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It’s in the numbers: rates of aneuploidy are lowest when 15-35 oocytes are retrieved
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IT’S IN THE NUMBERS: RATES OF ANEUPLOIDY ARE LOWEST WHEN 15-35 OOCYTES ARE RETRIEVED. N. Resetkova, MD, MBA,a,b D. Vaughan, MD,c A. Leung, MD,c A. Penzias, MD,a,b M. Alper, MD,a D. Sakkas, PhD.a aBoston IVF, Waltham, MA; bBeth Israel Deaconess Medical Center Department of Obstetrics and Gynecology, Harvard Medical School, Boston, MA; cTufts Medical Center Department of Obstetrics and Gynecology, Boston, MA.
TESTOSTERONE (T) USE IN MALE PARTNERS OF COUPLES PRESENTING FOR THE INITIAL INFERTILITY EVALUATION: PREVALENCE, USAGE PATTERNS AND FERTILITY LaTasha Craig, MD,a AWARENESS. Evan Reshef, BA,a a a Heather R. Burks, MD, Karl R. Hansen, MD, PhD, Puneet Sindhwani, MD,b Alexander M. Quaas, MD, PhD.a aUniversity of Oklahoma Health Sciences Center, Department of Obstetrics & Gynecology, Section of Reproductive Endocrinology & Infertility; bUniversity of Oklahoma Health Sciences Center, Department of Urology, Section of Andrology.
BACKGROUND: Much research has been done into PGS (Preimplantation Genetic Screening), but outcomes are typically analyzed with respect to the number of biopsies submitted for genetic analysis. A 2012 study using array CGH (Comparative Genome Hybridization) determined that aneuploidy is not correlated with the number of biopsied embryos (1). OBJECTIVE: To identify whether aneuploidy is correlated with the number of oocytes retrieved. MATERIALS AND METHODS: We retrospectively reviewed all PGS cycles at our facility over a 2 year timeframe encompassing 2012 and 2013. After exclusion of cycles evaluating single gene disorders only, a total of 370 cycles were examined, of which 295 resulted in a completed biopsy. Data was stratified into three groups based on the number of oocytes retrieved: 1-9, 10-14, and 15 or more oocytes. RESULTS: Aneuploidy rates were evaluated between groups. A significant difference was noted between groups, with 71.9% in the 9 or less oocyte, 63.1% in the 10-14 oocyte, and a 59.0% aneuploidy rate in the 15 and greater oocyte group (p¼0.025). Notably, a 72.2% aneuploidy rate was noted in patients with greater than 35 oocytes retrieved, with a sharp increase in aneuploidy at this level of response. 80% of samples were assessed with CGH (Comparative Genome Hybridization). 56.6% were performed as Day 3 biopsies, with the remaining as Day 5 biopsies, and freeze all cycles were excluded from analysis. The aneuploidy trends were consistent regardless of day of biopsy. Average age differed slightly but insignificantly between groups. The data was thus sub-analyzed among age groups, with the 36-38 year old age group representing the most patient cycles. Increased rates of aneuploidy with less oocytes retrieved was confirmed in this age range with 65.3% aneuploidy in the 15 or more group and 87.1% in the 1-9 group (p¼0.016). No significant differences in a per transfer pregnancy rate were observed among groups. Intuitively, more cycles resulted in no embryos available for transfer as the number of retrieved oocytes decreased. CONCLUSION: This study draws attention to the relevance of the number of oocytes retrieved to not only pregnancy rates per PGS cycle, but specifically aneuploidy rates. Generation of surplus embryos in a given cycle for genetic assessment does not appear to increase the rate of aneuploidy, unless the stimulation is very aggressive and greater than 35 oocytes are retrieved. FINANCIAL SUPPORT: No direct financial support for this study. Other disclosures listed below. Dr. Alan Penzias: OvaScience Advisory Board, Reprosource Board of Directors, Recipient of Ferring Honoraria Dr. Michael Alper: Consultant for Ferring, EMD Serono, Reprosource and Good Start Genetics. Dr. Denny Sakkas: Origio Board Advisor, Recipient of a grant from Ferring. Reference: 1. Ata B, Kaplan B, Danzer H, Glassner M, Opsahl M, Tan SL, et al. Array CGH analysis shows that aneuploidy is not related to the number of embryos generated. Reprod Biomed Online. 2012;24(6):614–20.
