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Reproductive Sciences

https://doi.org/10.1007/s43032-019-00088-3

ORIGINAL ARTICLE

Atosiban and Pregnancy Outcomes Following In Vitro


Fertilization Treatment for Infertile Women Requiring One, Two,
or More Embryo Transfer Cycles: A Longitudinal Cohort Study
Meng-Hsing Wu 1,2 & Chih-Wei Lin 1 & Pei-Fang Su 3 & Edward Chai-Cheng Lai 4,5,6 & Fei-Ci Sie 3 & Yu-Lin Mau 3 &
New Geok Huey 1 & Huang-Tz Ou 4,5,6

Received: 29 April 2019 / Accepted: 1 August 2019


# Society for Reproductive Investigation 2020

Abstract
We assessed the effect of atosiban on pregnancy outcomes following in vitro fertilization (IVF) treatment among infertile women
requiring different numbers of embryo transfer (ET) cycles (i.e., one, two, and more than two ET cycles). A longitudinal cohort
study was conducted by utilizing the data from the Assisted Reproductive Technology Center in a university tertiary hospital
during 2007–2017. Patients receiving IVF treatment with at least one ET cycle were included. Pregnancy outcomes following
IVF treatment, including biochemical, clinical, and ongoing pregnancies, were investigated. The association between atosiban
and IVF pregnancy was assessed using logistic generalized estimating equation models, with adjustment for time-varying clinical
characteristics (e.g., maternal age) across multiple ET cycles for an individual. 403 women with 838 ET cycles were included,
where 165 patients required one ET cycle, 133 patients required two ET cycles (a total of 266 ET cycles), and 105 patients
required more than two ET cycles (a total of 407 ET cycles). Atosiban use was not significantly associated with pregnancy
outcomes among all study infertile women undergoing IVF treatment. However, the results for women requiring more than two
ET cycles showed significantly increased pregnancy rates associated with atosiban use (i.e., odds ratios [95% confidence interval]
of 4.40 [1.52, 12.73] and 2.85 [1.45, 5.60] for clinical and ongoing pregnancies, respectively). This association was not observed
for the women requiring only one or two ET cycles. Atosiban is a potential treatment for enhancing IVF pregnancy, especially
among infertile women requiring more than two ET cycles.

Keywords In vitro fertilization . Atosiban . Pregnancy . Embryo transfer cycle

Meng-Hsing Wu and Chih-Wei Lin are co-first/equal authorship; these


two authors provided equal contribution to this work.
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s43032-019-00088-3) contains supplementary
material, which is available to authorized users.

* Huang-Tz Ou 3
Department of Statistics, National Cheng Kung University,
huangtz@mail.ncku.edu.tw Tainan, Taiwan
4
1
Institute of Clinical Pharmacy and Pharmaceutical Sciences, College
Department of Obstetrics and Gynecology, National Cheng Kung of Medicine, National Cheng Kung University, Tainan, Taiwan
University Hospital, College of Medicine, National Cheng Kung
5
University, Tainan, Taiwan School of Pharmacy, College of Medicine, National Cheng Kung
2 University, Tainan, Taiwan
Department of Obstetrics and Gynecology and Department of
6
Physiology, College of Medicine, National Cheng Kung University, Department of Pharmacy, National Cheng Kung University Hospital,
Tainan, Taiwan Tainan, Taiwan
Reprod. Sci.

