Effect of body mass index on

intrauterine insemination
cycle success
Rachel M. Whynott, M.D., Karen M. Summers, M.P.H., Bradley J. Van Voorhis, M.D., and Rachel B. Mejia, D.O.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Iowa Carver
College of Medicine, Iowa City, Iowa

Objective: To determine whether body mass index (BMI) affects intrauterine insemination treatment success.
Design: Retrospective cohort study.
Setting: Academic medical center.
Patient(s): A total of 3,217 intrauterine insemination treatment cycles in 1,306 patients.
Intervention(s): None.
Main Outcome Measure(s): Primary outcome was live birth rate stratified by BMI. Secondary outcomes included rates of clinical preg-
nancy (defined as an intrauterine pregnancy with a heartbeat present on ultrasound), multiple gestation, biochemical pregnancy, missed
abortion, ectopic, and spontaneous abortion.
Result(s): Women with BMI 25 to 29.99 kg/m2 or R30 kg/m2 were equally likely to have a live birth as women of normal BMI. Women
with BMI R30 kg/m2 did have a higher likelihood of biochemical pregnancy than women with normal BMI.
Conclusion(s): A BMI between 25 and 29.99 kg/m2 or R30 kg/m2 does not appear to have a negative effect on live birth after intra-
uterine insemination. Obesity may be associated with a higher risk of biochemical pregnancy after intrauterine insemination. (Fertil
SterilÒ 2021;115:221–8. Ó2020 by American Society for Reproductive Medicine.)
El resumen está disponible en Español al final del artículo.
Key Words: Body mass index, obesity, IUI, artificial insemination, overweight, infertility
Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/posts/30484

O
besity is defined as a body fecundity compared to women with a Intrauterine insemination (IUI) is
mass index (BMI) >30 kg/m2 normal BMI, even when they are an infertility treatment where pro-
and overweight is defined as having regular menstrual cycles (12). cessed and concentrated sperm is in-
a BMI 25.0 to 29.9 kg/m2. The most Obese women are also more likely to jected directly past the cervix into the
recent prevalence data suggest that experience miscarriage and recurrent uterine cavity to increase the number
36.5% of reproductive-aged US women pregnancy loss (8, 13). A 2019 meta- of motile sperm in the female reproduc-
are obese and 26.3% are overweight (1, analysis (14) that included 21 studies tive tract. As this is a common infer-
2), and modeling of obesity trends have evaluating the effect of obesity on live tility treatment, particularly for male
estimated that 51% of Americans will birth outcomes using in vitro fertiliza- factor, cervical factor, and unexplained
be obese by 2030 (3). Elevated BMI tion (IVF) found that obesity has a sig- infertility, it is important to understand
can lead to multiple health issues, nificant negative impact on live birth how BMI may impact the success of this
including problems with reproduction rate. Because of the high prevalence procedure. The goal of the present study
for men and women (4–8). For of this disease in reproductive-aged was to determine whether BMI affects
women, obesity can lead to menstrual women, it is important to understand IUI cycle success, including when used
irregularities, anovulation, infertility, the impact of increasing BMI on in unmedicated (‘‘natural’’) cycles, oral
and complications during pregnancy various other infertility interventions ovulation induction cycles (using letro-
(4, 6, 8–11). Women who are to better counsel patients considering zole, clomiphene citrate, or a combina-
overweight or obese have reduced these treatments. tion), injectable ovulation induction
cycles (using human menopausal
Received May 7, 2020; revised June 17, 2020; accepted July 1, 2020; published online October 15, 2020. gonadotropin), and canceled IVF cy-
R.M.W has nothing to disclose. K.M.S. has nothing to disclose. B.J.V.V. has nothing to disclose. R.B.M. cles. We hypothesized that women
has nothing to disclose.
Reprint requests: Rachel M. Whynott, M.D., 1360 North Dodge Street, Office 1408, Iowa City, Iowa who are overweight and obese would
52245 (E-mail: Rachel.m.whynott@gmail.com). have lower live birth rates and
Fertility and Sterility® Vol. 115, No. 1, January 2021 0015-0282/$36.00
increased abnormal pregnancy rates
Copyright ©2020 American Society for Reproductive Medicine, Published by Elsevier Inc. (such as ectopic pregnancy,
https://doi.org/10.1016/j.fertnstert.2020.07.003

