ORIGINAL ARTICLE: PREGNANCY

Association between ABO blood type

and live-birth outcomes in single
embryo transfer cycles
Nigel Pereira, M.D.,a Hency H. Patel, B.S.,b Logan D. Stone, B.A.,a Paul J. Christos, Dr.P.H., M.S.,c
Rony T. Elias, M.D.,a Steven D. Spandorfer, M.D.,a and Zev Rosenwaks, M.D.a
a
The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine; b Weill Cornell Medical College, New York;
and c Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medical
College, New York, New York

Objective: To investigate the association between ABO blood type and live-birth outcomes in patients undergoing IVF with day 5
single embryo transfer (SET).
Design: Retrospective cohort study.
Setting: University-affiliated center.
Patient(s): Normal responders, <40 years old, undergoing their first IVF cycle with fresh SET.
Intervention(s): None.
Main Outcome Measure(s): Live-birth rate was the primary outcome. Secondary outcomes were birth weight and gestational age at
delivery. Univariate and multivariable logistic regression was used to examine the association between blood type and live birth, while
controlling for confounders. Odds ratios (OR) with 95% confidence intervals (CI) for live birth were estimated.
Result(s): A total of 2,329 patients were included. The mean age of the study cohort was 34.6
4.78 years. The distribution of blood
types was as follows: A ¼ 897 (38.5%); B ¼ 397 (17.0%); AB ¼ 120 (5.2%); and, O ¼ 1,915 (39.3%) patients. There was no difference in
the baseline demographics, ovarian stimulation, or embryo quality parameters between the blood types. The unadjusted ORs for live
birth when comparing blood type A (referent) with blood types B, AB, and O were 0.96 (95% CI, 0.6–1.7), 0.72 (95% CI, 0.4–1.2),
and 0.96 (95% CI. 0.6–1.7), respectively. The adjusted ORs for live birth remained not significant when comparing blood type A to blood
types B, AB, and O individually. No difference in birth weight or gestational age at delivery was noted among the four blood types.
Conclusion(s): Our findings suggest that ABO blood type is not associated with live-birth rate, birth weight, or gestational age at
delivery in patients undergoing IVF with day 5 SET. (Fertil SterilÒ 2017;-:-–-. Ó2017 by American Society for Reproductive
Medicine.)
Key Words: In vitro fertilization, ABO blood type, single embryo transfer, live birth, outcomes
Discuss: You can discuss this article with its authors and with other ASRM members at https://www.fertstertdialog.com/users/
16110-fertility-and-sterility/posts/19238-24356

T
he ABO blood type system is a have played a vital role in immunology ovarian cancer (4), and ovarian hyper-
characterization of the human and transplant medicine, more recently, stimulation syndrome (5).
blood group antigens that are they have been implicated in the patho- There has been a historical interest
expressed on the surface of red blood physiology or increased risk of certain in the relationship between ABO blood
cells as well as other human cell types, diseases (2). In particular, some studies types and infertility (6). In fact, as early
including the epithelium, sensory neu- have reported a link between various as 1960, some investigators proposed
rons, and the vascular endothelium (1). ABO blood types and gynecological that ABO blood incompatibility could
While the ABO blood type antigens conditions, such as endometriosis (3), be associated with infertility (7). Further
research revealed that autoimmunity
Received May 16, 2017; revised July 16, 2017; accepted August 10, 2017.
and isoagglutination, in conjunction
N.P. has nothing to disclose. H.H.P. has nothing to disclose. L.D.S. has nothing to disclose. P.J.C. has with ABO blood group incompatibility,
nothing to disclose. R.T.E. has nothing to disclose. S.D.S. has nothing to disclose. Z.R. has nothing may contribute to infertility (8). More
to disclose.
P.J.C. was partially supported by a grant from the Clinical and Translational Science Center at Weill recently, studies have examined the
Cornell Medical College (UL1-TR000457-06). relationship of ABO blood type with
Reprint requests: Nigel Pereira, M.D., Weill Cornell Medicine, Ronald O. Perelman and Claudia Cohen
Center for Reproductive Medicine, 1305 York Avenue, New York, New York 10021 (E-mail: respect to ovarian reserve parameters.
nip9060@med.cornell.edu). For example, Nejat et al. (9) first sug-
gested that patients with blood type O
Fertility and Sterility® Vol. -, No. -, - 2017 0015-0282/$36.00
Copyright ©2017 American Society for Reproductive Medicine, Published by Elsevier Inc. were more likely to have diminished
http://dx.doi.org/10.1016/j.fertnstert.2017.08.019

