Does Psychological Stress Affect the Outcome of Ivf

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similar levels of state and trait anxiety. In another study, high

levels of anxiety and stress did not predict an adverse preg-

nancy outcome (Milad et al., 1998).

In contrast, other studies found an association between psy-

chological stress and the results of in vitro fertilization. In

these studies, the dependent variable was the outcome of IVF,

either as pregnancies or births. The independent variables were

anxiety (Demyttenaere et al., 1989, 1992, 1994; Merari et al.,

1992, 1996; Boivin and Takefman, 1995; Csemiczky et al.,

2000; Smeenk et al., 2001; Lancastle and Boivin, 2005),

depression (Reading, 1992; Merari et al., 1992, 1996; Smeenk

et al., 2001), coping patterns or coping resources (Demyttenaere

et al., 1992; Merari et al., 1992, 1996; Boivin and Takefman,

1995), psychosocial interventions ( Boivin, 2003), baseline and

procedural stress (Klonoff-Cohen et al., 2001), marital satis-

faction (Boivin and Takefman, 1995; Merari et al., 1996), per-

sonality (Kemeter, 1988), intensity of the child-wish (Stoleru

et al., 1996), sperm quality related to psychological stress

(Harrison et al., 1987; Ragni and Caccamo, 1992), participa-

tion in psychotherapy (Brandt and Zech, 1991), and vulnerabil-

ity to psychological stress (Facchinetti et al., 1997).

However, support for a causal relationship between psycho-logical stress and results of IVF is often weak. Few studies

indicating an association between psychological stress and IVF

outcome have tried to control for known confounders. In addi-

tion, the number of women included has often been low.

Thus, several studies have shown certain physiological

markers such as age, duration of infertility, number of earlier

failed IVF cycles, tubal indication for infertility, previous preg-

nancies, number of good quality embryos transferred and

number of oocytes to be independent predictors of IVF out-

come (Stolwijk et al., 1996; Templeton et al., 1996; Strandell

et al., 2000).

The aim of the present study was to investigate the effect

of psychological stress before and during IVF treatment onthe outcome of IVF, controlling for known physiological

predictors. The hypothesis was that psychological stress

may have a negative influence on the results of IVF. Psy-

chological stress is expressed here as a low level of general

psychological well-being including experienced negative

psychological effects of infertility, negative effects of infer-

tility on the woman’s relationship with her partner, high

intensity of the child-wish, experiencing infertility as a threat

to a positive self-picture, experiencing life as meaningless

and feeling little affinity with others, and a major difference

between an ideal life situation and the way the woman experi-

ences the life she is living.

Materials and methods

Design

This is a prospective, longitudinal study of women during their first

IVF cycle at Sahlgrenska University Hospital, Göteborg, Sweden. The

women were recruited between March 1999 and June 2002 from the

Reproductive Unit, Department of Obstetrics and Gynaecology. They

answered questionnaires concerning psychological and social factors

on two occasions during the IVF treatment. The study was approved

by the ethics committee at Göteborg University.

Subjects

Two hundred women planning to start their first IVF/ICSI treatment

were invited to participate in the study. Before their first visit to the

clinic, the women received a letter with information about the study.

Following an information meeting at the clinic, the women were

asked if they were interested in participating. The exclusion criteria

were inadequate knowledge of the Swedish language and participation

in other studies. A total of 166 women agreed to participate in the

study. The main reasons for not participating in the study were lack of

interest, considering the treatment too demanding, and not wantingany more obligations. The mean age of those who declined to particip-

ate in the study was 32.3 years and did not differ significantly from

that of participants. The pregnancy rate per started cycle among

women not participating in the study was 38.2%, which did not differ

significantly from the rate of those who participated (34.9%).

The demographic data for all women who received embryo transfer,

obtained from the women’s medical records, are presented in Table I.

The mean age of the women was 32.1 years. The majority (89.9%)

were working, 37.4% had a university/college level education, and

68.3% lived in urban areas. Among the women, 13% were smokers.

The cause of infertility was male factors in 41.7%, while the remain-

ing cases involved female factors, unknown factors and mixed factors.

Five women had a psychiatric history such as earlier depression, psy-

chosis, anxiety or anorexia. Somatic diseases such as diabetes,asthma, epilepsy, gastro-intestinal disorders and gynaecological dis-

eases such as endometriosis were observed frequently.

