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Population Research Unit, Faculty of Social Sciences, University of Helsinki, Helsinki, FinlandLaboratory of Population Health, Max Planck Institute for Demographic Research, Rostock, Germany
Population Research Unit, Faculty of Social Sciences, University of Helsinki, Helsinki, FinlandLaboratory of Population Health, Max Planck Institute for Demographic Research, Rostock, Germany
Medically assisted reproduction can negatively affect women’s mental health, particularly when the treatments do not result in a live birth. Although the number of women relying on medically assisted reproduction to conceive has grown rapidly, our knowledge about the mental health effects before, during, and after treatment is limited.
Objective
This study aimed to understand the long-term association between medically assisted reproduction and mental health outcomes for women before, during, and after their treatments, and according to whether the treatment resulted in a live birth.
Study Design
Using Finnish register data for the period from 1995 to 2018, we estimated the probability of psychotropic purchases (antidepressants, anxiolytics, hypnotics, and sedatives) for 3 groups of women who: (1) gave birth after natural conception, (2) gave birth after medically assisted reproduction treatments, or (3) underwent medically assisted reproduction but remained childless. We followed up women for up to 12 years before and 12 years after the reference date, which corresponded to the conception date for women who had a first live birth either after a natural or a medically assisted conception, or the date of the last medically assisted reproduction treatment for women with no live birth by the end of 2017. We estimated linear probability models before and after adjustment for sociodemographic characteristics.
Results
The results show that women who did not have a live birth after undergoing medically assisted reproduction treatments purchased more psychotropics than women who gave birth after conceiving naturally or through medically assisted reproduction, and that these differences did not attenuate over time. Twelve years after the reference date, 17.73% (95% confidence interval, 16.82–18.63) of women who underwent medically assisted reproduction but remained childless purchased psychotropics vs 11.11% of women who gave birth after natural conception (95% confidence interval, 10.98–11.26) and 12.17% (95% confidence interval, 11.65–12.69) of women who gave birth after medically assisted reproduction treatments. In addition, women who conceived naturally and through medically assisted reproduction had very similar psychotropic use patterns from 3 years before conception to 4 years after, and over the long term. Adjustment for women’s sociodemographic characteristics did not change the results.
Conclusion
The similarities in psychotropic purchases of women who had a live birth, whether naturally or through medically assisted reproduction, suggest that the higher psychotropic use among women who remained childless after undergoing medically assisted reproduction were likely driven more by involuntary childlessness than by treatment-related stress. The results highlight the importance of counseling for women undergoing medically assisted reproduction treatments, especially if their attempts to conceive are unsuccessful.
As childbearing is increasingly postponed and infertility treatments are becoming more widely available, the number of women relying on medically assisted reproduction (MAR), which includes techniques such as ovulation induction, artificial insemination, and assisted reproductive technology (including in vitro fertilization [IVF] and intracytoplasmic sperm injection), has grown rapidly across the globe.
The number of women relying on medically assisted reproduction (MAR) to conceive has grown rapidly, but our knowledge about their mental health as they undergo MAR treatments is limited.
Key findings
Women who did not have a live birth after undergoing MAR treatments purchased more psychotropic medication than women who gave birth after conceiving naturally or through MAR. Differences did not attenuate over time, even when adjusting for sociodemographic characteristics. Women who conceived naturally and through MAR had very similar psychotropic use from 3 years before conception to 4 years after, and over the long term.
What does this add to what is known?
Similarities in psychotropic purchases of women who had a live birth, whether naturally or through MAR, suggest that the higher psychotropic use among women who remained childless after undergoing MAR is likely to be driven more by involuntary childlessness than by treatment-related stress.
Previous studies have suggested that MAR treatments can negatively affect women’s psychological well-being and cause psychological distress, anxiety, and depression.
Astute Health Study Group Depression and anxiety outcomes associated with failed assisted reproductive technologies: a systematic review and meta-analysis.
have limitations. First, the beginning of the follow-up period was often around the time when the MAR treatments were initiated, that is, when the women were already struggling with subfertility. This approach makes it difficult to determine the extent to which the mental health levels of women who undergo MAR diverge from their pretreatment levels. Second, they tended to use small and nonrepresentative samples collected in MAR treatment clinics, which are subject to self-reporting and recall bias.
Finally, none of these studies directly documented differences between women who conceived naturally, women who conceived through MAR, and women who remained childless after MAR treatments.
In this study, we analyze the use of psychotropic medication among women who underwent MAR to conceive and compare it with that of women who conceived naturally. A key contribution is that we compared women who had a live birth after MAR with women who underwent MAR but remained childless. We expanded on the existing literature by investigating women’s psychotropic purchases both before and after the date of conception or the last treatment cycle using population register data from Finland, and by using a significantly larger observation window than previous studies.
Materials and Methods
Study population
We included all women in Finnish administrative registers who were born between 1950 and 1995, were childless in 1995, and gave birth to their first child (either after natural conception or MAR) between ages 20 and 45 from 1996 to 2016 or underwent MAR treatments from 1995 to 2016 but were childless in 2017.
Reference date
We set as the reference date the conception date (estimated as birthdate minus gestational age) for women who had a first live birth either after a natural or a MAR conception, or the date of the last MAR treatment for women with no live birth by the end of 2017.
Outcome
Psychotropic medications are commonly used to treat depression, anxiety, insomnia, and other related mental health problems.
Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines.
Information about psychotropic purchases prescribed in the public and private sectors between January 1995 and December 2018 was gathered from the National Prescription Register. In Finland, all psychotropic medication is prescribed by clinical doctors, and residents are entitled to reimbursement for medication expenses, usually provided directly at pharmacies. The prescription register includes information on the purchase date and medication type, classified according to the World Health Organization’s Anatomical Therapeutic Chemical (ATC) Classification System (WHO, 2013). We included all purchases of antidepressants (ATC codes N06A), anxiolytics (ATC codes N05B), and hypnotics and sedatives (ATC codes N05C).