VOL. - NO. - / - 2017 1

ORIGINAL ARTICLE: PREGNANCY
ovarian reserve (DOR). Similarly, Mu et al. (10) found that blood
type O was associated with DOR in their study of 14,875 women
undergoing IVF treatment. In contrast, Lin et al. (11) found that
Chinese patients with the B antigen were more likely to have
DOR. These data linking certain blood types with DOR have
been substantiated via mechanisms that include polymorphisms
of key receptors or mutations of genes involved in ovarian
development and function (9–11). However, subsequent
studies have reported no association between ABO blood
types and ovarian reserve or ovarian response (12–14).
Currently, there is a dearth of studies exploring the
relationship between ABO blood type and IVF cycle outcomes.
In one recent study of 626 patients, Goldsammler et al. (15)
suggested that blood type B was associated with an increased
likelihood of live birth (odds ratio [OR], 1.9; 95% confidence
interval [CI], 1.10–3.41) after adjusting for factors recognized
to impact IVF outcome. Of note, the study was limited by the
inclusion of patients regardless of whether the IVF attempt
was the first or repeat, patients had DOR, it was a cleavage-
or blastocyst-stage ET, or two or more embryos transferred.
To address the limitations of the aforementioned study, we
sought to investigate the association between ABO blood
type and live-birth outcomes in patients undergoing IVF
with day 5 single ET (SET).
MATERIALS AND METHODS
Inclusion and Exclusion Criteria
All couples initiating their first IVF cycle with fresh day 5 SET
at the Ronald O. Perelman and Claudia Cohen Center for
Reproductive Medicine between January 2004 and January
2014 were analyzed for potential inclusion. In this study,
only normal responder patients undergoing ovarian stimula-
tion were included. Normal responder status was defined by
the following parameters: age <40 years, cycle day 2/3 FSH
level %12 mIU/mL, and cycle day 2/3 antim€ ullerian hormone
(AMH) level R1 ng/mL (16). Patients with known polycystic
ovarian syndrome (PCOS) as diagnosed by the Rotterdam
criteria were excluded. This was primarily due to the high or
hyperovarian stimulation response that patients with PCOS
exhibit when compared with normal responders. Further-
more, patients with PCOS may often cryopreserve embryos
up front instead of undergoing fresh ET due to the risk of
ovarian hyperstimulation syndrome. Also excluded from the
analysis were patients R40 years, patients undergoing
cleavage-stage ET, or transfer of two or more day 5 embryos.
Patients using donor oocytes or with incomplete records were
excluded. Blastocysts biopsied for preimplantation genetic
screening (PGS) were also excluded as our center does not
routinely perform fresh ET of PGS tested embryos, that is,
these embryos are vitrified and thawed for transfer in a
subsequent natural menstrual cycle or medicated cycle.
All IVF, fresh ET, frozen ET, ovulation induction, and IUI
treatment cycles are recorded in our center's electronic med-
ical record, from which demographic and treatment data can
be exported into individual spreadsheets. A secure and dei-
dentified master spreadsheet of all IVF cycles was exported
for the purpose for this study. Of the 22,993 fresh IVF cycles
