Prayer Influence the Success of in Vitro
of a Masked, Randomized Trial
Kwang Y. Cha, M.D., Daniel P. Wirth, J.D.,
M.S., and Rogerio A. Lobo, M.D.
To assess the potential effect of intercessory
prayer (IP) on pregnancy rates in women being
treated with in vitro fertilization–embryo
DESIGN: Prospective, double-blind, randomized
clinical trial in which patients and providers
were not informed about the intervention. Statisticians
and investigators were masked until all the data
had been collected and clinical outcomes were
known. The setting was an IVF-ET program at Cha
Hospital, Seoul, Korea. IP was carried out by
prayer groups in the United States, Canada and
Australia. The investigators were at a tertiary
medical center in the United States. The patients
were 219 women aged 26–46 years who were consecutively
treated with IVF-ET over a four-month period.
Randomization was performed after stratification
of variables in two groups: distant IP vs. no
IP. The clinical pregnancy rates in the two groups
were the main outcome measure.
After clinical pregnancies were known, the data
were unmasked to assess the effects of IP after
assessment of multiple comparisons in a log-linear
model. The IP group had a higher pregnancy rate
as compared to the no-IP rate (50% vs. 26%, P=.0013).
The IP group showed a higher implantation rate
(16.3% vs. 8%, P=.0005).
Observed effects were independent of clinical
or laboratory providers and clinical variables.
A statistically significant difference was observed
for the effect of IP on the outcome of IVF-ET,
though the data should be interpreted as preliminary.
(J Reprod Med 2001;46:781–787)
Keywords: fertilization in vitro,
embryo transfer, prayer, complementary medicine,
data suggest a benefit of IP
vitro fertilization–embryo transfer (IVF-ET)
has emerged over the last 20 years as a viable
option for the treatment of infertility. While
the pregnancy rate was low in the first decade,
in recent years the success rate has been increasing.
The pregnancy rate for IVF-ET increased from 20.7%
deliveries per retrieval in 19841 to
28% in 19972 (the last United States
survey). Several factors have contributed to the
increased success of IVF-ET.3-6 Among
these are the greater experience of the clinical
teams and the use of certain regimens, such as
with a GnRH agonist.7 However, it is
generally agreed that advances in the laboratory
that result in good-quality embryos are perhaps
the most significant reason why the success rate
of IVF-ET has increased5,8 Variations
between the practices of physicians also has been
suggested as influencing success rates,9
as have biologic factors, such as cycle-to-cycle
variability. These factors warrant further assessment
by prospective, randomized trials.
of alternative or complementary medicine has been
increasing in popularity.10 These approaches
include the use of healing touch and prayer, with
several reports suggesting a potential therapeutic
benefit in a variety of disorders.11,12
However, from an evidentiary medical perspective,
these reports have not been substantiated.13
Specifically, intercessory prayer (IP) has been
studied, and while preliminary experiments have
been interpreted as suggesting a possible improvement
in patients with heart disease and AIDS,14,15
a recent review of the literature does not indicate
any conclusive benefit overall.16 However,
a recent study17 suggested benefit
for patients with heart disease, and another,18
the benefits of distal healing.
data demonstrate a 50%
statistically significant pregnancy rate
in the IP treatment group....
There have been no studies,
to our knowledge, on the application of IP to
the treatment of infertility. Therefore, we carried
out a prospective, randomized, double-blind study
in which the efficacy of IP was assessed in patients
undergoing treatment for IVF-ET who were unaware
of the study. We chose the setting of IVF-ET in
order to control for as many variables as possible
and designed the study to be masked to patients,
providers and investigators. In planning and conducting
this trial in as rigorous a fashion as possible,
we set out with the expectation that we would
show no benefit of IP. None of the authors are
employed by religious organizations, and we were
not asked by any religious groups to conduct this
trial, nor did we seek religious advice at any
Materials and Methods
hundred nineteen women aged 26–46 (mean, 33.9±4.7)
with weight 41–72 kg (mean, 54.7±5.2) were prospectively
but blindly enrolled into this randomized trial.
These women were consecutively treated between
December 1998 and March 1999. They were candidates
for IVF-ET; we did not consider patients destined
for tubal transfer (zygote or gamete intrafallopian
transfer). These patients were being seen at the
Cha General Hospital, Seoul, Korea. Twenty of
the 219 cases had incomplete data available due
to fragmentary E-mail transmission and were eliminated
from further consideration prior to randomization.
Patients beginning the cycles were ultimately
stratified based on: (1) age, (2) length of infertility,
(3) type of infertility, and (4) number (if any)
of prior attempts (all cases considered unless
tubal transfer was scheduled). They were then
randomized into two equal groups (described below)
to test the potential effects of IP. Patients
and their providers did not know that they were
participating in this study. Randomization and
data transmission for IP or no IP (described below)
were the responsibility of an independent statistician
in Korea and another in the U.S. who was not affiliated
with the authors. Randomization codes were made
available only when all pregnancy data were available
at completion of the study.
