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CP_10.06_Briz.FinalREV 9/20/06 10:52 AM Page 65 Current p SYCHIATRY How to treat depression, stress associated with infertility Tx Your understanding can ease the emotional roller coaster Shana Levy, MD Clinical instructor Department of psychiatry ® Dowden Health Media University of California, San Francisco Louann Brizendine,Copyright MD Clinical professor of psychiatry For personal use only Director, Women’s and teen girls’ mood and hormone clinic University of California, San Francisco Robert Nachtigall, MD Clinical professor of obstetrics, gynecology and reproductive sciences University of California, San Francisco Director, Reproductive endocrinology and infertility San Francisco General Hospital “ think it’s my fault we can’t get pregnant,” I says Mrs. S, who has been referred by her gynecologist for evaluation of anxiety and depres- sion. Mrs. S, age 33, and her husband have been trying to conceive their first child for 2 years. The couple has undergone infertility workups, including a semen analysis and hysterosalpingogra- phy, and results have been within normal limits. The gynecologist recommended intercourse every other day, but Mr. S developed stress-related erectile dys- function (which was treated with sildenafil). © 2006 Kari Van Tine / Getty continued VOL. 5, NO. 10 / OCTOBER 2006 65 For mass reproduction, content licensing and permissions contact Dowden Health Media. CP_10.06_Briz.FinalREV 9/20/06 10:52 AM Page 66 Infertility tually succeeds, anxiety often persists during Box 2 Infertility: Medical causes pregnancy. Your knowledge of medical infertility treatments’ emotional toll will help you under- are found in most cases stand, educate, and support infertile women and Infertility affects approximately 6 million U.S. their partners. women and their partners.3 As recently as the 1960s infertility was thought to be caused STRESS AND FERTILITY primarily by female psychological problems,4 Infertility—failure to conceive after 1 year of reg- such as neurotic, conflicted feelings about the ular unprotected intercourse—affects approxi- transition to adulthood or about sex, pregnancy, mately 10% of the reproductive-age U.S. popula- 5.6 labor, or motherhood. tion (Box).3-8 Does stress affect a woman’s chance This belief changed as researchers identified organic causes of infertility, such as blocked of becoming pregnant? Research into this ques- fallopian tubes, sperm abnormalities, and tion—voiced by Mrs. S—has produced conflict- anovulation. A definitive diagnosis can now ing results.5,9,10 be made in 85% to 90% of infertility cases, Stress does not universally prevent pregnan- and two-thirds of couples can conceive after cy; women have conceived as a result of rape. medical intervention.7 However, chronic extreme stress—such as that Age and fertility. Most experts recommend that imposed by war, imprisonment, or starvation— women age >35 who wish to conceive seek can change the menstrual cycle. Effects range gynecologic evaluation after 6 months of from subtle luteal-phase deficiency to menses unsuccessful intercourse. Chances of 9 becoming pregnant begin to decline at age 35 cessation. It may be that evolution favored and drop sharply after age 40.8 Beyond age 43, females of species who could “turn off ” fertility the only infertility treatment likely to be during stressful times to conserve physical successful is implanting an embryo created resources and “turn it back on” and bear offspring with an egg donated by a younger woman. after the threat passed. Neuroendocrine markers. Researchers examining the role of stress in infertility and its treatments have focused on the neuroendocrine system— Mrs. S has no personal or family history of particularly neurotransmitters such as prolactin, depression. Her depression has worsened as she endorphin, norepinephrine, dopamine, and corti- contemplates more invasive and expensive proce- sol. Although chronic anxiety and depression dures, such as intrauterine insemination (IUI) and in have been linked in animal models to neuroen- vitro fertilization (IVF). docrine mechanisms of infertility,4 findings in Her Beck Depression Inventory score of 22 indi- humans have been mixed (Table 1).11-15 cates mild depression. She is not actively suicidal, Psychological interventions. Some investigators but she sometimes doubts that life is worth living. have sought to determine whether psychological She feels like a failure and wants to know if you interventions can increase pregnancy rates in think stress is contributing to her infertility. infertile women. In one prospective, controlled, single-blind Women with a 2- to 3-year history of infertility study, 184 women who had been trying to conceive despite repeated treatments are at risk of stress, for 