occurring during the study period, 2,798 patients undergoing
2 VOL. - NO. - / - 2017
day 5 SET were identified after using the previously
mentioned exclusion and inclusion criteria. The Weill Cornell
Medical College Institutional Review Board approved the
retrospective study protocol and analysis.
Clinical, Laboratory, and Sperm Preparation
Protocols
A blood type and screen is obtained in all patients as part of
the initial infertility workup at our center. All patients in
the current study underwent uterine cavity evaluation via
saline sonography, hysterosalpingography, or hysteroscopy
before ovarian stimulation (16). Ovarian stimulation, hCG
trigger, oocyte retrieval, embryo culture, and ET were carried
out based on established protocols (17). Briefly, ovarian
stimulation was performed using gonadotropins (Follistim,
Merck; or, Gonal-F, EMD-Serono; and, Menopur, Ferring
Pharmaceuticals). Gonadotropin doses were based on age,
body mass index (BMI, kg/m2), antral follicle count (AFC),
and AMH level. Suppression of ovulation was achieved with
daily injections of ganirelix acetate (Merck), which was initi-
ated using a flexible protocol (16). HCG (Pregnyl, Merck; or
Novarel, Ferring Pharmaceuticals) was used as the ovulation
trigger and was administered when the two lead follicles at-
tained a mean diameter >17 mm. A previously described
sliding scale for hCG administration based on E2 was used
(18), that is, 10,000 IU for E2<1,500 pg/mL, 5,000 IU for E2
1,501–2,500 pg/mL, 4,000 IU for E2 2,501–3,000 pg/mL,
and 3,300 IU for E2>3,001 pg/mL. Oocyte retrieval was per-
formed approximately 34–35 hours after hCG administration
under conscious sedation with transvaginal ultrasound
guidance. All patients received IM P (50 mg daily) for luteal
support, irrespective of the hCG trigger dose (18).
Ejaculated samples were produced on the day of oocyte
retrieval and were evaluated for volume, count, concentra-
tion, and motility using 2010 World Health Organisation
criteria (19). Based on the semen sample and the couple's
reproductive history, fertilization of retrieved oocytes was
carried out with either conventional in vitro insemination
or intracytoplasmic sperm injection (ICSI) (20). Oocytes
were examined 14–17 hours after insemination or ICSI for
fertilization. The resulting embryos were cultured until the
blastocyst stage using a two-step in-house culture media
(21). The blastocysts were then graded based on their degree
of expansion, development of the inner cell mass, and
trophectoderm (22). All SETs were performed on day 5 with
Wallace catheters (Smiths Medical). Ultrasound guidance
was used only when the transfers were deemed difficult based
on the prior trial transfer (21). Supernumerary blastocysts
were subsequently cryopreserved on day 5 or day 6.
Study Variables
Baseline demographics recorded for each patient included age
(years), race, BMI (kg/m2), infertility diagnosis, ABO blood
type, and rhesus factor type. Baseline IVF characteristics
included cycle day 2/3 FSH (mIU/mL) level, cycle day 2/3
AMH (ng/mL) level, and AFCs. Ovarian stimulation parame-
ters recorded were duration of ovarian stimulation (days),
dosage of gonadotropins administered (IU), E2 level (pg/mL)
 Fertility and Sterility®