We divided our follow-up period into 6-month intervals before and after the reference date. For each interval, the outcome variable takes a value of 1 if a woman purchased psychotropics, and of 0 otherwise.
Medically assisted reproduction treatments
We identified women undergoing MAR treatments between 1995 and 2016 using administrative data from the prescription, healthcare, and birth registers.
To identify MAR treatments in the prescription register, we updated Hemminki et al’s
algorithm by including 2 drugs introduced after 2000 and some restrictions on stand-alone treatments (more information in the Appendix 1). We identified children conceived through MAR by combining each woman’s purchases of fertility drugs with her child’s birthdate (retrieved from the Finnish Medical Birth Register). We excluded purchases of drugs used in infertility treatment when also plausibly used to treat other medical conditions, such as cancer. The healthcare register contains information on dates and types of MAR procedures in the public sector. We identified children conceived through MAR by combining the dates of MAR procedures with the child’s birthdate. Finally, to complement this information, we identified in the birth register children born after MAR treatments from 2004 onward.
Our 3 groups of interest were women who: (1) had their first live birth after a natural conception (NC), (2) had their first live birth after a MAR conception (MAR+), and (3) remained childless after MAR treatments (MAR−). Women who conceived after MAR treatments could be identified from any of the 3 sources, and women who underwent MAR treatments not resulting in a live birth were identified using the procedure and/or drug registers. We assumed a woman conceived naturally if none of the data sources indicated that her child was conceived through MAR.
Treatment length
We defined treatment length as the time between the first and last MAR treatment, and created a binary variable that takes a value of 1 for women who underwent treatments for >2 years, and of 0 otherwise. The 2-year threshold was chosen on the basis of the average treatment length (1.98 years) in our sample. For cases in which MAR treatment was identified only through the birth register (11.5% of MAR+ women)—which does not provide information on treatment length—we imputed the first treatment date using age-specific average times between the start of MAR treatments and conception.
Period of observation
Data on psychotropic purchases from 1995 to 2018 and MAR treatments between 1995 and 2016 allowed us to follow women for up to 12 years before and after the reference date, resulting in an unbalanced panel with a total of 48 6-month intervals (24 years), and a median follow-up of 35 intervals (18 years) (appendix Table 2A).
Exclusions
We excluded from the sample women who were aged <20 or >45 years at the reference date. We excluded women with triplet pregnancies, which are associated with more distress.
We excluded psychotropic purchases that occurred before women reached the age of 18 years. Furthermore, we excluded women who were living abroad in any given year because medication purchases are recorded only for women residing in Finland. Finally, we excluded observations with missing values in the covariates (0.07%). This resulted in a sample of 575,921 women. Of them, 97.73% had a first birth from 1996 to 2016 (5.89% after MAR), and 2.27% remained childless after undergoing MAR treatments.
Statistical analysis
We estimated generalized estimating equation linear models using the 6-month intervals as repeated panel observations and robust standard errors with exchangeable correlation structure. We modeled changes in psychotropic purchases by interacting the 3 groups of interest (women who had a live birth after a natural or a MAR conception, and women who remained childless after MAR treatments) with the 6-month period variable (time-varying), which resulted in 96 coefficients representing the probability of psychotropic use for MAR+ and MAR− against NC women for each period.
We estimated 2 models. In Model 1, we adjusted for calendar year to control for increasing psychotropic use over time,
Model 2 additionally controls for time-varying sociodemographic factors: household income decile (categorical), cohabitation status (binary), and hospital district of residence (categorical). Because psychotropic purchases may be affected by transition to a higher-parity birth, Model 2 also adjusts for transition to a second-, third-, or higher-order birth (binary). To investigate whether treatment duration moderated the association between MAR treatments and psychotropic purchases, we estimated Model 1 by interacting the period variable with a variable that identified the 3 interest groups and their treatment length, resulting in 5 categories: NC, MAR+ >2 years, MAR+ <2 years, MAR− >2 years, and MAR− <2 years.
All analyses were conducted in Stata, version 16 (StataCorp, College Station, TX). The study was exempt from institutional review board approval because it was not necessary given the previous institutional approval of the overall project (European Research Council grant #803958).
Results
Table shows that 33.4% of women purchased psychotropics in at least 1 6-month period during the 24-year follow-up, with 15% having purchased at least once in the 12 years before the first conception or last MAR cycle, and 27.3% in the following 12 years. Psychotropic use differed across the 3 groups: 14.5% and 18.9% of NC and MAR+ women, respectively, purchased psychotropics before they conceived their first child, vs 25% of MAR− women.
TablePsychotropic purchases before and after conception or last medically assisted reproduction treatment
Psychotropic purchases
NC
MAR+
MAR−
Total
Mean (%)
SD
Mean (%)
SD
Mean (%)
SD
Mean (%)
SD
Before conception or last cycle date
14.48
35.19
18.85
39.11
25
43.3
14.98
35.68
After conception or last cycle date
27.04
44.42
27.87
44.84
37.9
48.52
27.33
44.57
Before and/or after conception or last cycle date
32.93
47
36.15
48.04
45.24
49.77
33.4
47.16
Number of observations
528,913
33,942
13,066
575,921
MAR+, women who conceived after medically assisted reproduction treatments; MAR−, women who underwent medically assisted reproduction treatments and remained childless; NC, women who conceived naturally; SD, standard deviation.
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
We observed substantial differences across groups over time (Figure 1). Differences in psychotropic purchases between women who underwent MAR treatments and women who conceived naturally emerged as early as 9 to 10 years before conception or last treatment cycle, with the latter being more likely to purchase psychotropics (MAR−: 3.25%; 95% confidence interval [CI], 2.71–3.79; MAR+: 2.51%; 95% CI, 2.27–2.75) than the former (1.48%; 95% CI, 1.14–1.58).
Figure 1Predicted probabilities of psychotropics purchases, by group (Model 1)
Model 1 adjusts for calendar year and age. Full Model results in appendix Table 3A.
MAR+, women who conceived after medically assisted reproduction treatments; MAR−, women who underwent medically assisted reproduction treatments but did not deliver a live birth by the end of 2017; NC, women who conceived naturally.
