Adrenal response to cosyntropin (ACTH) stimulation in patients with premature ovarian senescence

normal weight subjects (34 vs. 32 years, p¼0.03). Adjusted for age, FSH had a slight negative correlation with AMH (OR 0.93, p¼0.03), and AFC had a positive correlation with AMH (OR 1.36, p<0.0001). While these associations did not differ by BMI, there was a moderately significant interaction by diagnosis of PCOS (p¼0.08). Specifically, higher levels of FSH were associated with lower levels of AMH among those without PCOS (OR 0.94, p¼0.05) and higher levels of AMH among those with PCOS (OR 1.65, p¼0.16), though the latter association was not statistically significant. CONCLUSION: In our population of infertile women, BMI did not impact the relationship of FSH or AFC with AMH. Our study confirms known correlations between these markers of ovarian reserve and that PCOS but not BMI can impact this relationship. Supported by: UAB Center for Clinical and Translational Science Grant Number UL1TR000165.

P-44 Tuesday, October 15, 2013 DOES HYSTERECTOMY WITH OVARIAN PRESERVATION AFFECT OVARIAN FUNCTION IN EARLY POSTOPERATIVE PERIOD? S. Chun,a Y. I. Ji,a Y. H. Koo.b aInje University Haeundae Paik Hospital, Busan, Republic of Korea; bBusan Maria Fertility Hospital, Busan, Republic of Korea. OBJECTIVE: The aim of this study was to assess the impact of hysterectomy on ovarian reserve in early postoperative period. DESIGN: Prospective Observational Study. MATERIALS AND METHODS: Seventy premenopausal women aged 30 - 47 years who underwent scheduled hysterectomy with conservation of both ovaries participated in this study (laparoscopy-assisted vaginal hysterectomy, n ¼ 59; and total abdominal hysterectomy, n ¼ 11). Preoperative and postoperative day 3 serum samples were collected and assayed for anti -M€ullerian hormone (AMH) levels, and changes between the two samples were analyzed. RESULTS: Postoperative day 3 AMH levels (2.22  0.23 ng/ml) were significantly lower than preoperative AMH levels (2.71  0.25 ng/ml). There were significant reductions in serum AMH levels after hysterectomy (21.31  3.03%, P < 0.001). CONCLUSION: Our results suggest that hysterectomy may reduce ovarian reserve in early postoperative period. P-45 Tuesday, October 15, 2013 DOES THE ENDOMETRIOMA EFFECT THE OVARIAN RESERVE? E. Demircivi Bor,a M. Oncul,b N. Atakul,c H. Yilmaz,b A. I. Tekirdag,a S. Sahmay.b aObstetrics and Gynecology Department, Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey; b Obstetrics and Gynecology Department, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; cObstetrics and Gynecology Department, Istanbul Education and Research Hospital, Istanbul, Turkey. OBJECTIVE: Endometrioma is the ectopic endometriotic tissue in the ovary which producing cyst.Ovarian reserve is defined as the functional potential of the ovary which reflects the number and quality of the follicles left in the ovary at any given time. Recently, serum antimullerian hormone (AMH) measurement is the reliable and frequently using test for ovarian reserve. Existing of endometrioma or other benign ovarian cysts are important for the patients who are in reproductive age and expecting pregnancy. Our propose in this study to observe that the endometrioma and the other benign ovarian cysts effect on the ovarian reserve by measuring via sensitive and recent serum marker AMH. DESIGN: Cross-sectional study. MATERIALS AND METHODS: In this study we evaluate totally 147 patients who were applied to gynecology clinic. Inclusion criterias were as follows: patients who were under age 40, no hormonal dysfunction, without polycystic ovarian syndrome and no previous ovarian surgery history and had cyst over 4 cm and persisted which were double checked in two months interval with ultrasonographically. We divided the patients in to three group as G1:endometrioma (n:63),G2: other benign ovarian cyst (n:23) and G3:control group (n:61). All the patients were operated and verified the diagnosis with ovarian histology. RESULTS: There is no statistical differences between groups for age(G1:30.95.7; G2:28.910; G3:31.74). But we found statistically significant (p<0,05) lower AMH level at endometrioma(G1:1.952.03) than other benign ovarian cyst (G2:3.273.34).

