NAME OF RESEARCHER
Dr Lauren Carson
NAME OF SUPERVISOR
Professor Robert Stewart
PROJECT TITLE:
Associations between Assisted Reproductive Technologies and Women's Mental Health: an investigation using clinical data linkage
CLINICAL ACADEMIC GROUP:
N/A
START & FINISH DATES:
1st October 2019 – 20th December 2022
PROJECT DESCRIPTION:
Recent estimates suggest that approximately 20,000 children are born through assisted reproduction technologies (ART) each year in the UK (1, 2), a figure likely to rise based on current trends (3). Whilst an ART pregnancy can bring great joy, this proposal focusses on the less recognised and underexplored consequences of an ART pregnancy on the mental health of the mother and her child.
Infertility per se induces considerable life stress and can include societal repercussions, personal suffering, and mental health disorders (4); superimposed on this, engaging in ART is in itself inevitably stressful, with many expectations, disappointments, and reports of stress, anxiety and mental health issues (5-8). Once pregnant, the mother who has conceived by ART may also be at risk of adverse obstetric, perinatal and infant outcomes (9), which in turn may increase maternal perinatal anxiety. Despite isolated
reports, remarkably little is known about the influence of ART on the mental health of the mother. One study using Swedish health registers have reported 10-years post ART treatment, that women who had undergone ART treatment were at an increased risk of adjustment disorder (a group of symptoms, such as stress, feeling sad or hopeless, and physical symptoms that can occur after you go through a stressful life event), compared to controls (assessed through psychiatric hospitalisation) (10). Since maternal mental health disorders (anxiety, depression and stressful life events) in the perinatal period (11) are known to affect behavioural, cognitive and emotional development of the child (12-14) the consequences may be far reaching.
To date, the few studies on ART pregnancies and maternal mental health have been predominantly cross-sectional in design and have used self-perceived mental health assessments, rather than clinical diagnosis. Findings are ambiguous, although several have suggested an association with increased rates of anxiety and depression throughout and after pregnancies conceived through ART (15-17), another predicting relapse of mental health disorders following infertility treatment (18), and one finding no association (19). None has been conducted in the UK. There is also a potential for bias due to the “healthy cohort effect”, as women who are experiencing mental health disorders are less likely to consent to research studies (10). A recent study from Taiwan found that psychological health was poorest during the first trimester and at two-months postpartum of women who had an ART pregnancy compared to controls (15). These authors also highlighted the need to conduct further research beyond two months postpartum to explore the impact of ART on longer term maternal mental health outcomes.
Studies conducted at the population level (health register-based research) are likely to provide the most reliable data. The few to have used national registers to examine ART and maternal mental health include a report from the Netherlands, in which women with a depression diagnosis before ART treatment received fewer ART treatments and were less likely to achieve an ART live birth, leading to the conclusion that these women may be more vulnerable to later mental health relapses (20). In a Swedish national register-based cohort study (n= 23,557), 4.4% of women had been diagnosed with depression/anxiety and/or dispensed antidepressants before their first IVF cycle. This in turn was associated with reduced odds of pregnancy or a live birth (21). However, long-term mental health post-treatment was not assessed. Research into the relationship between exposure to ART and maternal mental health disorders is therefore limited, and none as yet in contemporary UK populations. Furthermore, no attention has been paid to the reasons for ART (female or male causes of infertility) and it is not known if the use of donated (third party) gametes puts the mother at increased risk of mental health disorders.
We will retrospectively examine data from women within CRIS who have experienced a maternity episode at GSTT or KCH. This will provide a unique cohort who have accessed secondary mental health care or psychological therapies (IATPUS) and have also accessed maternity services. The mental health disorders of the women pre- and post-exposure to ART (and maternity services) will thus be accessible and measurable through contact rates with SLaM Services, as well as linkage with ART data from the HFEA. These retrospective data will allow us to examine the relationship between maternal mental health service use and ART.
This research will benefit the many women who have a child conceived by ART and who experience both short- and long-term mental health problems. Further beneficiaries including their health care providers (Maternity staff, GP, Health Visitors and Mental Health Workers), and their families. Given that maternal mental health is known to impact upon the risk of increased mental health problems in the child, the child is the most likely to benefit. Academic beneficiaries will include, those working in the field of
infertility, maternal mental health and life course sciences, all of whom will gain from an improved evidence base to their work.
References
1. Fertility treatment 2014–2016 – Trends and figures [press release]. 2018.
2. Ledger WL, Anumba D, Marlow N, Thomas CM, Wilson ECF, the Cost of Multiple Births Study G. Fertility and assisted reproduction: The costs to the NHS of multiple births after IVF treatment in the UK. BJOG: An International Journal of Obstetrics & Gynaecology. 2006;113(1):21-5.
3. Ferraretti AP, Nygren K, Andersen AN, de Mouzon J, Kupka M, Calhaz-Jorge C, et al. Trends over 15 years in ART in Europe: an analysis of 6 million cycles†. Human Reproduction Open. 2017;2017(2).
