Infertility is an emotionally challenging experience in
women’s lives. Fertility loss can cause various mental
problems such as feeling of loss of control, low self-
esteem, stress, depression, marital distress, and sexual
Therefore, depression itself may contribute to SD and
Both cognitive behavioral therapy and drug therapy
are effective in treating depression in women with infertility
While behavioral and pharmacological treatments are effective in treating depression and SD in infertility, few studies have assessed these treatments for depression in infertile women with sexual dysfunction. To our knowledge, there are no published studies that have compared the effect of psychosexual therapy (PST) and bupropion, in the extended release (ER) formulation, in this population. Hence, the present study aimed to compare the effectiveness of bupropion extended-release versus psychological intervention on depression symptoms in depressed women with infertility and SD in Fatemeh Zahra Infertility and Reproductive Health Research Center of Babol University of Medical Sciences, Iran.
The authors carried out an open-label randomized controlled clinical trial between December 2014 to June 2015 at the Fatemeh Zahra Infertility and Reproductive Health Research Center, Babol, Iran. The study design was confirmed by the Ethics Committee (4930, 12 Jan 2014) and then registered in IRCT. Primary objective of this project was based on the treatment of SD with subsequent improvement of depression symptoms.
Women with infertility less than 45 years of age were eligible for the research under the following criteria: a score of =10 in beck depression index (BDI), a score of =26.55 on Iranian version of the female sexual function index (IV-FSFI), an infertility duration of greater than one year, were literate, ability to read and write, weren’t undergone any fertility treatment in the next 2 months and were sexually active in the past four weeks. Subjects were excluded from the study if they had a history of seizures, were taking medications that could lower the seizure threshold or were known to effect sexual function, had a history of head trauma, had a major change in living conditions, or had psychological support. Exclusion criteria also included serious medical conditions and mental health problems under the treatment of a physician, having actively suicidal, having major depressive disorder (MDD) in the clinical interview by a female psychologist.
Subjects have been assessed for eligibility by two midwives
with no clinical involvement in the study. Sample
size was calculated in accordance with 22 subjects
in each group, with accuracy=6.6, confidence interval
(CI)=95%, and approximate SD=6.8 based on previous
Flow diagram of participants through each stage of a randomized clinical trial.
The PST interventions focused on educational programs
that mainly contained eight weeks of two-hour sessions
including mindfulness-based cognitive therapy (MBCT),
relaxation training, behavior sex therapy (Mixed method)
based on the Crowe and Ridley model, and also booklet
of tranquility, mindfulness and medication (
The control group did not receive intervention, but educational
package was given to them, and were referred to
a sex therapy clinic after the end of study. Study duration,
and bupropion dosage were different in previous studies (4-
24 week, and 100-450 mg/day) (
A total of 90 participants completed the study. At first, the research protocol was described for participants, and then written informed consent was obtained from each subject. A secure and confidential environment was considered for collecting data. The researcher used a binder for each participant to keep individual information.
Demographic information was collected. All subjects completed the BDI at baseline and after treatment at the end of the study. The BDI is a self-reported measure consisting of 21 questions to assess the severity of depression symptoms, Created by Beck in 1961, it has an approved validity (0.89); reliability (0.96) during the first decade following its introduction. The translated and Persian of BDI had Cronbachs alpha 0.87 in the Iranian population.
The intensity of the item rates on a 4-point scale (0-3)
and the test is scored by summing the ratings given to
each of the 21 items. The total score range between 0 and
63 and the results range as follows: 0-9 as no depression,
10-18 as mild depression, 19-29 as moderate depression,
and 30 and greater as severe depression (
Data analyses were performed using Paired t tests, Pearson’s correlation, χ2 test, analysis of covariance (ANCOVA), and Tukey’s test (SPSS software, version 21) in an ITT analysis, with P<0.05 indicating statistical significance. Paired t tests was applied to show significant inter individual changes in BDI score within each treatment group. The chi-square test was used for comparing categorical variables between three groups. The ANCOVA was used as a statistical technique to control for variability (with baseline BDI scores as a covariate variable).
