Kris Bevilacqua

Implications of diminished ovarian reserve (DOR) extend well beyond reproductive concerns.

Objectives:To investigate whether a diagnosis of diminished ovarian reserve (DOR) in premenopausal years has adverse implications for skeletal health and quality of life. Design:This was a cross-sectional study of infertile, albeit healthy, mid-reproductive-age women (younger than 42 y) attending an academic infertility practice. Results:Eighty-nine women with varying causes of infertility were prospectively enrolled. Serum (cycle d 1-3) was collected for markers of ovarian reserve, bone metabolism, testosterone, and free androgen index. Bone mineral density (BMD) was assessed and categorized as low if the Z score was less than −1.0). Infertile women with DOR (n = 28) demonstrated significantly higher serum follicle-stimulating hormone levels (P < 0.001), lower müllerian-inhibiting substance (MIS) levels (P < 0.001), smaller ovarian dimensions (P < 0.05), lower testosterone levels (P = 0.035), lower free androgen index (P = 0.019), and enhanced bone metabolism (P = 0.003); although the prevalence of low BMD was higher in women with DOR who were younger than 41, this relationship was not of statistical significance (P = 0.106). Women younger than 41 years of age with DOR were significantly more likely to manifest disturbed sleep (P = 0.049) and acknowledge dissatisfaction with sexual intimacy (P = 0.004) compared with those with infertility and normal ovarian reserve. After adjustment for potential confounders, a diagnosis of DOR was significantly associated with low BMD, increased bone turnover, sexual dissatisfaction, and disturbed sleep. Conclusions:Our data suggest that DOR unmasked in the context of infertility evaluation has adverse implications for a womans well-being that extend well beyond the thus far appreciated reproductive concerns. A decline in ovarian hormones, specifically estrogen and testosterone, concomitant with DOR may be hypothesized as a mechanism that can explain the observed multisystem ramifications of DOR including increased bone turnover, low BMD, sexual distress, and disturbed sleep.

Chronic psychosocial stressors are detrimental to ovarian reserve: a study of infertile women

Objective. In a cross sectional study of 89 infertile women, we explore a relationship between aspects of psycho-social stress and ovarian reserve parameters. Methods. Questionnaires assessed general health and mood (profile of mood state) were administered. Serum (cycle days 1–3) was collected for biomarkers of ovarian reserve (follicle stimulating hormone (FSH), Mullerian Inhibitory Substance, Inhibin B) and stress (Cortisol). Multivariable regression analyses evaluated associations between parameters of interest (dysphoric mood, morning serum cortisol levels reflecting current stress; personal history of abuse, family and/or personal history of substance abuse reflecting chronic stress), with ovarian reserve biomarkers and with the likelihood of being diagnosed with diminished ovarian reserve (DOR). Results. Women with DOR were almost four times more likely to acknowledge personal history of recreational substance use (0.023) and family history of early menopause (p = 0.018). Adjusted analyses demonstrated advancing age, family history of early menopause, body mass index and chronic psycho-social stressors as independent correlates to serum FSH levels; age, family history of early menopause and chronic stress were predictive of likelihood for DOR. No demonstrable relationship was observed between ovarian reserve and current stress. Conclusions. Our findings identify aspects reflecting ‘chronic’ lifetime psycho-social stressors (i.e., personal history of abuse and of recreational drug use and/or family history of drug use) rather than ‘current’ stress (as reflected by dysphoric mood score and morning serum cortisol level) as detriments to ovarian reserve (i.e., were predictive of higher FSH levels and of an enhanced likelihood for DOR).