VOL. 115 NO. 1 / JANUARY 2021 221

ORIGINAL ARTICLE: INFERTILITY
spontaneous abortion, missed abortion, and biochemical
pregnancy) compared to women with normal BMI.
MATERIALS AND METHODS
The University of Iowa institutional review board approved
this retrospective cohort study. Intrauterine insemination cy-
cles using fresh samples between July 1, 2009 and December
31, 2018 at the University of Iowa Hospitals and Clinics were
included. Cycles in which pregnancy outcome data were un-
available were excluded (n ¼ 116). Due to the low number of
cycles in patients with a BMI <18.5 kg/m2, these data were
also excluded from the analysis (n ¼ 85). Because we included
only fresh semen samples, donor insemination cycles were
excluded. Fresh semen samples were used for this study to
reduce the number of confounding variables, as cryopre-
served sperm has been shown to yield lower live birth rates
in insemination cycles (15–17). The primary objective was
to determine whether there were differences in live birth
rate based on women’s BMI. Secondary objectives were to
evaluate differences in rates of ongoing clinical pregnancy
(defined as an intrauterine pregnancy with a heartbeat on
ultrasound), multiple gestation, missed abortion,
spontaneous abortion, ectopic pregnancy, and biochemical
pregnancy stratified by BMI. Biochemical pregnancies were
defined as a positive initial beta-human chorionic gonado-
tropin (b-hCG) that subsequently declined.
Demographic and medical data were extracted, including
patient age, weight, BMI, smoking history, current smoking
status, gravidity, parity, antral follicle count, IUI cycle num-
ber, diagnosis (diminished ovarian reserve, endometriosis,
anovulation, tubal factor, uterine factor, cervical factor,
male factor, inadequate sperm exposure [e.g., due to vagi-
nismus], advanced maternal age, dyspareunia, pelvic adhe-
sions, and unexplained infertility), and treatment type
(unmedicated cycle, oral ovulation induction, injectable
ovulation induction, or canceled IVF cycle). We also assessed
the total motile sperm for each insemination. Inseminations
were prepared on a two-layer density gradient at our institu-
tion. Postwash data was used as this is the most accurate
assessment of semen characteristics used in treatment, and
a recent study (18) found that prewash total motile count is
a poor predictor of live birth in IUI cycles. All women present-
ing with infertility were tested for thyroid dysfunction at our
facility, and all women with obesity were screened for dia-
betes mellitus.
Our power analysis found that we would need 3,177 IUI
cycles to be able to detect a 3.5 percentage point difference
with two-tailed z-tests when alpha is set at 0.05, power at
0.8, and allocation ratio of 0.5 overweight-to-normal and
0.6 obese-to-normal. We assumed a 10% live birth rate per
IUI cycle for the normal BMI category to determine power
(18). Generalized estimating equations were used to examine
the relationship between individual factors and the outcome
of live birth, yet controlling for multiple observations per pa-
tient. Purposeful selection as described by Bursac et al. (19)
was used to determine factors retained in the final model.
Odds ratios (OR) were calculated for candidate factors for in-
clusion, with factors meeting the prescribed criteria of P< .25
222
entered into the regression model. Through an iterative pro-
cess of variable selection, covariates were removed from the
model if they did not meet significance of 0.1 alpha level or
were not found to change any remaining parameter estimate
by >15%. Finally, each variable not selected for inclusion in
the original multivariate model was added back one at a time,
with any variable significant at an alpha level of 0.1 retained.
RESULTS
A total of 3,217 IUI treatment cycles in 1,306 patients were
included in the analysis. Table 1 summarizes the demographic
and medical characteristics stratified by BMI categories:
normal weight, overweight, and obese. The BMI ranged
from 18.5 to 53.1 kg/m2, with a mean BMI of 27.5 kg/m2
and a median BMI of 25.5 kg/m2. Forty-seven percent of
the cycles were in normal weight women, 24.1% in over-
weight women, and 28.3% in obese women. The mean (stan-
dard deviation) BMI for obese subjects was 37.3  5.1 kg/m2.
The mean age for all subjects was 32 years. The percentage of
women who were current smokers was statistically higher in
the obese category compared with the normal BMI patients
(P< .001). The total motile sperm in the inseminate was
similar for all BMI groups. The most common diagnosis was
unexplained infertility (30%) followed by male factor (19%),
and anovulation (16%). Anovulation was the most common
diagnosis in the obese category, at 25%.
Unmedicated IUI cycles were used in 14% of cases, oral
ovulation induction in 61% of cases, and injectable ovulation
induction in 23% of cases. Treatment type was found to vary
between BMI classes (P< .001). Cycles in women with obesity
involved injectable ovulation induction more often than cy-
cles in other BMI classes, at 29% (P< .05). Two percent of
IUI cycles were canceled IVF cycles. There were no differences
in the live birth rates for the various treatment cycle types
(Table 2).
Table 3 reports the frequencies and adjusted odds ratios
for pregnancy outcomes by BMI. There was no difference in
live birth rates between women with a normal BMI and those
with obesity (10% vs. 11%; adjusted OR 1.02, 95% confidence
interval [CI] 0.76–1.37). When analyzing BMI as a continuous
variable in model correcting for age, diagnosis, and parity, the
odds ratio per every unit increase in BMI was 1.00 (95% CI
0.984–1.019; P ¼ .906). There was no difference in rates of
clinical pregnancy, multiple gestation, or multiple delivery
for women with obesity compared to women with normal
BMI. When miscarriage, ectopic pregnancy, and biochemical
pregnancy rates were analyzed separately, biochemical preg-
nancy was found to be more likely in women with BMI R30
kg/m2 than in women in the normal BMI range (adjusted OR
2.37; 95% CI 1.33–4.25). Women with obesity were no more
or less likely to have a miscarriage or an ectopic pregnancy,
although we were not powered to adjust for diagnosis or par-
ity, and therefore, only adjusted for age.
Predictors in our model for live birth are presented in
Table 4. Factors included in the model were maternal age, an-
ovulation diagnosis, unexplained infertility diagnosis, BMI,
and parity. Increasing maternal age was negatively associated
with live birth, whereas the diagnoses of anovulation and
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TABLE 1