IVF treatment

All women were treated using a stimulation procedure including down-

regulation with a GnRH agonist according to a long protocol starting

either in the follicular phase or the luteal phase (1.2 mg/day nasally or

1.0 mg/day as a subcutaneous injection; Suprecur or Suprefact;

Hoechst, Frankfurt, Germany). Down-regulation was followed by stim-

ulation with recombinant FSH (Gonal-F, Serono, Geneva, Switzerland

or Puregon, Organon, Oss, Netherlands). Monitoring was carried out by

vaginal ultrasound scans and serum estradiol measurements. When ade-

quate stimulation was achieved (≥3 follicles of ≥18 mm diameter),

10,000 IU HCG (Profasi, Serono) was administered.

Fertilization was performed by conventional IVF or by ICSI follow-

ing standard techniques. In general, two embryos were transferred two

or three days after oocyte retrieval using a Wallace or a Frydman cathe-

ter. Luteal support was given either with s.c. HCG or with progesterone

(i.m. or vaginally). Additional embryos of good quality were cryopre-

served and replaced later. Pregnancy was defined as a positive HCG test

in urine on day 19 post-transfer. Clinical pregnancy was defined as

ultrasound verified pregnancy 5 weeks after embryo transfer.

Measures

The women answered extensive questionnaires concerning psy-

chological factors. The first questionnaire was filled in directlyafter the information meeting one month before onset of down-

regulation, and the second questionnaire one hour before

oocyte retrieval. The questionnaires included the following.

First occasion of measurement

Psychological well-being

General psychological well-being during recent weeks was

measured by the Psychological General Well-Being (PGWB)

index (Dupuy, 1984). PGWB contains 22 items with six response

alternatives (1–6). The higher the value, the better the well-being.



Psychological stress of in vitro fertilizati

297

In addition to a total score for the index, there are sub-scores for

anxiety, depressed mood, positive well-being, self-control, gen-

eral health and vitality. In the current study, we focused on the

total score and two sub-scores—depressed mood and anxiety.

The scale has been translated into Swedish and tested on

Swedish patients (Dimenäs et al., 1996). PGWB has shown

satisfactory reliability and validity (Dupuy, 1984; Naughton

and Wiklund, 1993).

In addition to the well-evaluated PGWB, psychological

effects of infertility were measured by 14 items (guilt, success,

anger, contentment, frustration, happiness, isolation, confid-

ence, anxiety, satisfaction, depression, powerlessness, compe-

tence and control). These items were devised for the present

study and seek to capture aspects of experiences oftenexpressed by infertility patients. The items were formulated as

questions like ‘How much of the following feelings do you

experience during the present days: guilt, success, etc?’. The

items were analysed separately.

Each item was graded from 1 to 5. Low figures indicate

well-being.

Relationship with her partner

The effects of infertility on the woman’s relationship with her

partner were estimated by two questions: (i) do you feel that

infertility has caused problems in your marriage? and (ii) do you

find it harder to talk to each other now than before? These items

were also graded from 1 to 5 (1 = not at all, 5 = very much). Intensity of the child-wish

The strength of the child-wish was estimated by seven ques-

tions [visual analogue scale (VAS)] covering perceptions of

the woman’s own wishes (six questions) and of the expecta-

tions of others (one question).

Meaning of reproduction

The meaning of reproduction was estimated by six items (VAS)

covering aspects of self-picture, meaningfulness and affinity

(Möller and Fällström, 1991).

Difference between the ideal and the real-life situation

Seven items were formulated concerning the woman’s perce

tions of the correspondence between how she wanted her life

be and how she thought it was. The answers were given on

VAS. The items covered work, leisure time, social contac

with friends and relatives, relation with her partner, sexual lif

and life in general.

Optimism versus pessimism

Optimism/pessimism was captured by two questions: (i) wh

do you think about the results of the treatment you are about

start? And (ii) how do you describe yourself, as an optimist

a pessimist? The answers were given on a VAS.

Second occasion of measurement

The same 14 items regarding psychological effects of inferti

ity were assessed as at the first measurement occasion. Th

same two questions regarding the relationship were asked as

the first measurement occasion.

Subgroups

The following subgroups were analysed in relation to pregna

versus non-pregnant:

(i) those with scores on the PGWB in the lowest quartil

i.e. those who experienced the poorest psychological we

being (n = 39);

(ii) those with scores for psychological effects of infertility

the highest quartile at the second measurement occasion, i.e. tho

who experienced the most negative effects of infertility (n = 35)

(iii) those who answered ‘no’ to the question as to wheth

they could consider an alternative to IVF (n = 36);

(iv) a combination of groups 1–3 (n = 8).