Tukey’s test was used for pair wise comparisons. Subsequent tests included the homogeneity of variances, the linear relationship between the dependent variable and the covariate, and the normality of distributions (Skewness and Kurtosis test). The change of depression level from baseline to end of study was calculated for each group. Improvement in depression symptoms was defined as a pre- to post treatment decrease in BDI depression level (severe to moderate, moderate to mild, and mild to no depression). Worsening of depression was defined as an increase in BDI depression level from baseline to end of study (mild to moderate, moderate to severe).
The demographic characteristics of subjects are
showed in Table 1. The majority of participants were
unemployed (78.5%), while the majority of the participants’
spouses were self-employed (44.1%). The mean
age of participants was 29 ± 5.44 years. The economical
situation in more than one third of participants was poor
(38.7%). The type of housing for the majority of participants
was private (65.6%). Nearly two thirds (62.4%) of
participants had primary infertility. There were no statistically
significant differences in baseline factors, occupation,
husband occupation, educational level, economic
status, type of housing, infertility type, and infertility
etiology between the three groups (
The mean BDI score of participants was 22.35 ± 8.70
at baseline. Mean BDI scores at baseline and at the end
of study for the three groups are given in
Changes in depression level (pre to post treatment)
showed that 79.1% of participants in the treatment
groups(PST and BUP) improved from their baseline depression
level, while 8.05% had a worse depression level,
and 12.9% had no change. In the control group, 38.7% of
participants improved from their baseline depression level,
while 16.1% had a worse depression level, and 45.2% had
no change. The improved depression levels were showed
more in PST group compared to others groups (
Distribution of the participarts according to the sociodemographic charecteristics
|Variable||Treatment group||Control n=31 n (%)||P value||Total n=93 n (%)|
|PST n=31 n (%)||BUPER n=31 n (%)|
|Unemployed||21 (67.7)||27 (87.1)||25 (80.6)||73 (78.5)|
|Employed||10 (32.3)||4 (12.9)||6 (19.4)||20 (21.5)|
|Unemployed||1 (3.2)||1 (3.2)||1 (3.2)||3 (3.2)|
|Worker||8 (25.8)||10 (32.3)||5 (16.1)||23 (24.7)|
|Employee||7 (22.6)||8 (25.8)||11 (35.5)||26 (28.0)|
|Self-employed||15 (48.4)||12 (38.7)||14 (45.2)||41 (44.1)|
|Type of housing||0.716|
|Private||20 (64.5)||19 (61.3)||22 (71.0)||61 (65.6)|
|Rental||11 (35.5)||12 (38.7)||9 (29.0)||32 (34.4)|
|Primary||17 (54.8)||23 (74.2)||18 (58.1)||58 (62.4)|
|Secondary||14 (45.2)||8 (25.8)||13 (41.9)||35 (37.6)|
|0-12 (Y)||24 (77.4)||25 (80.6)||19 (61.3)||68 (73.1)|
|>12 (Y)||7 (22.6)||6 (19.4)||12 (38.7)||25 (26.9)|
|Female||2 (6.5)||2 (6.5)||5 (16.1)||9 (9.7)|
|Male||11 (35.5)||11 (35.5)||9 (29)||31 (33.3)|
|Both||9 (29)||10 (32.2)||7 (22.6)||26 (28)|
|Unknown||9 (29)||8 (25.8)||10 (32.3)||27 (29)|
PST; Psychosexual therapy and BUPER; Bupropion extended-release. χ2 test was used for comparing categorical variables between three groups.
The changes of final levels of baseline depression in three groups. PST; Psychosexual therapy, BUP ER; Bupropion extended-release. n=93 (each group of 31 participants). P<0.001 (χ2 test).