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TABLE 1. Cycle Characteristics.
# Oocytes Retrieved # Cycles Represented Average Age (years) Average # oocytes Average # blastocyst Aneuploidy Rate (%) Live Birth Rate/Transfer (%) Live Birth Rate/Biopsy Cycle (%)
FERTILITY & STERILITYÒ
BACKGROUND: Male factor infertility is the primary or contributing factor in 30-40% of couples presenting for infertility evaluation. The proportion of male factor infertility secondary to exogenous androgen supplementation is currently unknown. Even though exogenous androgen supplementation has only been approved and recommended for the treatment of clinically significant hypogonadism in males (1), there has been a recent sharp increase in the advertising and prescribing of exogenous androgens in specialized centers and men’s clinics for unapproved indications such as fatigue, stress, depression and lack of libido. OBJECTIVE: To examine 1) the prevalence of testosterone (T) use in male partners of consecutive couples presenting for initial infertility evaluation; 2) usage patterns of T supplementation, including the indication for treatment, source of T (prescribed or over-the-counter), and route of administration; 3) the awareness of patients of the effect of exogenous T use on fertility, and 4) whether counseling by the prescribing provider on fertility effects had occurred at the time of treatment initiation. MATERIALS AND METHODS: The prevalence of exogenous T use was examined in a retrospective cohort of 303 consecutive couples presenting for initial infertility evaluation at a university-based infertility clinic from January 1, 2013 to October 1, 2015. For male partners reporting exogenous T use, the results of the initial semen analysis (SA) were recorded, and subjects were contacted by phone to participate in a detailed questionnaire about T usage patterns and fertility awareness. Data was analyzed using descriptive statistics. RESULTS: The prevalence of exogenous T use was 17/303 (5.6%). The SA was abnormal in 11/17 cases of T use (64.7%), with a diagnosis of azoospermia in in 3/17 (17.6%). Of the 17 identified male partners, 13 (76.5%) agreed to participate in the phone survey. 7/13 (53.8%) used physician-prescribed T. 4/13 (23.1%) used over-the-counter supplements containing T. 2/13 (15.4%) denied T use, despite having reported it at the time of initial consultation. Of the 7 patients using prescription T supplementation, all 7 (100%) used T injections, with 2/ 7 (28.6%) reporting additional use of a gel, and 1/7 (14.3%) reporting additional use of a patch. The indication for T supplementation was ‘‘low T’’ in all cases. T therapy was prescribed by family physicians (4/7) or urologists (3/ 7). In 2/7 subjects (28.6%), fertility implications were discussed at the time of prescription, and 3/7 (42.9%) reported awareness of detrimental effects of T use on fertility at the time of treatment initiation. CONCLUSIONS: Exogenous T use in the male partner was identified in 5.6% of couples presenting for initial infertility evaluation. Asking about T use should be part of the routine initial infertility evaluation. Only a minority of patients were counseled on the potentially detrimental fertility effects of T use at the time of treatment initiation. FINANCIAL SUPPORT: None. Reference: 1. Bhasin, S. et al. ‘‘Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline’’. The Endocrine Society’s Clinical Guidelines. Journal of Clinical Endocrinology & Metabolism. June 2010, Vol. 95(6):2536-2559.
15 and more oocytes
10-14 oocytes
1-9 oocytes
152 35.9 22.0 10.0 71.9 36.1 31.7
73 37.1 12.0 3.9 63.1 33.3 25.7
70 37.5 6.3 2.3 59.0 42.7 18.8
ENDOMETRINÒ/PROMETRIUMÒ VERSUS INTRAMUSCULAR PROGESTERONE ADMINISTRATION FOR LUTEAL PHASE Daniel B. Williams, MD,a,b SUPPORT. Reem Sabouni, MD,a Jason Griffith, MD,a,b Ghassan Haddad, MD,a,b Wei-Hua Wang, PhD,b Craig A. Witz, MD.a,b aDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Medical School at Houston/Memorial Herman Program, Houston, TX; bHouston Fertility Institute, PA, Houston, TX. BACKGROUND: The ideal method of endometrial preparation for a frozen embryo transfer (FET) is not defined1. Intramuscular (IM)
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IT’S IN THE NUMBERS: RATES OF ANEUPLOIDY ARE LOWEST WHEN 15-35 OOCYTES ARE RETRIEVED. N. Resetkova, MD, MBA,a,b D. Vaughan, MD,c A. Leung, MD,c A. Penzias, MD,a,b M. Alper, MD,a D. Sakkas, PhD.a aBoston IVF, Waltham, MA; bBeth Israel Deaconess Medical Center Department of Obstetrics and Gynecology, Harvard Medical School, Boston, MA; cTufts Medical Center Department of Obstetrics and Gynecology, Boston, MA.
