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The psychological impact of ovarian reserve testing: a qualitative analysis
CONCLUSIONS: pET is associated with significant improvement in PR and trend towards increase IR and OP versus regular ET or DET. Personalization of the endometrial factor in the diagnostic work-up of the infertile couple must be considered. Supported by: Igenomix. On behalf of the ERA RCT Consortium. ClinicalTrials.gov NCT 01954758. O-116 Tuesday, October 18, 2016 11:30 AM DIMINISHED BUT NOT DECLINING: LONGITUDINAL ANDROGEN PRODUCTION AND FOLLICULAR MEASURES OF OVARIAN RESERVE IN CANCER SURVIVORS COMPARED TO M. D. Sammel,b HEALTHY CONTROLS. K. Cameron,a M. M. Prewitt,c M. E. Lynch,d C. Gracia.a aUniversity of Pennsylvania, Philadelphia, PA; bBiostatistics and Epidemiology, Univ. of Pennsylvania, Perelman School of Medicine, Philadelphia, PA; cObstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA; dUniversity of Pennsylvania School of Medicine, Ardmore, PA. OBJECTIVE: Recent studies have examined levels and the rates of change of follicular measures of ovarian reserve in cancer survivors over time. No data exist examining androgen production in this population, which is important for folliculogenesis and sexual health. This study sought to examine levels and rate of change in testosterone and dehydroepiandrosterone sulfate (DHEAS) in a cohort of cancer survivors compared to similar-aged healthy controls. DESIGN: Prospective cohort. MATERIALS AND METHODS: Participants were seen for annual visits that included early follicular phase hormone analyses and pelvic ultrasounds. Changes in free testosterone, DHEAS, anti-mullerian hormone (AMH) and antral follicle count (AFC) were modeled over the study period using random effects linear regression. Exogenous hormone use was an exclusion criterion. RESULTS: One hundred and nine cancer survivors (age range 18-39 years, mean 10 years after treatment) and 86 controls were followed on average for 15 months. The absolute levels of hormones differed between the groups. In adjusted models, geometric mean (GM) AMH levels in the cancer survivors at age 30 were 70% lower than in controls (0.64 ng/mL vs. 2.14 ng/mL, p<0.001), AFC was 52% lower (GM 23 vs. 11 follicles, p<0.001), testosterone was 25% lower (GM 0.45 nmol/L vs 0.60 nmol/L, p<0.001) and DHEAS was 33% lower (GM 0.91 nmol/L vs 1.36 nmol/L, p<0.001). The rate of change over time in AMH and AFC differed in the 2 groups: AMH declined at a rate of 0% per year in survivors, compared to 4% per year in controls (p¼0.048). Decline in AFC was 0.1% per year for survivors, compared to 3% in controls (p¼0.11). In both controls and survivors, the levels of testosterone and DHEAS remained stable, (p¼0.73 and 0.66, respectively). Neither BMI nor race confounded associations. CONCLUSIONS: This is the first longitudinal study to examine changes in androgens and follicular measures of ovarian reserve over time in young cancer survivors. The rate of change of measures of ovarian reserve is faster in controls than survivors, likely related to lower baseline levels in survivors. However, despite different baseline androgen levels, neither group shows any appreciable decline over time, appearing to remain constant with age. A better understanding of these measures may have implications for follicle quality, fertility, and long term sexual health; additional longitudinal data in this population is needed. Supported by: 1R01HD062797 O-117 Tuesday, October 18, 2016 11:45 AM THE PSYCHOLOGICAL IMPACT OF OVARIAN RESERVE TESTING: A QUALITATIVE ANALYSIS. Y. O’Brien,a a b a M. Wingfield, C. Kelleher. Reproductive Medicine, Merrion FertilityClinic, National Maternity Hospital, Dublin 2, Ireland; bPHS Department of Psychology, Royal College of Surgeons in Ireland, Dublin 2, Ireland. OBJECTIVE: To investigate the psychological and emotional responses of women being informed of their Anti-Mullerian Hormone (AMH) result with a view to informing the possible introduction of universal AMH screening for young women. DESIGN: Prospective qualitative study using semi-structured in-depth interviews of women attending a reproductive medicine clinic who had ovarian
FERTILITY & STERILITYÒ
