Does a poor-quality embryo have an adverse impact on a good-quality embryo when transferred together?

Abstract

Background
In some in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles, we may consider transferring one poor-quality embryo with one good-quality embryo. Previous studies have indicated that the poor-quality embryo transferred with a good-quality embryo does not negatively affect the clinical pregnancy rate or live birth rate. The purpose of this study was to evaluate pregnancy outcomes and neonatal outcomes in this context. Methods
This was a retrospective study that included 1646 cycles from our centre. Patients were divided into two groups (group A: one good-quality embryo was transferred with one poor-quality embryo; group B: two good-quality embryos were transferred). The primary outcomes were the clinical pregnancy rate and live birth rate. Additionally, we investigated the implantation rate, ectopic pregnancy rate, abortion rate, multiple pregnancy rate, birthweight and gestational age. ResultsWe found that there were no differences in the clinical pregnancy rate and live birth rate between group A and group B. However, the implantation rate and multiple pregnancy rate were higher in group B than in group A. Conclusions
The poor-quality embryo does not have a significant influence on the good-quality embryo when transferred together.

Full text

R E S E A R C H Open Access
Does a poor-quality embryo have an
adverse impact on a good-quality embryo
when transferred together?
Jiaheng Li
1†
, Mingze Du
1†
, Zhan Zhang
1*
, Yichun Guan
1
, Xingling Wang
1
, Xiao Zhang
2
, Jing Liu
1
, Zhouhui Pan
1
,
Bijun Wang
1
and Wenxia Liu
1
Abstract
Background: In some in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles, we may consider
transferring one poor-quality embryo with one good-quality embryo. Previous studies have indicated that the poor-
quality embryo transferred with a good-quality embryo does not negatively affect the clinical pregnancy rate or live
birth rate. The purpose of this study was to evaluate pregnancy outcomes and neonatal outcomes in this context.
Methods: This was a retrospective study that included 1646 cycles from our centre. Patients were divided into two
groups (group A: one good-quality embryo was transferred with one poor-quality embryo; group B: two good-
quality embryos were transferred). The primary outcomes were the clinical pregnancy rate and live birth rate.
Additionally, we investigated the implantation rate, ectopic pregnancy rate, abortion rate, multiple pregnancy rate,
birthweight and gestational age.
Results: We found that there were no differences in the clinical pregnancy rate and live birth rate between group A
and group B. However, the implantation rate and multiple pregnancy rate were higher in group B than in group A.
Conclusions: The poor-quality embryo does not have a significant influence on the good-quality embryo when
transferred together.
Keywords: Embryo quality, Live birth rate, Clinical pregnancy rate, Neonatal outcome
Background
The frequency of the use of assisted reproductive tech-
nology is increasing. Globally, the number of fresh cycles
has increased by 6.4% between 2008 and 2010, and the
number of frozen embryo transfer cycles has increased
by 27.6% [1]. Double-embryo transfers (DETs) still hold
a dominant position despite the increasing number of
single-embryo transfer (SET) procedures. In Europe, the
rates of SET and DET were 22.4% and 53.2%, respect-
ively, in 2008 and 31.4% and 56.3%, respectively, in 2012
[2,3]. A meta-analysis found that the live birth rate was
lower for SET than for DET, while the live birth rate of a
repeated SET (two cycles of SET) was not different from
that of a DET [4]. In another meta-analysis, SET re-
duced the probability of a live birth by 38% and of mul-
tiple births by 94%. However, the cumulative live birth
rate remained unchanged [5]. Although DET has a
higher multiple birth rate than SET, DET also has a
higher live birth rate per cycle than SET.
Additionally, the quality of the embryo influences the
results of assisted reproductive technology treatment
[6–8]. A good-quality embryo is predictive of a better
outcome than a poor-quality embryo. However, we can-
not guarantee that all embryos are good-quality em-
bryos. What should be done with a poor-quality embryo
in assisted reproductive technology treatments? One
study indicated that the poor quality of one embryo may
influence the quality of another embryo [9]. The blasto-
cyst rate is indeed decreased due to the influence of a
poor-quality embryo. Regarding embryo transfer into the
uterus, one study pointed out that a poor-quality embryo
* Correspondence: zhangzhan1616@126.com
†
Jiaheng Li and Mingze Du contributed equally to this work.
