-hCG) levels, a conservative approach, utilizing multiple doses of systemic methotrexate (MTX) injections, was employed to preserve fertility at the Regional Perinatal Center in Aktobe, Kazakhstan. Treatment efficacy was monitored through β-hCG levels and ultrasound imaging, with successful resolution of both EPs and preservation of reproductive function. The present case highlighted the safety and efficacy of MTX therapy in managing complex EP presentations, emphasizing the necessity of individualized treatment approaches in reproductive medicine, particularly in terms of preserving fertility in patients undergoing ART. Multiple high doses of MTX injections were beneficial for pregnancy with two distinct regions, fetal cardiac activity, and elevated serum β-hCG level. Further research is required to explore optimal treatment strategies for EP, considering patient-specific factors and treatment goals.
... The various factors found responsible for ectopic pregnancy are history of pelvic inflammatory disease, tubal factor infertility, and deep fundal transfer technique. [17][18][19] Abortions was observed in 24% patients in present study. This is in concordance with various studies depicting the pregnancy losses after IVF/ICSI ranging from 18.5% to 21.8% in singleton pregnancies. ...
... Ectopic pregnancy has become more prevalent, particularly with the widespread adoption of assisted reproductive techniques. The incidence of ectopic pregnancies has seen a notable rise, escalating from 2%, which is after natural conception, to 8.6% in pregnancies resulting from in vitro fertilization after embryo transfer [2]. Also, despite the widespread availability of modern diagnostic and therapeutic modalities in recent years, ectopic pregnancy remains the most common cause of maternal mortality during the first trimester of pregnancy. ...
Article
Full-text available
Interstitial ectopic pregnancy is rare (2%-4% of ectopic pregnancies). The atypical clinical presentation of interstitial ectopic pregnancy associated with massive vaginal bleeding is extremely rare and makes early preoperative diagnosis even more difficult. The presentation of our case concerns the early diagnosis and surgical treatment of a patient with an interstitial ectopic pregnancy without rupture, which presented atypically with painless, severe vaginal bleeding. A 27-year-old fourth-term pregnant woman presented with massive painless vaginal bleeding. Secondary amenorrhea was calculated at eight weeks and four days. Transvaginal ultrasound and transvaginal Doppler ultrasound combined with the quantification of beta-chorionic gonadotropin hormone raised the suspicion of interstitial ectopic pregnancy. Intraoperatively, the presence of a large swelling of the right horn of the uterus was established, and a wedge resection was performed with the removal of the corresponding fallopian tube. Three weeks after surgery, the serum beta-chorionic gonadotropin hormone value was zero. In this paper, the rarity of interstitial ectopic pregnancy, the difficulties related to early and correct preoperative diagnosis, and the selection of the appropriate available therapeutic procedures are emphasized, the correct application of which can significantly contribute to reducing the morbidity and mortality of these patients.
... Ectopic pregnancy (EP) could be defined as any embryo that got implanted in any site rather than the endometrial cavity, and it prevailed in about 2% of all naturally occurring pregnancies in contrast to 2.1-8.6 in vitro fertilization (IVF) assisted ones [1]. ...
Article
Full-text available
Ectopic pregnancy (EP) could be defined as any embryo that got implanted in any site rather than the endometrial cavity. Lately, different types of EP were reportedly managed by high‐intensity focused ultrasound (HIFU). We aimed to pool all available data in a systematic review without meta‐analysis and investigate the efficacy and safety tendencies of HIFU among different types of EP. We applied our comprehensive terms in Google Scholar, PubMed, Scopus, Ovid, and PubMed Central databases from their inception until September 23. Retrieved references were gathered using EndNote in which we omitted the duplicates and exported the record for screening. Data regarding characteristics, safety and efficacy outcomes, and baseline information of the enrolled population were extracted. The eligible case reports were assessed using a tool by Murad and colleagues, while the quality of the included cohorts was appraised using the NIH tool. We retrieved 6637 studies, which were scrutinized by titles and abstracts. We scrutinized the full texts of 36 studies and ultimately included a total of 17 studies. All studies were conducted in China, and on different types of ectopic pregnancy including tubal, cervical, intramural, caesarian scar, and corneal ectopic pregnancy. The mean age of enrolled patients was 33.03 years, and we pooled a total sample of 853 patients. The follow‐up period varied widely among the included studies, ranging from 1.3 months to up to 69 months. Normal menstruation recurred after a mean of 35 days, as reported by nine studies. Most of the included studies reported normal β‐HCG after around 30–40 days. Twelve studies with 757 patients reported a cumulative incidence of 179 cases of abdominal pain after HIFU. Neither of the enrolled patients reportedly complained of skin burn after HIFU. We suggested managing EP patients with HIFU, especially when seeking further conceiving. High‐quality randomized controlled trials are required to draw a stronger level of evidence.