reserve testing performed via measurement of serum AMH levels, as part of their fertility work-up. MATERIALS AND METHODS: A semi-structured interview schedule was developed after a review of the literature. Hospital Ethics Committee approval and participant informed consent were obtained. A broad range of women, in terms of age and AMH levels, were recruited. Data collection continued until thematic saturation was reached (n¼10). Interviews were audiotaped, transcribed verbatim and imported into QSR NVivo for analysis. The following areas were explored: (i) Pre-test knowledge of AMH testing (ii) Experience of being informed of the result (iii) Initial feelings when given AMH result (iv) Longerterm feelings regarding result (v) Effect, if any, of AMH result, on childbearing intentions of the woman and of the couple, (vi) Subjective views of the advantages and disadvantages of having an AMH test and (vii) Feedback for the clinic regarding experience of AMH testing to help improve patient experience. Using thematic analysis, the sorted categories evolved into a coding system, which was applied independently to each transcript. RESULTS: Interview analysis identified the following dominant themes. Women were often unaware of the clinical relevance of the test, and their main source of information was the internet, rather than a medical practitioner. The result of the test determined the woman’s initial and subsequent feelings about the result. Those with a low AMH level reported feelings of devastation, isolation and loss of femininity and purpose. With a normal result, the overwhelming theme was reassurance and surprise that the result was normal. Overall, women felt that knowledge of their ovarian reserve was of paramount importance and it guided their decision making in relation to childbearing intentions. These opinions and views were consistent among the interviewees regardless of their AMH result. CONCLUSIONS: This is the first study to investigate the psychological impact of AMH testing. Although an exploratory study, the women in this study advocated to provision of ovarian reserve testing. However, knowledge of a low AMH result has a negative psychological impact. This must be anticipated and appropriate supports put in place prior to implementing universal screening. The results of this initial qualitative study will be used to identify suitable measures and develop a detailed quantitative questionnaire for the next stage in this study which will recruit a larger and more representative sample of women. O-118 Tuesday, October 18, 2016 12:00 PM FSH PROMOTES PREMATURE PROGESTERONE OUTPUT IN HUMAN GRANULOSA CELLS WITHOUT LUTEINIZATION BY UPREGULATING THE EXPRESSION OF 3b-HSD AND INDUCING DISPROPORTIONAL INCREASES BETWEEN 17a-OH AND G. Bildik,a OTHER STEROIDOGENIC ENZYMES. N. Akin,a A. Seyhan,b B. Urman,c,b O. Oktem.c,b aSchool of Medicine and the Graduate School of Health Sciences, Koc University, Istanbul, Turkey; bWomen’s Health Center Assisted Reproduction Unit, American Hospital, Istanbul, Turkey; cObstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey. OBJECTIVE: Serum progesterone (P) level may prematurely rise before ovulation trigger in stimulated IVF cycles. We aimed in this study to explore if gonadotropin stimulation up-regulates the expression of the enzyme 3b-HSD, which converts pregnenolone to P, and alters the expression of ovarian steroidogenic enzymes that facilitates premature P output without luteinization. DESIGN: A translational research study. MATERIALS AND METHODS: Human ovarian cortical samples (n¼15) and non-luteinizing mitotic granulosa cells (HGrC1) were stimulated with rec-FSH at 12.5-25- 50 mIU/mL concentrations for 24 and 48 hrs. Luteal granulosa cells were obtained during oocyte retrieval procedure from patients undergoing pure natural (n¼20) and stimulated IVF cycles with GnRH agonist (n¼30) and antagonist (n¼30) protocols. The real-time quantitative qRT-PCR, immunoblotting and ELISA assays were used. RESULTS: Intracellular cAMP level was significantly increased in a dose-dependent manner in the mitotic granulosa cells from a baseline level of 2.2 nM to 4.9, 7.9 and 13 nM after stimulation with FSH at 12.5, 25 and 50 mIU/mL concentrations respectively. FSH at the same doses induced 1.52, 1.78 and 2.63 fold increases in the mRNA level of 3b-HSD at 24 hrs compared to baseline level (p<0.001). There was a dose-dependent increase in the protein levels of 3b-HSD and
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FERTILITY & STERILITYÒ