Introduction Materials and Methods

Although in vitro fertilization (IVF) is widely used for Data Source


treating infertility, published success rates of IVF remain
suboptimal. In the early 1980s, the IVF pregnancy rate We used data from the Assisted Reproductive Technology
was between 13% and 25% per oocyte retrieval cycle Center at National Cheng Kung University Hospital for the
[1–4]; in the 2000s, the estimated IVF pregnancy rates period 2007–2017. Patients’ data were extracted from medical
were 29% and 39% in Europe [5] and the United States charts and electronic medical records. The information for
[6], respectively. Embryo transfer (ET) is a critical step in each patient was collected on the basis of individual ET cycle
IVF treatment, where oocytes extracted from infertile for the corresponding demographic characteristics and associ-
women and fertilized in vitro are transferred into the uter- ated laboratory measurements, including the maternal age,
ine cavity. However, about 30% of patients undergoing body mass index (BMI), gravidity, parity, history of pregnan-
ET experience frequent uterine contractions (> 5 per min- cy loss, history of ET failure, infertility factors (i.e., from
ute), which lead to worse pregnancy outcomes [7]. Less male, female, both, or unknown), infertility duration, anti-
than 50% of transferred embryos remain in the uterus Müllerian hormone (AMH), fresh or frozen embryos trans-
1 hour after the transfer [8], and approximately 15% of ferred, and number (e.g., first, second, etc.) and date of ET.
embryos are present in the vagina following ET [9]. IVF treatment procedures (including atosiban administration)
Hence, the absence of excessive uterine contractions is and pregnancy outcomes were also recorded for each ET.
important to ensure ideal endometrial receptivity and a Permission for this study was obtained from the Institutional
stable uterine environment for successful embryo implan- Review Board of National Cheng Kung University Hospital,
tation [10]. However, high frequency of uterine contrac- Tainan, Taiwan (B-ER-105-114). This study included patients
tions is usually found with increasing number of ET cy- undergoing IVF and having at least one ET cycle. We excluded
cles [11]. In addition, when women have more uterine those with poor quality of embryos, canceled IVF cycles, diffi-
contractions, they typically have higher circulating oxyto- cult ETs, or lost to follow-up from analysis. Poor quality of
cin or vasopressin levels and poor pregnancy outcomes embryos is defined as severe fragmentation (> 25%), not
following IVF treatment [12]. stage-specific cell size, presence of multi-nucleation in
Atosiban, a mixed oxytocin/vasopressin V1A receptor cleavage-stage embryos, not distinguishable inner cell mass with
antagonist, has been suggested to be administered during few cells, and poor or uneven appearance of trophectoderm with
embryo implantation to enhance the success of IVF preg- very few cells in blastocysts. And, the difficulty of ETs means
nancy by reducing uterine contractions, inhibiting the re- that the catheter was hard to insert into the uterine cavity for
lease of oxytocin/PGF2α, and increasing endometrial per- smooth embryo release. As a result, the ET procedure was can-
fusion [13]. Evidence suggests that atosiban may be use- celed and the embryos were refrozen for further cervical dilation.
ful for women who are at risk of high frequency of uterine In particular, we used the same standard catheter (i.e., Cook®
contractions (e.g., patients undergoing three or more ET Sydney IVF Embryo Transfer Catheter Set (Cook Medical,
cycles [11, 14], those with repeated implantation failures USA)) for all ETs, which was comprised of an outer firm guide
[RIFs] [10, 14–19]), while playing a limited role in the catheter and a soft inner transfer catheter. And, the post-loading
IVF success among all infertile women [20]. Specifically, technique was adopted. That is, the inner transfer catheter loaded
previous studies showed that the use of atosiban was not with embryos was introduced through the guided catheter,
significantly associated with successful IVF pregnancy which had been placed beyond the cervix, to release the embry-
among all infertile women [20], while it improved im- os into the uterine cavity. Moreover, all ETs were performed
plantation and clinical pregnancy rates for IVF women under transabdominal ultrasound guidance, with an assistant
undergoing their third or subsequent ET cycles [11, 14]. holding the transducer. The bladder was well-distended, which
However, one of these studies that assessed clinical ef- helps visualize the cervical canal clearly under the guidance of
fects of atosiban during different numbers of ET cycles transabdominal ultrasound during the procedure of embryo
[11] had a limited sample size (i.e., 69, 76, 54, and 43 transfer. We could rotate the tip of the catheter based on the
patients at the first, second, third, and subsequent 3 ET utero-cervical angle and then release the embryo into the appro-
cycles, respectively). priate position of uterine cavity where hyperechogenic point can
Against this background, we utilized longitudinal cohort be visualized from the loading of the embryo-associated bubble.
data with a large sample size and long follow-up to evaluate For all IVF cycles, controlled ovulation hyperstimulation, either
the clinical effects of atosiban on IVF pregnancy (i.e., bio- via a gonadotropin-releasing hormone (GnRH) agonist or a
chemical, clinical, and ongoing pregnancies), especially for GnRH antagonist protocol, was used. When the leading follicles
infertile women requiring different numbers of ET cycles reached 18–20 mm, recombinant human chorionic gonadotro-
(i.e., one, two, and more than two ET cycles). pin (hCG) was administered, followed by transvaginal oocyte
Reprod. Sci.