Reproductive implications of psychological distress for couples undergoing IVF

ObjectiveTo study implications of psychological distress on in vitro fertilization (IVF) outcome of an infertile couple.MethodsProspective study in an academic infertility practice setting. Couples undergoing embryo transfer (ET) following IVF were offered participation. Female patient (n = 89) and partner (n = 77) completed questionnaires reflecting dysphoria (POMS) and pessimism (LOT) after undergoing ET. Relationship between dysphoria and pessimism and implications of individual and couple’s psychological distress on IVF cycle parameters and outcomes were assessed using multivariable analyses.ResultsStatistically significant correlations between dysphoria and pessimism were observed within the individual and between partners, (p < 0.01). Higher couple pessimism correlated with longer duration of controlled ovarian hyperstimulation (COH, p = 0.02); higher partner psychological distress related to lower fertilization rate (FR, p = 0.03). On adjusted analyses, partner’s depression score was an independent predictor of reduced likelihood of clinical pregnancy (p = 0.03).ConclusionsOur data validate the concept of a “stressed couple”. Adverse implications of a couple’s psychological distress for gamete biology (longer duration of COH and lower FR with increasing distress) are suggested. Partner’s depressive scores negatively correlated with IVF success. These findings suggest the importance of including partner’s evaluation in studies that focus on effects of psychological stress on IVF outcome; future studies should examine whether interventions aimed at reducing psychological stress for the infertile couple may improve IVF cycle success.

Is affect associated with infertility treatment outcome

Infertility is a unique diagnosis consisting of a functional medical aspect and a psychologic recognition on the part of the patient that not being able to have a child is a life goal problem. In previous unpublished research performed by the authors, it was noted that approximately one third of patients who were initially identified as part of a research study had left treatment before the study was completed. Similar statistics were previously noted by Strauss et al. (1) and Camilleri (2). The aim of this study was to observe the correlation between psychologic effect and patient treatment status over time, and to determine why so many patients failed to follow through with treatment recommendations.

Sibling and self ovum donation for sisters with an intermediate FMR1 mutation: what's a program to do?

OBJECTIVE To increase awareness of the unique clinical and ethical considerations invoked by the request of a patient with premature ovarian failure (POF) and her nulliparous sister, both with intermediate-size mutations in fragile X mental retardation 1 (FMR1), to pursue sibling ovum donation. DESIGN Case report. SETTING Academic medical center. PATIENT(S) A 32-year-old woman with POF and her 26-year-old sister with occult diminished ovarian reserve, both of whom are carriers of an intermediate-size mutation in FMR1. INTERVENTION(S) Prospective donor ovarian function testing, genetic testing and consultation, and psychological evaluation; institutional assisted reproduction ethics committee consultation, and controlled ovarian hyperstimulation-IVF with cryopreservation of embryos for potential future self-use. MAIN OUTCOME MEASURE(S) Successful cryopreservation of embryos for autologous use by the prospective donor (younger sister) before ovum donation. RESULTS(S) Three blastocysts were frozen. CONCLUSION(S) Requests for sibling ovum donation, while understandable and ethically sanctioned under typical circumstances, prove particularly challenging in some patients with POF given uncertainties regarding the prognosis of the currently asymptomatic sister, risks of genetic transmission of POF, and fiduciary responsibilities to address the reproductive interests of the prospective donor. A multidisciplinary approach was highly beneficial in this case.

Full-sibling embryos created by anonymous gamete donation in unrelated recipients

OBJECTIVE To report the rare occurrence of full-sibling embryos in unrelated women using independently chosen donor sperm and donor oocytes in two different cycles unintentionally created at our IVF program, and to discuss the concept of disclosure to the patients. DESIGN Case report. SETTING Academic IVF program. PATIENT(S) Two women independently undergoing donor recipient cycles with anonymous donor oocytes and donor sperm. INTERVENTION(S) Both women received oocytes from the same donor several months apart and then by coincidence selected the same anonymous sperm donor to create anonymous full-sibling embryos. MAIN OUTCOME MEASURE(S) Clinical pregnancy after donor-recipient IVF cycle. RESULT(S) Both women conceived using the same donor sperm and donor oocytes in independent cycles, resulting in simultaneous pregnancy of full siblings. CONCLUSION(S) As providers with the knowledge that anonymous full sibling embryos have been created, we may have an obligation to disclose this information to the patients.

Primary Ovarian Insufficiency (POI) and Mood Disorders

Mood dysregulation is a common feature among women with premature ovarian insufficiency (POI), both before and after diagnosis. The etiology of POI may stem from endocrinological, genetic, surgical, or unknown causes, and all causes appear to have mood disorders at a rate that may be higher than that of the general female population. This chapter reviews the most common mood disorders, i.e., depression and anxiety, found in association with POI, the timing of their onset, theories of pathogenesis, and approaches to management. While not every patient with POI experiences a form of depression or anxiety, when a mood disorder is present, it should be clinically addressed.