Protocol (IVF-ET and IP)
patients were treated with an identical protocol
including the use of a GnRH agonist and gonadotropins
(usually 3–75 IU ampules/d) until at least three
follicles were mature. ET was carried out three
days after retrieval.
study examined the effect of a combination of
directed and nondirected distant petitionary,
or intercessory, prayer (IP) with patients undergoing
IVF in a two-tier system. Petitionary or intercessory
prayer is prayer participants’ requesting God’s
intervention or assistance for the benefit of
another individual.19 Directed IP is
praying for a specific outcome for an individual
or individuals—i.e., prayers for conception.20
All prayer participants in this study were of
various Christian denominations. There were two
tiers of prayer groups. Tiers 1 and 2 each consisted
of four blocks of prayer participants (A–D). Most
intercessors were known by one of the authors
(D.P.W.), and others were referred by known intercessors.
Within each block (A–D), intercessors knew each
other. Prayer participants in tier 1 prayed in
a directed manner with a specific intent to increase
the pregnancy rate of the patients. Tier 2 prayer
participants prayed in a directed manner for tier
1 prayer participants with the intent to increase
their prayer efficacy.
patients were assigned to these prayer groups
after randomization. For each treatment session,
members of one prayer block in each tier randomly
received a single sheet of paper with five IVF
patients’ pictures (a treatment unit) and were
asked to pray for these patients. Prayer for a
treatment unit commenced within five days of initial
hormone injection and continued for three weeks.
Tier 1A participants prayed in a directed manner
with the intent to increase the rate of pregnancy
for each group of five patients, and tier 2A participants
prayed in a directed manner for tier 1A prayer
participants with the intent to increase the efficacy
of prayer intervention and in a nondirected manner
for the patients with the intent that God’s will
or desire be fulfilled in the life of the patient.
The groups of four blocks with two tiers each
were distributed in three countries, and each
group was composed of 3–13 participants. In addition
to the above, a separate group of three individuals
prayed in a general, nonspecific manner with the
intent that God’s will or desire be fulfilled
for the prayer participants in tiers 1 and 2.
pictures and informational data, which are routinely
obtained for all infertility patients, were collected
at the Cha Medical Center during the trial dates
by an independent statistician and transmitted
to the United States via E-mail. E-mail was log-in
and password protected, and the password was changed
on a regular basis.
pictures of treatment patients, for those patients
randomized after stratification to IP, were pooled
and divided into units of five pictures per unit.
Five was an optimum number for this visual display.
Each treatment unit of five pictures was digitally
assembled onto one page and transmitted to the
prayer participants via asynchronous facsimile
transmission or express mail. Transmissions occurred
electronically over secured systems and were sent
only to prayer groups. No patient-identifying
data (names, ages, etc.) were included. As stated
above, prayer for a single treatment unit commenced
within five days of initial hormone injection
and continued for three weeks such that all patients
randomized to IP had the intervention throughout
the course of IVF-ET treatment.
were randomly divided after stratification of
infertility status by computer allocation into
treatment and control groups consisting of IP
and no intercessory prayer (NIP), respectively.
Figure 1 is the flow diagram of the randomized
experimental protocol for this study was approved
by the internal review board of Cha General Hospital.
Intercessory prayer was carried out in the United
States, Canada and Australia without knowledge
of the providers or patients.
patient was informed about this study. After the
independent Korean statistician retrieved the
data and transmitted it to the U.S. a second independent
statistician in the U.S., randomized subjects
and transmitted pictures to the prayer groups
in different countries for subjects randomized
to IP. The prayer groups had only pictures and
did not have any patient information. Once pregnancy
data were available for all the subjects over
this trial period, these data were transmitted
to the independent statistician in the U.S. to
compile the results. The compiled results were
then seen by the authors for the first time.
Participant Flow and Follow-up
randomization, 16 patients had their cycles cancelled,
and 14 cases did not result in ET. These 30 cases
did not result in ET. Eighteen cases were eliminated
from the NIP group and 12 from the IP group. The
number of patients eliminated from each group
was not statistically different. We therefore
had 169 completed cases available for analysis
1 Flow chart of 219 women
aged 26–46 planning IVF-ET randomized to IP
vs. NIP. In groups of five, pictures of patients
randomized to IP were sent to prayer groups
in tiers 1 and 2.
cases were eliminated after we had pregnancy data
available for the 169 patients who had undergone
IVF-ET. The 169 cases that had been randomized
were divided into 88 having IP and 81 with NIP.
