The tragedy of another loss: Helping patients with recurrent miscarriage Ruth Lathi, MD Director of Recurrent Pregnancy loss Stanford University

Disclosures No financial disclosures I am not a psychologist or licensed therapist Do we have any in the audience?

Learning objectives Review emotional aspects of pregnancy loss Define normal grief response Identify patients who are at risk for major depression Discuss how and when to refer patients

Miscarriage Most women with miscarriage or RM have never experienced limitations in their health before General knowledge about miscarriage is limited My personal experience is that emotional reactions to miscarriage affect patient care in a variety of ways Distrust Inability to concentrate/remember Lack of engagement in treatment Giving up Poor self care Loss of social support – social withdrawl They are shocked or surprised after the first miscarriage. Often can accept that it is a random event. Then the second one can hit even harder. The third harder still. Its understandable that RM is associated with many psychological responses including depression, anxiety, guilt, marital discord, and other social complications. Distrust in medical profession, distrust in their ability to carry pregnancy A commonly held belief in general population that miscarriage is preventable, and related to a womans activity in pregnancy.

5 stages of Grief Denial Anger Bargaining Depression Acceptance Overly simplistic and not linear – variable Experiencing pain, accepting loss, adjusting to new world Kubler-Ross 1969

Major Depression Uncomplicated Grief Hopelessness Tearfulness Insomnia Loss of Appetite Loss of concentration Decreased libido Somatic s symptoms Guilt Hopelessness Decreased Self Esteem and Feelings of Worthlessness Suicidal Ideation Anhedonia Anergy Preservation of Self Esteem Ability to Imagine a Future Greif reaction is a normal reaction to a tragedy or loss.

Major Depression and Miscarriage Controlled studies report that miscarriage is associated with an increased risk for, or recurrence of major depression Women with a previous history of major depression are an especially high risk group for recurrence of MDD Increased risk for depression lasts up to one year after miscarriage Poor social support, low self esteem, prior losses increase risk of depression (Neugebauer et. al. JAMA, 277(5): 383-8,1997; Klier et al, J Affect Disord 59: 15-21, 2000) ) JAMA. 1997 Feb 5;277(5):383-8.Major depressive disorder in the 6 months after miscarriage.Neugebauer R, Kline J, Shrout P, Skodol A, O'Connor P, Geller PA, Stein Z, Susser M..OBJECTIVE: Women miscarrying have increased risk for first or recurrent MD In 6 months s/p loss Increased risk associated with: childless, prior repro loss, age > 35 years To test whether risk associated with stage of pregnancy or attitude towards pregnancy DESIGN: Cohort study. SETTING: The miscarriage cohort consisted of women attending a medical center for a spontaneous abortion (n=229); the comparison group was a population-based cohort of women drawn from the community (n=230). of a nonviable intrauterine pregnancy before 28 completed weeks of gestation MAIN OUTCOME MEASURE: Reliable: DIS RESULTS: NOTE: 54% of women w/previous h/o MDE had recurrence Low rates compared to other community studies of MDE in women but showed higher risk: 10.9% experienced an episode of major depressive disorder, compared with 4.3% of community women. The overall (RR) for an episode of major depressive disorder for miscarrying women was 2.5 (95% confidence interval [CI], 1.2-5.1) Pertinent for infertility clinic: CHILDLESS HAVE HIGHER RISK = 5 vs. 1.3 w/children Higher for childless women (RR, 5.0; 95% CI, 1.7-14.4) than for women with children (RR, 1.3; 95% CI, 0.5-3.5) (P<.06).

Prevalence of Major Depression in Women with Recurrent Miscarriage Maryanne: can you move the 30% SC Klock et al. Psychological distress among women with recurrent spontaneous abortion. Psychosomatics, 1997 38: 503-507 Hypothesis: Increased rates of depression with increasing numbers of miscarriage Having a child would decrease risk for depression 100 consecutive women at the Brigam and Women’s Recurrent Miscarriage clinic in Bostonanonymous questionnaires incl. Marlow crowne Social Desirability Scale, BDI, STAI, Rosenberg Self Esteem Scale, Dyadic Adjustment Scale and Multidimensional Health Locus of control Scale. 32% had BDI >14=clinically significant depression. 43-70% reported mild-moderate neurovega symptoms of MDE, even if didn’t meet criteria MDE Mean levels of state and trait anxiety elevated and wide ranges in response Decreased self esteem correlated with greater anxiety and approx 16% of women had decreased self esteem Interestingly, in this study higher scores for external locus of control—chance and others Marital adjustment average levels Important finding that having a child didn’t decrease the risk for depression and anxiety Women with a history of recurrent miscarriage are at an increased risk for depression compared to women without this history Interestingly 50% of the women had had some psychotherapy, with average duration of 10 month while 8% had had meds in past 40-70% of women with RPL had some symptoms of Depression without meeting clinical criteria for MDD Klock SC et al. Psychosomatics 1997; 38: 503-507.