TABLE 1

Overall demographics and baseline IVF characteristics of patients undergoing day 5 single embryo transfer stratified by blood type (n [ 2,329).
Blood type
Parameter A (n [ 897) B (n [ 397) AB (n [ 120) O (n [ 915) P value
Age (y) 34.6
4.62 34.3
4.68 34.9
4.85 34.7
4.97 .49
Race (%) .63
White 546 (60.9) 219 (55.2) 67 (55.8) 537 (58.7)
Black 42 (4.6) 20 (5.0) 5 (4.2) 37 (4.0)
Asian 68 (7.6) 37 (9.3) 11 (9.2) 61 (6.7)
Other 241 (26.9) 121 (30.5) 37 (30.8) 280 (30.6)
Body mass index (kg/m2) 22.8
4.83 22.7
5.16 23.1
4.25 23.1
5.61 .48
Infertility diagnoses (%) .98
Anovulation 83 (9.25) 36 (9.07) 12 (10.0) 87 (9.51)
Tubal factor 57 (6.35) 23 (5.97) 9 (7.5) 60 (6.56)
Male factor 311 (34.7) 141 (35.5) 30 (25.0) 323 (35.3)
Unexplained 138 (15.4) 61 (15.4) 24 (20.0) 129 (14.1)
Combined 308 (34.3) 136 (34.2) 45 (37.5) 316 (34.5)
Cycle day 2/3 FSH level (mIU/mL) 4.82
2.53 4.89
2.64 5.09
2.41 4.88
2.36 .72
Cycle day 2/3 AMH level (ng/mL) 2.31
1.63 2.36
1.70 2.44
1.41 2.32
1.50 .82
AFC count (n) 10.7
2.86 10.9
2.75 10.9
2.39 10.7
2.85 .67
Note: Data presented as mean
SD and n (%).
Pereira. ABO blood type and SET outcomes. Fertil Steril 2017.

on the day of trigger, peak endometrial thickness (mm), total
number of oocytes, and total number of mature oocytes. The
percentage of ICSI cycles, number of supernumerary embryos
available for cryopreservation, and alpha-numeric grading of
blastocysts were also recorded. The primary outcome of
interest was live-birth rate after SET, defined as any birth after
24 weeks of gestation. Secondary outcomes were birth weight
(g) and gestational age at delivery (weeks). Any live birth
>37 weeks and <37 weeks of gestational age was defined
as a term birth and preterm birth, respectively.
Statistical Analysis
Continuous variables were expressed as mean
standard
deviation (SD) or median and interquartile range, after assess-
ment for normality by the Shapiro-Wilk normality test. Cate-
gorical variables were expressed as number of cases (n) with
percentage of occurrence (%). Statistical comparison of base-
line categorical demographics and IVF characteristics between
blood type groups was performed by the c2 test. Statistical
comparison of baseline continuous demographics and IVF
characteristics between blood type groups was performed by
the analysis of variance test. A Bonferroni multiple compari-
sons correction was applied where indicated. Baseline
demographics, ovarian stimulation parameters, and embryo
quality parameters were also compared between patients
with and without live births after SET. Univariate and multi-
variable logistic regression was used to analyze the association
between blood type and live birth, while controlling for
confounders of interest. ORs with 95% CIs for live birth after
day 5 SET were estimated from the model. Adjusted odds ratios
were then calculated by simultaneously evaluating the
following variables: blood type A, B, AB, or O; age; race;
BMI; duration of ovarian stimulation; gonadotropin dose;
peak endometrial thickness; elective SET; supernumerary em-
bryos cryopreserved; and ultrasound-guided SET. The blood
type with the lowest live-birth rate was considered the referent
blood type for univariate and multivariable logistic regression
models. Statistical significance was set at P< .05. All statistical
analyses were performed using STATA version 14.
RESULTS
From the initial pool 22,993 fresh IVF cycles, 16,875 were
excluded due to age >40 years or transfer of cleavage-stage
ET, and 3,320 were excluded due to incomplete records. Of
the 2,798 patients undergoing day 5 ET, 469 (16.8%), patients
were excluded due to transfer of more than one blastocyst.
Thus, a total of 2,329 patients undergoing fresh IVF with
day 5 SET met the inclusion criteria. The distribution of these
patients based on blood type was as follows: 897 (38.5%)
patients with blood type A; 397 (17.0%) patients with blood
type B; 120 (5.2%) patients with blood type AB; and 915
(39.3%) patients with blood type O. This distribution of ABO
blood types is similar to the overall blood group distribution
in the United States, albeit with slightly different percentages:
42% with blood type A; 10% with blood type B; 4% with
blood type AB; and, 44% with blood type O (23).
Table 1 compares the baseline demographics and IVF cy-
cle characteristics of the study cohort stratified by blood type.
The mean age and BMI of the study cohort were 34.6