... Medical management by intramuscular methotrexate (MTX) injection is the current standard for medical management of EPs [2]. It has some contraindications which include hemodynamic instability, anemia, leukopenia, thrombocytopenia, pelvic pain or hemoperitoneum [10], indicative of EP rupture, renal or hepatic insuf iciency, pulmonary disease, active peptic ulcer disease, coinciding IUP, breastfeeding, fetal cardiac activity, serum β-hCG levels > 5000 mIU/mL, or EP > 4 cm in diameter. ...
Article
Full-text available
Background: Ectopic pregnancy (EP) is a common and serious early pregnancy problem with a significant morbidity rate and the potential for maternal death. Women commonly present with minimal vaginal bleeding and abdominal pain. Objective: The main objective of the study was to evaluate the risk factors, clinical presentation, sites, and management outcomes of ectopic pregnancies. Methodology: It was a prospective descriptive, cross-sectional hospital-based study conducted at Bashair Teaching Hospital during the period January 2021–June 2021. An interview questionnaire was used, and eighty-two (82) women were included after informed consent. Demographic and clinical data concerning personal history, symptoms of presentation, risk, site, and type of management were recorded. Results: Ectopic pregnancy incidence was 2% and most risk factors were infection 29.3%, surgery 15.9%, miscarriage 13.4%, infertility 12.2%, tubal surgery 4.9%, previous ectopic pregnancy 4.9%, intrauterine contraceptive device (IUCD) 3.6%, and tubal ligation 2.4%. Women presented with bleeding and abdominal pain at 47.5%, bleeding at 18.3%, abdominal pain at 9.7%, and shock at 8.5%. The sites are ampullary (57.3%), fimbria (9.7%), interstitial (8.5%), isthmus (8.5%), ovarian (7.3%), cervical (4.8%), and abdominal (3.6%). Surgical management was 93.9%, medical and surgical management was 3.6% and medical management was 2.4%. A blood transfusion was received at 37.8%. Conclusion: The study concluded that women of reproductive age are at risk of ectopic pregnancy, so healthcare providers and doctors should have a high index of suspicion, prompt diagnosis, and intervention for ectopic pregnancy. Assessment of women at risk factors and modifications will reduce incidence.
... Currently, there was no consensus on the risk factors for ectopic pregnancy after IVF treatment, however, tubal factor infertility; high estrogen levels before embryo transfer seem to increase the incidence of ectopic pregnancy. On the contrast, blastocyst transfer was a protective factor as compared with cleavage stage embryo transfer (11,15,16). ...
Article
Full-text available
Background The relationship between endometrial thickness and pregnancy safety after in vitro fertilization treatment is an important topic that should provoke attention. The aim of this study was to demonstrate the relationship between endometrial thickness on day of embryo transfer and early pregnancy complications, including ectopic pregnancy and early miscarriage, in frozen thawed embryo transfer (FET) cycles. Methods Patients undergoing their first FET cycles were included into this study from January 2010 to December 2021. Patients were divided into three groups according to endometrial thickness on day of embryo transfer: Thin, ≤ 7 mm; Medium, 7-14 mm; Thick, ≥ 14 mm. Ectopic pregnancy and early miscarriage were the two primary outcomes. Endometrial thickness was the main measured variable. The risk factors of these two compilations were determined based on univariate analysis and multivariate logistic regression analysis. Results A total of 11138 clinical pregnancies were included. The overall ectopic pregnancy and early spontaneous miscarriage rates were 2.62% and 13.40%. The ectopic pregnancy and early spontaneous miscarriage rates were significantly higher in patients with thin endometrium as compared with those in the other two groups (ectopic pregnancy rate: 5.06% vs. 2.62% vs. 1.05%; P < 0.001; early spontaneous miscarriage rate: 15.18% vs. 13.45% vs. 11.53%; P < 0.001). In multivariate logistic regression analysis, thin endometrium was an independent factor to predict ectopic pregnancy [adjusted odds ratio (aOR): 5.62; 95% confidence interval (CI): 2.51–12.58, P < 0.001], and to predict early spontaneous miscarriage rate (aOR: 1.57; 95% CI: 1.21–1.74, P < 0.001). Conclusion Thin endometrium on day of embryo transfer in FET cycles is an independent predictor for early pregnancy compilations, including ectopic pregnancy and early spontaneous miscarriage.