DSM V Criteria Major Depression Five or more of the following symptoms have been present during the same 2 week period and represent a change from previous functioning and at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure: depressed mood most of the day markedly diminished interest or pleasure in activities significant weight changes insomnia or hypersomnia psychomotor agitation or retardation fatigue or loss of energy feelings of worthlessness or inappropriate guilt diminished ability to think or concentrate, indecisiveness recurrent thoughts of death

Anniversary reactions Need to make sense of the experience Psychological reactions and adaptation after miscarriage Common Themes Profound Grief Anniversary reactions Need to make sense of the experience Sense of responsibility Harris and Daniluk, Human Reproduction, 2010 Grief: 5 stages DABDA Denial Anger Bargaining Depresion Acceptance Dl Harris and JC Daniluk. The experience of spontaneous pregnancy loss for infertile women who have conceived through assisted reproductive technology. Human Reproduction 2010 25(3):714-720 Psychological reactions/adaptation may be different in women with fertility issues. Previous miscarriage work has focused on women without prior h/o infertility. Infertility can be defined as either problem with conceiving and or live birth. Study of women with infertility, which included 10 women with previous miscarriages Phenomenological interview study b/c so little work done What helped: 1) Support from close friends and family in terms of rides/meals 2) Sharing of experience w/others close friends/family who had been through it 3) Plan for next medical steps In grief of all kinds, people need support and structure—infertility asks for its own kind of support and structure, as can be seen in What didn’t help 1) Evaluative statements :not very pregnant” “lucky so early” 2) Not close people asking questions 3) Family probing about when try again Note re disengagement: one woman even said she wanted the test to come back negative b/c couldn’t imagine all the anxiety for 9 months Note theme of actue loss on chronic loss

Miscarriage: Gender Specific Issues Sexual Issues Both Men and Women: Body image distortions + Lowered self esteem=decreased libido and sexual dysfunction Grief Symptoms Women: Longer duration of grief; more intrusion Men: More avoidance Communication Issues Women: Intensity of grief directly related to perceived sense of communication quality Men: Sexual satisfaction directly related to perceived communication Serrano and Lima Recurrent Miscarriage: Psychological and relational consequences for couples. Psychological PsychologyandPsychotherapy:Theory,ResearchandPractice(2006),79,585–594 30 couples with at least 3 miscarriages and no living children Gender differences: women experience higher levels of intrusion, avoidance and overall stress than men as measured by Impact of Life Events Scale Grief scores, as measured by perinatal grief scale, were higher for women although it is clear that men grieve In general interpersonal communication, tenderness and satisfaction high, but decreased sexual frequency post miscarriage Grief related to quality of communication in women and sexual satisfaction in men Breutel et al, 1996; Conway & Russel, 2000

Gender Differences in Major Depressive Disorder (MDD) Major depression is approximately twice as common in women as in men Onset of gender difference is in early adolescence 1 month point prevalence: Women 5%-9% Men: 2%-3% Lifetime risk Women: 10%-25% Men: 5%-12% Kessler et al. J Affect. Disord 1993

Psychological Reactions in Women with History of Recurrent Miscarriage and Infertility Psychological disengagement from future pregnancies/fertility treatments* Intense feeling of lack of control* Shared sense of loss with partner* Strong sense of injustice/unfairness* Extreme sense of social awkwardness* Harris and Daniluk, Human Reproduction, 2010

Gender Differences in Clinical Features of Major Depression Women are more likely to present with atypical depression (increased appetite and weight gain, hypersomnia, rejection sensitivity) Women are more likely to have a seasonal pattern with onset of depression during fall/winter Women are more likely to have associated somatic/pain symptoms

Gender Differences in MDD Co-Morbidities Women with MDD have higher rates of co-morbid anxiety and eating disorders compared to men Men with MDD have higher rates of co-morbid substance abuse Marcus, SM. J Affect Disord 2005; 87: 141-50. Remember what we learned that panic d/o is more common in women--twice as common and substance abuse more common in men

Psychopharmacological Treatment for Major Depression Antidepressants Buproprion Serotonin Reuptake Inhibitors (SSRIs) Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Psychological Treatments for Major Depression in Women Cognitive Behavioral Therapy Interpersonal Psychotherapy Grief Interpersonal Role Transitions Interpersonal Role Disputes Interpersonal Deficits Psychodynamic Psychotherapy

Risk Factors for Major Depression Female Sex Age Family History Early parental loss/separation Negative Life Events Previous history of depression Women 2:1 Age 20-40 Family history 1.5-3 Note that risk of recurrence increaes with each successive episode leading to concept of KINDLING=lowering of the threshold for the impact of an event

When to Refer impairment of normal activities, work, fun, sleep etc.. suicidality (of course) persistent tearfulness Persistent guilt/ perseveration/delusion grief symptoms lasting more than 1 month? patient request concern of partner H/O depression or anxiety

Summary That’s where we come in! Miscarriage is a vulnerable time for most women. Helpful to know how to differentiate normal grief from symptoms concerning for MDD Low threshold for referral –or screen everyone CBT can help Not everyone needs medication Tender loving care is proven to help – That’s where we come in!

Moving forward - TLC Patients should be reassured that they did NOTHING wrong RPL patients have a high chance of live birth with persistence We don’t need an answer to give patients realistic prognosis (“counsel with confidence”)

Keep the door open Most women have a live birth Give hope whenever possible Tragic when patients give up without knowing all facts

Thank you Questions?