retrieval 34–36 h later. In vitro embryo culture with or without over the observation period as time-varying covariates in the
intracytoplasmic sperm injection was then conducted. ET was multivariate analysis. We did this because we considered pa-
performed on Day 2–5 with good-quality embryos based on a tients’ clinical characteristics (e.g., maternal age), which could
morphological study. For frozen ET cycles, previously cryopre- vary over time across multiple ET cycles for a given person
served good-quality embryos were thawed for transfer per stan- and thus might confound the analyses. In addition, logistic
dard protocol. GEE with an exchangeable working correlation matrix spec-
For cycles with infusion of atosiban (Tractocile; Ferring ified was used for dichotomous data of pregnancy outcomes.
Pharmaceuticals), a single bolus dose (6.75 mg, 0.9 mL) was The odds ratios (ORs) and 95% confidence intervals (CIs) are
administered intravenously before ET, followed by continu- presented. Of note, we did not further impute missing values
ous infusion of the remaining dose (30.75 mg, 4.1 mL) in for variables of interest, and patients with missing values for
500 mL of normal saline for 1.5 h. We classified all ET cycles the variables of interest were excluded from the analyses.
on the basis of treatment of atosiban exposure (i.e., atosiban- We further stratified study patients by the number of ET
treated ET or non-atosiban-treated ET). cycles required (i.e., one, two, and more than two ET cycles)
to evaluate the clinical effects of atosiban among infertile
Pregnancy Outcomes women having different numbers of ET cycles. All statistics
and figures were prepared with R software (version 3.4.0). All
The primary outcomes of this study included biochemical, statistical tests were 2-sided, with a p value of less than 0.05
clinical, and ongoing pregnancies. We confirmed biochemical considered to indicate statistical significance.
pregnancy by a blood sample β-HCG level of above 30 IU/L,
which is typically found in the blood of pregnant women as
early as 10 days after conception. A test for β-human chori-
onic gonadotropin hormone (β-HCG) was given 14 days after Results
ET. Clinical pregnancy was confirmed by the presence of
gestational sacs with a heartbeat at the 10th week of gestation- A total of 403 women with 838 ET cycles were included in this
al age. Ongoing pregnancy was confirmed on the basis of the study, in which 165 patients required one ET, 133 patients re-
documentation of a live fetus (or fetuses) at the 24th week. quired two ET cycles, and 105 patients required more than two
ET cycles (a total of 407 ET cycles). Table 1 shows the charac-
teristics for all study patients and stratified by the number of ET
Statistical Analysis cycles. Overall, the average maternal age (standard deviation) at
ET was 35.88 (4.66) years, infertility duration was 4.81 (3.33)
We tabulated descriptive statistics, means with standard devi- years, female infertility was a factor for about 40.1% of study
ations and frequencies with percentages for continuous and patients, and most transferred embryos were fresh (56.5%).
categorical variables, respectively. We calculated the rates of Table 2 summarizes the results of the association between
pregnancy outcomes and compared the effectiveness of ET the use of atosiban and pregnancy outcomes based on our
cycles with and without exposure to atosiban. Because the overall study population (n = 403). Univariate and multivari-
pregnancy outcomes of multiple ET cycles from a given per- ate GEE analyses indicate nonsignificantly increased chances
son were likely to be correlated, we applied the logistic gen- of pregnancy (i.e., biochemical, clinical, and ongoing preg-
eralized estimating equation (GEE) model to assess the asso- nancies) with atosiban use among all infertile women under-
ciation between atosiban use and IVF pregnancy outcomes. going IVF treatment.
The logistic GEE is a specific statistic that accounts for the Figure 1 summarizes the results of the association of
correlation of repeated measures (i.e., pregnancy outcomes) atosiban with IVF pregnancy outcomes in the overall study
across multiple ET cycles within a person to adjust for con- population and in subgroups stratified by the number of ET
founding by time-invariant factors from unmeasured underly- cycles (i.e., one, two, and more than two ET cycles).
ing characteristics of individuals [21]. Specifically, we first Supplementary Tables 1–3 show the detailed results for the
conducted univariate logistic GEE analyses where associa- association of atosiban use and pregnancy outcomes stratified
tions between each individual clinical characteristic (i.e., by the number of ET cycles. We found that the women who
listed in Table 1) and pregnancy outcomes were tested sepa- required more than two ET cycles had significantly increased
rately to identify significant characteristics. Second, multivar- chances of clinical and ongoing pregnancies associated with
iate logistic GEE analysis was performed to assess the effect atosiban use (i.e., ORs [95% CI] of 4.40 [1.52, 12.73] and
of atosiban on pregnancy outcomes, with adjustment for sig- 2.85 [1.45, 5.60], respectively; Supplementary Table 3), while
nificant characteristics associated with pregnancy outcomes atosiban use among those having one or two ET cycles was
from univariate analyses. In particular, we treated patients’ not significantly associated with IVF pregnancy outcomes
clinical characteristics measured from individual ET cycles (Supplementary Tables 1 and 2).
Reprod. Sci.