4.78 years and 22.9
4.92 kg/m2, respectively. As evident
in Table 1, there was no difference in the age, distribution
of races, BMI, distribution of infertility diagnoses, cycle day
2/3 FSH level, cycle day 2/3 AMH level, or AFC between the
blood type groups. Table 2 compares the baseline demo-
graphics, ovarian stimulation parameters, and embryo quality
parameters between patients with and without live births after
day 5 SET. The overall live-birth rate of the study cohort was
43.6%. The live-birth rates stratified by blood types A, B, AB,
and O were 42.7%, 43.6%, 50.8%, and 43.6%, respectively.
Patients with live births were younger compared with those

VOL. - NO. - / - 2017 3

ORIGINAL ARTICLE: PREGNANCY

TABLE 2

Comparison of baseline demographics, baseline IVF characteristics, ovarian stimulation, and embryo quality parameters in patients with and
without live births after day 5 single embryo transfer (n [ 2,329).
Parameter Live birth (n [ 1,016) No live birth (n [ 1,313) P value
Baseline demographics and IVF characteristics
Age (y) 34.7
4.81 35.1
4.77 .04
Race (%) .13
White (n ¼ 1,369) 790 (57.7) 579 (42.3)
Black (n ¼ 104) 42 (40.4) 62 (59.6)
Asian (n ¼ 177) 83 (46.9) 94 (53.1)
Other (n ¼ 679) 351 (51.7) 328 (48.3)
Body mass index (kg/m2) 22.9
5.28 22.7
5.04 .35
Infertility diagnoses (%) .90
Anovulation (n ¼ 218) 113 (51.8) 105 (48.2)
Tubal factor (n ¼ 149) 63 (42.3) 86 (57.7)
Male factor (n ¼ 805) 331 (41.1) 474 (58.9)
Unexplained (n ¼ 352) 171 (48.6) 181 (51.4)
Combined (n ¼ 805) 338 (42.0) 467 (58.0)
Blood type (%) .97
A (n ¼ 897) 383 (42.7) 514 (57.3)
B (n ¼ 397) 173 (43.6) 224 (56.4)
AB (n ¼ 120) 61 (50.8) 59 (49.2)
O (n ¼ 915) 399 (43.6) 516 (56.4)
Rh .80
Positive (n ¼ 2,027) 891 (44.0) 1,136 (56.0)
Negative (n ¼ 302) 125 (41.4) 177 (58.6)
Cycle day 2/3 FSH level (mIU/mL) 4.94
2.49 4.89
2.78 .65
Cycle day 2/3 AMH level (ng/mL) 2.47
1.44 2.51
1.27 .48
AFC (n) 10.9
2.27 10.8
2.43 .31
Ovarian stimulation parameters
Protocol type (%) .95
GnRH-agonist (n ¼ 1,052) 461 (43.8) 591 (56.2)
GnRH-antagonist (n ¼ 1,277) 555 (43.5) 722 (56.5)
Duration of ovarian stimulation (d) 9.37
1.68 9.48
1.70 .12
Dosage of gonadotropins (IU) 2,240.2
1,283.7 2,345.2
1,396.1 .06
E2 level on the day of hCG trigger (pg/mL) 2,014.6
756.8 1,996.4
757.5 .57
Peak endometrial thickness (mm) 11.1
2.68 10.9
2.81 .08
Total oocytes retrieved (n) 13.7
5.47 13.4
5.39 .09
Mature oocytes retrieved (n) 11.1
4.54 10.8
4.95 .13
ICSI, yes (%) 713 (70.2) 940 (71.6) .83
Elective SET, yes (%) 277 (27.3) 363 (27.6) .84
Supernumerary embryos cryopreserved (n) 2.53
1.35 2.40
1.62 .03
Embryo quality parameters
Blastocoele grading (%) .91
2 (n ¼ 774) 352 (45.5) 422 (54.5)
3 (n ¼ 1,208) 521 (43.1) 687 (56.9)
4 (n ¼ 347) 143 (41.2) 204 (58.8)
Inner cell mass grading (%) .94
A (n ¼ 686) 304 (44.3) 382 (55.7)
B (n ¼ 1,443) 618 (42.8) 825 (57.2)
C (n ¼ 200) 94 (47.0) 106 (53.0)
Trophectoderm grading (%) .90
A (n ¼ 600) 247 (41.2) 353 (58.8)
B (n ¼ 1,652) 737 (44.6) 915 (55.4)
C (n ¼ 77) 32 (41.6) 45 (58.4)
Ultrasound-guided ET (%) 124 (12.2) 196 (14.9) .58
Note: Data presented as mean
SD and n (%).
Pereira. ABO blood type and SET outcomes. Fertil Steril 2017.