Book
Üreme Organlarının Anatomisi ve Fizyolojisi Asiye AKBAŞ ÇELEBİ Doğurganlık Bilinci ve İnfertilite Açısından Önemi Ece KAPLAN Simge ZEYNELOĞLU İnfertilitenin Epidemiyolojisi, Etiyolojisi ve Risk Faktörleri Pınar KARA Evşen NAZİK İnfertil Çiftlerin Değerlendirilmesi ve Hemşirenin Rolü Ahu AKSOY Duygu VEFİKULUÇAY YILMAZ İnfertilitede Kullanılan Tedavi Yöntemleri ve Hemşirenin Rolü Aysu BULDUM Tuba GÜNER EMÜL İnfertilite Tedavi Sürecinde Ortaya Çıkan Komplikasyonlar ve Hemşirelik Yaklaşımı Aslıhan AKSU Tuba GÜNER EMÜL İnfertil Çiftlerde Sağlıklı Yaşam Biçimi Davranışları Geliştirmenin Önemi ve Hemşirenin Rolü Gülendam KARADAĞ Nuray ÖZTÜRK İnfertilite Tanı ve Tedavisinde Bireyin/Çiftin Eğitim ve Danışmanlık Gereksinimleri İlknur ATASEVER Gülten KOÇ İnfertilitenin Psikososyal ve Psikoseksüel Etkileri Arzu ABİÇ Tuba GÜNER EMÜL İnfertilite Tedavi Sürecinde Stresle Başetme Yöntemleri Elçin ALAÇAM Mualla YILMAZ İnfertilite Hemşireliğinde Kanıta Dayalı Uygulamalar İlknur YEŞİLÇINAR Gülten GÜVENÇ İnfertilite Tedavi Sürecinde Etik Sorunlar ve Yasal Düzenlemeler Gülengül MERMER Ebru BULUT Yardımla Üreme Tekniklerinde Teknolojik Gelişmeler Selin HAZIR Üremeye Yardımcı Tedavi Uygulamalarında Risk Yönetimi Filiz DEĞİRMENCİ Duygu V. YILMAZ İnfertilite Hemşiresinin Rol ve Sorumlulukları Şule ERGÖL
Chapter
Assisted Reproductive technologies and procedures employ the use of fertility medication and surgical techniques. Certain complications may arise, either at technique implementation or later in early or late postsurgical period. Ovarian hyperstimulation and ectopic pregnancy, despite at a very small percentage, are clinical entities that need scoring systems to either predict or treat patients. In addition, other pathologies, such as thrombosis and preeclampsia, are also linked to their application. Therefore, various methods have been developed for disease prediction and triage, surgical technique stimulation for increased effectiveness and skills development. This chapter presents the most important methods for this purpose and validates its efficiency.KeywordsART complicationsEctopic pregnancy triageOocyte retrieval simulationEmbryo-transfer simulationPreeclampsia triageOvarian hyperstimulation triage
Article
A human embryo in transition between a morula and blastocyst after culture in vitro was reintroduced into the mother's uterus via the cervix. The resulting pregnancy was closely monitored and was found to be located in the oviduct. The ectopic embryo was removed at 13 weeks gestation.
Article
The number of programs reporting increased in 1998, as did the number of cycles of ART (12.1%), with an increased overall probability of success. The increase in number of cycles reported is largely attributable to the increase in the number of clinics combined with an increase in numbers of treatments at many higher-volume clinics. This increased reporting activity probably relates to the implementation of the Federal Fertility Clinic Success Rate and Certification Act. The increase (20.0%) in clinics reporting may also be attributable to enforcement of the CDC’s definition of a reporting clinic, which requires discrete business entities completing treatments at the same laboratory to report separately, as well as an increase in the number of new programs first reporting in 1998. The continued efforts of SART to ease the burden of ART reporting, the requirement of all SART member clinics to report their results, and the requirement to participate in the on-site validation process or lose their SART membership may have also increased compliance with reporting.