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
Five years before conception or the last cycle, the psychotropic purchases of women undergoing MAR diverged (Figure 1; full model results in appendix Table 3A). The share of women taking psychotropics remained at 4.86% for MAR+ women (95% CI, 4.59–5.13), but increased to 6.45% (up 16.02% from the previous year) among MAR− women.
Women who had a child either through MAR or naturally had similar levels of psychotropic use from 3 years before conception to 4 years after. Nonetheless, although the probability of purchasing psychotropics decreased gradually from 2 years before conception onward among MAR+ women, no shift occurred among NC women until immediately before conception. Conversely, women who remained childless after MAR increased their psychotropic use sharply after the last MAR cycle. This resulted in a large gap in psychotropic purchases around the reference date, with 9.82% (95% CI, 9.29–10.36) of MAR− women purchasing psychotropics vs 2.83% (95% CI, 2.78–2.88) of NC women and 2.49% (95% CI, 2.31–2.66) of MAR+ women. The psychotropic purchases of both NC and MAR+ women increased immediately following childbirth, which resulted in an attenuation of the differences between NC, MAR+, and MAR− groups. From 6 years after the reference date onward, the gap in psychotropic purchases between childbearing and childless women remained relatively stable. The gap never fully attenuated; 12 years after the reference date, women who underwent unsuccessful MAR treatments were 45.69% and 59.48% more likely to purchase psychotropics than women who delivered a live birth through MAR or naturally, respectively.
To illustrate the fluctuations in psychotropic purchases among women who underwent MAR treatments and either gave birth or remained childless, Figure 2 shows the ratio of predicted margins estimated using the delta method for these women relative to women who conceived naturally. The figure shows a clear peak in psychotropic purchases among MAR− women.
Figure 2Ratio of predicted probability of psychotropics purchases, estimated from Model 1
Ratios calculated after the estimation of Model 1. Horizontal red line in y=1 represents equal predicted probabilities between each of the MAR and NC groups.
MAR+, women who conceived after medically assisted reproduction treatments; MAR−, women who underwent medically assisted reproduction treatments but did not deliver a live birth by the end of 2017; NC, women who conceived naturally.
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
When adjusting for sociodemographic characteristics in Model 2, differences in psychotropic purchases across groups remained consistent with Model 1 (appendix Figure 1A; appendix Table 3A). We re-estimated all models, excluding women who underwent fertility treatments but conceived naturally, and the results held (appendix Figure 2A).
Lengthier MAR treatments were associated with higher psychotropic purchases regardless of the treatment result (Figure 3; appendix Table 4A). For example, women undergoing lengthier treatments were 37.28% (MAR+) and 32.47% (MAR−) more likely to purchase psychotropics around the date of conception or last cycle compared with their counterparts undergoing shorter treatments, and these differences shrank after the reference date. Nonetheless, the results were consistent with those of Model 1: women who had a child following MAR had lower psychotropic use than women who underwent MAR and remained childless.
Figure 3Predicted probability of psychotropics purchases, by group (Model 1), by group and length of MAR treatment (unadjusted Model)
MAR+, women who conceived after medically assisted reproduction treatments; MAR−, women who underwent medically assisted reproduction treatments but did not deliver a live birth by the end of 2017; NC, women who conceived naturally.
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
The results show that psychotropic use was higher among women who remained childless after MAR than among women who conceived naturally or through MAR. This pattern persisted over the long term, in line with findings of other studies.
Adjustment for sociodemographic characteristics did not change the pattern of results.
Although women who conceived via MAR had higher psychotropic use than women who conceived naturally at the beginning of the observation window, their psychotropic use was similar from 3 years before to 4 years after conception, and the differences over the longer term remained small, and were unlikely to be clinically relevant.
Results in the context of what is known
Although the finding of similarities in long-term psychotropic use between women who conceived naturally and through MAR is consistent with previous studies,
in this study we were able to significantly extend the observation window, and thus provide further evidence about the mental well-being of this growing population sub-group.
Our results significantly deepen the understanding of the link between MAR and mental health in 3 ways. First, we showed that differences between women for whom MAR treatments did not result in a live birth and women who delivered a live birth either naturally or through MAR arose as early as 5 years before the date of conception or last MAR cycle, with the former increasing their psychotropic uptake more than the latter. A possible explanation for the emergence of this gap well before women ended MAR treatments is that the former may have already received a diagnosis of subfertility and began the infertility treatment process. There is evidence that the start of infertility treatments is related to increased levels of depression and anxiety.
Second, we showed that there was a sharp increase in psychotropic purchases following the last failed treatment cycle, which could have been driven by participants experiencing negative emotions on realizing that they were unlikely to have a biological child.
adjusting for partnership status in the analyses did not alter the results. By contrast, women who had a live birth either naturally or after undergoing MAR treatments reduced their psychotropic purchases when trying to conceive and while pregnant. The reasons for this could be two-fold: on the one hand, the decrease and slow return to preconception psychotropic purchase levels (around 36 months) could be related to a temporary increase in subjective well-being around the time of first birth.
Third, although the psychotropic purchases of the 2 MAR groups were similar at the beginning of the observation window, they began diverging from around 6 years before conception or the last MAR cycle, and the differences never fully attenuated during follow-up. The stark increase in psychotropic uptake that occurred around the last treatment date for women who remained childless could suggest that their worse mental health outcomes were driven more by involuntary childlessness than by treatment-related stress. The analyses on the moderating role of the MAR treatment length further supported this hypothesis. Within the MAR+ and MAR− groups, women who underwent MAR for ≥2 years had higher psychotropic use at the beginning and end of the follow-up period. However, the differences became smaller over the longer term as the purchases of women who underwent longer MAR processes in both the MAR+ and MAR− groups tended to converge with those of their counterparts who underwent shorter MAR processes; that is, childbearing status was more important in determining women’s psychotropic purchases than MAR treatment length. The results reinforce the hypothesis that higher psychotropic purchases were associated with unintended childlessness after undergoing MAR treatments, whereas the moderating effect of the length of the MAR process was small.