1
The Reproduction Center, The Third Affiliated Hospital of Zhengzhou
University, 7 Kangfuqian Road, Zhengzhou 450052, Henan, People’s Republic
of China
Full list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Li et al. Journal of Ovarian Research (2018) 11:78
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would affect a good-quality embryo in DET [10]. This
study also found that the implantation rates were higher
in the control group (transferred two good-quality em-
bryos or one good-quality embryo) than in the study
group (transferred one good-quality embryo and one
poor-quality embryo). Although previous studies have
discussed these problems, the sample sizes have been
small. Additionally, previous studies did not discuss the
birthweight, gestational age and abortion rate. Therefore,
whether we should transfer a poor-quality embryo with
a good-quality embryo needed to be evaluated again.
The aim of our research was to determine whether we
should transfer a poor-quality embryo with a good-quality
embryo.
Methods
Study design
This retrospective study was approved by the Ethics
Committee of the Third Affiliated Hospital of Zheng-
zhou University. All patients who underwent in vitro
fertilization (IVF) or intracytoplasmic sperm injection
(ICSI) at the reproduction centre of the Third Affiliated
Hospital of Zhengzhou University between January 2012
and December 2015 were included in this study. Patients
who underwent transfer of one or two cleavage-stage
embryos were included in our study. We divided these
patients into two groups: group A comprised cycles in
which one poor-quality embryo was transferred with one
good-quality embryo, and group B comprised cycles in
which two good-quality embryos were transferred. The
outcomes we analysed were the implantation rate, the
clinical pregnancy rate, the ectopic pregnancy rate, the
abortion rate, the live birth rate, the number of foetuses,
birthweight, gestational age, and the incidence of low
birth weight and preterm birth.
Clinical pregnancy was diagnosed by transvaginal ultra-
sound of at least one gestational sac or definitive clinical
signs of pregnancy. Live birth was defined as one or more
new-borns after 20 completed weeks of gestation. Ectopic
pregnancy was defined as a pregnancy that did not occur
inside the uterine cavity. Low birth weight was defined as
a newborn weight less than 2500 g. Preterm birth was de-
fined as a gestational age of less than 37 weeks.
Embryo quality
Embryo quality was determined according to a ranking
system. Class I embryos were defined as those with six
to ten cells on day 3 and < 5% embryo fragmentation.
Class II embryos were defined as those with six to ten
cells on day 3 and 5–20% embryo fragmentation. Class
III embryos were defined as those with uneven cell size,
irregular cell morphology, and embryo fragmentation
from 21% to 49%. Class IV embryos were defined as
those with extremely uneven cell size, a large number of
intracellular vacuoles, arrest of embryonic development
or embryo fragmentation of over 50%. Class I embryos
and Class II embryos were defined as good-quality em-
bryos. Class III embryos were defined as poor-quality
embryos, and Class IV embryos were defined as unavail-
able embryos.
Inclusion criteria
The inclusion criteria were as follows: fresh IVF/ICSI cy-
cles occurring between January 2012 and December
2015, and patients aged ≤35 years.
Exclusion criteria
The exclusion criteria were as follows: patients with
uterine malformations, patients using donor oocytes, pa-
tients who opted for PGD/PGS, and patients with van-
ishing twins.
Statistical analysis
The objective of this study was to determine the influ-
ence of a poor-quality embryo on a good-quality em-
bryo. The primary outcomes were the clinical pregnancy
rate and live birth rate. The secondary outcomes of the
study were the implantation rate, the abortion rate, the
ectopic pregnancy rate, the multiple pregnancy rate,
birthweight and gestational age. Analyses were per-
formed using SPSS (Statistical Package for the Social Sci-
ences) 22.0. We used chi-square tests to evaluate
categorical variables. For continuous variables, we used
Student’s t-test or the Mann-Whitney test. Logistic re-
gression was performed for live birth and clinical preg-
nancy using the following variables: maternal age, male
age, insemination method, type of infertility, duration of
infertility, body mass index, reason for infertility, endo-
metrial thickness and type of cycle. All pvalues less than
0.05 were considered statistically significant.