Their ages, duration of infertility and number
of prior attempts at IVF-ET were similar (Table
I). Once pregnancy data were available, the study
was completed. Patients were not informed about
the study or results.
data were subjected to multiple comparisons in
a log-linear model. The end point in this study
was a clinical pregnancy defined by an intrauterine
fetal pole with a heartbeat on ultrasound. Possible
confounders were taken into account in a stepwise
fashion, where we used a model of logistic regression.
Data were analyzed using ANOVA and the least squares
method. The sole outcome of the study was the
pregnancy rate. No sample size could be projected
because there have been no previous such studies.
their treatment cycles, the groups (IP and NIP)
had similar numbers of oocytes retrieved (11.4±7
vs. 10.0±5.9) (Figure 2), numbers of oocytes fertilized
(8.9±6 vs. 7.7±4.9) and preembryos transferred
(4.3±1.2 vs. 4.3±1.4). The IP group, however,
had a significantly higher pregnancy rate as compared
to the controls (44/88, 50% vs. 21/81, 26%; P=.0013)
(Table I, Figure 2). After seven weeks of pregnancy
there were three spontaneous losses in the NIP
group and three in the IP group. All other pregnancies
delivered at term, and obstetric outcomes were
similar in the two groups. Adjusting for the pregnancy
loss data, the term pregnancy rates were 22.2%
in the NIP group and 46.6% in the IP group (P<.001).
2 Number of oocytes retrieved
and percentage pregnancy rate per ET in the
control (NIP) and treatment (IP) groups. NS=no
significance in the number of oocytes retrieved
in the two groups. *Significantly higher pregnancy
rate with IP (P<.0013).
following variables were assessed using logistic
regression: age, duration of infertility, type
of infertility and number of prior attempts. None
of these variables affected the pregnancy rate.
The adjusted odds ratio for pregnancy (IP vs.
non-IP) was 3.3 (95% CL, 1.6–6.6).
of the number of oocytes retrieved are in Table
II. The fertilization rates were similar, but
the cleavage rate was higher in the IP group after
adjustment for variables (73% vs. 69%, P<.0269).
The unadjusted cleavage rate was of borderline
significance (P<.07). The implantation
rate was significantly higher in the IP group
(16.3% vs. 8%, P=.0005). The number of
multiple pregnancies was also higher in the IP
group (17% vs. 4.9%, P=.0126).
higher rate of pregnancies in the IP group was
independent of the type of infertility. The rate
in the tubal factor group was 26/51 (51%) for
IP vs. 11/43 (26%) for NIP (P=.0125); in
the nontubal-factor group the rate was 18/37 (49%)
vs. 10/38 (26%) (P=.0470).
in the two groups were analyzed according to various
age groups: <30, 30–39 and >39. There was
a consistent statistically higher pregnancy rate
for IP in the 30–39-year group and in the >39-year
group but not in the <30-year group. IP vs.
NIP in the 30–39-year group was 51% (29/57) vs.
23% (14/62) (P=.0013), 42% (5/12) vs. 23%
(3/13) in the >39-year group and 53% (10/19)
vs. 67% (4/6) in the <30-year group. We could
not identify a difference in pregnancy rates in
women <30, in whom the pregnancy rates were
with the higher implantation rate in the IP group,
a greater number of preembryos reached the eight-cell
stage in the IP group (66% vs. 45.5%, P=.0001).
At the time of ET there were fewer preembryos
at the five- to seven-cell stage in the IP group
(14.5% vs. 28.6%, P=.0001) and more seven-
to eight-cell embryos in the IP group (69.2% vs.
49.6%, P=.0001). Morphologic grading of
embryos in the two groups did not differ significantly.
overall pregnancy rate for IVF-ET during the study
(December 1998–March 1999) was 38.5% when all
pregnancies (both groups) were taken into account.
This rate was similar to the historical rate for
the center’s program; the rate during the preceding
months, January–November 1998, was 32.8%. Data
were analyzed for each of the seven clinician
providers who carried out procedures during the
treatment period. The total pregnancy rates for
the six providers were similar and ranged from
36% to 50%. One provider had only 18 cases and
an 11% pregnancy rate. For each of the other six
providers, the pregnancy rates for the IP group
vs. NIP were 46% vs. 38%, 60% vs. 33%, 57% vs.
22%, 53% vs. 25%, 36% vs. 36% and 67% vs. 22%.