Clinical implications
Considering the increasing use of MAR treatments, the results of this study underscore the importance of offering counseling to women undergoing MAR treatments, particularly if their attempts to conceive through MAR are unsuccessful. The provision of psychological support and counseling during the MAR process may reduce the likelihood of women ending treatments prematurely because of stress; prepare women better for the potential failure of treatments; and help women deal with the grieving process if their desire to have a child is unfulfilled.
However, more evidence is needed to determine whether and to what extent such psychological support is effective.
Research implications
We found that involuntary childlessness has associated mental health costs, but more work is necessary to establish the mechanisms underlying this association. Moreover, the results show that the estimation of the MAR effect on mental health is sensitive to time of measurement during the MAR process, that is, could be over- or underestimated depending on how the baseline and follow-up are defined with respect to conception/last MAR cycle.
Strengths and limitations
This study has several strengths. First, the use of a large and nationally representative register allowed us to investigate the association between MAR treatments and psychotropic purchases free of self-reporting biases, and to investigate this association before, upon, and after the conception date (or the last cycle date for unsuccessful MAR cases) in 6-month intervals. Second, the long follow-up allowed us to observe psychotropic purchases when women were most likely not yet struggling with infertility or MAR treatments. Third, we identified and compared women who had a live birth naturally or after MAR with women who underwent MAR but whose treatments did not result in a live birth, which is relevant for understanding how MAR treatments and their outcomes affect women’s mental health. Finally, by focusing on psychotropics, which are widely used to treat depression and anxiety in women of reproductive age, we were able to observe common psychiatric disorders and not only the more acute or severe cases (eg, psychiatric hospitalizations).
The study also has limitations. First, the analysis focused on Finland, a context with subsidized medical care and medication costs, which could limit the generalizability of our findings to other settings. However, in contexts where MAR treatments are not as well subsidized as in Finland, the association between psychotropic uptake and MAR treatments could be even stronger because of higher levels of stress related to income loss. Second, although the analysis of psychotropic purchases allowed us to observe women who suffer from common psychiatric disorders, there are other nonpharmacologic interventions such as therapy and counseling that we did not consider. Thirdly, we were unable to establish whether the association between MAR treatments and psychotropic purchases was causal given that subfertility is associated with higher levels of stress,
Nevertheless, additional analyses (provided in the appendix figure 3A) demonstrate that our results remain similar when excluding all women who had purchased psychotropics before the reference date, suggesting that our conclusions are unlikely to be primarily related to an underlying higher propensity to use psychotropic medications among women who undergo MAR and remain childless. Fourth, although the use of administrative registers has many advantages, they do not provide information on the causes of infertility or cases of abnormal pregnancies. Finally, we were unable to account for the role of pregnancy loss because registry data record only those that require hospitalization. Nevertheless, it is unlikely that results were driven by miscarriages because we did not observe differences in psychotropic uptake before the reference date between MAR+ and NC women although the former experience, on average, a higher number of miscarriages because they suffer from subfertility.
Conclusions
The similarities in the psychotropic purchases of women who had a live birth, whether naturally or through MAR, suggest that the higher psychotropic use among women who remained childless after undergoing MAR were likely driven more by involuntary childlessness than by treatment-related stress. The results highlight the importance of counseling for women undergoing MAR treatments, especially if their attempts to conceive are unsuccessful.
Supplementary Material
Appendix 1: To identify women undergoing medically assisted reproduction (MAR) and children conceived through MAR, we used the algorithm by Hemminki et al. (2003), modified and further developed by Alina Pelikh to use data from the national prescription, healthcare, and birth registers:
Table 1AMAR algorithm sources
Prescription register
Healthcare register
Birth register
Period covered
1995-2018
1996-2017
1987-2017 (information on MAR since 2004)
MAR identification
Data on purchases of fertility drugs.
Updated algorithm developed by (Hemminki et al. 2003) calculating intervals since the last purchase of drugs and childbirth.
4
types of MAR:
•
Ovulation induction
•
IVF and other ART
•
Other MAR
Data on infertility diagnoses and MAR procedures. Algorithm calculating interval since the last MAR procedure and childbirth. 5 types of MAR:
•
Ovulation induction
•
Insemination
•
IVF
•
FET
•
ICSI
Data on births and pregnancy. 3 types of MAR
•
Ovulation induction
•
Insemination
•
IVF
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
We identified MAR treatments and children conceived through MAR between 1996 and 2016 using administrative data from the prescription register, the healthcare register, and the birth register. These sources cover different periods: the prescription register contains data from 1995 to 2018, the healthcare register contains data for the 1996-2017 period, and the birth register contains data on MAR births for the 2004-2017 period only.
Prescription register
To identify MAR in the prescription register, an original algorithm developed by (Hemminki et al. 2003) was updated by including corofollitropin alfa and combination products of gonadotropin. As these drugs were not used in significant volumes until 2012, these were minor changes, but they added a few MAR cases. Some of the ovulation induction drugs (e.g., clomifen) were no longer reimbursed after the year 2000. All other new drugs that could have been added to the algorithm (i.e. letrozole, ganirelix, cetrorelix) were unfortunately not recorded in the prescription register. However, the number of such cases is likely small because most of these drugs are used in combination with other fertility drugs, which are included in the register and were used consistently across the study period.
Healthcare register
The healthcare register contains information on diagnoses of infertility and MAR procedures carried out in public sector clinics. To identify MAR children from the healthcare register, a threshold of 44 weeks between a MAR procedure (ovulation induction; insemination; IVF; FET; ICSI;) and the birth of a child was used. If multiple procedures fell into this window, the procedure closest to the birthdate was chosen). A sensitivity analysis in which we extended the window up to 46 weeks showed that only a small number of cases (<200) would have been added to those already identified.
Birth register
From 2004 onwards, children could be identified as conceived through MAR treatments including ovulation induction, insemination, and IVF.