Demographic characteristics reported per intrauterine insemination cycle stratified by body mass index categories.
BMI category
Factor Full sample (n [ 3,217) 18.5–24.99 kg/m2 (n [ 1,538) 25–29.99 kg/m2 (n [ 802) ‡30 kg/m2 (n [ 877) P value
Maternal age (y) 32.42  4.70 (20–47) 32.32  4.55 (20–47) 32.40  4.84 (21–47) 32.61  4.83 (21–46) .357d
BMI (kg/m2) 27.5  6.9 (18.5–53.1) 22.2  1.7 (18.5–24.99) 27.2  1.3 (25.0–29.99) 37.3  5.1 (30.0–53.1) < .001d
Maternal smoking history 506 (16) 214 (14) 119 (15) 173 (20) .001e
Maternal smoking current 161 (5) 40 (3) 48 (6) 73 (9) < .001e
Gravidity 0.64  1.06 (0–11) 0.60  1.03 (0–9) 0.62  1.02 (0–7) 0.74  1.15 (0–11) .008d
Parity 0.29  0.61 (0–6) 0.27  0.60 (0–5) 0.29  0.56 (0–5) 0.30  0.65 (0–6) .543d
Diagnosis
Advanced maternal age/ 194 (6) 92 (6) 47 (6) 55 (6) < .001e
diminished ovarian reserve
Endometriosis 100 (3) 53 (3) 26 (3) 21 (2)
Anovulation 528 (16) 204 (13) 107 (13) 217 (25)
Tubal factor/pelvic adhesions 86 (3) 36 (2) 21 (3) 29 (3)
Uterine/cervical factor/infrequent 136 (4) 56 (4) 52 (6) 28 (3)
intercourse/dyspareunia
Male factor 625 (19) 302 (20) 151 (19) 172 (20)
Unexplained infertility 966 (30%) 537 (35%) 253 (32) 176 (20)
Multiple diagnoses 582 (18) 258 (17) 145 (18) 179 (20)
AFCa 23.59  12.30 (0–82) 23.08  11.89 (0–82) 24.34  12.24 (2–75) 23.88  13.05 (0–78) .115d
Cycle no. 2.30  1.69 (1–15) 2.26  1.55 (1–12) 2.44  1.94 (1–15) 2.25  1.68 (1–14) .049d
Treatment cycle type
Natural cycle 433 (14) 210 (14) 129 (16) 94 (11) < .001e
Oral ovulation induction 1976 (61) 971 (63) 495 (62) 510 (58)
Injectable ovulation induction 748 (23) 329 (21) 164 (20) 255 (29)
Cancelled IVF cycle 60 (2) 28 (2) 14 (2) 18 (2)
Total motile sperm inseminated (n ¼ 20.91  27.91 (0.00–20.91) 21.23  28.62 (0.01–328.68) 21.38  27.78 (0.00–260.27) 19.92  26.75 (0.01–212.87) .468c
3,175)b
Note: Data presented as mean  standard deviation (range) or n (%), unless stated otherwise. Variables missing <3% of data: maternal smoking history 56 (2%), maternal smoking history current 61 (2%), gravidity 5 (<0.01%), and parity 6 (<0.01%). BMI ¼ body mass
index; IUI ¼ intrauterine insemination; IVF ¼ in vitro fertilization.
a
Missing 982 observations for AFC (30.5%).
b
Missing 42 observations for postwash motile sperm/mL (1%)
c
P value for analysis of variance.
d
P value for Welch test.
e
P value for c2.