Results
We included 1646 cycles in the present study. A total of
1200 cycles involved transfers of two good-quality em-
bryos (group B), and 446 cycles involved transfers of one
poor-quality embryo with one good-quality embryo
(group A). Body mass index, the reason for infertility,
the cause of infertility, male age, endometrial thickness and
the insemination method were not significantly different
between group A and group B (Table 1). However, we
found that male age was lower in group B than in group A
(p= 0.01). Regarding the outcome of assisted reproductive
technology treatment, we found that only the implantation
ratewasdifferentbetweengroupAandgroupB.GroupB
had a higher implantation rate (54.8% vs 49.2%, P=0.01)
than group A (Table 2). Additionally, group A had a lower
multiple pregnancy rate than group B (41.3% vs 33.6%,
P= 0.02). However, we did not find other differences in
Li et al. Journal of Ovarian Research (2018) 11:78 Page 2 of 5
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the clinical pregnancy rate, the ectopic pregnancy rate, the
abortion rate, the live birth rate, birthweight, gestational
age, and the incidence of low birth weight or preterm
birth. To adjust for confounding factors, we used logistic
regression to investigate whether a poor-quality embryo
affected a good-quality embryo in terms of the clinical
pregnancy rate and live birth rate. We did not observe any
differences in the primary outcomes (Table 3).
Discussion
A poor-quality embryo can provide a chance to achieve
pregnancy. However, a previous study suggested that
transfer of a poor-quality embryo would lead to a reduc-
tion in the clinical pregnancy rate and live birth rate.
However, there were no differences between transfer of
a poor-quality embryo and transfer of a good-quality
embryo in terms of the abortion rate, pregnancy compli-
cations, maternal complications or neonatal complica-
tions [6]. In another study, authors found that a
poor-quality embryo may affect a good-quality embryo
in vitro [9]. Therefore, we wondered whether a
poor-quality embryo had an adverse influence on a
good-quality embryo. Two experts have previously dis-
cussed this topic. One expert suggested that the
poor-quality embryo would influence the pregnancy rate
and implantation rate [11], and the other expert indi-
cated that transfer of one poor-quality embryo with one
good-quality embryo resulted in a lower implantation
rate than transfer of two good-quality embryos [10].
However, those researchers did not find a difference in
the clinical pregnancy rate, live birth rate, abortion rate,
ectopic pregnancy rate or multiple pregnancy rate.
Compared with groups that underwent transfer of one
good-quality embryo, group A and group B had higher
Table 1 Basic information of patients in the two groups
Group A (n= 446) Group B (n= 1200) P
Maternal age (y) 29.0 ± 3.8 28.6 ± 3.2 0.05
Body mass index (kg/m
2
) 22.9 ± 3.3 22.7 ± 3.1 0.17
Duration of infertility (y) 3.5 ± 2.5 3.4 ± 2.5 0.35
Male age (y) 30.5 ± 4.8 29.9 ± 4.6 0.01
Type of infertility 0.47
Primary infertility 266 (59.6%) 692 (57.7%)
Secondary infertility 180 (40.4%) 508 (42.3%)
Cause of infertility 0.12
Tubal disease 248 (55.6%) 688 (57.3%)
Male factor 110 (24.7%) 297 (24.8%)
Endometriosis 62 (13.9%) 176 (14.7%)
Unexplained 26 (5.8%) 39 (3.3%)
Endometrial thickness (mm) 11.4 ± 2.3 11.3 ± 2.2 0.33
Insemination method 0.81
IVF 326 (73.1%) 870 (72.5%)
ICSI 120 (26.9%) 330 (27.5%)
Table 2 Clinical and neonatal outcomes in the two groups
Group A (n= 446) Group B (n= 1200) P
Implantation rate 49.2% (439/892) 54.8% (1314/2400) 0.01
Clinical pregnancy rate 71.3% (318/446) 74.7% (896/1200) 0.17
Ectopic pregnancy rate 1.3% (4/318) 2.7% (24/896) 0.15
Abortion rate 8.8% (28/318) 9.7% (87/896) 0.64
Live birth rate 64.1% (286/446) 65.4% (785/1200) 0.63
Number of foetuses 0.02
Singleton 190 (66.4%) 461 (58.7%)
Twin 96 (33.6%) 324 (41.3%)
Birthweight
Singleton 3346 ± 545 3318 ± 563 0.67
Twin 2596 ± 402 2567 ± 436 0.40
Low birth weight
Singleton 4.2% (8/190) 4.8% (22/461) 0.76
Twin 35.4% (68/192) 39.0% (253/648) 0.36
Gestational age
Singleton 38.8 ± 1.5 38.7 ± 1.8 0.42
Twin 36.5 ± 1.9 36.4 ± 1.9 0.86
Preterm birth
Singleton 7.9% (15/190) 5.9% (27/461) 0.34
Twin 39.6% (38/96) 36.4% (118/324) 0.57
Table 3 Logistic regression of clinical pregnancy and live births
Predictors AOR
a
(95%CI) P
Clinical pregnancy
Maternal age 0.959 (0.922–0.996) 0.032
Body mass index 1.031 (0.995–1.069) 0.094
Duration of infertility 0.886 (0.685–1.147) 0.359
Type of infertility 0.952 (0.750–1.208) 0.686
Male age 0.991 (0.957–1.026) 0.612
Endometrial thickness 1.098 (1.044–1.155) < 0.001