4. Domar AD, Gross J, Rooney K, Boivin J. Exploratory randomized trial on the effect of a brief psychological intervention on emotions, quality of life, discontinuation, and pregnancy rates in in-vitro fertilization patients. Fertility and Sterility. 2015;104(2):440-51.e7.
5. Haimovici F, Anderson JL, Bates GW, Racowsky C, Ginsburg ES, Simovici D, et al. Stress, anxiety, and depression of both partners in infertile couples are associated with cytokine levels and adverse IVF outcome. American Journal of Reproductive Immunology. 2018;79(4):e12832.
6. Rooney KL, Domar AD. The relationship between stress and infertility. Dialogues in clinical neuroscience. 2018;20(1):41-7.
7. Cousineau TM, Domar AD. Psychological impact of infertility. Best Practice & Research Clinical Obstetrics & Gynaecology. 2007;21(2):293-308.
8. Ying L, Wu LH, Loke AY. The effects of psychosocial interventions on the mental health, pregnancy rates, and marital function of infertile couples undergoing in vitro fertilization: a systematic review. Journal of assisted reproduction and genetics. 2016;33(6):689-701.
9. Sullivan-Pyke CS, Senapati S, Mainigi MA, Barnhart KT. In Vitro fertilization and adverse obstetric and perinatal outcomes. Seminars in perinatology. 2017;41(6):345-53.
10. Yli-Kuha AN, Gissler M, Klemetti R, Luoto R, Koivisto E, Hemminki E. Psychiatric disorders leading to hospitalization before and after infertility treatments. Human reproduction. 2010;25(8):2018-23.
11. Glover V, Ahmed-Salim Y, Capron L. Maternal Anxiety, Depression, and Stress During Pregnancy: Effects on the Fetus and the Child, and Underlying Mechanisms. In: Reissland N, Kisilevsky SB, editors. Fetal Development: Research on Brain and Behavior, Environmental Influences, and Emerging Technologies. Cham: Springer International Publishing; 2016. p. 213-27.
12. Glover V. Prenatal Stress and Its Effects on the Fetus and the Child: Possible Underlying Biological Mechanisms. In: Antonelli MC, editor. Advances in Neurobiology: Perinatal Programming of Neurodevelopment. Advances in Neurobiology. 10: Springer New York; 2015. p. 269-83.
13. O'Connor TG, Caprariello P, Blackmore ER, Gregory AM, Glover V, Fleming P, et al. Prenatal mood disturbance predicts sleep problems in infancy and toddlerhood. Early human development. 2007;83(7):451-8.
14. O'Connor TG, Heron J, Golding J, Beveridge M, Glover V. Maternal antenatal anxiety and children's behavioural/emotional problems at 4 years: Report from the
Avon Longitudinal Study of Parents and Children. The British Journal of Psychiatry. 2002;180(6):502-8.
15. Huang M-Z, Kao C-H, Lin K-C, Hwang J-L, Puthussery S, Gau M-L. Psychological health of women who have conceived using assisted reproductive technology in Taiwan: findings from a longitudinal study. BMC Women's Health. 2019;19(1):97.
16. Monti F, Agostini F, Fagandini P, La Sala GB, Blickstein I. Depressive symptoms during late pregnancy and early parenthood following assisted reproductive technology. Fertility and Sterility. 2009;91(3):851-7.
17. Lee S-H, Liu L-C, Kuo P-C, Lee M-S. Postpartum Depression and Correlated Factors in Women Who Received In Vitro Fertilization Treatment. Journal of midwifery & women's health. 2011;56(4):347-52.
18. Holley SR, Pasch LA, Bleil ME, Gregorich S, Katz PK, Adler NE. Prevalence and predictors of major depressive disorder for fertility treatment patients and their partners. Fertility and sterility. 2015;103(5):1332-9.
19. Vikström J, Sydsjö G, Hammar M, Bladh M, Josefsson A. Risk of postnatal depression or suicide after in vitro fertilisation treatment: a nationwide case–control study. BJOG: An International Journal of Obstetrics & Gynaecology. 2017;124(3):435-42.
20. Sejbaek CS, Hageman I, Pinborg A, Hougaard CO, Schmidt L. 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. Human Reproduction. 2013;28(4):1100-9.
21. Cesta CE, Viktorin A, Olsson H, Johansson V, Sjölander A, Bergh C, et al. Depression, anxiety, and antidepressant treatment in women: association with in vitro fertilization outcome. Fertility and Sterility. 2016;105(6):1594-602.e3.
PROGRESS IN PAST YEAR:
In the past year we have been able to complete data linkage between the HFEA dataset and CRIS. Following this, analysis of the dataset is underway but has been delayed due to the PI (Dr Carson) being on maternity leave from November 2022 – November 2023.
PUBLICATIONS & CONFERENCES ATTENDED:
None to date but publication detailing the linkage between the HFEA and CRIS datasets in preparation.