Article
Objective: To summarize the procedures and outcomes of assisted reproductive technologies (ART) that were initiated in the United States in 2001. Design: Data were collected electronically using the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System software and submitted to the American Society for Reproductive Medicine/SART Registry. Participant(s): Three hundred eighty-five clinics submitted data on procedures performed in 2001. Data were collated after November 2002 [corrected] so that the outcomes of all pregnancies would be known. Main outcome measure(s): Incidence of clinical pregnancy, ectopic pregnancy, abortion, stillbirth, and delivery. Result(s): Programs reported initiating 108,130 cycles of ART treatment. Of these, 79,042 cycles involved IVF (with and without micromanipulation), with a delivery rate per retrieval of 31.6%; 340 were cycles of gamete intrafallopian transfer, with a delivery rate per retrieval of 21.9%; 661 were cycles of zygote intrafallopian transfer, with a delivery rate per retrieval of 31.0%. The following additional ART procedures were also initiated: 8,147 fresh donor oocyte cycles, with a delivery rate per transfer of 47.3%; 14,509 frozen ET procedures, with a delivery rate per transfer of 23.5%; 3,187 frozen ETs employing donated oocytes or embryos, with a delivery rate per transfer of 27.4%; and 1,366 cycles using a host uterus, with a delivery rate per transfer of 38.7%. In addition, 112 cycles were reported as combinations of more than one treatment type, 8 cycles as research, and 85 as embryo banking. As a result of all procedures, 29,585 deliveries were reported, resulting in 41,168 neonates. Conclusion(s): In 2001, there were more programs reporting ART treatment and a significant increase in reported cycles compared with 2000.
Article
The incidence of ectopic pregnancy after IVF is increased approximately 2.5-5-fold compared with natural conceptions; however, the aetiology for this increased risk remains unclear. One proposed practice change to decrease the incidence of ectopic pregnancy is blastocyst embryo transfer on day 5 rather than cleavage-stage embryo transfer on day 3. A retrospective cohort study was conducted to compare the risk of ectopic pregnancy following fresh day-5 embryo transfer with day-3 embryo transfer among women who underwent IVF and achieved pregnancy from 1998 to 2011. There were 13,654 eligible pregnancies; 277 were ectopic. The incidence of ectopic pregnancy was 2.1% among day-3 pregnancies and 1.6% among day-5 pregnancies. The adjusted risk ratio for ectopic pregnancy from day-5 compared with day-3 transfer was 0.71 (95% confidence interval 0.46-1.10). Although this analysis included 13,654 cycles, with a two-sided significance level of 0.05, it had only 21.9% power to detect a difference between the low incidence of ectopic pregnancy among both day-3 and day-5 transfers. In conclusion, this study was not able to demonstrate a difference in the risk of ectopic pregnancy among day-3 compared with day-5 transfers.
Article
Objective: To summarize the procedures and outcomes of ART initiated in the United States in 2000. Design: Data were collected electronically using the SART Clinical Outcome Reporting System software and submitted to the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Participant(s): Three hundred eighty-three programs submitted data on procedures performed in 2000. Data were collated after November 2000 so that the outcome of all pregnancies established would be known. Main Outcome Measure(s): Incidence of clinical pregnancy, ectopic pregnancy, abortion, stillbirth, and delivery. Result(s): Programs reported initiating 99,989 cycles of ART treatment. Of these, 73,406 cycles involved fresh nondonor IVF (46.6% with intracytoplasmic sperm injection [ICSI]), with a delivery rate per retrieval of 29.9%; 549 were cycles of gamete intrafallopian transfer, with a delivery rate per retrieval of 24.7%; 763 were cycles of zygote intrafallopian transfer, with a delivery rate per retrieval of 29.9%. The following additional ART procedures were also initiated: 7,581 fresh donor oocyte cycles, with a delivery rate per transfer of 43.7%; 13,083 frozen embryo transfer procedures, with a delivery rate per transfer of 20.4%; 2,721 frozen embryo transfers using donated oocytes or embryos, with a delivery rate per transfer of 23.5%, and 1,200 cycles using a host uterus, with a delivery rate per transfer of 35.8%. In addition, 326 cycles were reported as combinations of more than one treatment type, 41 cycles as research, and 319 as embryo banking. As a result of all procedures, 25,394 deliveries were reported, resulting in 35,345 neonates, of which 35,031 were live born and 314 stillborn. Conclusion(s): In 2000, there were more programs reporting ART treatment and a significant (13.5%) increase in reported cycles compared to 1999. In comparable cycle types, overall success rate (deliveries per retrieval) exhibited an actual increase of 0.6%, which represents an increase of 2.2% when compared to the success rate for 1999. (Fertil Steril((R)) 2004;81:1207-20. (C) 2004 by American Society for Reproductive Medicine.).
Article
Objective: To compare the incidence of ectopic pregnancy (EP) after fresh ET and thawed ET. Design: Retrospective cohort study. Setting: Private fertility center. Patient(s): This retrospective study included 2,150 blastocyst transfers, including all 1,460 fresh autologous blastocyst transfers and all 690 transfers of autologous blastocysts derived from post-thaw extended culture of thawed bipronuclear oocytes in the 8-year study period 2004-2011. Intervention(s): None. Main outcome measure(s): Visualized EP and treated persistent pregnancy of unknown location. Result(s): The rate of visualized EP was 1.5% in pregnancies in fresh autologous cycles, which was significantly more than the rate of 0 with autologous post-thaw extended culture. The rates of treated persistent pregnancy of unknown location were 2.5% and 0.3% in these two groups, respectively, a difference that was also statistically significant (relative risk 7.3, 95% confidence interval 1.7-31.0). Conclusion(s): Relative to fresh transfer, thawed ET was associated with significantly reduced incidence of EP. These findings are consistent with ovarian stimulation increasing the risk of EP.