Table 1 Clinical characteristics for all study patients and subgroups stratified by number of embryo transfer (ET) cycles

Overall Subgroups by time of ET cycle


(403 patients
with 838 ET cycles) Only 1 ET Only 2 ET cycles ≥ 3 ET cycles
(165 patients (133 patients (105 patients
with 165 ET cycles) with 266 ET cycles) with 407 ET cycles)

Characteristics # of ET cycles Mean (sd) # of ET cycles Mean (sd) # of ET cycles Mean (sd) # of ET cycles Mean (sd)
or % or % or % or %

Age (years) 804 35.88 159 35.73 259 36.81 386 35.33
(4.66) (3.98) (4.36) (5.02)
BMI 832 22.45 164 22.61 265 22.21 403 22.54
(3.54) (3.90) (3.58) (3.37)
AMH (ng/mL) 380 3.24 (2.92) 136 3.56 (3.40) 109 3.07 (2.93) 135 3.07 (2.33)
Gravida 834 0.61 (0.96) 165 0.55 (0.81) 265 0.53 (1.00) 404 0.68 (0.99)
Parity 834 0.18 (0.44) 165 0.21 (0.51) 265 0.16 (0.46) 404 0.19 (0.40)
Infertility duration (years) 836 4.81 (3.33) 164 4.20 (3.03) 265 5.04 (3.46) 407 4.90 (3.34)
Number of oocytes retrieved 411 9.14 (6.1) 79 9.70 (5.24) 129 8.27 (5.66) 203 9.47 (6.63)
Number of embryos 805 2.58 (0.96) 164 2.49 (0.89) 258 2.53 (0.94) 383 2.65 (1.01)
transferred
Day of ET 414 3.56 (1.24) 154 3.61 (1.24) 111 3.66 (1.22) 149 3.43 (1.24)
Day 1–3 238 57.49% 81 52.60% 62 55.86% 95 63.76%
Day 4–5 176 42.51% 73 47.40% 49 44.14% 54 36.24%
HRV before ET 351 1.91 (1.94) 147 1.72 (1.83) 102 2.01 (1.94) 102 2.09 (2.07)
HRV after ET 324 1.43 (1.52) 134 1.46 (1.62) 94 1.52 (1.66) 96 1.29 (1.19)
Number of previous ET cycles 432 1.94 (1.83) 154 1.48 (1.09) 116 1.77 (1.26) 162 2.51 (2.48)
ET failure history
None 238 43.83% 112 70.00% 66 39.76% 60 27.65%
At least one 305 56.17% 48 30.00% 100 60.24% 157 72.35%
Pregnancy loss history
None 306 70.51% 112 72.26% 89 76.72% 105 64.42%
At least one 128 29.49% 43 27.74% 27 23.28% 58 35.58%
Infertility factor
Male 323 38.68% 59 35.76% 98 36.98% 166 40.99%
Female 335 40.12% 64 38.79% 102 38.49% 169 41.73%
Both 74 8.86% 18 10.91% 17 6.42% 39 9.63%
Unknown 103 12.34% 24 14.55% 48 18.11% 31 7.65%
Type of embryo transferred
Fresh 463 56.53% 89 53.94% 145 56.20% 229 57.83%
Frozen-thawed 356 43.47% 76 46.06% 113 43.80% 167 42.17%
Atosiban administration
Yes 311 37.88% 25 15.92% 108 41.54% 178 44.06%
No 510 62.12% 132 84.08% 152 58.46% 226 55.94%

Abbreviations: sd standard deviation, BMI body mass index, AMH anti-Müllerian hormone, ET embryo transfer, HRV heart rate variability

Discussion women requiring only one or two ET cycles. These results


support the rational use of atosiban based on the number of
This longitudinal cohort study of infertile women undergoing ET cycles to improve the pregnancy rates of IVF patients.
IVF treatment found that the use of atosiban among women Emerging evidence suggests that atosiban might be an ef-
requiring more than two ET cycles was significantly associated fective treatment for IVF women to avoid excessive uterine
with successful pregnancy (i.e., clinical and ongoing pregnan- contractions following multiple ET cycles [11, 14]. Atosiban
cies), while it might not be beneficial for IVF pregnancy among can directly inhibit uterine contractions and decrease the
Reprod. Sci.

