Depression in Women With Infertility

REPRODUCTIVE
PSYCHIATRY
Depression in Women
With Infertility
Lisa A. Catapano, MD, PhD
FOCUSPOINT
Despite the high prevalence of depression,
and of infertility, in women of
childbearing age, the issue of depression
in infertility is inadequately studied
and understood. The majority of people
with infertility do not develop a major psychiatric
disorder, as defined by
The existing
data support a
correlation between
depression and infertility,
but the nature
of the relationship
between the two
is not clear.
The relationship between depression and
infertility is complex. An understanding of
the separate disorders and their treatments,
as well as their interconnections, is
important for improving patient care in
those who suffer from these conditions.
the Diagnostic and Statistical
Manual of Mental Disorders.
Nonetheless, there is evidence
for an increased rate of
major depressive disorder
(MDD) in infertile women,
and lesser degrees of emotional
distress, as well as associated
symptoms such as
anxiety, are common. 1
The nature of the relationship
between depression and
infertility is not clear. Does infertility
cause depression? One
would expect it might, given
the traumatic nature of the
experience. Does depression
cause infertility? There is some
evidence for this as well. Given the frequency
with which these 2 disorders affect women, and
the great morbidity associated with both, it is
critical to understand how each might cause or
Lisa A. Catapano, MD, PhD, is Assistant Professor of Psychiatry,
Department of Psychiatry and Behavioral Sciences,
George Washington University, Washington, DC.
exacerbate the other and how that should guide
treatment.
The risk for MDD in women is greatest during
childbearing years. The overall lifetime risk for
MDD is 16.6% and is significantly higher in
women than in men. 1 Infertility affects about 1
in 7 couples. Approximately 50% of cases are attributed
to female factors, 35% to male factors,
and 10% to unknown causes. This is a significant
change from 2 generations ago, when 50% of infertility
was attributed to unknown causes and
assumed to be due to emotional problems in the
female partner. 2 The availability and success of
fertility treatments have exploded in recent decades.
However, the experience of infertility
continues to be characterized by grief, shame,
and social isolation.
PREVALENCE OF
DEPRESSION IN INFERTILITY
Many women with infertility experience depressive
symptoms, including demoralization,
hopelessness, and guilt. A subset of these
meet the criteria for MDD, which includes
sleep and appetite disturbance, poor energy,
poor concentration, psychomotor retardation,
and in some, suicidal ideation. Few studies
address the prevalence of MDD in infertile
women, and relevant studies are hampered by
the fact that only 50% of people with infertility
actually seek medical treatment. 3 Most studies
of women seeking infertility treatment show
significant rates of depressive symptoms, persisting
even after pregnancy is attained. 1,4
However, few studies use valid diagnostic criteria
for MDD. In aggregate, these studies
show a trend toward an increase in MDD in
infertile subjects, but few show a clear, significant
difference. Conversely, some studies
have examined rates of infertility in women
with mood disorders (MDD and bipolar disorder);
most showed significantly decreased fertility
in these subjects. 1
20 The Female Patient | VOL 35 JULY 2010 All articles are available online at www.femalepatient.com.