1 to 2 years were randomly assigned to 10 ses- anxiety, and depression.1 Even if treatment even- sions of group cognitive-behavioral therapy (CBT), 66 Current VOL. 5, NO. 10 / OCTOBER 2006 p SYCHIATRY CP_10.06_Briz.FinalREV 9/20/06 10:52 AM Page 67 Current p SYCHIATRY Table 1 Does stress reduce fertility? Research results are mixed Study design (year of publication) Results Controlled prospective trial, IVF success rates were comparatively lower among 40 women undergoing IVF (1992)11 women with high cortisol concentrations Women with high prolactin concentrations had greater numbers of oocytes but lower fertilization rates Failure to conceive was associated with high depression symptom scores, maladaptive coping strategies, and avoidance behavior Controlled prospective trial, Depressed women had a lower pregnancy rate after 330 infertile women (1993)12 a first IVF-ET, compared with nondepressed women Uncontrolled prospective trial, Mean adrenaline, norepinephrine, and cortisol levels 13 women without a history excreted in urine were not significantly different in of infertility (1997)13 menstrual cycles when women conceived, compared with nonconception cycles Little relationship seen between psychological measures of mood state and excretion of adrenaline and cortisol Controlled, prospective trial, Patients who conceived with IVF-ET had lower systolic blood 49 infertile women (1997)14 pressures and slower heart rates under stress-test conditions than did those who did not conceive Controlled prospective trial, No difference in hormonal stress markers during first 40 women after successful 27 days of pregnancy between women who later gave birth IVF-ET (1998)15 and those who experienced miscarriages Physiologic stress hormone concentrations showed little association with psychological scores, and high anxiety and stress levels did not appear to prevent pregnancy IVF: In vitro fertilization IVF-ET: In vitro fertilization with embryo transplant a standard support group, or usual care. Sixty-four pregnancy rates, compared with 25 women who women withdrew before the study ended. After 1 received usual care.16 Conversely, a literature review year, women who received psychological interven- and evaluation of 25 studies found psychosocial tions—47 in the CBT group and 48 in the standard interventions unlikely to improve pregnancy rates support group—had statistically significant higher in infertile women.17 continued VOL. 5, NO. 10 / OCTOBER 2006 67 CP_10.06_Briz.FinalREV 9/20/06 10:53 AM Page 68 Inferrtility Methodologic problems. Most studies of stress’ An infertile woman might respond to psycho- influence on fertility are small, and many have logical counseling or psychotherapy even when a methodologic problems.4 In some, researchers pregnancy is not achieved.4,17,19 lumped together women whose infertility was caused by disparate diagnoses such as male-factor CASE CONTINUED: STRAIN AND ANGER infertility, blocked fallopian tubes, and advanced You begin to see Mrs. S weekly for supportive ther- age. Retrospective studies also must be interpret- apy, using cognitive restructuring and relaxation ed with caution because: techniques to alleviate her anxiety and depression. • patients who did not become pregnant may She decides not to start an antidepressant because have exaggerated the degree of their depression she does not want to be on medication if she and its effects becomes pregnant. • those with pre-existing medical problems During the next 2 months would know they were unlikely she finishes an unsuccessful IUI to conceive and might have been cycle and reports that her relationship more depressed before and dur- Terms such as with her husband has become strained. ing infertility treatments.18 ‘incompetent cervix’ She avoids friends who have children and The literature on infertility and ‘old eggs’ lead feels angry when she sees a pregnant and stress is dominated by corre- infertile women woman. She dislikes going to family events lational studies. Because of insuf- to blame themselves because relatives sometimes ask, “When ficient controlled data, it is are you going to get pregnant?” unclear whether stress affects the Her work as a manager is suffering reproductive system.4 because of her many visits to fertility spe- Recommendation. When counseling patients cialists. Her Beck Depression Inventory score has about the role of stress in infertility and its treat- increased to 33, indicating worsening depression. ment, we recommend emphasizing that: • infertility can cause stress in many areas of INFERTILITY’S PSYCHOLOGICAL TOLL life Patients rarely accept infertility with equanimity, • the effect of stress on fertility, if any, is like- and their responses include shock, denial, anger, ly to be minimal for most women. isolation, guilt, and