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TABLE 2

Live birth rate by treatment cycle type.

BMI 18.5–24.99 kg/m2 (n [ 210) BMI 25–29.99 kg/m2 (n [ 129) BMI ‡30 kg/m2 (n [ 94)
Factor Live birth rate, n (%) Adjusted OR (95% CI) Live birth rate, n (%) Adjusted OR (95% CI) Live birth rate, n (%) Adjusted OR (95% CI)
Unmedicated cycle þ IUI 18 (9) Ref 5 (4) 0.43 (0.14–1.37) 15 (16.0) 2.03 (0.94–4.37)
Oral ovulation induction þ IUI 91 (9.4) Ref 56 (11.3) 1.23 (0.85–1.79) 48 (9.4) 1.01 (0.69–1.47)
Injectable ovulation induction þ IUI 44 (13.4) Ref 20 (12.2) 0.90 (0.50–1.60) 31 (12.2) 0.90 (0.54–1.48)
Note: Odds ratios adjusted for age. BMI ¼ body mass index; CI ¼ confidence interval; IUI ¼ intrauterine insemination.
Whynott. Effect of BMI on IUI cycle success. Fertil Steril 2020.

TABLE 3

Frequency and adjusted odds ratios for body mass index and pregnancy outcome by cycle.
BMI 18.5–24.99 kg/m2 BMI 25–29.99 kg/m2 BMI ‡30 kg/m2
Factor Frequency, n (%) Adjusted OR (95% CI) Frequency, n (%) Adjusted OR (95% CI) Frequency, n (%) Adjusted OR (95% CI)
Live birth 154/1,538 (10) Ref 83/802 (10) 0.99 (0.74–1.34) 95/877 (11) 1.02 (0.76–1.37)
Clinical pregnancy 179/1,538 (12) Ref 103/802 (13) 1.08 (0.83–1.42) 114/877 (13) 1.07 (0.82–1.40)
Ectopica 5/1,538 (0.3) Ref 7/802 (0.9) 2.70 (0.87-8.40) 5/877 (0.6) 1.73 (0.50-5.97)
Miscarriagea 25/1,538 (1.6) Ref 18/802 (2.2) 1.39 (0.77–2.51) 19/877 (2.2) 1.32 (0.73–2.38)
Biochemicala 22/1,538 (1.4) Ref 13/802 (1.6) 1.15 (0.56–2.37) 29/877 (3.3) 2.37 (1.33–4.25)
Multiple gestation (n ¼ 322)b 12/147 (8) Ref 6/82 (7) 0.96 (0.37–2.49) 10/93 (11) 1.51 (0.67–3.37)
Multiple delivery (n ¼ 326)c 9/152(6) Ref 5/81 (6) 1.12 (0.36–3.43) 10/93 (11) 1.95 (0.76–5.03)
VOL. 115 NO. 1 / JANUARY 2021