Group C 0.839 (0.655–1.076) 0.166
Live birth
Maternal age 0.936 (0.895–0.980) 0.005
Body mass index 1.003 (0.971–1.037) 0.843
Duration of infertility 1.065 (0.838–1.355) 0.605
Type of infertility 1.067 (0.856–1.329) 0.563
Male age 1.008 (0.976–1.042) 0.615
Endometrial thickness 1.096 (1.046–1.148) < 0.001
Group 0.952 (0.755–1.200) 0.676
AOR adjusted odds ratios
a
Adjusted for maternal age, male age, insemination method, type of infertility,
duration of infertility, body mass index, reason for infertility and endometrial
thickness
Li et al. Journal of Ovarian Research (2018) 11:78 Page 3 of 5
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clinical pregnancy rates and live birth rates. However, we
did not observe differences between group A and group
B. Hence, the poor-quality embryo may not affect these
outcomes. After adjusting for confounding factors, we
did not find that the conditions of the two groups had
any influence on the outcomes. Consistent with a previ-
ous article, we did not find evidence that the
poor-quality embryo affected the live birth rate or preg-
nancy rate. Additionally, we found that the implantation
rate was lower in group A than in group B, although
two previous articles had indicated that good-quality
embryos were easier to implant and develop than
poor-quality embryos. However, we found that the mul-
tiple pregnancy rate was higher in group B. In other
studies, the multiple pregnancy rate was not significantly
different between patients who underwent different em-
bryo transfer schemes. We hypothesized that a high im-
plantation rate was related to a high multiple pregnancy
rate. After all, a good-quality embryo has a higher
chance of implantation and development than a
poor-quality embryo [7,8]. Regarding the abortion rate
and ectopic rate, there were no differences between the
two groups. We also specifically investigated the birth-
weight, gestational age, and incidence of low birth
weight and preterm birth. However, after dividing preg-
nancies into singletons and twins, we found no differ-
ences in these outcomes. Hence, the poor-quality
embryo did not influence birthweight or gestational age.
In summary, we found that only the implantation rate
and multiple pregnancy rate were different between group
A and group B. We did not find significant differences in
the other parameters. A high multiple pregnancy rate is
associated with high risks of infant death, low birth
weight, deformational plagiocephaly, and other problems
[12]. To reduce the risk of a multiple pregnancy, we
should consider the conditions of group A as an alterna-
tive transfer scheme with no difference in the live birth
rate compared to that in group B.
The clinical pregnancy rate (74.7% vs 71.3%, P= 0.17)
and live birth rate (65.4% vs 64.1%, P= 0.63) were higher
in group B than in group A; however, the difference was
not statistically significant. We tried our best to reduce
the influence of confounding factors by optimizing the
inclusion and exclusion criteria. However, our study has
several limitations. First, this study was a retrospective
study, and perhaps a randomized controlled trial would
be more persuasive. Second, the criteria for the evalu-
ation of embryo quality were subjective. Finally, add-
itional big-data research studies and a systematic review
are required to confirm these findings.
Conclusion
The poor-quality embryo does not significantly influence
the good-quality embryo when transferred together.
Abbreviations
DET: Double-embryo transfer; ICSI: Intracytoplasmic sperm injection; IVF: In
vitro fertilization; SET: Single-embryo transfer
Funding
This research study did not receive any funding.
Availability of data and materials
All data are shown in these tables.
Authors’contributions
ZZ proposed the design ideas. LJH and DMZ checked the data and
constructed the tables. LJH, DMZ, WXL, GYC, LJ, PZH, WBJ and LWX wrote
the manuscript. All authors approved the final version of this article. LJH and
DMZ contributed equally to this paper.
Ethics approval and consent to participate
This study was approved by the Ethics Committee of the Third Affiliated
Hospital of Zhengzhou University.
Consent for publication
Not applicable
Competing interests
All authors have declared that they have no competing interests.
Publisher’sNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
The Reproduction Center, The Third Affiliated Hospital of Zhengzhou
University, 7 Kangfuqian Road, Zhengzhou 450052, Henan, People’s Republic
of China.
2
Waterstone Clinic, Lotamore House, Tivoli, Cork, Ireland.
Received: 5 July 2018 Accepted: 27 August 2018
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