The clinical protocols were all identical. The
number of embryos transferred and the cleavage
stages of the embryos were similar in the cases
carried out by the seven providers. There were
no changes in the schedules of the team of three
embryologists, who all participated equally in
the cases during this time, and there were no
changes in the laboratory protocols or techniques
or new batches of reagents or media used.
of known male factor, 41 of the 169 patients had
intracytoplasmic sperm injection (ICSI) performed
at the time of their cycles. The pregnancy rate
in the two groups were not significantly different,
IP 11/24 (46%) vs. NIP 9/17 (53%). Nevertheless,
in the couples not receiving ICSI, the IP group
had a higher pregnancy rate (33/64, 52% vs. 12/64,
factors are known to either positively or negatively
affect the success of IVF-ET procedures. The majority
of physicians trained in allopathic medicine,
however, would not consider prayer intervention
to be one of them.21 This was our view
in designing this trial. The findings of this
study suggest, however, that the inclusion of
prayer intervention in the treatment protocol
may provide a significant impact upon the success
of IVF-ET in women over age 30. This is demonstrated
by the IP treatment group, which exhibited statistically
increased pregnancy rates for two categories of
IVF patients who traditionally demonstrate decreased
pregnancy rates, patients 30–39 years of age and
those >39. Randomization took into account
such variables such as type of infertility. The
overall treatment success during the time of the
study was in line with the current rates of the
findings of this study are enhanced by the utilization
of a methodologic design that eliminated belief,
expectation and a placebo effect as confounding
variables.22 The fact that patients
and clinician providers were unaware of the existence
of the study and the investigators were also kept
blind to treatment and control groupings ensured
isolation of the treatment intervention. Further
design restrictions ensured that prayer participants
were from a different country and had no information
about the IVF patients, thereby eliminating any
confounding effect or bias.
data suggest that the higher pregnancy rates in
the IP group occurred as a result of increased
implantation in that the oocyte yield and fertilization
rates were comparable, as were the numbers of
preembryos transferred. IP began early in the
ovarian stimulation cycle, and there were no effects
of it on the characteristics of the cycle. Because
this experiment required a uterine ET, most patients
who were candidates for this study had evidence
of tubal disease. Although our data suggest an
effect of IP on implantation, we cannot speculate
further about a mechanism for this observation.
We are highly cognizant of multiple unknown variables,
which might affect pregnancy rates.
only two groups who did not show any benefit from
IP by subanalysis were couples undergoing ICSI
and women <30. At least two possibilities may
exist to explain this discrepancy: the smaller
number of subjects in these groups and the high
pregnancy rates. A minority of patients, 25, were
under 30. Similarly, only 41 couples underwent
ICSI procedures. In both these groups, the pregnancy
rates were extremely high (56% overall in the
<30-year group, 49% with ICSI). A much greater
number of subjects would have been needed to show
an effect if there was one. Further, in randomization
of the 25 women <30 years in whom the pregnancy
rates were similar, there were more women (n=19)
in the prayer group. Nevertheless, these pregnancy
rates were extremely high and not statistically
different. Age was not a confounding variable
in these data.
data demonstrate a 50% statistically significant
pregnancy rate in the IP treatment group; it was
well above the 26% pregnancy rate in the control
group, which in turn was similar in the crude
pregnancy rate for this IVF program during the
time period. The 50% pregnancy rate is also statistically
higher than the overall pregnancy rate in the
program for the year before the trial period (32.8%).
However, we view these data as preliminary. We
are keenly aware of the multiple biologic factors
and unknown variables inherent in the treatment
process of IVF-ET.23,24 Nevertheless,
confidence in pursuing future work in this area
is enhanced by the unique prospective, double-blind
protocol utilized. Imperative to the integrity
of this protocol was the design feature that ensured
that patients and clinician providers were unaware
of the details of the intervention.
this study was approved by the internal review
board, in Korea, the fact that subjects were unaware
of the intervention remains an area of controversy
for future studies but was necessary in our view
to eliminate any bias. Additional factors, which
need to be explored in subsequent studies, include
religiosity and psychological profiles of the
participants, the type and duration of IP, and
the mechanisms explaining the purported benefit.
data suggest a benefit of IP on IVF-ET. However,
we reiterate that we view these data to be preliminary
and that they may not be confirmed in future investigations.
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From the Department of Obstetrics and Gynecology,
Columbia University College of Physicians and
Surgeons, New York Presbyterian Hospital, Columbia-Presbyterian
Center, New York, New York; Cha Hospital, Seoul,
South Korea; and Wirth & Wirth Esq., North
Dr. Cha is Associate Research Scientist.
Dr. Wirth is Attorney with the law firm of Wirth
& Wirth Esq.
Dr. Lobo is Professor and Chairman, Department
of Obstetrics and Gynecology, Columbia University
College of Physicians and Surgeons.
Address reprint requests to: Rogerio A. Lobo,
M.D., Department of Obstetrics and Gynecology,
Columbia University College of Physicians and
Surgeons, 622 West 168th Street, New York, NY
Financial Disclosure: The authors have
no connection to any companies or products mentioned
in this article.
The Journal of Reproductive Medicine®,
Journal of Reproductive