Table 2ANumber of observations in each period before and after the date of conception or the last cycle, unbalanced panel
Period
NC
MAR+
MAR-
Total
138-144 months before
190,996
16,740
5,422
213,158
132-138 months before
201,172
17,600
5,682
224,454
126-132 months before
211,895
18,302
5,916
236,113
120-126 months before
222,334
19,053
6,320
247,707
114-120 months before
233,048
19,709
6,607
259,364
108-114 months before
243,466
20,464
6,917
270,847
102-108 months before
254,654
21,161
7,183
282,998
96-102 months before
265,340
21,892
7,484
294,716
90-96 months before
276,838
22,413
7,764
307,015
84-90 months before
287,792
23,073
8,091
318,956
78-84 months before
299,337
23,638
8,395
331,370
72-78 months before
310,504
24,237
8,716
343,457
66-72 months before
251,050
24,088
8,974
284,112
60-66 months before
270,488
25,123
9,389
305,000
54-60 months before
291,611
26,057
9,751
327,419
48-54 months before
312,311
27,111
10,182
349,604
42-48 months before
336,010
28,142
10,556
374,708
36-42 months before
358,962
29,245
10,997
399,204
30-36 months before
385,255
30,217
11,384
426,856
24-30 months before
412,110
31,241
11,780
455,131
18-24 months before
444,837
32,137
12,136
489,110
12-18 months before
477,121
33,080
12,546
522,747
6-12 months before
511,668
33,657
12,807
558,132
0-6 months before
528,877
33,905
12,993
575,775
0-6 months after
528,877
33,905
12,993
575,775
6-12 months after
528,595
33,922
12,693
575,210
12-18 months after
524,118
33,478
12,407
570,003
18-24 months after
513,347
32,523
12,081
557,951
24-30 months after
503,128
31,573
11,750
546,451
30-36 months after
492,271
30,660
11,424
534,355
36-42 months after
482,104
29,812
11,132
523,048
42-48 months after
471,123
28,864
10,813
510,800
48-54 months after
460,816
27,987
10,525
499,328
54-60 months after
450,196
27,004
10,215
487,415
60-66 months after
439,746
26,144
9,928
475,818
66-72 months after
428,677
25,143
9,609
463,429
72-78 months after
418,132
24,264
9,333
451,729
78-84 months after
407,125
23,257
9,027
439,409
84-90 months after
396,526
22,351
8,795
427,672
90-96 months after
385,221
21,362
8,519
415,102
96-102 months after
374,159
20,596
8,292
403,047
102-108 months after
362,956
19,635
7,982
390,573
108-114 months after
352,105
18,826
7,767
378,698
114-120 months after
341,049
17,989
7,521
366,559
120-126 months after
330,329
17,178
7,301
354,808
126-132 months after
319,587
16,257
7,011
342,855
132-138 months after
308,874
15,528
6,809
331,211
138-144 months after
297,745
14,646
6,522
318,913
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
Table 3AModel (1) and Model (2) full estimation results (generalized estimating equation linear models)
VARIABLES
Model (1)
Model (2)
2.period
0.001∗∗∗
-0.001∗∗∗
(0.000)
(0.000)
3.period
0.002∗∗∗
-0.001∗∗∗
(0.000)
(0.000)
4.period
0.003∗∗∗
-0.002∗∗∗
(0.000)
(0.000)
5.period
0.004∗∗∗
-0.002∗∗∗
(0.000)
(0.000)
6.period
0.006∗∗∗
-0.002∗∗∗
(0.000)
(0.000)
7.period
0.007∗∗∗
-0.002∗∗∗
(0.000)
(0.000)
8.period
0.009∗∗∗
-0.001∗∗∗
(0.000)
(0.000)
9.period
0.011∗∗∗
-0.000
(0.000)
(0.000)
10.period
0.013∗∗∗
0.001∗∗
(0.000)
(0.000)
11.period
0.015∗∗∗
0.002∗∗∗
(0.000)
(0.000)
12.period
0.017∗∗∗
0.004∗∗∗
(0.000)
(0.000)
13.period
0.023∗∗∗
0.009∗∗∗
(0.001)
(0.001)
14.period
0.025∗∗∗
0.010∗∗∗
(0.001)
(0.001)
15.period
0.026∗∗∗
0.012∗∗∗
(0.001)
(0.001)
16.period
0.028∗∗∗
0.013∗∗∗
(0.001)
(0.001)
17.period
0.030∗∗∗
0.014∗∗∗
(0.001)
(0.001)
18.period
0.032∗∗∗
0.016∗∗∗
(0.001)
(0.001)
19.period
0.033∗∗∗
0.018∗∗∗
(0.001)
(0.001)
20.period
0.035∗∗∗
0.020∗∗∗
(0.001)
(0.001)
21.period
0.036∗∗∗
0.021∗∗∗
(0.001)
(0.001)
22.period
0.037∗∗∗
0.022∗∗∗
(0.001)
(0.001)
23.period
0.038∗∗∗
0.024∗∗∗
(0.001)
(0.001)
24.period
0.036∗∗∗
0.023∗∗∗
(0.001)
(0.001)
26.period
0.016∗∗∗
0.003∗∗∗
(0.001)
(0.001)
27.period
0.013∗∗∗
-0.000
(0.001)
(0.001)
28.period
0.025∗∗∗
0.011∗∗∗
(0.001)
(0.001)
29.period
0.031∗∗∗
0.016∗∗∗
(0.001)
(0.001)
30.period
0.034∗∗∗
0.020∗∗∗
(0.001)
(0.001)
31.period
0.037∗∗∗
0.026∗∗∗
(0.001)
(0.001)
32.period
0.041∗∗∗
0.031∗∗∗
(0.001)
(0.001)
33.period
0.046∗∗∗
