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Assisted Reproductive Technologies Present – 1991 2013

Assisted Reproductive Technologies Present – 1991 2013. Clinical developments and progress Novel laboratory techniques Improvement in take home baby rates Reduction in multiple pregnancy rates Ethics, Law, Psychology & Philosophy of ART.

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Assisted Reproductive Technologies Present – 1991 2013

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  1. Assisted Reproductive Technologies Present – 1991 2013 Clinical developments and progress Novel laboratory techniques Improvement in take home baby rates Reduction in multiple pregnancy rates Ethics, Law, Psychology & Philosophy of ART

  2. In Vitro Fertilization and the Right to Reproduce SuzzaneUniacke Bioethics; 1:241-254, 1987

  3. Conclusions The United Nations Declaration of Human Rights includes the right to found a family for women and men. It will seem greatly to strengthen the case of a particular procedure that it aims not simply to alleviate distress, but also to fulfill a fundamental human right. Robert Edwards and Patrick Steptoe have already cited the Declaration for men and women as a justification for their work

  4. Psychological Adjustment to Infertility and its Treatment : Male and Female Responses at Different Stages at IVF/ET Treatment Beaurepaire J et al J. Psychosom . Res. 38:229-240, 1994

  5. Results Anxiety & Depression Women Men Study Groups First IVF cycle (N= 113) * Repeat IVF cycle (N= 217) 30% 25% 30% 15% * Statistically significant

  6. Conclusions Evaluation of emotional distress in relation to stage of IVF / ET treatment cycle indicated that a major difficulty faced by both men and women regardless of stage of treatment was anxiety. Anxiety is well known to occur in response to perceived threat of some loss. It is not difficult to see this occurring within the IVF / ET context (uncertainty of treatment outcome, physical reactions to drugs, juggling the demands of career and treatment, etc.). Depression on the other hand results from actual loss !

  7. Conclusions Our study has attempted to move beyond evaluating male and female differences per se, to considering the context in which these differences may take on significance in terms of understanding the psychosocial adjustment of IVF couples. Men and women differ in how they cope, and there are differences in psychological states, dependent on the stage of IVF treatment. These issues may have implications for psychological support in IVF treatment programs

  8. Impact of the In - Vitro - Fertilization Process on Emotional, Physical and Relational Variables BoivinJ. et al Human Reprod. 4:903-907, 1996

  9. Mean Difference Between In Vitro-Fertilization and No-Treatment Daily Scores as a Function of the Phase-Stage of the Cycle and the Type of Reaction 0.6 0.4 Stress Optimism 0.2 Difference Score Physical discomfort Social support 0 0.2- Follicular/ Stimulation Ovulatory/ Retrieval- Transfer Luteal/ Waiting Period Phase/Stage

  10. Conclusions These findings suggest that the emotional impact of IVF might be mostly pronounced during the actual treatment process than is generally assumed from studies focusing on the impact of treatment failure. Variables such as optimism and physical discomfort which have previously received less attention in the literature significantly affected IVF treatment

  11. An Increased Vulnerability to Stress is Associated with a Poor Outcome of IVF Treatment Facchinetti F. et al Fertil. Steril. 67:309-314, 1997

  12. Hormonal and Clinical Parameters in Patients Submitted to IVF-ET Obtaining a Pregnancy (Success) or Not (Failure) Success (n=16) Failure (n=33) P *E2(pg/mL) *P (ng/mL) No. of follicles Mature oocytes Fertilized oocytes ETs 1847+69 1.8+1.3 10.9+5.4 2.3.+2.6 3.8+2.6 2.6+1.0 1636+42 1.6+1.2 9.4+7.2 1.8.+1.6 2.5+1.4 2.1+0.9 NS# NS NS NS 0.038 0.049 * Conversion factors to SI units are so follows: E2, 3.671;P, 3.180 NS#, not significant

  13. Performance on the Stroop Color and Word Conflict in Women Becoming Pregnant (Success) or Not (Failure) After IVF-ET Success Failure P No. of words No. of colors No. of colors-words Expected CW Interference 99.3+16.5 83.1+19.4 48.1+7 44+6.6 4.1+4.8 117.0+14.3 77.3+13.4 49.4+8.3 46.2.+4.5 3.1+4.5 0.0004 NS NS NS NS Values are means + SD