Note: the covariates selected in the multivariate analyses (e.g., maternal age) were significantly associated with IVF pregnancy in univariate analyses. Other patients’ characteristics (listed in Table 1) were
release of PGF2α in human uterine smooth muscle cells [22].

p value

< 0.001
0.4379
The blockage of oxytocin receptors and subsequent uterine

0.497

0.003
PGF2α production, which have been linked to increased em-
Ongoing pregnancy

bryonic survival, are important to ensure the success of IVF

Biochemical pregnancy was confirmed by blood sample β-HCG level of above 30 IU/L, which is typically found in the blood of pregnant women as early as 10 days after conception
388 patients with 1.12 (0.81, 1.57)

383 patients with 1.15 (0.81, 1.63)

1.65 (1.18, 2.31)


0.92 (0.88, 0.95)
pregnancy [23]. Atosiban was also found to relax uterine ar-
OR (95% CI)
(> 24 weeks)

teries in rats in near-term pregnancies [22], which decreased


the contractility of the myometrium and increased endometrial
Results of association of atosiban with IVF pregnancy outcomes in all study population (univariate and multivariate analyses using generalized estimating equations)

perfusion to reduce the expulsion rate of the embryo and thus


support embryo implantation [10]. He et al. recently analyzed
780 ET cycles

768 ET cycles
# of patients, #

several subgroups of infertile women undergoing different


of ET cycles

numbers of ET cycles and found that the use of atosiban sig-


nificantly increased clinical and implantation rates among IVF
patients undergoing third or subsequent ET cycles, but no
statistical significance was observed for the efficacy of
atosiban in the first- and second-ET patient groups. The pres-
p value

< 0.001
0.4298

0.001
0.299

ent study, which used larger numbers of ET cycles (i.e., our


study vs. He et al.’s study [11]: 165 vs. 69 in the first ET
Clinical pregnancy

group, 266 vs. 76 in the second ET group, and 407 vs. 97 in


256 patients with 1.20 (0.76, 1.88)
391 patients with 1.19 (0.86, 1.66)

0.89 (0.84, 0.94)


1.43 (1.15,1.77)

also tested in univariate analyses for IVF pregnancy, but they were not significant and thus not included in the multivariate analyses
OR (95% CI)
(> 10 weeks)

the third or subsequent ET group) showed that atosiban use


was not only associated with positive biochemical and clinical
pregnancy outcomes but also significantly improved the rate
of ongoing pregnancy. We also found that atosiban was not
792 ET cycles

381 ET cycles

effective for women who required only one or two ET cycles,


p value # of patients, #
of ET cycles

which is consistent with the results of He et al.’ study [11]. He


et al. [11] have found that low levels of serum oxytocin and
PGF2α among patients undergoing the first or second ET cycle
were associated with low uterine contractions, which implies
Abbreviations: ref. reference; OR odds ratio, 95%, CI 95% confidence interval; ET embryo transfer
Biochemical pregnancy a

1.42 (1.17, 1.73) < 0.001


0.90 (0.85, 0.95) < 0.001

a stable uterine environment and explains the lack of response


1.14 (0.85, 1.53) 0.400

0.94 (0.59, 1.51) 0.799

to atosiban observed among these patients.


Our findings also support that atosiban might improve IVF
OR (95% CI)

pregnancy for patients who are likely to have RIFs, which are
typically defined as good-quality embryos failing to implant
following multiple transfer cycles (e.g., commonly at least
three consecutive ET attempts). RIFs have been linked to ex-
391 patients with

256 patients with


792 ET cycles

384 ET cycles

cessive uterine contractions, which suggest a significantly un-


# of patients, #
of ET cycles

stable uterine environment, and thus lead to ET failure [10,


15]. However, the contractions of the uterus are not typically
included in diagnostic measures for infertile women undergo-
ing IVF treatment and are thus likely to be ignored. Excessive
(frozen-thawed vs. fresh = ref.)

contractions may thus persist among multiple ET attempts and


may lead to RIFs. The endometrial epithelium hyperactivated
Type of embryo transferred

autocrine/paracrine oxytocin/oxytocin receptor system has


(Yes vs. No = ref.)