reserve testing performed via measurement of serum AMH levels, as part of their fertility work-up. MATERIALS AND METHODS: A semi-structured interview schedule was developed after a review of the literature. Hospital Ethics Committee approval and participant informed consent were obtained. A broad range of women, in terms of age and AMH levels, were recruited. Data collection continued until thematic saturation was reached (n¼10). Interviews were audiotaped, transcribed verbatim and imported into QSR NVivo for analysis. The following areas were explored: (i) Pre-test knowledge of AMH testing (ii) Experience of being informed of the result (iii) Initial feelings when given AMH result (iv) Longerterm feelings regarding result (v) Effect, if any, of AMH result, on childbearing intentions of the woman and of the couple, (vi) Subjective views of the advantages and disadvantages of having an AMH test and (vii) Feedback for the clinic regarding experience of AMH testing to help improve patient experience. Using thematic analysis, the sorted categories evolved into a coding system, which was applied independently to each transcript. RESULTS: Interview analysis identified the following dominant themes. Women were often unaware of the clinical relevance of the test, and their main source of information was the internet, rather than a medical practitioner. The result of the test determined the woman’s initial and subsequent feelings about the result. Those with a low AMH level reported feelings of devastation, isolation and loss of femininity and purpose. With a normal result, the overwhelming theme was reassurance and surprise that the result was normal. Overall, women felt that knowledge of their ovarian reserve was of paramount importance and it guided their decision making in relation to childbearing intentions. These opinions and views were consistent among the interviewees regardless of their AMH result. CONCLUSIONS: This is the first study to investigate the psychological impact of AMH testing. Although an exploratory study, the women in this study advocated to provision of ovarian reserve testing. However, knowledge of a low AMH result has a negative psychological impact. This must be anticipated and appropriate supports put in place prior to implementing universal screening. The results of this initial qualitative study will be used to identify suitable measures and develop a detailed quantitative questionnaire for the next stage in this study which will recruit a larger and more representative sample of women. O-118 Tuesday, October 18, 2016 12:00 PM FSH PROMOTES PREMATURE PROGESTERONE OUTPUT IN HUMAN GRANULOSA CELLS WITHOUT LUTEINIZATION BY UPREGULATING THE EXPRESSION OF 3b-HSD AND INDUCING DISPROPORTIONAL INCREASES BETWEEN 17a-OH AND G. Bildik,a OTHER STEROIDOGENIC ENZYMES. N. Akin,a A. Seyhan,b B. Urman,c,b O. Oktem.c,b aSchool of Medicine and the Graduate School of Health Sciences, Koc University, Istanbul, Turkey; bWomen’s Health Center Assisted Reproduction Unit, American Hospital, Istanbul, Turkey; cObstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey. OBJECTIVE: Serum progesterone (P) level may prematurely rise before ovulation trigger in stimulated IVF cycles. We aimed in this study to explore if gonadotropin stimulation up-regulates the expression of the enzyme 3b-HSD, which converts pregnenolone to P, and alters the expression of ovarian steroidogenic enzymes that facilitates premature P output without luteinization. DESIGN: A translational research study. MATERIALS AND METHODS: Human ovarian cortical samples (n¼15) and non-luteinizing mitotic granulosa cells (HGrC1) were stimulated with rec-FSH at 12.5-25- 50 mIU/mL concentrations for 24 and 48 hrs. Luteal granulosa cells were obtained during oocyte retrieval procedure from patients undergoing pure natural (n¼20) and stimulated IVF cycles with GnRH agonist (n¼30) and antagonist (n¼30) protocols. The real-time quantitative qRT-PCR, immunoblotting and ELISA assays were used. RESULTS: Intracellular cAMP level was significantly increased in a dose-dependent manner in the mitotic granulosa cells from a baseline level of 2.2 nM to 4.9, 7.9 and 13 nM after stimulation with FSH at 12.5, 25 and 50 mIU/mL concentrations respectively. FSH at the same doses induced 1.52, 1.78 and 2.63 fold increases in the mRNA level of 3b-HSD at 24 hrs compared to baseline level (p<0.001). There was a dose-dependent increase in the protein levels of 3b-HSD and
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