Note: Odds ratios adjusted for age, diagnosis, and parity. BMI ¼ body mass index; CI ¼ confidence interval; OR ¼ odds ratio.
a
Odds ratio adjusted for age.
b
Seventy-four cases (19%) with documented clinical pregnancy missing ultrasound number of fetal heart rate data.
c
Six cases (1.8%) with documented live birth missing total birth type.
Whynott. Effect of BMI on IUI cycle success. Fertil Steril 2020.

TABLE 4
Adjusted binary logistic regression model for predictors of live birth
(n [ 3,217 cycles in 1,301 patients) using generalized estimating
equations.
Factor Adjusted OR (95% CI)
2
BMI (kg/m )
Normal weight Ref
Overweight 0.99 (0.74–1.34)
Obese 1.02 (0.76–1.37)
Maternal age (y) 0.96 (0.93–0.98)
Anovulation diagnosis 1.97 (1.45–2.69)
Unexplained diagnosis 1.46 (1.08–1.98)
Parity 1.16 (0.95–1.41)
Note: BMI ¼ body mass index; CI ¼ confidence interval; OR ¼ odds ratio.
Whynott. Effect of BMI on IUI cycle success. Fertil Steril 2020.
unexplained infertility were positively correlated with live
birth. When further classifying women with obesity by the
World Health Organization categories, we had 294 cycles in
obesity class I patients (152 unique women), 279 cycles in
obesity class II patients (124 unique women), and 209 cycles
in obesity class III patients (94 unique women). When running
the model with these groups, the further stratified BMI groups’
live birth rates did not significantly differ from that of the
normal BMI group (class I obesity OR 1.06, 95% CI 0.70–
1.61; P ¼ .77; class II obesity OR 1.03, 95% CI 0.69–1.54;
P ¼ .89; class III obesity OR 0.95, 95% CI 0.59–1.55; P ¼ .85).
DISCUSSION
Our study of 3,217 IUI cycles for infertility did not support our
hypothesis, as women with a BMI R25 kg/m2 had the same
rate of live birth as women with a normal BMI after adjusting
for significant covariates. Women with obesity were also no
more likely to experience an ectopic pregnancy or missed or
spontaneous abortion, although they were more likely than
women with normal BMI to experience a biochemical
pregnancy.
Our large and diagnostically diverse study is a valuable
addition to the literature on the effect of obesity on infertility
treatment outcomes. Important, 28.3% of our cycles (877/
3,217) were in 371 women with a BMI R30 kg/m2 (28.4%),
which is close to the current rate of obesity in the general
US population. In addition, the mean BMI in our obese cate-
gory was 37.3 kg/m2, with a range of 30.0 to 53.1 kg/m2,
which is higher than the mean BMI for obese subjects in prior
studies. We hope this will give clinicians more representative
information with which to make treatment decisions for their
patients.
Another important aspect of our study is our inclusion of
the total motile sperm count of the inseminate, which did not
vary significantly between the different female BMI cate-
gories. Although we did not assess partner BMI, the finding
that total motile sperm count of the inseminate did not differ
between groups is valuable as previous studies (20, 21) have
shown that decreased total motile sperm counts negatively
impacts IUI success. The impact of male obesity on sperm pa-
rameters is not yet clearly understood in the literature, as
VOL. 115 NO. 1 / JANUARY 2021
Fertility and Sterility®
studies differ on the impact of high BMI on sperm parameters
(22–25).
At present results have been mixed on whether and how
obesity impacts IUI success. Several previous studies (26–31)
have also found that obesity does not have a negative impact
P value on cycle fecundity in superovulation with IUI treatment. In
fact, there has also been a study (32) indicating that
overweight and obese patients have a higher fecundity than
.968 normal-weight women when undergoing controlled ovarian
.882 hyperstimulation with IUI. One possible explanation is that
.001 the positive correlation between BMI and endometrial thick-
< .001
.013 ness may give women with more adipose tissue an advantage
.145 as endometrial development is associated with IUI success
(31). Other reproductive issues that are common in obese
women, such as anovulation or ovulatory subfertility, might
be overcome with the use of ovulation induction or superovu-
lation agents. These agents may help to even out the likeli-
hood of pregnancy between women with a normal BMI and
those with obesity when using IUI. Another possibility is
considering that IUI overall has a lower success rate than
IVF, and that many women will choose to move on to IVF
if they do not have success with IUI after several cycles.
More investigation is needed into why obesity does not
impact live birth with use of IUI when it clearly impacts IVF
success.
Other studies (14, 33, 34) have found negative effects of
female obesity on IUI and IVF treatment success. In other
studies (13, 35) of ovulation induction and therapeutic oocyte
donation, women with obesity have been shown to suffer
from more adverse pregnancy outcomes, including missed
and spontaneous abortions. Whereas a few older studies
(36, 37) have suggested that weight loss may improve the
probability of having a live birth for women with obesity, ran-
domized controlled trials (38, 39) have not shown weight loss
to improve live birth. Although our study did not assess
whether weight reduction or lifestyle changes altered out-
comes, we did find that women with an elevated BMI had
an increased incidence of biochemical pregnancy, in compar-
ison to women with a normal BMI.
The increased volume of distribution in obese individuals
compared with individuals of normal BMI has been shown to
affect the pharmacokinetics of various medications and the
measurements of endogenous and exogenous hormones,
including b-hCG and progesterone (40–44). Our finding of
increased biochemical pregnancies in women with obesity
has led us to speculate that this may be due to a relatively
lower concentration of b-hCG and progesterone in these
individuals, leading to early pregnancy loss. Consideration
should be made for a future study to assess the impact of
progesterone supplementation on biochemical pregnancy
rates in the obese population undergoing IUI treatments.
Our study is limited in that the data are from a single cen-
ter with a predominantly white population and thus the re-
sults may not be applicable to more diverse populations. For
example, the risk of miscarriage and the likelihood of success
with assisted reproductive technologies has been reported to
vary by race and/or ethnicity (45, 46). Thus, future studies
should assess the effect of obesity on live birth rate after IUI
in a more diverse population. From the standpoint of
225
ORIGINAL ARTICLE: INFERTILITY
infertility pathophysiology, however, our study group was
very heterogeneous, making our findings more widely appli-
cable to unspecified IUI populations. In conclusion, although
women with obesity may have a higher risk of biochemical
pregnancy after IUI, having a BMI R25.0 kg/m2 or R30.0
kg/m2 does not appear to have a negative effect on live birth
rate after infertility treatments that include IUI.
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ORIGINAL ARTICLE: INFERTILITY