TESTOSTERONE (T) USE IN MALE PARTNERS OF COUPLES PRESENTING FOR THE INITIAL INFERTILITY EVALUATION: PREVALENCE, USAGE PATTERNS AND FERTILITY LaTasha Craig, MD,a AWARENESS. Evan Reshef, BA,a a a Heather R. Burks, MD, Karl R. Hansen, MD, PhD, Puneet Sindhwani, MD,b Alexander M. Quaas, MD, PhD.a aUniversity of Oklahoma Health Sciences Center, Department of Obstetrics & Gynecology, Section of Reproductive Endocrinology & Infertility; bUniversity of Oklahoma Health Sciences Center, Department of Urology, Section of Andrology.
BACKGROUND: Much research has been done into PGS (Preimplantation Genetic Screening), but outcomes are typically analyzed with respect to the number of biopsies submitted for genetic analysis. A 2012 study using array CGH (Comparative Genome Hybridization) determined that aneuploidy is not correlated with the number of biopsied embryos (1). OBJECTIVE: To identify whether aneuploidy is correlated with the number of oocytes retrieved. MATERIALS AND METHODS: We retrospectively reviewed all PGS cycles at our facility over a 2 year timeframe encompassing 2012 and 2013. After exclusion of cycles evaluating single gene disorders only, a total of 370 cycles were examined, of which 295 resulted in a completed biopsy. Data was stratified into three groups based on the number of oocytes retrieved: 1-9, 10-14, and 15 or more oocytes. RESULTS: Aneuploidy rates were evaluated between groups. A significant difference was noted between groups, with 71.9% in the 9 or less oocyte, 63.1% in the 10-14 oocyte, and a 59.0% aneuploidy rate in the 15 and greater oocyte group (p¼0.025). Notably, a 72.2% aneuploidy rate was noted in patients with greater than 35 oocytes retrieved, with a sharp increase in aneuploidy at this level of response. 80% of samples were assessed with CGH (Comparative Genome Hybridization). 56.6% were performed as Day 3 biopsies, with the remaining as Day 5 biopsies, and freeze all cycles were excluded from analysis. The aneuploidy trends were consistent regardless of day of biopsy. Average age differed slightly but insignificantly between groups. The data was thus sub-analyzed among age groups, with the 36-38 year old age group representing the most patient cycles. Increased rates of aneuploidy with less oocytes retrieved was confirmed in this age range with 65.3% aneuploidy in the 15 or more group and 87.1% in the 1-9 group (p¼0.016). No significant differences in a per transfer pregnancy rate were observed among groups. Intuitively, more cycles resulted in no embryos available for transfer as the number of retrieved oocytes decreased. CONCLUSION: This study draws attention to the relevance of the number of oocytes retrieved to not only pregnancy rates per PGS cycle, but specifically aneuploidy rates. Generation of surplus embryos in a given cycle for genetic assessment does not appear to increase the rate of aneuploidy, unless the stimulation is very aggressive and greater than 35 oocytes are retrieved. FINANCIAL SUPPORT: No direct financial support for this study. Other disclosures listed below. Dr. Alan Penzias: OvaScience Advisory Board, Reprosource Board of Directors, Recipient of Ferring Honoraria Dr. Michael Alper: Consultant for Ferring, EMD Serono, Reprosource and Good Start Genetics. Dr. Denny Sakkas: Origio Board Advisor, Recipient of a grant from Ferring. Reference: 1. Ata B, Kaplan B, Danzer H, Glassner M, Opsahl M, Tan SL, et al. Array CGH analysis shows that aneuploidy is not related to the number of embryos generated. Reprod Biomed Online. 2012;24(6):614–20.