  14. Results mmHg Systolic Blood Pressure Diastolic Blood Pressure mmHg 140 90 80 + 130 + + 70 + + 60 120 -Success +Failure 50 Baseline 1 st 2 nd 3 rd Recovery sheet 110 Heart Rate beats / min 100 -Success +Failure 95 + 100 Baseline 1 st 2 nd 3 rd Recovery 90 sheet + • Changes in SBP, DBP, and HR in infertile women submitted to the Stroop Color and Word Test . Patients showing a biochemical pregnancy are reported in soli lines, whereas patients failing to conceive are reported in dotted Lines. • 1st, 2nd, and 3rd, measurements made after reading the three sheets of the test. • R measurements made 10 minutes after • the end of testing 85 + 80 75 -Success +Failure 70 Baseline 1 st 2 nd 3 rd Recovery sheet

  15. Conclusions The findings of the present study demonstrating a negative correlation between stress susceptibility and outcome of IVF-ET treatment. This gives further substantiation to the idea that programs of psychological support to infertile couples would increase the success of Assisted Reproduction Techniques

  16. Coping Style and Depression Level Influence Outcome in In-vitro Fertilization Demyttenaere K. et al Fertil. Steril. 69:1026-1033, 1998

  17. Psychometric Characteristics (Zung Depression Scale and Utrechtse Coping List) of the 98 Investigated Women Psychometric characteristics Score (mean +SD) Zung Depression Scale Utrechtse Coping list Active coping Palliative coping Avoiding Social support seeking Depressive coping Expression of negative emotions Comforting ideas 52.5+9.8 17.8+2.9 18.5+3.3 15.2+3.2 15.2+3.7 11.8+2.6 6.4+1.6 13.6+2.4

  18. Psychometric Variables (Zung Depression Scale and UtrechtseCoping List) in the Total Study Group (n=98) According to IVF Outcome IVF outcome Psychometric variable Not pregnant (n=75) Pregnant (n=23) t -test P value Zung Depression Scale Utrechtse Coping list Active coping score Palliative coping score Avoiding score Social support seeking score Depressive coping score Expression of negative emotions score Comforting ideas score 52.4+10.1 17.8+2.8 18.1+3.1 15.1+3.1 15.2+3.7 1.8+2.5 6.6+1.5 13.5+2.5 52.8+8.8 17.8+3.5 19.8+3.6 15.4+3.4 15.3+3.6 11.5+2.9 5.7+1.6 13.9+2.1 -0.19 -0.03 -2.17 -0.36 -0.17 0.39 2.44 -0.64 0.85 0.97 0.03 0.72 0.87 0.70 0.01 0.52 Note: The scores are given as means +SD

  19. Psychometric Variables (Zung Depression Scale and UtrechtseCoping List) in the Subgroup of Women with a Female Indication for IVF (n=39) According to IVF Outcome IVF outcome Psychometric variable Not pregnant (n=32) Pregnant (n=7) t -test Pvalue Zung Depression Scale Utrechtse Coping list Active coping score Palliative coping score Avoiding score Social support seeking score Depressive coping score Expression of negative emotions score Comforting ideas score 54.7+9.3 17.7+3.1 18.3+3.6 15.8+3.3 14.8+3.6 13.2+2.4 6.8+1.3 13.7+2.5 46.7+6.0 17.6+4.2 18.6+3.6 16.8+1.9 14.6+4.4 10.1+1.8 5.8+2.0 13.6+2.5 2.87 0.10 -0.17 -1.10 0.17 3.78 1.60 0.17 0.01 0.92 0.87 028 0.87 0.003 0.12 0.87 Note: The scores are given as means +SD