Efecto del índice de masa corporal en el exito del ciclo de inseminaci

on intrauterina.
Objetivo: determinar si el índice de masa corporal (IMC) afecta el exito del tratamiento de inseminaci
on intrauterina.
~o: Estudio retrospectivo de cohorte.
Disen
Entorno: Centro medico academico.
Paciente(s): Un total de 3,217 ciclos de tratamiento de inseminaci
on intrauterina en 1,306 pacientes.
Intervencion(es): Ninguna.
Principales medidas de resultado: El resultado primario fue la tasa de recien nacidos vivos estratificada por el IMC. Los resultados
secundarios incluyeron las tasas de embarazo clínico (definido como un embarazo intrauterino con un latido cardíaco presente en la
ecografía), gestaci
on m
ultiple, embarazo bioquímico, aborto retenido, ect
opico y aborto espontaneo.
Resultado(s): Las mujeres con un IMC de 25 a 29.99 kg/m2 o R 30 kg/m2 tenían la misma probabilidad de tener un nacido vivo que las
mujeres con un IMC normal. Las mujeres con un IMC R 30 kg/m2 tenían una probabilidad mayor de embarazo bioquímico que las
mujeres con un IMC normal.
Conclusion(es): Un IMC entre 25 y 29.99 kg/m2 o R 30 kg/m2 no parece tener un efecto negativo sobre los nacidos vivos despues de la
inseminacion intrauterina. La obesidad puede estar asociada con un mayor riesgo de embarazo bioquímico despues de la inseminacion
intrauterina.

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