Statistics

Means, standard deviations, medians and ranges are descriptiv

statistics. Continuous and ordered variables were compared b

Table I. Background variables for pregnant and non-pregnant women in patients receiving embryo transfer

*One woman in the pregnant group and nine women in the non-pregnant group had previously undergone 1–3 IVF-cycles at a private IVF clinic.

Pregnant (n = 58) Non-pregnant (n = 81) P

Age (years), mean (SD) (range) 32.2 (3.4) (25.0–38.0) 31.9 (3.7) (24.0–43.0) 0.Duration of infertility (years), mean (SD) (range) 4.7 (2.6) (1.5–17.0) 4.2 (2.1) (1.5–12.0) 0.Waiting period for IVF-treatment (months), mean (SD) (range) 18.6 (9.0) (2.0–48.0) 17.6 (8.2) (2.0–36.0) 0.No. of previous IVF cycles,* mean (SD) (range) 0.02 (0.13) (0.0–1.0) 0.17 (0.54) (0.0–3.0) 0.Cause of infertility, n (%)

Male 24 (41.4) 34 (42.0) 1.Female 34 (58.6) 47 (58.0)

No. of women with previous pregnancies, n (%) 22 (37.9) 31 (38.3) 1.No. of women with children in earlier relationship, n (%) 6 (10.3) 10 (12.4) 0.No. of women with current somatic disease, n (%) 12 (20.7) 31 (38.3) 0.No. of women with previous somatic disease, n (%) 5 (8.6) 12 (14.8) 0.No. of women with current psychiatric disorder, n (%) 3 (5.3) 2 (2.5) 0.Smoking, n (%) 5 (8.6) 13 (16.0) 0.College/university,n (%) 19 (32.8) 33 (40.7) 0.Urban residence, n (%) 41 (70.7) 54 (66.7) 0.Rural residence, n (%) 17 (29.3) 27 (33.3) 0.Working, n (%) 53 (91.4) 72 (88.9) 0.Studying, n (%) 2 (3.5) 6 (7.4) 0.Unemployed, n (%) 3 (5.2) 2 (2.5) 0.



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the Mann–Whitney U -test, dichotomous variables by Fisher’s

exact test and the Mantel–Haenszel χ2 test for the variable

number of previous IVF cycles. A stepwise forward logistic

regression analysis was performed for the dependent variable

clinical pregnancy. Variables with P < 0.1 in the univariate

analysis were included in the model. All significance tests

were two-sided and performed at a significance level of 0.05.

ResultsDemographic and treatment variables for the pregnant and

non-pregnant groups are shown in Tables I and II. No differ-

ences between pregnant and non-pregnant women were found

regarding age, length of infertility or number of previous preg-

nancies/previous births. The total number of good quality

embryos, the number of good quality embryos transferred, and

the number of embryos transferred were significantly higher in

the pregnant than in the non-pregnant group (Table II).

All 166 women answered the first questionnaire and 151

women answered the second questionnaire. In seven patients,

the IVF cycle was cancelled before oocyte aspiration due to

poor ovarian response. Embryo transfer was performed in 139

(83.7%) out of 166 patients. Reasons for not reaching embryo

transfer were: risk of ovarian stimulation syndrome (n = 3);

fertilization failure (n = 3); bad quality embryos (n = 12); and

freezing of all embryos due to myoma uteri or intrauterine pol-

yps that had not been detected earlier (n = 2).

First measurement occasion

Psychological well-beingPGWB results did not differ between pregnant and non-pregnant

women. In general, PGWB values were comparable with

Swedish reference values (Dimenäs et al., 1996) reflecting that

the women starting IVF treatment were in good psychological

health.

When analysing each of the 14 items in the questionnaire

concerning the psychological effects of infertility, no signific-

ant difference was found. The mean scores for each of the 14

items were mainly in the middle of the scale (Table III). How-

ever, there was considerable variation between individual

women.