0.036∗∗∗
(0.001)
(0.001)
34.period
0.050∗∗∗
0.041∗∗∗
(0.001)
(0.001)
35.period
0.054∗∗∗
0.045∗∗∗
(0.001)
(0.001)
36.period
0.057∗∗∗
0.049∗∗∗
(0.001)
(0.001)
37.period
0.061∗∗∗
0.053∗∗∗
(0.001)
(0.001)
38.period
0.063∗∗∗
0.055∗∗∗
(0.001)
(0.001)
39.period
0.066∗∗∗
0.058∗∗∗
(0.001)
(0.001)
40.period
0.069∗∗∗
0.061∗∗∗
(0.001)
(0.001)
41.period
0.072∗∗∗
0.063∗∗∗
(0.001)
(0.001)
42.period
0.076∗∗∗
0.066∗∗∗
(0.001)
(0.001)
43.period
0.079∗∗∗
0.069∗∗∗
(0.001)
(0.001)
44.period
0.082∗∗∗
0.071∗∗∗
(0.001)
(0.001)
45.period
0.085∗∗∗
0.073∗∗∗
(0.001)
(0.001)
46.period
0.088∗∗∗
0.075∗∗∗
(0.001)
(0.001)
47.period
0.093∗∗∗
0.079∗∗∗
(0.001)
(0.001)
48.period
0.096∗∗∗
0.082∗∗∗
(0.001)
(0.001)
49.period
0.099∗∗∗
0.085∗∗∗
(0.001)
(0.001)
1.art_treat (ref= NC)
0.005∗∗∗
0.001
(0.001)
(0.001)
2.art_treat (ref= NC)
0.013∗∗∗
0.010∗∗∗
(0.003)
(0.003)
2.period#1.art_treat (ref= NC)
0.002∗
0.002∗∗
(0.001)
(0.001)
2.period#2.art_treat (ref= NC)
0.005∗
0.005∗∗
(0.002)
(0.002)
3.period#1.art_treat (ref= NC)
0.003∗∗
0.004∗∗∗
(0.001)
(0.001)
3.period#2.art_treat (ref= NC)
0.001
0.003
(0.003)
(0.003)
4.period#1.art_treat (ref= NC)
0.005∗∗∗
0.006∗∗∗
(0.001)
(0.001)
4.period#2.art_treat (ref= NC)
0.005
0.006∗∗
(0.003)
(0.003)
5.period#1.art_treat (ref= NC)
0.005∗∗∗
0.007∗∗∗
(0.001)
(0.001)
5.period#2.art_treat (ref= NC)
0.009∗∗∗
0.011∗∗∗
(0.003)
(0.003)
6.period#1.art_treat (ref= NC)
0.005∗∗∗
0.007∗∗∗
(0.001)
(0.001)
6.period#2.art_treat (ref= NC)
0.006∗
0.009∗∗∗
(0.003)
(0.003)
7.period#1.art_treat (ref= NC)
0.006∗∗∗
0.009∗∗∗
(0.001)
(0.001)
7.period#2.art_treat (ref= NC)
0.008∗∗
0.012∗∗∗
(0.003)
(0.003)
8.period#1.art_treat (ref= NC)
0.007∗∗∗
0.010∗∗∗
(0.002)
(0.002)
8.period#2.art_treat (ref= NC)
0.011∗∗∗
0.015∗∗∗
(0.003)
(0.003)
9.period#1.art_treat (ref= NC)
0.005∗∗∗
0.009∗∗∗
(0.002)
(0.002)
9.period#2.art_treat (ref= NC)
0.012∗∗∗
0.016∗∗∗
(0.003)
(0.003)
10.period#1.art_treat (ref= NC)
0.006∗∗∗
0.010∗∗∗
(0.002)
(0.002)
10.period#2.art_treat (ref= NC)
0.014∗∗∗
0.018∗∗∗
(0.003)
(0.003)
11.period#1.art_treat (ref= NC)
0.008∗∗∗
0.012∗∗∗
(0.002)
(0.002)
11.period#2.art_treat (ref= NC)
0.015∗∗∗
0.020∗∗∗
(0.004)
(0.004)
12.period#1.art_treat (ref= NC)
0.008∗∗∗
0.013∗∗∗
(0.002)
(0.002)
12.period#2.art_treat (ref= NC)
0.013∗∗∗
0.019∗∗∗
(0.004)
(0.004)
13.period#1.art_treat (ref= NC)
0.004∗∗
0.009∗∗∗
(0.002)
(0.002)
13.period#2.art_treat (ref= NC)
0.008∗∗
0.014∗∗∗
(0.003)
(0.003)
14.period#1.art_treat (ref= NC)
0.005∗∗∗
0.010∗∗∗
(0.002)
(0.002)
14.period#2.art_treat (ref= NC)
0.009∗∗
0.015∗∗∗
(0.004)
(0.004)
15.period#1.art_treat (ref= NC)
0.005∗∗∗
0.010∗∗∗
(0.002)
(0.002)
15.period#2.art_treat (ref= NC)
0.013∗∗∗
0.020∗∗∗
(0.004)
(0.004)
16.period#1.art_treat (ref= NC)
0.004∗∗
0.010∗∗∗
(0.002)
(0.002)
16.period#2.art_treat (ref= NC)
0.014∗∗∗
0.020∗∗∗
(0.004)
(0.004)
17.period#1.art_treat (ref= NC)
0.001
0.007∗∗∗
(0.002)
(0.002)
17.period#2.art_treat (ref= NC)
0.014∗∗∗
0.021∗∗∗
(0.004)
(0.004)
18.period#1.art_treat (ref= NC)
0.002
0.008∗∗∗
(0.002)
(0.002)
18.period#2.art_treat (ref= NC)
0.013∗∗∗
0.020∗∗∗
(0.004)
(0.004)
19.period#1.art_treat (ref= NC)
0.001
0.007∗∗∗
(0.002)
(0.002)
19.period#2.art_treat (ref= NC)
0.015∗∗∗
0.022∗∗∗
(0.004)
(0.004)
20.period#1.art_treat (ref= NC)
-0.002
0.005∗∗∗
(0.002)
(0.002)
20.period#2.art_treat (ref= NC)
0.011∗∗∗
0.018∗∗∗
(0.004)
(0.004)
21.period#1.art_treat (ref= NC)
-0.002
0.004∗∗
(0.002)
(0.002)
21.period#2.art_treat (ref= NC)
0.012∗∗∗
0.018∗∗∗
(0.004)
(0.004)
22.period#1.art_treat (ref= NC)
-0.005∗∗∗
0.001
(0.002)
(0.002)
22.period#2.art_treat (ref= NC)
0.012∗∗∗
0.017∗∗∗
(0.004)
(0.004)
23.period#1.art_treat (ref= NC)
-0.006∗∗∗
-0.001
(0.002)
(0.002)
23.period#2.art_treat (ref= NC)
0.013∗∗∗
0.018∗∗∗
(0.004)
(0.004)
24.period#1.art_treat (ref= NC)
-0.007∗∗∗
-0.003∗
(0.002)
(0.002)
24.period#2.art_treat (ref= NC)
0.016∗∗∗
0.020∗∗∗
(0.004)
(0.004)
26.period#1.art_treat (ref= NC)
-0.009∗∗∗
-0.005∗∗∗
(0.002)
(0.002)
26.period#2.art_treat (ref= NC)
0.057∗∗∗
0.060∗∗∗
(0.004)
(0.004)
27.period#1.art_treat (ref= NC)
-0.004∗∗
-0.001
(0.002)
(0.002)
27.period#2.art_treat (ref= NC)