(Yes vs. No = ref.)

been proposed for patients having previous failure cycles


[11], which may explain poor pregnancy outcomes in these
Maternal age

patients. Therefore, the use of atosiban during ET could be


Day of ET
Multivariate analysis Atosiban
Atosiban
Variable

beneficial for IVF patients who are inclined to high frequency


of uterine contractions such as those undergoing more than
two ET cycles or those who are likely to have RIFs.
Univariate analysis

Several observational studies had assessed the efficacy of


atosiban on IVF pregnancy with limited numbers of different
clinical characteristics between groups (i.e., atosiban-treated
Table 2

and non-treated patients) adjusted in the analyses [15–17],


which may have led to confounding bias, made comparisons
a
Reprod. Sci.

Figure 1 Summary of results of association of atosiban with IVF pregnancy outcomes in all study population and subgroups of patients stratified by
number of embryo transfer (ET) cycles (univariate and multivariate analyses using generalized estimating equations)

at an aggregated level (e.g., crude pregnancy rates in treatment ethnically Chinese women. Ethnically Chinese people are dis-
group vs. that in non-treatment group) [16, 19, 24], or had tributed over a large geographic area and are likely to have
limited numbers of study patients (e.g., n = 52 [16]). Some differences in dietary habits, physical activity, and even treat-
evidence was based only on case reports [10, 19]. In contrast, ment approaches. Second, we did not measure uterine contrac-
the present study has several methodological strengths to en- tions after atosiban administration and did not track congenital
sure the validity of our results. First, when women had multi- abnormalities in newborns. Third, this observational study in-
ple ET cycles, pregnancy outcomes (e.g., pregnant or not at cluded all patients who attend study medical center during
different ET cycles) for a given patient are likely to be corre- study period so no formal sample size calculations were con-
lated. For example, if women did not achieve a successful ducted. Fourth, the present study only assessed biochemical
pregnancy at the first ET cycle, she may request further ET pregnancy, clinical pregnancy, and ongoing pregnancy, and
cycles and might be prone to have poor pregnancy outcomes thus, future research is needed to corroborate our findings on
in the later ET cycles. She is also likely to use atosiban in the live birth outcome. Lastly, this was a retrospective study, and
later cycles to enhance pregnancy rates. This implies that the thus the associated limitations could not be avoided (e.g., selec-
pregnancy outcomes in different ET cycles for a given person tion bias). Nevertheless, prospective studies are needed to fully
are not independent. Considering this, we applied GEE anal- elucidate the mechanisms of the action and clinical efficacy of
ysis [21], rather than traditional logistic regression analysis atosiban among women undergoing IVF treatment. In addition,
where outcome data from subjects are assumed to be indepen- optimal dosage and treatment duration of atosiban administra-
dent. GEE analysis is recognized as the most appropriate an- tion during embryo implantation for achieving successful IVF
alytic procedure for IVF data collected from multiple cycles pregnancy should be investigated in future studies.
[25]. Second, by using GEE analysis in which comparisons In conclusion, the use of atosiban, especially among wom-
were made within individuals, all time-invariant confounding en who required more than two ET cycles, was positively
(e.g., infertility factor) from individuals was eliminated. Third, associated with successful IVF pregnancy. These women are
considering that patients’ and clinical characteristics (e.g., ma- likely to have high levels of serum oxytocin/ PGF2α and thus
ternal age, type of embryo transferred [i.e., fresh or frozen], are inclined to high frequency of uterine contractions, leading
number of embryos transferred) varied over time in different to poor pregnancy outcomes following IVF treatment. In this
ET cycles and that these clinical characteristics could possibly regard, atosiban is a potential treatment for these women.
influence the success of IVF pregnancy, we adjusted these
time-varying clinical characteristics from multiple ET cycles Acknowledgments We gratefully acknowledge the support from
National Cheng Kung University Hospital.
in the GEE analysis. Therefore, we believe that our analyses
lay a solid foundation for future prospective studies to fully
elucidate the mechanisms of the action and clinical value of
atosiban among infertile women undergoing IVF treatment.
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