Table II. Treatment variables for pregnant and non-pregnant women in patients receiving embryo transfer

Pregnant (n = 58) Non-pregnant (n = 81) P

IVF, n (%) 26 (44.8) 33 (40.7) 0.73ICSI, n (%) 32 (55.2) 48 (59.3) 0.60No. of oocytes aspirated

mean (SD) 12.7 (5.3) 12.6 (6.9) 0.48median (range) 12.0 (2.0–28.0) 12.0 (2–35.0)

No. of good quality embryos totalmean (SD) 4.4 (2.9) 3.6 (3.0) 0.04median (range) 4.0 (1.0 – 12.0) 3.0(0.0–12.0)

No. of good quality embryos transferredmean (SD) 1.9 (0.3) 1.6 (0.7) 0.001median (range) 2.0 (1.0–2.0) 2.0 (0.0–2.0)

No. of embryos transferredmean (SD) 1.9 (0.3) 1.8 (0.4) 0.05median (range) 2.0 (1.0–2.0) 2.0 (1.0–2.0)

Table III. Psychological variables for pregnant and non-pregnant women in patients receiving embryo transfer

Pregnant (n = 58) Non-pregnant (n =81) P

Mean (SD) (range)

PGWBTotal for items 1–22 100.9 (14.0) (62–120) 100.3 (15.9) (53–127) 0.89Depressed mood 15.4 (2.2) (9.0–18.0) 15.5 (2.5) (4.0–18.0) 0.53Anxiety 21.0 (4.7) (9.0–29.0) 21.8 (4.8) (8.0–30.0) 0.32

Effect of infertility, the first measurementGuilt 1.5 (0.7) (1.0–4.0) 1.4 (0.6) (1.0–3.0) 0.35Success 3.1 (0.8) (2.0–5.0) 3.0 (1.0) (1.0–5.0) 0.32Anger 2.1 (1.0) (1.0–4.0) 2.2 (1.1) (1.0–5.0) 0.79Contentment 3.1 (0.9) (1.0–5.0) 3.0 (1.0) (2.0–5.0) 0.44Frustration 3.0 (1.1) (1.0–5.0) 2.8 (1.2) (1.0–5.0) 0.24Happiness 2.5 (0.8) (1.0–4.0) 2.6 (1.0) (1.0–5.0) 0.98Isolation 1.5 (0.9) (1.0–4.0) 1.5 (0.9) (1.0–5.0) 0.67Confidence 2.4 (0.8) (1.0–5.0) 2.2 (0.9) (1.0–5.0) 0.15Anxiety 2.9 (3.0) (1.0–5.0) 2.7 (1.1) (1.0–5.0) 0.48Satisfaction 2.8 (0.8) (1.0–5.0) 2.9 (0.9) (1.0–5.0) 0.62Depression 1.8 (0.9) (1.0–4.0) 1.8 (1.0) (1.0–5.0) 0.84Powerlessness 2.9 (1.2) (1.0–5.0) 2.8 (1.3) (1.0–5.0) 0.76Competence 2.9 (1.0) (1.0–5.0) 2.8(1.1) (1.0–5.0) 0.68Control 2.9 (0.9) (1.0–5.0) 3.0 (0.9) (1.0–5.0) 0.34




297

There were no differences between women who got preg-

nant and those who did not with regard to the relationship with

her partner, intensity of the child-wish, meaning of reproduc-

tion, difference between ideal and real-life situations, and opti-

mism versus pessimism. For problems in the marriage, we

found a mean of 1.5 (SD 0.8) (range 1–4) in the pregnant group

versus a mean of 1.6 (SD 0.8) (range 1–4 ) in the non-pregnant

group. Regarding intensity of the child-wish (the sum of six

items), the pregnant women scored a mean of 35.7 (SD 10.0)

(range 14.6–54.9) compared with 34.9 (SD 10.2) (range

13.6–58.3) in the non-pregnant group.

Second measurement occasion

The results of the 14 items covering psychological effects of

infertility and the two questions covering the woman’s rela-

tionship with her partner did not differ between the women

who got pregnant and those who did not. In the pregnant group,

frustration measured a mean of 2.5 (SD 1.2) (range 1.0–5.0)

versus 2.8 (SD 1.4) (range 1.0–5.0) in the non-pregnant group.

The item anxiety scored a mean of 2.8 (SD 1.1) (range 1.0–5.0)

by the pregnant women and a mean of 2.9 (SD 1.2) (range

1.0–5.0) by the non-pregnant.When analysing the subgroups, scores on the PGWB in the

lowest quartile (n = 39), scores for psychological effects of

infertility in the highest quartile (n = 35), those who could not

consider an alternative to IVF (n = 36) and a combination of

these groups (n = 8), no statistically significant differences

were found between the women who got pregnant and those

who did not [PGWB group (P = 0.70), effects of infertility (P =

0.32), those who could not consider an alternative (P = 0.85)

and a combination of the three subgroups (P = 0.46)].