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TABLE 1. Cycle Characteristics.
# Oocytes Retrieved # Cycles Represented Average Age (years) Average # oocytes Average # blastocyst Aneuploidy Rate (%) Live Birth Rate/Transfer (%) Live Birth Rate/Biopsy Cycle (%)
FERTILITY & STERILITYÒ
BACKGROUND: Male factor infertility is the primary or contributing factor in 30-40% of couples presenting for infertility evaluation. The proportion of male factor infertility secondary to exogenous androgen supplementation is currently unknown. Even though exogenous androgen supplementation has only been approved and recommended for the treatment of clinically significant hypogonadism in males (1), there has been a recent sharp increase in the advertising and prescribing of exogenous androgens in specialized centers and men’s clinics for unapproved indications such as fatigue, stress, depression and lack of libido. OBJECTIVE: To examine 1) the prevalence of testosterone (T) use in male partners of consecutive couples presenting for initial infertility evaluation; 2) usage patterns of T supplementation, including the indication for treatment, source of T (prescribed or over-the-counter), and route of administration; 3) the awareness of patients of the effect of exogenous T use on fertility, and 4) whether counseling by the prescribing provider on fertility effects had occurred at the time of treatment initiation. MATERIALS AND METHODS: The prevalence of exogenous T use was examined in a retrospective cohort of 303 consecutive couples presenting for initial infertility evaluation at a university-based infertility clinic from January 1, 2013 to October 1, 2015. For male partners reporting exogenous T use, the results of the initial semen analysis (SA) were recorded, and subjects were contacted by phone to participate in a detailed questionnaire about T usage patterns and fertility awareness. Data was analyzed using descriptive statistics. RESULTS: The prevalence of exogenous T use was 17/303 (5.6%). The SA was abnormal in 11/17 cases of T use (64.7%), with a diagnosis of azoospermia in in 3/17 (17.6%). Of the 17 identified male partners, 13 (76.5%) agreed to participate in the phone survey. 7/13 (53.8%) used physician-prescribed T. 4/13 (23.1%) used over-the-counter supplements containing T. 2/13 (15.4%) denied T use, despite having reported it at the time of initial consultation. Of the 7 patients using prescription T supplementation, all 7 (100%) used T injections, with 2/ 7 (28.6%) reporting additional use of a gel, and 1/7 (14.3%) reporting additional use of a patch. The indication for T supplementation was ‘‘low T’’ in all cases. T therapy was prescribed by family physicians (4/7) or urologists (3/ 7). In 2/7 subjects (28.6%), fertility implications were discussed at the time of prescription, and 3/7 (42.9%) reported awareness of detrimental effects of T use on fertility at the time of treatment initiation. CONCLUSIONS: Exogenous T use in the male partner was identified in 5.6% of couples presenting for initial infertility evaluation. Asking about T use should be part of the routine initial infertility evaluation. Only a minority of patients were counseled on the potentially detrimental fertility effects of T use at the time of treatment initiation. FINANCIAL SUPPORT: None. Reference: 1. Bhasin, S. et al. ‘‘Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline’’. The Endocrine Society’s Clinical Guidelines. Journal of Clinical Endocrinology & Metabolism. June 2010, Vol. 95(6):2536-2559.
15 and more oocytes
10-14 oocytes
1-9 oocytes
152 35.9 22.0 10.0 71.9 36.1 31.7
73 37.1 12.0 3.9 63.1 33.3 25.7
70 37.5 6.3 2.3 59.0 42.7 18.8
ENDOMETRINÒ/PROMETRIUMÒ VERSUS INTRAMUSCULAR PROGESTERONE ADMINISTRATION FOR LUTEAL PHASE Daniel B. Williams, MD,a,b SUPPORT. Reem Sabouni, MD,a Jason Griffith, MD,a,b Ghassan Haddad, MD,a,b Wei-Hua Wang, PhD,b Craig A. Witz, MD.a,b aDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Medical School at Houston/Memorial Herman Program, Houston, TX; bHouston Fertility Institute, PA, Houston, TX. BACKGROUND: The ideal method of endometrial preparation for a frozen embryo transfer (FET) is not defined1. Intramuscular (IM)
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