0.064∗∗∗
0.067∗∗∗
(0.004)
(0.004)
28.period#1.art_treat (ref= NC)
-0.003∗∗
-0.000
(0.002)
(0.002)
28.period#2.art_treat (ref= NC)
0.052∗∗∗
0.055∗∗∗
(0.004)
(0.004)
29.period#1.art_treat (ref= NC)
-0.002
0.001
(0.002)
(0.002)
29.period#2.art_treat (ref= NC)
0.049∗∗∗
0.053∗∗∗
(0.004)
(0.004)
30.period#1.art_treat (ref= NC)
-0.003∗
-0.001
(0.002)
(0.002)
30.period#2.art_treat (ref= NC)
0.049∗∗∗
0.051∗∗∗
(0.004)
(0.004)
31.period#1.art_treat (ref= NC)
-0.004∗∗
-0.001
(0.002)
(0.002)
31.period#2.art_treat (ref= NC)
0.049∗∗∗
0.048∗∗∗
(0.004)
(0.004)
32.period#1.art_treat (ref= NC)
-0.002
0.001
(0.002)
(0.002)
32.period#2.art_treat (ref= NC)
0.047∗∗∗
0.044∗∗∗
(0.004)
(0.004)
33.period#1.art_treat (ref= NC)
-0.000
0.003
(0.002)
(0.002)
33.period#2.art_treat (ref= NC)
0.048∗∗∗
0.044∗∗∗
(0.004)
(0.004)
34.period#1.art_treat (ref= NC)
0.002
0.005∗∗
(0.002)
(0.002)
34.period#2.art_treat (ref= NC)
0.043∗∗∗
0.038∗∗∗
(0.004)
(0.004)
35.period#1.art_treat (ref= NC)
0.002
0.006∗∗∗
(0.002)
(0.002)
35.period#2.art_treat (ref= NC)
0.039∗∗∗
0.033∗∗∗
(0.004)
(0.004)
36.period#1.art_treat (ref= NC)
0.002
0.006∗∗∗
(0.002)
(0.002)
36.period#2.art_treat (ref= NC)
0.048∗∗∗
0.041∗∗∗
(0.004)
(0.004)
37.period#1.art_treat (ref= NC)
0.003
0.006∗∗∗
(0.002)
(0.002)
37.period#2.art_treat (ref= NC)
0.045∗∗∗
0.038∗∗∗
(0.004)
(0.004)
38.period#1.art_treat (ref= NC)
0.003
0.007∗∗∗
(0.002)
(0.002)
38.period#2.art_treat (ref= NC)
0.041∗∗∗
0.033∗∗∗
(0.004)
(0.004)
39.period#1.art_treat (ref= NC)
0.003
0.007∗∗∗
(0.002)
(0.002)
39.period#2.art_treat (ref= NC)
0.040∗∗∗
0.031∗∗∗
(0.004)
(0.004)
40.period#1.art_treat (ref= NC)
0.006∗∗∗
0.010∗∗∗
(0.002)
(0.002)
40.period#2.art_treat (ref= NC)
0.046∗∗∗
0.038∗∗∗
(0.005)
(0.005)
41.period#1.art_treat (ref= NC)
0.009∗∗∗
0.012∗∗∗
(0.002)
(0.002)
41.period#2.art_treat (ref= NC)
0.048∗∗∗
0.039∗∗∗
(0.005)
(0.005)
42.period#1.art_treat (ref= NC)
0.008∗∗∗
0.010∗∗∗
(0.002)
(0.002)
42.period#2.art_treat (ref= NC)
0.048∗∗∗
0.040∗∗∗
(0.005)
(0.005)
43.period#1.art_treat (ref= NC)
0.009∗∗∗
0.012∗∗∗
(0.003)
(0.003)
43.period#2.art_treat (ref= NC)
0.049∗∗∗
0.041∗∗∗
(0.005)
(0.005)
44.period#1.art_treat (ref= NC)
0.009∗∗∗
0.013∗∗∗
(0.003)
(0.003)
44.period#2.art_treat (ref= NC)
0.049∗∗∗
0.042∗∗∗
(0.005)
(0.005)
45.period#1.art_treat (ref= NC)
0.012∗∗∗
0.016∗∗∗
(0.003)
(0.003)
45.period#2.art_treat (ref= NC)
0.047∗∗∗
0.040∗∗∗
(0.005)
(0.005)
46.period#1.art_treat (ref= NC)
0.010∗∗∗
0.015∗∗∗
(0.003)
(0.003)
46.period#2.art_treat (ref= NC)
0.049∗∗∗
0.044∗∗∗
(0.005)
(0.005)
47.period#1.art_treat (ref= NC)
0.008∗∗∗
0.013∗∗∗
(0.003)
(0.003)
47.period#2.art_treat (ref= NC)
0.054∗∗∗
0.048∗∗∗
(0.005)
(0.005)
48.period#1.art_treat (ref= NC)
0.007∗∗
0.012∗∗∗
(0.003)
(0.003)
48.period#2.art_treat (ref= NC)
0.056∗∗∗
0.051∗∗∗
(0.005)
(0.005)
49.period#1.art_treat (ref= NC)
0.005∗
0.010∗∗∗
(0.003)
(0.003)
49.period#2.art_treat (ref= NC)
0.053∗∗∗
0.048∗∗∗
(0.005)
(0.005)
Women’s age
0.002∗∗∗
0.005∗∗∗
(0.000)
(0.000)
Women’s age, squared
-0.000∗∗∗
-0.000∗∗∗
(0.000)
(0.000)
Reference Date between 2000-2005 (ref = 1995-2000)
0.001∗∗∗
(0.000)
Reference Date between 2005-2010 (ref = 1995-2000)
0.022∗∗∗
(0.000)
Reference Date after 2010 (ref = 1995-2000)
0.026∗∗∗
(0.000)
3.Hospital District
0.012∗∗∗
(0.003)
4.Hospital District
0.009∗∗∗
(0.003)
5.Hospital District
0.011∗∗∗
(0.003)
6.Hospital District
0.011∗∗∗
(0.003)
7.Hospital District
0.008∗∗∗
(0.003)
8.Hospital District
0.007∗∗
(0.003)
9.Hospital District
0.006∗∗
(0.003)
10.Hospital District
0.006∗
(0.003)
11.Hospital District
0.011∗∗∗
(0.003)
12.Hospital District
0.010∗∗∗
(0.003)
13.Hospital District
0.011∗∗∗
(0.003)
14.Hospital District
0.007∗∗
(0.003)
15.Hospital District
0.008∗∗∗
(0.003)
16.Hospital District
0.005∗
(0.003)
17.Hospital District
0.004
(0.003)
18.Hospital District
0.004
(0.003)
19.Hospital District
0.002
(0.003)
20.Hospital District
0.001
(0.003)
21.Hospital District
0.003
(0.003)
25.Hospital District
0.010∗∗∗
(0.003)
Household Income Decile = 2
0.005∗∗∗
(0.000)
Household Income Decile = 3
0.003∗∗∗
(0.000)
Household Income Decile = 4