  20. Psychometric Variables (Zung Depression Scale and Utrechtse Coping List) in the Subgroup of Women with a Male Indication for IVF (n=52) According to IVF Outcome IVF outcome Psychometric variable Not pregnant (n=75) Pregnant (n=23) t -test Pvalue Zung Depression Scale Utrechtse Coping list Active coping score Palliative coping score Avoiding score Social support seeking score Depressive coping score Expression of negative emotions score Comforting ideas score 49.5+10.2 17.6+2.4 18.1+2.7 15.0+2.7 15.2+3.8 10.5+1.8 6.2+1.6 13.4+2.5 57.0+7.9 18.3+3.2 20.5+3.4 15.1+3.9 16.0+3.5 12.4+3.3 5.6+1.5 14.3+1.8 -2.77 -0.82 -2.31 -0.04 -0.66 -2.70 1.24 -1.53 0.009 0.42 0.03 0.97 0.52 0.01 0.23 0.13 Note: The scores are given as means +SD

  21. Conclusions Moreover, the expression of negative emotions is positively correlated with depressive symptomatology when the indications for IVF is female subfertility (emotions are transformed into quality directed against the women herself) but is negatively correlated with depressive symptomology when the indication for IVF is male subfertility (the emotions are transformed into anger directed toward the male partner)

  22. Psychological Reactions During In–Vitro Fertilization: Similar Response Pattern in Husbands and Wives Boivin J. et al Human Reprod. 13:3262-3267, 1998

  23. Results 2 Women Women Men 3.1 Men 1.75 3 2.9 Distress Optimism 1.5 2.8 2.7 1.25 2.6 1 2.5 HMG HCG HCG HMG Stage Stage Transfer Outcome Transfer Outcome Days 1-7 Days 8+ -1 Retrieval Days 1-7 Retrieval Days 8+ Retrieval -1 Retrieval Fertilization Fertilization Distress level as a function of in vitro fertilization (IVF) stage and sex Optimismlevel as a function of in vitro-fertilization (IVF) stage and sex

  24. Results 4 3.5 Women Women Men Men 3. 3.75 2.5 Fatigue Intimacy 3.5 2 3.25 1.5 1 3 HCG HMG Stage HMG HCG Stage Transfer Outcome Outcome Transfer -1 Retrieval Retrieval Days 1-7 Days 8+ Fertilization -1 Retrieval Days 8+ Retrieval Days 1-7 Fertilization Intimacy level as a function of in vitro fertilization (IVF) stage and sex Fatigue level as a function of in vitro fertilization (IVF) stage and sex

  25. Conclusions Couples responded in a similar way to IVF, indicating that different approaches to psychological care for men and women may not be warranted during that actual treatment cycle. We propose the most important psychological determinant of reactions during IVF is the uncertainty of treatment procedures

  26. Conclusions Spouses appear to be equally sensitive to this uncertainty and both appear to respond to it with ambivalent feelings involving distress and more positive feelings of hope and emotional closeness

  27. Treatment-Related Stresses and Depression in Couples Undergoing ART Treatment by IVF or ICSI Beutel M. et al Andrologia 31:27-35, 1999

  28. Effect of Treatment Outcome and Sex Depression Score (D-S) Presented are Means and Standard Deviations (1;2)*** 18 16 14 Women Men 12 10 Depression Score (D-S) 8 8.5 7.6 6 6.4 6.4 4.9 4 4.0 2 0 No pregnant (n=211 couples) Pregnant (n=39 couples) Delivery (n=31 couples) Presented are means and standard deviations. Groups are compared by two-way ANOVA (outcome by sex): Main effects for (1) outcome F (2) =6.67; and F(1)=32.93; interaction. N.S. Additional Students t-tests between the group “not pregnant” and “delivery” were significant (P<0.05) for women; t(65)=2.49 and men: t(68)=2.60; *** p<0.001

  29. Effect of the Number of Unsuccessful Treatment Cycles and Sex Depression Score (D-S) Women (1:2)*** 22 Men 20 18 16 14 12 Depression Score (D-S) 10 11.1 8 8.3 7.9 6 6.8 4 5.1 4.9 2 0 1 treatment cycle n=89 couples 2 treatment cycles n=91 couples > 3 treatment cycles n=31 couples Only couples without pregnancy or delivery are included. Presented are means and standard deviations. Groups are compared by two-way ANOVA (outcome by sex): Main effects for (1) number F (2) =3.85; and F(2) sex :F(1) =25.93; interaction. N.S. *** p<0.001; * p<0.005

