Incidence of depression and influence of depression on the number of treatment cycles and births in a national cohort of 42,880 women treated with ART.

STUDY QUESTION: Does prior depression in women treated with assisted reproduction technology (ART) influence the number of treatment cycles and ART live births? SUMMARY ANSWER: Women with a depression diagnosis prior to ART treatment initiated statistically significantly fewer ART treatment cycles and had a lower mean number of ART live births compared with women with no history of depression. WHAT IS KNOWN ALREADY: Previous studies have shown an increased prevalence of depressive symptoms in fertility patients than in the comparison groups. STUDY DESIGN, SIZE, DURATION: A register-based national cohort study, including all women (n = 42,915) treated with IVF, ICSI, frozen embryo transfer and oocyte recipient cycle in Denmark from 1 January 1994 to 30 September 2009 extracted from the IVF register (ART cohort). Data on births and depression diagnoses were obtained by linking to the Danish Medical Birth Register (1994-2010) and the Danish Psychiatric Central Research Register (1969-2010). PARTICIPANTS/MATERIALS, SETTING, METHODS: For each woman in the ART cohort, we included five age-matched women from the female background population not having received ART treatment. This comparison group was cross-linked with identical register data as the ART cohort. Women with incomplete ART information or a depression diagnosis before 18 years of age were excluded; remaining n = 42,880. The ART cohort was grouped into (i) women with a depression diagnosis and (ii) women never diagnosed with depression. In the ART group with depression, analyses were specified on women with their first depression prior to ART treatment. In total, 2.6% of the women in the ART cohort had a depression diagnosis. For the incidence rate ratio (IRR) 39,194 women from the ART cohort (3686 women were excluded due to migration) were compared with 206,005 women from the age-matched comparison group who did not receive ART treatment. MAIN RESULTS AND THE ROLE OF CHANCE: Of the women in the ART cohort with a depression diagnosis, 34.7% had their first depression diagnosis prior to ART treatment, 4.7% during ART treatment and 60.7% after ART treatment. The mean number of initiated ART cycles was significantly lower in the ART group of women having a depression diagnosis prior to ART treatment [2.55 (±1.78)] compared with the ART group of women without a depression diagnosis [3.22 (±2.31); P < 0.001; P < 0.001]. Women having a depression diagnosis prior to ART treatment had a lower mean number of ART live births [0.82 (±0.73)] compared with women without a depression diagnosis [1.03 (±0.81); P < 0.001]. The incidence rate of first and recurrent depression diagnoses in the ART cohort was significantly lower compared with the age-matched background population group; IRR = 0.80 (P < 0.001) and IRR = 0.77 (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Only clinical depression diagnoses treated in a psychiatric hospital setting are included. The age-matched comparison group from the background population is heterogeneous as it consists of women differing in fertility status (both mothers and childless women). WIDER IMPLICATIONS OF THE FINDINGS: Fewer women in the ART cohort developed depression over time compared with the age-matched background population, which might reflect a healthy patient effect of the women seeking ART treatment. Women with a depression diagnosis before ART treatment receive fewer ART treatments and are less likely to achieve an ART live birth. These women might be more vulnerable and we recommend that they be offered more psychiatric attention before starting, as well as during and after ART treatment. STUDY FUNDING/COMPETING INTEREST(S): Research grants are funded by the Danish Health Insurance Foundation and Merck Sharp & Dohme. The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Depression among men in ART treatment: a register-based national cohort study.