0.001∗∗
(0.000)
Household Income Decile = 5
-0.001∗∗
(0.000)
Household Income Decile = 6
-0.002∗∗∗
(0.000)
Household Income Decile = 7
-0.003∗∗∗
(0.000)
Household Income Decile = 8
-0.004∗∗∗
(0.000)
Household Income Decile = 9
-0.004∗∗∗
(0.000)
Household Income Decile = 10
-0.005∗∗∗
(0.000)
Second Birth
-0.021∗∗∗
(0.000)
Third+ Birth
-0.019∗∗∗
(0.001)
Partnership Status
-0.021∗∗∗
(0.000)
-0.040∗∗∗
-0.072∗∗∗
Constant
(0.001)
(0.003)
19,203,536
19,203,536
Observations
575,921
575,921
Number of id
0.001∗∗∗
-0.001∗∗∗
Note: Standard errors in parentheses. ∗∗∗ p<0.01, ∗∗ p<0.05, ∗ p<0.1. Art_treat is a categorical variable that takes value 0 for women who conceived naturally, 1 for women who conceived through Medically Assisted Reproduction (MAR) treatments and 2 for women who remained childless after undergoing MAR treatments. Coefficients on the interaction between period and art_treat represent the probability of antidepressant use for women in the MAR+ and MAR- groups against women in the NC group. Second and Third+ birth are binary variables that take value one in the period a second or third and higher parity child is born and all period after that and 0 otherwise. Partnership status is a binary variable that takes value 1 if the woman is married or cohabiting in each 6 months period and 0 otherwise.
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
Note: NC refers to women who conceived naturally, MAR+ refers to women who conceived after MAR treatments and MAR- to women who underwent MAR treatments but did not deliver a live birth by the end of 2017. Model 2 estimates are adjusted for calendar year, age, household income decile (categorical), cohabitation status (binary), hospital district of residence, and transition to a second-, third-, or higher-order birth.
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
Note: NC refers to women who conceived naturally, MAR+ refers to women who conceived after MAR treatments and MAR- to women who underwent MAR treatments but did not deliver a live birth by the end of 2017. Estimates adjusted for calendar year and age.
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
Note: NC refers to women who conceived naturally, MAR+ refers to women who conceived after MAR treatments and MAR- to women who underwent MAR treatments but did not deliver a live birth by the end of 2017. Estimates are adjusted for calendar year, age, household income decile (categorical), cohabitation status (binary), hospital district of residence, and transition to a second-, third-, or higher-order birth.
Goisis. Medically assisted reproduction and mental health in Finland. Am J Obstet Gynecol 2023.
Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines.
A.G., M.P., and A.P. were supported by the European Research Council (#803958) and the Economic and Social Research Council (ES/M001660/1) grants. P.M. was supported by the Academy of Finland (#308247, #345219), the European Research Council (#101019329), and the Max Planck – University of Helsinki Center on Social Inequalities in Population Health. M.M. was supported by the Strategic Research Council (SRC), FLUX Consortium (#345130 and #345131).
The funders had no role in the study design, data collection, analysis, interpretation, or writing of the report. The corresponding author had full access to all data in the study, and had the final responsibility for the decision to submit it for publication.
Researchers may apply for permission from Statistics Finland to use the data. After permission has been granted, data will be available in the remote access system provided by the register holders. The code used in the analyses of this article may then be uploaded to the remote access system by contacting the authors.
Cite this article as: Goisis A, Palma M, Metsä-Simola N, et al. Medically assisted reproduction and mental health: a 24-year longitudinal analysis using Finnish register data. Am J Obstet Gynecol 2023;228:311.e1-24.
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