FERTILITY & STERILITYÒ

CONCLUSION: According to our data, endometrioma effects negatively the ovarian reserve compared with other benign ovarian cysts. Due to the fact that we are advising preoperative AMH measurement and non traumatic surgery techniques must be considered for endometriomas which are on patients planing pregnancy in future.There are many studies show that operation type and hemostasis techniques during operation effects the ovarian reserve. Further study is needed. P-46 Tuesday, October 15, 2013 DO WOMEN WITH PRIMARY ANTIPHOSPHOLIPID SYNDROME HAVE LOW OVARIAN RESERVE? L. Y. S. Yamakami,a P. C. Serafini,a D. B. Araujo,b,d E. Bonfa,b E. C. Baracat,a C. A. Silva.b,c aDepartment of Gynecology, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; bDivision of Rheumatology, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; cPediatric Rheumatology Unit, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; d Department of Rheumatology, Hospital do Servidor Publico Estadual de Sao Paulo, Sao Paulo, Brazil. OBJECTIVE: To determine ovarian reserve in primary antiphospholipid syndrome (PAPS) women. DESIGN: Cross sectional, ongoing. MATERIALS AND METHODS: From 04/2010 to 03/2013, 85 female aged 18-40 years old were screened. After exclusion of 67 patients, 18 PAPS patients were evaluated. Ten women with PAPS had been on medroxyprogesterone acetate (150 mg every 3 months) to avoid menses and ovarian hemorrhage. The PAPS and the control group (24 healthy women) were evaluated early follicular phase with ovarian reserve tests as follicle stimulating hormone (FSH), estradiol (E2), anti-M€ullerian hormone (AMH) carried out by ELISA test and sonographic antral follicle count (AFC). Serum measurement of anti-corpus luteum antibody (anti-CoL) was determined by immunoblot analysis. Above mentioned analyzes were completed after at least 6 months from the last intake of medroxyprogesterone and resumption of menstruation. RESULTS: The mean age PAPS and controls were 33.05.0 vs. 30.47.0 years old; p¼0.189. Serum FSH and E2 were similar in both groups. AntiCoL was solely observed in 2 PAPS patients (11%). The frequencies of low AFC (% 10) and very low AFC (% 5) were significantly higher in PAPS patients than controls (56% vs. 22%, p¼0.042; 37% vs. 9%, p¼0.045). Tendencies of greater frequency of low (<0.5 ng/mL) and negligible (<0.2 ng/mL) AMH levels were obtained in PAPS patients (p¼0.07 and p¼0.07; respectively). CONCLUSION: Women suffering from PAPS possessed reduced ovarian reserve, with prevalence greater than 50%, emphasizing fertility counseling and family planning. The presence of anti-CoL is of relevance conceivably indicating an early forewarning of autoimmune oophoritis. Supported by: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (#11/12471-2), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (#301411/2009-3 and #302724/2011-7), Federico Foundation and Nucleo de Apoio a Pesquisa ‘‘Saude da Crianca e do Adolescente’’ da USP.

P-47 Tuesday, October 15, 2013 ADRENAL RESPONSE TO COSYNTROPIN (ACTH) STIMULATION IN PATIENTS WITH PREMATURE OVARIAN SENESCENCE. V. A. Kushnir,a E. Himaya,a,b D. H. Barad,a,c a a,c a A. Shohat-Tal, N. Gleicher. Center for Human Reproduction, New York, NY; bCentre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada; cFoundation for Reproductive Medicine, New York, NY. OBJECTIVE: Diminished functional ovarian reserve (DFOR) is associated with low testosterone (T), suggesting that DFOR may reflect ovarian-adrenal dysfunction. We investigated adrenal response of women with DFOR to cosyntropin (synthetic ACTH) stimulation. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We assessed serum glucocorticoid, progestin and androgen levels after ACTH stimulation (250 mg cosyntropin) in 28 infertile women at initial evaluation. Patients were divided into: Group I, normal FOR and Group II, prematurely DFOR (above previously established 95% CIs for age-specific FSH levels and/or below 95% CIs for age-specific