STUDY QUESTION: Are male factor infertility or remaining childless risk factors for unipolar depression among men in assisted reproductive technology (ART) treatment? SUMMARY ANSWER: Male factor infertility was not associated with a significantly increased risk of unipolar depression and men remaining childless did not have a significantly increased risk of developing unipolar depression compared to men in ART treatment who became fathers. WHAT IS KNOWN ALREADY: Men in medically assisted reproduction due to male factor infertility are more distressed and have more negative emotions such as feelings of loss, stigma and low self-esteem compared to men in fertility treatment due to other infertility diagnosis. Stress is in general a risk factor for depression. However, previous studies show conflicting results whether male factor infertility is a risk factor for depression. STUDY DESIGN SIZE DURATION: This national, register-based cohort study consisted of 37 913 cohabitant male partners of women in ART treatment recorded in the Danish IVF register (1994-2009). Via a national register, the men's personal identification number data were linked to the Danish Psychiatric Central Research Register (PCRR) (1969-2009) which records psychiatric diagnoses including unipolar depression, based on the ICD-8 and ICD-10 classification system. PARTICIPANTS/MATERIALS SETTING METHODS: The full cohort of male partners (n = 37 913) was included in the initial analysis on prevalence of unipolar depression before or after ART treatment initiation. The association between male factor infertility and unipolar depression diagnosis after initiating ART treatment was analysed with Cox regression analysis in a sub-study population of men with the exclusion of men having a depression prior to ART treatment or not having full data on educational level and infertility diagnosis (n = 34 817). MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 1.2% (n = 446) of the men were diagnosed with unipolar depression either before initiating ART treatment (n = 146) or during follow-up (n = 300). In all, 76.0% of men with depression prior to or after ART treatment achieved fatherhood compared to 82.3% of men without depression (P < 0.001). In the sub-study population (n = 34 817, which included 266 men with a unipolar depression diagnosis), male factor infertility was not associated a significantly increased risk of depression (adjusted hazard ratio (aHR) = 1.04, 95% CI: 0.79-1.36, P = 0.804), and ART-treated men who remained childless did not have a significantly increased risk of developing depression compared to ART treated men who became fathers (aHR = 1.13, 95% CI: 0.87-1.48, P = 0.355). LIMITATIONS REASONS FOR CAUTIONS: Only severe cases of depression are recorded and included in this national register-based study given that only men with clinically diagnosed unipolar depression recorded in a psychiatric hospital (in-patient and out-patient) are included in the Danish PCRR. It is difficult to completely rule out an association between the exposures and depression as this outcome is so rare, and therefore the results are still statistically uncertain despite a large cohort. Furthermore, only men in ART treatment were included in this study, and caution should be taken in generalising findings to the total population of men in all areas of medically assisted reproduction or infertile men who have not sought treatment. WIDER IMPLICATIONS OT THE FINDINGS: This large national cohort study suggests that despite evidence showing that male factor infertility is a potential severe stressor for men, which can increase psychological distress and negative emotions, infertile men in ART treatment and men remaining childless after ART are not at a significantly increased risk of developing clinically diagnosed unipolar depression. STUDY FUNDING/COMPETING INTERESTS: C.S.S. was funded by unrestricted research grants received by Lone Schmidt from The Danish Health Insurance Foundation (J.nr. 2008B105) and Merck Sharp & Dohme (MSD). The sponsors had no influence on how data were retrieved and analysed or on the conclusions of the study. C.S.S. and L.S. have declared conflicts of interests; the remaining co-authors have no conflicts of interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

The impact of social relations on the incidence of severe depressive symptoms among infertile women and men.

BACKGROUND: The present study investigates anticipated support and perceived appreciation as well as perceived negative aspects of social relations as determinants of the incidence of severe depressive symptoms among women and men in unsuccessful fertility treatment. METHODS: A prospective cohort study of consecutively recruited, new couples in fertility treatment completed questionnaires immediately before initiating treatment (T1) and at 1-year follow-up (T2) (response rates 80%, 88%). The study population included 695 participants (355 women and 340 men) who had no severe depressive symptoms at T1, who had no child together at T1 and whose treatment had failed. We measured severe depressive symptoms with Mental Health Inventory 5 from Short-Form 36, functional aspects of general social relations and of infertility-specific social relations. RESULTS: Fifteen per cent of women and 6% of men in unsuccessful treatment reported severe depressive symptoms at T2. Among men, low emotional support, low appreciation and high excessive demands from the partner were significant determinants of the incidence of severe depressive symptoms. Among women and men, low appreciation from the family, many conflicts and high excessive demands from family, friends and neighbours were significant determinants of severe depressive symptoms. The analyses were controlled for gender. Duration of infertility, infertility diagnosis and socio-economic position did not confound the associations. CONCLUSIONS: More women than men report severe depressive symptoms after 1 year of unsuccessful treatment. It is important to be aware of the possible negative impact of relational strain among fertility patients in unsuccessful treatment.