Selected psychological variables in the univariate analysis

are presented in Table III.

A stepwise forward logistic regression analysis was per-

formed for variables that showed a difference at P < 0.1 in theunivariate analysis (number of good quality embryos trans-

ferred, total number of good quality embryos, number of

embryos transferred, number of previous IVF cycles, number

of women with current somatic disease). The only variable that

was significantly associated with pregnancy was the number of

good quality embryos transferred.

Discussion

During IVF treatment, patients frequently ask about the rela-

tionship between psychological stress and IVF outcome. They

often express worries that their own stress might have a nega-

tive influence on the outcome. The results of the present pro-spective study do not indicate any relationship between

perceived psychological stress or perceived psychological

well-being before or during the first IVF treatment and out-

come of IVF. These results can be regarded as reassuring and

can help to decrease the stress experienced by patients.

Our findings are in accordance with some earlier studies

(Harlow et al., 1996; Slade et al., 1997, Ardenti et al., 1999).

However, we had expected to find such a relationship regard-

ing at least some of the variables or for the group of women

who scored in the lowest quartile on the PGWB index and in

the highest quartile for the questions on psychological effec

of infertility. A recent study from the Netherlands (Smeen

et al., 2001) showed that psychological factors were indepen

ently related to treatment outcome. Differences in populatio

and choice of questionnaires may explain these differences.

our study, a relatively large number of patients were include

several different psychological measurements were used, an

the design was prospective. Even when analysing the subgrou

of patients with very high scores for stress, the results chang

only marginally and no significant differences between pre

nant and non-pregnant women were noted.

Analysing all data including those patients not achieving

embryo transfer did not change the overall results

According to the PGWB results and those for other question

the women in this study, as a group, expressed surprising

good psychological well-being prior to the IVF treatmen

although there were large inter-individual differences. Th

finding was somewhat unexpected and did not correspond wi

our earlier clinical impression. One possible reason for th

could be that patients’ answers were more positive than whthey actually experienced, and that they kept their worries an

anxiety to themselves because they had great expectatio

regarding both themselves and the anticipated treatment. Pe

haps they also wanted to show how well they felt and that the

could handle the treatment. It has been reported that infertili

patients suppress their feelings of stress because they want

show the clinic that they are functioning well both socially an

psychologically (Demyttenaere et al., 1998).

Time points for questionnaires could, of course, always b

discussed. The choice of the first measurement was because w

wished to study the psychological status before any appoin

ments at the clinic apart from the information meeting. Th

second measurement was chosen based on our clinical experence that patients often express feelings of anxiety and stre

just before the oocyte retrieval. The day of embryo transfer

certainly also a distressing moment for the patients and perha

it could have been valuable to measure on that occasion.

One of the chosen instruments, PGWB, has proven goo

reliability and validity. It is also sensitive to changes (Dimen

et al., 1996). The other instruments have been devised for th

present study and have not been psychometrically evaluate

The instruments were chosen in order to capture aspects

stress seen in the literature and expressed by infertility patien

One cannot exclude, however, that the failure to find an assoc

ation between psychological stress and outcome of IVF is du

to a lack of sensitivity of the instruments used.Another aspect, at least in Sweden, is the observation th

patients tend to express negative emotions and psychologic

strain in verbal interviews rather than in questionnaires (Sjögre

1989; Forsberg-Wärleby et al., 2002). It could be regarded

more ‘definitive’ and ‘dangerous’ to put experiences of negati

feelings in writing rather than expressing these feelings verbal

in an interview. The tendency to level out one’s responses

more pronounced when filling in questionnaires.

However, it is also true that when IVF treatment is imm

nent, women have great hope for success. Couples have wait



L.Anderheim et al .

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for this possibility for years and their view is that ‘at last’

something concrete and hopeful is going to happen. If this

study had been performed after failed IVF treatments, the

results might have been different.

In conclusion, this study could not demonstrate an associa-

tion between psychological stress and IVF outcome. This

information should be reassuring and should help to reduce

women’s stress and worry during infertility treatment.

Acknowledgements

We would like to thank Nils-Gunnar Pehrsson and Mattias Molin forstatistical assistance. The study was supported by grants from theVardal Foundation and Sahlgrenska Academy.

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Submitted on April 29, 2005; resubmitted on June 17, 2005; accepted July 4, 2005

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