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AMH levels). All tests were performed in AM; values obtained at baseline, 30 and 60 minutes. RESULTS: Ages were similar (32.7  3.3 vs. 34.4  3.9 years; N.S.). FSH levels were significantly higher in Group II (6.82.4 vs. 21.623.9; P<0.001). While cortisol, DHEA, or 17OHP did not differ significantly at baseline and after stimulation, all three showed trend toward stronger adrenal response to stimulation in Group II. Molar ratios of cortisol/DHEA (rC/D) were in both groups similar to those established in healthy subjects (J Clin Endocrinol Metab. 2012 97:3655-62). Baseline rC/D were marginally higher in Group II (29.19.1 vs. 48.733.0; P¼0.06), converging at 30 and 60 minutes. CONCLUSION: Adrenal cortex of women with prematurely DFOR at baseline appears mildly activated but capable of response to ACTH stimulation. That rC/A in Group II at baseline is marginally higher but mimics that of Group I upon ACTH stimulation suggests that ACTH-stimulation disproportionally increases DHEA/androgen synthesis compared to cortisol, providing further evidence for a possible adrenal-produced androgen stimulation factor, previously suggested regarding immune observations in women with premature ovarian senescence (Gleicher et al., ESHRE 2013/Reprod Biol Endocrinol 2013; In press). Supported by: Foundation for Reproductive Medicine, Center for Human Reproduction and Centre Hospitalier de l’Universite de Montreal. P-48 Tuesday, October 15, 2013 ANALYSIS OF TWO ASSAYS FOR THE MEASUREMENT OF AMH IN WOMEN WITH LOW OVARIAN RESERVE. R. Fleming,a C. Fairbairn,a D. Lucas,a M. Gaudoin,a R. A. Anderson.b aGlasgow Centre for Reproductive Medicine, Glasgow, Strathclyde, United Kingdom; bMRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, Lothian, United Kingdom. OBJECTIVE: The measurement of AMH is increasingly well validated as a marker of the functional ovarian reserve, but there is a lack of standardization of assays, which may be of particular importance at the extremes of the working range. In this study we have assessed the Ansh Labs and BeckmanCoulter GenII AMH assays in two groups of women with identified low ovarian reserve. DESIGN: Comparison of two AMH assays, in women about to have IVF, or with breast cancer during and following chemotherapy. MATERIALS AND METHODS: Women (n¼ 69) with low ovarian reserve (AMH < 7.5 pmol/L) pre IVF had a further blood sample taken 2 days prior to starting stimulation, (Flare protocol, 225 IU rFSH daily). Samples were obtained from women with breast cancer (n¼57, 90 samples) after starting chemotherapy. Serum samples were analysed using both GenII and Ansh assays. RESULTS: The limit of sensitivity was 1.5pmol/l for Gen II and estimated to be 0.2 for Ansh. The absolute values for AMH correlated closely (r¼0.96 and 0.92 in the two groups) in the two assays, although the Ansh values were 34% higher. There remained a good relationship even at very low values (<4pmol/l), r¼0.81. In breast cancer samples, AMH was undetectable in 52 using GenII, but the Ansh assay showed detectable AMH in 11 of these, mean 1.5pmol/l. Both assays showed significant ability to predict oocyte yield in the IVF cohort, but there was no difference in the relationship between oocyte yield and AMH. The assays showed similar discrimination between women with oocyte yield of 0-3 vs R4 eggs. CONCLUSION: AMH values were consistently higher with the Ansh assay, by approx 30% but there was a very close correlation between the 2 assays, even at the extreme low end. These results are consistent with the Ansh assay having a greater sensitivity, which may be of value in some clinical situations such as following chemotherapy, but does not appear to be of clinical value prior to IVF. Supported by: We acknowledge the generous provision of assay materials by Beckman Coulter and Ansh Labs.

P-49 Tuesday, October 15, 2013 GENETICS OF EXOGENOUS DEHYDROEPIANDROSTERONE (DHEA) CONVERSION TO TESTOSTERONE (T) IN HYPOANDROGENIC WOMEN AS TOOL TO INDIVIDUALIZED INFERTILITY TREATMENTS. A. Shohat-Tal,a V. A. Kushnir,a D. H. Barad,a,b N. Gleicher.a,b aCenter for Human Reproduction, New York, NY; bFoundation for Reproductive Medicine, New York, NY.