who did not have live births (34.7
4.81 vs. 35.1
4.77 years,
respectively; P¼ .04). There was also a nonsignificant trend
toward a higher proportion of white patients, shorter ovarian
stimulation duration, lower dosage of gonadotropins, higher
peak endometrial thickness, and higher total and mature
oocytes retrieved in the live birth group. However, no differ-
ences were noted in the distribution of blood types, Rh types,
or other ovarian stimulation or embryo quality parameters
between patients with and without live births. The number
of patients undergoing elective SET was also comparable
between the two groups.
Table 3 summarizes the univariate and multivariable
logistic regression analyses for variables of statistical or
biological significance. As noted in Table 3, the unadjusted
and adjusted ORs for live birth were not significant when
comparing blood type A (referent) to all other blood types

4 VOL. - NO. - / - 2017

 Fertility and Sterility®

TABLE 3

Univariate and multivariable logistic regression analysis to examine the association between blood type and live birth, while controlling for
confounders of interest.
Live birth Unadjusted odds ratio (95% CI) P value Adjusted odds ratio (95% CI) P value
Blood type A (referent) 1.0 — 1.0 —
Blood type B vs. referent 0.96 (0.6–1.7) .89 1.0 (0.9–1.8) .80
Blood type AB vs. referent 0.72 (0.4–1.2) .25 0.91 (0.7–1.1) .40
Blood type O vs. referent 0.96 (0.6–1.7) .89 0.94 (0.8–1.2) .57
Age (y)a 0.86 (0.7–1.2) .09 0.82 (0.7–1.3) .25
Raceb 1.06 (0.7–1.5) .17 0.97 (0.7–1.1) .29
BMI (kg/m2)c 0.95 (0.5–1.7) .87 1.01 (0.9–1.8) .67
Duration of ovarian stimulation (d)d 0.93 (0.8–1.2) .71 0.98 (0.9–1.3) .83
Gonadotropin dose (IU)e 1.1 (0.9–2.4) .57 1.21 (0.9–2.5) .49
Peak endometrial thickness (mm)f 1.1 (0.8–1.8) .39 1.04 (0.9–1.6) .15
Mature oocytesg 1.01 (0.8–1.8) .39 1.1 (0.8–1.9) .21
Elective SETh 0.98 (0.8–1.2) .84 0.87 (0.7–1.1) .17
Supernumerary embryos cryopreservedi 1.1 (0.7–1.8) .30 1.2 (0.6–2.0) .29
Ultrasonogram-guided ETj 0.89 (0.7–1.9) .61 0.96 (0.8–1.9) .44
a
<35 (referent) vs. R35 years.
b
White vs. black, Asian, or other.
c
<25 (referent) vs. R25 kg/m2.
d
<9 (referent) vs. R9 days.
e
<2,000 (referent) vs. R2,000 IU.
f
<10 (referent) vs. R10 mm.
g
<10 vs. R10.
h
Yes (referent) vs. no.
i
<2 (referent) vs. R2.
j
yes (referent) vs. n.
Pereira. ABO blood type and SET outcomes. Fertil Steril 2017.