The change from baseline in BDI score was analyzed by
ANCOVA and significant differences between the three
groups were found (P<0.001). Pair wise comparisons on
mean BDI showed that only PST decreased significantly
compared to control group (P<0.0001). The decrease in
mean BDI score in the BUP group was not significantly
different compared to control group (P<0.282). There
was a significant diference in mean BDI scores between
PST and BUP groups (P<0.005) (post-hoc ANCOVA).
Statistical power for this analysis was approximately
than 95.4%. As a result, the assumption of research on
the effects of therapeutic interventions on BDI score with
a probability of 95.4% in infertile women was accepted
Covariance analysis test for total score in beck depression and pair wise comparisons in the groups
|Variable||Sum of squares||Mean square||df||F statistics||Observed power||P value|
BDI; Beck depression inventory, PST; Psychosexual therapy, BUP ER; Bupropion extended-release, n=93 (each group of 31 participants), df; Degrees of freedom, and F; Test statistic. ANCOVA test was used to compare the change from baseline in BDI score between the three groups; post-hoc ANCOVA was used for pair wise comparisons. There was a significant diference in mean BDI scores between PST and control groups (P<0.0001), PST and BUP ER groups (P<0.005); but not between BUP and control groups (P<0.282).
The mean scores of BDI in three groups of infertile women at beginning and end of the study
|Variable BDI||Pre-test Mean ± SD||Post-test Mean ± SD||P value|
|PST||24.59 ± 7.76||10.42 ± 9.01||0.0001|
|BUP ER||22.42 ± 10.70||16.09 ± 11.81||0.002|
|Control||20.06 ± 6.83||17.35 ± 10.46||0.105|
BDI; Beck depression inventory, PST; Psychosexual therapy, BUP ER; Bupropion extended-release, n=93 (each group of 31 participants). Paired t test was used to compare the pre-to-post depression BDI mean score in each group.
Study participants with SD showed where they were
at risk for depression symptoms and had a high average
of depression scores. This finding suggests that women
with infertility and SD are more likely to experience
symptoms of depression. Previous studies by Pasha et
We found that BDI scores decreased significantly from
baseline at the end of study in each treatment group (PST
and BUP). In both treatment groups combined, more than
two thirds of participants showed improvement in their
depressive symptoms levels (pre to post treatment). The
similar studies showed that both psychosocial and pharmaceutical
therapeutic strategies, such as psychotherapy
and antidepressants, are well established in the treatment
of depression (
Also bupropion is an effective antidepressant medication,
which is used to treat remission of depressive
disorder. The effectiveness of bupropion in improving
depression found in clinical trials with the drug (
After adjusting for baseline values, data showed a significant improvement in depression symptoms for women exposed to the psychosexual intervention compared with women in the BUP and control groups. Group PST was better than bupropion treatment in improving depression symptoms. PST was not only a reliable treatment approach to improving depression symptoms, but also it was superior to bupropion treatment to alleviate depression symptoms in women with infertility and SD. These results suggest that PST may be more effective compared with pharmacological therapy to treat depression symptoms in women with infertility and SD.
Consistent with this; study conducted by Faramarzi et
Our findings showed that the decrease in the mean BDI
score with BUP dosage of 150 mg per day was not statistically
significant compared to the control group, although
BUP group showed statistically significant improvement
in depression symptom from beginning to end of research.
Many trials showed that bupropion was efficacious in
treatment MDD (
It was found as an important antidepressant, and used to
treat MDD (
Psychosocial therapy was a superior treatment compared to bupropion for alleviating depression symptoms in women with infertility and SD. Therefore, counseling services and social support to recognize and treat depression and SD are necessary to establish in fertility centers.
There were a few limitations in this study. First, the data were collected from a small sample size of Iranian women with infertility; therefore, the findings cannot be generalized to all women with infertility or other populations and would require to be investigated in future research of a larger sample size. Another weakness of study was leak of follow-up. The strengths of this research include its use of a validated, self-reported Iranian version of the BDI. Also, for more effective treatment methods suggested that future studies consider the PST plus bupropion compared to each of them individually.