Article
Advances in cell culture media have led to a shift in in vitro fertilization (IVF) practice from early cleavage embryo transfer to blastocyst stage transfer. The rationale for blastocyst culture is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos thus resulting in higher implantation rates. To determine if blastocyst stage (Day 5 to 6) embryo transfers (ETs) improve live birth rate and other associated outcomes compared with cleavage stage (Day 2 to 3) ETs. Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. The last search date was 21 February 2012. Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. Of the 50 trials that were identified, 23 randomised controlled trials (RCTs) met the inclusion criteria and were reviewed (five new studies were added in this update). The primary outcome was rate of live birth. Secondary outcomes were rates per couple of clinical pregnancy, cumulative clinical pregnancy, multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos and cryopreservation. Quality assessment, data extraction and meta-analysis were performed following Cochrane guidelines. Twelve RCTs reported live birth rates and there was evidence of a significant difference in live birth rate per couple favouring blastocyst culture (1510 women, Peto OR 1.40, 95% CI 1.13 to 1.74) (Day 2 to 3: 31%; Day 5 to 6: 38.8%, I(2) = 40%). This means that for a typical rate of 31% in clinics that use early cleavage stage cycles, the rate of live births would increase to 32% to 42% if clinics used blastocyst transfer.There was no difference in clinical pregnancy rate between early cleavage and blastocyst transfer in the 23 RCTs (Peto OR 1.14, 95% CI 0.99 to 1.32) (Day 2 to 3: 38.6%; Day 5 to 6: 41.6%) and no difference in miscarriage rate (13 RCTs, Peto OR 1.18, 95% CI 0.86 to 1.60). The four RCTs that reported cumulative pregnancy rates (266 women, Peto OR 1.58, 95% CI 1.11 to 2.25) (Day 2 to 3: 56.8%; Day 5 to 6: 46.3%) significantly favoured early cleavage. Embryo freezing rates (11 RCTs, 1729 women, Peto OR 2.88, 95% CI 2.35 to 3.51) and failure to transfer embryos (16 RCTs, 2459 women, OR 0.35, 95% CI 0.24 to 0.51) (Day 2 to 3: 3.4%; Day 5 to 6: 8.9%) favoured cleavage stage transfer. This review provides evidence that there is a small significant difference in live birth rates in favour of blastocyst transfer (Day 5 to 6) compared to cleavage stage transfer (Day 2 to 3). However, cumulative clinical pregnancy rates from cleavage stage (derived from fresh and thaw cycles) resulted in higher clinical pregnancy rates than from blastocyst cycles. The most likely explanation for this is the higher rates of frozen embryos and lower failure to transfer rates per couple obtained from cleavage stage protocols. Future RCTs should report miscarriage, live birth and cumulative live birth rates to enable ART consumers and service providers to make well informed decisions on the best treatment option available.
Article
To compare success rates between fresh ETs after ovarian stimulation and frozen-thawed ETs (FET) after artificial endometrial preparation, to compare endometrial receptivity. Randomized, controlled trial. Private fertility center. There were 53 patients completing fresh blastocyst transfer (fresh group) and 50 patients completing FET (cryopreservation group). All were first-time IVF patients aged <41 years, with cycle day 3 FSH <10 mIU/mL and 8-15 antral follicles. Randomized to fresh or thawed ET. Clinical pregnancy rate per transfer. The clinical pregnancy rate per transfer was 84.0% in the cryopreservation group and 54.7% in the fresh group. The implantation rates were 70.8% and 38.9%, respectively. The ongoing pregnancy rates per transfer (at 10 weeks' gestation) were 78.0% and 50.9%, respectively. The attributable risk percentage of implantation failure due to reduced endometrial receptivity in the fresh group was 64.7%. The clinical pregnancy rate per transfer was significantly greater in the cryopreservation group than in the fresh group. These results strongly suggest impaired endometrial receptivity in fresh ET cycles after ovarian stimulation, when compared with FET cycles with artificial endometrial preparation. Impaired endometrial receptivity apparently accounted for most implantation failures in the fresh group. ClinicalTrials.gov Identifier: NCT00963625.