individually. The unadjusted and adjusted ORs for live birth
when comparing blood type A to any other blood type were
0.94 (95% CI, 0.5–1.6; P¼ .83) and 0.98 (95% CI, 0.6–1.8;
P¼ .79), respectively. Overall, there was no association
between live birth and age, ABO blood type, or other variables
included in the multivariable logistic regression model.
The mean birth weights after day 5 SET, stratified by
blood types A, B, AB, and O were, respectively, as follows:
3,180.2
622.1, 3,060.7
582.2, 3,124.5
436.7, and
3,156.6
672.9 g. This represented an overall birth weight of
3,130.5
518.3 g for the study cohort. Figure 1A demonstrates
no difference in live birth weights after day 5 SET in the four
blood types (P¼ .66). The distribution of mean gestational age
at delivery based on blood types A, B, AB, and O was as follows:
37.2
4.2, 38.6
3.9, 37.9
3.2, and 37.5
3.5 weeks, respec-
tively. Figure 1B highlights no difference in the rates of term
and preterm birth by blood type (P¼ .97).
DISCUSSION
The current retrospective study assessed the live-birth
outcomes of 2,329 patients undergoing fresh IVF with day 5
SET. Our results demonstrate that ABO blood type is not asso-
ciated with the primary outcome of live-birth rate in patients
undergoing day 5 SET. Furthermore, there was no difference
in the secondary outcomes of birth weight or gestational
age at delivery when comparing the different blood types.
These results remained unchanged even after multivariable
adjustment for other factors of interest.
The ABO gene is located on chromosome 9q34 and
encodes glycosyltransferases that catalyze the transfer of
nucleotide sugars to the H antigen, thereby forming the ABO
blood group antigens (24). Although the role of ABO blood
type has been well established in the domain of blood transfu-
sion and organ transplantation, there have been several
epidemiologic studies reporting the association of ABO blood
types with cancer and coronary heart disease (25, 26).
Furthermore, several other epidemiologic studies in diverse
ethnic groups have also reported an association between
ABO blood type and increased risk of different cancers (27–30).
Within the realm of fertility treatment, retrospective and
cross-sectional studies have reported an association between
certain blood types and ovarian reserve (9–11). Although such
associations appear contentious, a few putative mechanisms
have been offered to substantiate these findings. Nejat et al.
(9) found that blood type O was associated with DOR and
that the A antigen was protective for ovarian reserve given
the higher representation of blood type A and AB in the
group with normal ovarian reserve. To explain these
findings, they speculated that an enzyme associated with
the A antigen called A transferase played a critical role in
oocyte accrual (9). Mu et al. (10) also found an association
between blood type O and DOR, which they hypothesized to
be due to biologic alterations of FSH and LH receptors. It is
known that FSH and LH receptors play a vital role in
follicle development and maturation and that the biologic
activity of these receptors requires glycosylation (15).
However, the glycosyltransferase enzyme is encoded by the
O allele; thus, those with blood type O would lack the
allele and, therefore, the glycosyltransferase activity,
consequently contributing to DOR (8, 31). The authors also
identified genes associated with ovarian function, such as
nuclear receptor 5A1 (NR5A1) and transforming growth
factor b receptor (TGFBR1), to be in close proximity of the