  30. Conclusions The treatment outcome had a significant impact on the depression scores for women and men. In cases where the women had already delivered, both partners had the lowest depression scores. For men and women depression scores increased with a higher number of unsuccessful treatment cycles

  31. Evaluations of Emotional Reactions and Coping Behaviors as Well as Correlated Factors for Infertile Couples Receiving Assisted Reproduction Hsu. Y.L & KuoB.J J. Nursing Res. 10:291-301, 2002

  32. Conceptual Framework Diagram: Evaluation of Emotional Reactions and Coping Behaviors with Related Factors for Infertility Couples Receiving Assisted Reproductive Technologies Demographic Variables: sex age education level existing number of children Emotional reactions of infertile couples receiving assisted reproductive technologies Coping behaviors Infertile treatment factors: treatment duration treatment frequency infertility cause

  33. Correlation Between Emotional Reactions and Coping Behavior for Infertile Husbands Receiving Assisted Reproductive Technologies (N=120 Males) POMS total scale Variables r Confronting Distancing Self-Control Seeking Social Support Accepting Responsibility Escape-Avoidance Planful Problem Solving Positive Reappraisal Total Scale .40** -.03 .17 .11 .51** .64** .02 -.05 .32** *p<.05 **p<.01

  34. Correlation Between Emotional Reactions and Coping Behavior for Infertile Wives Receiving Assisted Reproductive Technologies (N=120 Females) POMS total scale Variables r Confronting Distancing Self-Control Seeking Social Support Accepting Responsibility Escape-Avoidance Planful Problem Solving Positive Reappraisal Total Scale .46** -.00 .36** -.07 .65** .65** -.09 -.30* .36* *p<.05 **p<.01

  35. Conclusions • This research indicated that, for infertile couples receiving ART treatment there are differences in emotional reactions between men and women. • Based on the fact that there are differences • in the coping behaviors adopted by infertile couples receiving ART treatment, medical • staff can acknowledge the individual differences in the coping behaviors adopted • by infertile couples facing treatment

  36. Conclusions • The research results show that emotional reactions and negative coping behaviors of infertile couples receiving ART treatments are correlated significantly. • The emotional reactions of infertile couples receiving ART treatments varied with different fundamental properties and infertility treatment factors

  37. Personality Factors and Emotional Responses to Pregnancy Among IVF Couples in Early Pregnancy: a Comparative Study Hjelmstedt A. et al Acta Obstet. Gynecol. Scand. 82:152-161, 2003

  38. Background Data Collected in Pregnancy Week 13 for the Women who had Undergone IVF (IVF Women) and their Male Partners (IVF Men) and for the Women who had Conceived Naturally (Control Women) and their Male Partners in the Control Group (Control Men) Women IVF (n=57) Controls (n=43) Statistics Controls (n=39) Statistics Men IVF (n=55) Year of age Mean +SD Range Education (%) Primary education Secondary education College/university Number of women with previous miscarriages and /or ectopic pregnancies Number of women with previous abortions Number of men with children by a previous partner 32.3+2.1 29-36 3.5 38.6 57.9 20 3 31.2+1.8 29-36 2.3 27.9 69.8 4 22 t -value=2.87 p-value =<0.01 34.0+2.1 27-51 7.2 49.1 43.6 5 33.1+2.8 27-39 0 20.5 79.5 5 t -value=1.33 NS X=12.85, d.f.=1 P-value<0.01 X=1.59,d.f.=1 NS x= 41.49, d.f.=2 NS x=8.93, d.f.=1 p<0.01 X=27.54, d.f.=1 p<0.0001

  39. Multivariate regression analyzes between the Infertility Raction Scale Total Scores (Independent variable) and the Scores of Ambivalence and Anxiety related to the Pregnancy Scales (Dependent Variables) for the IVF Women and the IVF Men Women (n=51) R2 p-value Men (n=51) R2 p-value Ambivalence Anxiety about loosing the pregnancy Anxiety related to the health of the baby -0.11 0.09 0.04 <0.05 <0.05 NS 0.02 0.04 0.11 NS NS <0.05