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ASRM Abstracts

OBJECTIVE: To review whether within a framework of DHEA supplementation in women with hypoandrogenism the genetic control of DHEA metabolism to T can be diagnostically utilized to individualize infertility care. DESIGN: Literature search of PubMed and Google Scholar up to April 2013. MATERIALS AND METHODS: We searched under appropriate keywords for polymorphism/mutations affecting T levels, in vitro studies and animal models, the molecular basis of genetic variants and mechanisms by which they may affect female hormone profiles, and treatment options which can affect serum T levels by targeting genes in steroidogenic pathways. RESULTS: Common genetic polymorphisms and/or mutations affecting serum androgen levels include those in DHEA sulfotransferase, aromatase, 5a-reductase, androgen receptor (AR), sex-hormone binding globulin (SHBG), fragile-X mental retardation ([italics]FMR1[/italics]), and [italics]BRCA1[/italics] genes. These variants may, in some hypoandrogenic patients, even after DHEA supplementation, underlie persistently low T levels. Various examples are presented. Treatment options used to raise T levels and can affect in vitro fertilization (IVF) outcomes include direct administration of T or treatments involving aromatase or 5a- reductase inhibition, which target enzymes coded by some of these genes. CONCLUSION: Short of screening for all possible genetic variants, a woman’s hormonal profile following DHEA supplementation may point to deficiencies in specific genes and/or pathways, thus suggesting preferred treatment approaches. Such a new diagnostic approach may, in analogy to other medical specialties, based on genetic markers, initiate more individualized and rationally designed infertility treatments for patients with androgen-deficient forms of ovarian senescence, including premature ovarian aging (occult primary ovarian insufficiency) and diminished functional ovarian reserve, both recently demonstrated to be hypoandrogenic states. Supported by: Foundation for Reproductive Medicine and Center for Human Reproduction.

P-50 Tuesday, October 15, 2013 OVARIAN RESERVE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND IRREGULAR BLEEDING. A. MoralesMartınez,a C. Salas-Castro,a L. H. Sordia-Hernandez,a M. R. GarcıaGarza,a J. G. Gonzalez-Gonzalez,b M. A. Garza-Elizondo.c aUniversity Centre of Reproductive Medicine, Hospital Universitario Dr. Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico; bEndocrinology Unit, Hospital Universitario Dr. Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico; c Rheumatology Unit, Hospital Universitario Dr. Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico. OBJECTIVE: To determine ovarian reserve using antim€ullerian hormone levels (AMH) in patients with Systemic Lupus Erythematosus (SLE) with and without irregular bleeding and the impact in the cumulative dose of treatment. DESIGN: A retrospective, comparative and non-blind cohort analysis. MATERIALS AND METHODS: Sixty-four patients with a diagnosis of SLE between 18 and 39 years old were included. Serum levels of AMH were determined in patients and serum prolactin (PRL),thyroid stimulating hormone (TSH) and testosterone were measured in patients with SLE. Statistical analysis was made with the Mann-Whitney U test with a confidence interval of 95%. RESULTS: The prevalence of irregular bleeding in patients with SLE was of 60%, being oligomenorrhea the most frequent etiology. Only 3 patients with SLE had a serum AMH level below 0.38 ng/dl. Four patients were diagnosed with endocrine pathology, 3 patients were found to receive high-dose steroids and 1 patient was diagnosed with Cushing’s syndrome. There was no difference in AMH values in patients with and without irregular bleeding as well as the value of the cumulative dose of cyclophosphamide, corticosteroids and methotrexate. The cumulative dose of hydroxichloroquine was higher in patients with irregular bleeding than without them (265.21ng/mL vs. 254.5 ng/ mL, p¼0.04). CONCLUSION: No relationship was found between the cumulative dose of cyclophosphamide and amenorrhea, as well as in serum AMH values when both groups were compared. Endocrine diseases are frequent in SLE patients, and should be considered along with ovarian reserve tests when irregular bleedings are present.

Vol. 100, No. 3, Supplement, September 2013