Catapano
RELATIONSHIP BETWEEN
DEPRESSION AND INFERTILITY
The existing data support a correlation between
depression and infertility, but the nature of the
relationship between the two is not clear. Evidence
that infertility causes depression is suggestive,
but not definitive. Again, most studies investigate
depressive symptoms rather than MDD.
The numerous studies that demonstrate an association
between depressive symptoms and infertility
do not provide evidence of causality. A few
have examined rates of depression in newly diagnosed
infertile women. 1 Such studies are intended
to identify cases in which depression
predates infertility; however, women with newly
diagnosed infertility, by definition, have been
trying unsuccessfully to get pregnant for at least
one year, so the time course of the depression
relative to the infertility is not known. In any case,
the results of these studies are mixed. Many studies
show a correlation between depression and
length of infertility treatment (and, therefore, infertility).
1 Others show an association between
depression and poor outcome of fertility treatment.
2 Both are suggestive of causality.
Similarly, there is circumstantial evidence that
depression may cause or exacerbate infertility.
For example, several studies show that the presence
of depressive symptoms in patients undergoing
assisted reproductive techniques (ART) is
associated with lower pregnancy rates. A number
of studies have demonstrated menstrual abnormalities
in women with mood disorders. 1 These
studies do not address causality but provide a
possible biologic mechanism by which MDD
may reduce fertility. Another potential mechanism
is behavioral: Neurovegetative symptoms of
MDD—decreased energy, decreased libido, poor
self-care, and psychomotor retardation—might
be expected to reduce fertility, but there are no
studies that directly address this theory.
A related set of questions, critical from a treatment
perspective, emerge: Do depression treatments
cause (or exacerbate) infertility? Do infertility
treatments cause depression?
Two small studies investigated the effect of selective
serotonin reuptake inhibitors on fertility in
women undergoing ART and showed a decrease
in pregnancy and birth rates that was not statistically
significant. 5,6 One meta-analysis showed a
significant increase in miscarriages associated
with antidepressants, although the effect of MDD
itself could not be ruled out. 7
What are the effects of infertility treatments on
depression? As noted above, studies that show
FOCUSPOINT
For many
depressed and
infertile patients,
the primary (but often
unspoken) goal of
psychiatric care is
not to treat depression
but to get
pregnant.
increased rates of depression in
women undergoing fertility
treatment are unable to separate
out the effects of infertility.
However, many fertility medications
have known effects on
mood. Clomiphene citrate, the
most commonly used fertility
drug, has side effects that include
anxiety, irritability, and
mood swings, similar to premenstrual
syndrome. Progesterone
and progesterone-containing
oral contraceptive pills
may cause depression and
emotional lability. Gonadotropin-releasing
hormone agonists,
which down-regulate pituitary function,
cause menopause-like symptoms, including
depression. 2
TREATMENT OF DEPRESSION IN INFERTILITY
The treatment of MDD in infertility is complicated
by the need to consider the effects of chosen
pharmacotherapies on (1) conception, (2)
pregnancy, (3) neonatal health, and (4) breastfeeding.
As discussed above, antidepressants
have not been shown to have a significant effect
on fertility rates but may increase the risk of
miscarriage. 5-7
The safety of antidepressants in pregnancy
and the postpartum period is a widely discussed
and controversial topic. A comprehensive discussion
is beyond the scope of this review. In
brief, according to the most recent guidelines
published jointly by the American Psychiatric
Association and ACOG, antidepressants are associated
with reductions in birth weight, neonatal
irritability (“poor neonatal adaptation”), and
persistent pulmonary hypertension of the newborn.
8 According to the report, the current data
do not support an increased risk of congenital
malformations from antidepressant exposure.
However, evidence for increased risk of cardiac
defects associated with paroxetine has led many
practitioners to restrict its use in women of
childbearing age. The guidelines endorse antidepressant
use in pregnant women with MDD,
particularly when symptoms are severe or the
patient has previously relapsed following antidepressant
discontinuation.
Psychotherapy is a powerful, safe, and effective
tool in women who are pregnant or trying to become
pregnant. Interpersonal, group, and cognitive
behavioral therapies have been proven
Follow The Female Patient on and The Female Patient | VOL 35 JULY 2010 21

REPRODUCTIVEPSYCHIATRY
Depression in Women With Infertility
FOCUSPOINT
Patients who
suffer from depression
and infertility
easily fall into the
assumption that
their depressive
symptoms will
resolve once they
are pregnant.
effective for depression in patients with infertility
in a number of studies, although one recent
meta-analysis did not show a significant effect. 8,9
Psychotherapy provides a
means to address the significant
themes in infertility: loss,
grief, guilt, shame, anger, identity,
self-esteem, social isolation,
marital discord, and sexual
dysfunction.
It is worthwhile noting that for
many depressed and infertile
patients, the primary (but often
unspoken) goal of psychiatric
care is not to treat depression
but to get pregnant. There is
some evidence, in fact, that psychotherapy
leads to increased
pregnancy rates. 9 Clearly this is
an issue that warrants further
exploration.
PREGNANCY AFTER INFERTILITY
Patients who suffer from depression and infertility
commonly attribute their depression to their
inability to have a child, and they easily fall into
the assumption that their depressive symptoms
will resolve once they are pregnant. In fact, the
risk for depression in pregnancy may be higher
in women who experienced infertility. 4 A key
theme in psychotherapy with previously infertile
patients is proper acknowledgement of their
losses, which are not nullified upon pregnancy
or the birth of a healthy infant. These include
loss of opportunity for spontaneous pregnancy;
possible loss of genetic connection to the baby;
and injury to marriage, friendships, and career
during the course of infertility.
Pregnant women with a history of infertility
often experience persistent feelings of inadequacy
with respect to their reproductive capacity,
associated with a belief that their infertility was a
sign that they do not deserve to be a parent. In
patients with such beliefs, conceiving through
ART, while circumventing infertility, does not correct
their perceived underlying deficits. These
feelings may persist into parenthood. The opportunity
to address these feelings in psychotherapy
should not be missed.
CONCLUSION
The relationship between depression and infertility
is complex. There is evidence that major
depression (and its pharmacologic treatments)
may reduce fertility, and that infertility (and its
treatments) may cause major depression. This
clearly complicates management of patients
with both MDD and infertility, requiring clinicians
to strike a delicate balance between effectively
treating each disorder and not exacerbating
the other. A clearer understanding of the
relationship between these disor ders, and their
treatments, is critical. Future studies should not
overlook the point that the majority of infertile
women do not develop depression. Understanding
sources of vulnerability and resilience may
ultimately be key to improving mental health in
women with infertility.
The author reports no actual or potential conflict
of interest in relation to this article.
Acknowledgement: The author acknowledges
Dr Joan Liebermann for helpful comments on
the manuscript.
REFERENCES
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2. Burns LH. Psychiatric aspects of infertility and infertility
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8. Yonkers KA, Wisner KL, Stewart DE, et al. The management
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For a patient handout on depression in
women with infertility, please go to page 49
for English or page 50 for Spanish. Patient
handouts can also be accessed online at
www.femalepatient.com/html/han/han.asp.
22 The Female Patient | VOL 35 JULY 2010 All articles are available online at www.femalepatient.com.