  40. Conclusions • This study showed that during early pregnancy both IVF women and IVF men seem to be more anxious about loosing the pregnancy compared with couples who have conceived naturally. It is likely that the degree of prior infertility distress affects how IVF subjects respond emotionally to their pregnancy. • It seems that couples who have conceived after IVF need additional emotional support in early pregnancy even though they score within the normal range on global anxiety. Possible ways of reducing with the IVF and antenatal clinics during early pregnancy stress management programs or support groups. Further studies are needed to investigate the effectiveness • of such interventions

  41. Should Fertilization Treatment Start with Reducing Stress? Campagne D.M. Human Reprod. 21:1651-1658, 2006

  42. Stressful Event Psychological Factors (Coping , Habituation, Resilience) • Stress • Autonomic System • Paraventricular Nucleus • Vasopresin • CRH • Sympathetic • System • Endorphin • ACTH • GnRH Pulse • LH, FSH • Adrenal • Medula • Adrenal • Cortex • Ovary • Estradiol • Progesterone • Adrenaline • Cortisol • Metabolic • Cardiovascular • Activation • HPG • Inhibition • Behavioral Activation • HP • Activation

  43. Short–Term Goals for Male and Female Fertility Patients (Pook et al. 1999) Reduction of feelings of helplessness, though coping with infertility Changes in sexual behavior Modification of negative cognitions as to infertility Overcoming deficiencies in knowledge about fertility Improving marital communication skills

  44. Markers for Stress Relevance for acute/chronic stress Relevance as stress marker for IVF outcome Substance/method • High (at OR, ET) • High (only at ET) • High • Questioned • ? • Site - dependent • ? • Probable • Questioned • Probable • ? • High • High • High • Probable • Probable • High • High • Questioned • Some • Questioned • Adrenaline • Noradrenaline • ACTH • Amylase • Dehydroepiandrosterone • Cortisol • Estrogen • Prolactin • Progesterone/allopregnanolone • LH • Vasopressin • NK cells • Cardiovascular reaction • to provoked stress • Depression (even subclinical) • High active coping • High avoidance • High expression of emotion • State anxiety • State –anxiety self –report • Trait anxiety • Trait –anxiety self -report • High • High • High • Variable • High • Variable • Variable • Probable • Variable • Probable • High • High • High • High • High • High • High • High • Questioned • Some • Questioned

  45. Diagnosis of Fertility Establish male and female chronic and acute stress levels with validated questionnaires If over thresholds Intensive stress reduction techniques for 3 months Establish stress levels and referral to fertility clinic Establish male and female chronic and acute stress levels with psychological and biological assays If over thresholds Intensive stress reduction through psychological and adjuvant/dietary treatments for 3 months When and if reduction is obtained: initiation fertility treatment with concurrent male and female stress management

  46. Interventions for Stress Control and Fertility Treatment • Protocols to include patient selection according to • existing chronic stress levels and response to acute • stressors • Preliminary treatment to reduce anxiety and depression before fertilization cycles are initiated • Cognitive-behaviural therapy • Relaxation training • Differential orientation as to infertility • Fertility sabbatical permit • Frozen back-up semen samples taken at low-stress • moments outside the fertilization cycle • Further refinement of fertilization techniques, such as removal of the acrosome before ICSI (Morozimi and Yanagimachi, 2005) • Establishing individual baselines and specific • stress markers • Establishing thresholds for referring • Monitoring for stress before and during fertility treatment • Procedural means • Psychological means • Technical means • Neurobiological • means

  47. Conclusions • The available evidence dictates that fertility treatment protocol should indicate stress management and stress reduction, as a factor of major importance consensus should be reached as to established protocol of stress management

  48. Conclusions • Stress reduction is non invasive less expensive and ethically acceptable way of improving fertility. The professional in reproductive medicine should always test for chronic stress before initiating fertility treatment and adjust selection and treatment protocol accordingly

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