VOL. - NO. - / - 2017 5

ORIGINAL ARTICLE: PREGNANCY
FIGURE 1
Comparison of mean birth weights (A) and term and preterm birth rates (B) stratified by blood type.
Pereira. ABO blood type and SET outcomes. Fertil Steril 2017.
9q34 locus of the ABO gene (8, 32). Thus, recombination could
occur between these genes, increasing the chances of
inheriting allele combinations associated with DOR (8, 33).
In addition to the aforementioned mechanisms, several
studies have also shown that certain ABO blood types may
be associated with an altered immune or inflammatory
response. For example, certain ABO blood type gene polymor-
phisms have been associated with increased tumor necrosis
factor alpha (TNF-alpha) and soluble intercellular adhesion
molecule 1 levels (34, 35). Other blood type polymorphisms
may also affect plasma levels of plasma soluble E-selectin
levels or tissue expression of integrins and cadherins (36, 37).
It is important to note that some of these immune mediators
(selectin, integrins, cadherins) have been implicated in early
embryo implantation as well as subsequent placentation
(38–40). Thus, it is reasonable to posit that the immunologic
or inflammatory milieu associated with certain ABO blood
types could affect the early implantation and subsequent
growth of embryos during IVF.
Two prior studies have reported no association between
ABO blood type and IVF outcomes (41, 42); however, these
studies were limited by a simple comparison of pregnancy
rates in different ABO blood groupings. Using a better study
design and a cohort of 626 patients, Goldsammler et al. (15)
reported an increased likelihood of live birth in patients
with blood type B. However, the study cohort was
heterogeneous in nature—inclusion of patients with DOR,
over-representation of patients with ovulatory disturbance,
and inclusion of cleavage and blastocyst transfers, as well
as first and repeat IVF attempts—limiting its generalizability.
In contrast to Goldsammler et al.'s study, our findings sug-
gest no association between ABO blood type and live-birth
outcomes in SET cycles. Perusal of the study's strengths may
account for the difference in results. The study cohort was
homogenous given the inclusion of only normal responder
patients <40 years undergoing their first IVF cycle with day
5 SET. By including only SETs, we were able to assess IVF
outcomes on a per-embryo and per-patient basis (43). Further-
more, day 5 SET also reflects recent practice shifts. The use of
multivariable logistic regression accounted for several
confounders and increased the statistical robustness of our
findings. Finally, our analysis also included birth weights
6 VOL. - NO. - / - 2017
and gestational ages at delivery, which have not been evalu-
ated with respect to ABO blood types in previous studies.
Despite its strengths, the current study has two major lim-
itations. First, the retrospective nature of the current study limits
its overall generalizability. For example, race has been identified
as an independent predictor of IVF outcomes in previous studies
(44, 45). The distribution of races was similar among ABO blood
types as well as among patients with and without live births in
the current study. However, it is possible for independent study
cohorts to have different distributions of race and blood type
and, therefore, different results when compared with our
study. It is also important to note that the absence of any
association between blood type and our primary and
secondary outcomes does not exclude individual associations
between individual confounders and outcomes of interest.
Thus, larger population-based or prospective studies are needed
to validate our results. Second, like prior studies, our study did
not investigate the genetic or immunologic mechanisms
contributing to IVF outcomes, if any, in patients with different
ABO blood types. The NR5A1 and TGFBR1 genes could be can-
didates for further investigations, given their proximity to the
9q34 locus of the ABO gene (32). Furthermore, because muta-
tions in these genes are known to be detrimental to ovarian
development and function, one might speculate that these mu-
tations could impact oocyte quality or early implantation (32).
Previous investigations have also recognized that the circu-
lating levels of TNF-alpha, interleukin-1, insulin-like growth
factor, and brain-derived neurotrophic factor can impact IVF
success (34, 46–48). Exploring the association between the
serum levels of these immunologic factors with ABO blood
type could be worthwhile.
Conclusion
In conclusion, the current study demonstrates no association
between ABO blood type and live-birth rate, birth weight, or
gestational age at delivery in a large cohort of patients under-
going their first IVF cycle with SET. These results remain
unchanged even after accounting for confounders such as
age, race, BMI, duration of ovarian stimulation, gonadotropin
dose, and peak endometrial thickness. Validation of these
results is required in large-scale population-based studies

and basic scientific investigations to elucidate the mecha-
nistic role of ABO blood type in IVF outcomes.
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