Embryo cohort size does not affect euploidy

Embryo cohort size does not affect euploidy

OVARIAN STIMULATION: ART O-281 Wednesday, October 19, 2011 11:15 AM EFFECT OF UNILATERAL OOPHORECTOMY ON OVARIAN RESERVE AND IVF STIMULATION OUTCOMES...

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OVARIAN STIMULATION: ART O-281 Wednesday, October 19, 2011 11:15 AM EFFECT OF UNILATERAL OOPHORECTOMY ON OVARIAN RESERVE AND IVF STIMULATION OUTCOMES. Z. Khan, R. P. Gada, Z. M. Tabbaa, S. K. Laughlin, C. C. Coddington, E. A. Stewart. Department of OB/GYN, Division of Reproductive Endocrinology & Infertility, Mayo Clinic, Rochester, MN. OBJECTIVE: After a unilateral oophorectomy (UO), it is assumed based on animal studies that the remaining ovary compensates in premenopausal women. Human data are lacking. This study investigates the effect of UO on ovarian reserve (OVR) and stimulation outcomes of women undergoing IVF. DESIGN: Cohort study with age-matched controls MATERIALS AND METHODS: Women undergoing ART from 19962011 who gave IRB consent were considered for analysis. Data from women with UO were compared to the ipsilateral ovary of women with both ovaries. A control group was matched by age and year of stimulation in a 2:1 manner. Measures for OVR were Day 3 FSH and Antral Follicle Counts (AFC). Number of follicles aspirated and oocytes retrieved were outcomes measures. Means were compared with t-tests and logistic regression models were used to adjust for age, BMI, Day 3 FSH and AFC. RESULTS: 51 women with UO were compared to 102 controls. Baseline demographics and OVR were not different, yet women with UO had significantly more follicles and oocytes than their matched controls. TABLE 1

Age BMI Day 3 FSH AFC Follicles Aspirated Oocytes Aspirated

Unilateral Oophorectomy

Ipsilateral Ovary

P-value

33.20  3.7 25.34  5.4 7.92  3.7 15.21  8.5 14.35  8.3 9.76  7.3

32.94  3.7 25.32  5.7 7.16  2.6 9.71*  6.3 10.41  5.7 6.26  3.9

.69 .98 .23 < .001 < .005 < .005

* Where ovary-specific data not available half of total AFC reported Median number of follicles and oocytes for both groups was 10 and 7 respectively. A stimulated ovary from a woman with UO was twice as likely to yield more than 10 follicles (OR ¼ 2.25) and 7 oocytes, (OR ¼ 2.32) when compared to ipsilateral stimulated ovary in women without UO. This association was stronger after adjusting for confounders (OR [95% CI] for follicles aspirated 10.57[2.3-66.9] OR [95%CI] for oocytes retrieved 6.80[1.61-35.9]) CONCLUSION: Our results demonstrate that the remaining ovary does compensate, confirming animal data. AFC appears to be a significant predictor of oocyte yield. Women with UO can be reassured regarding stimulation outcomes.

O-282 Wednesday, October 19, 2011 11:30 AM HORMONAL CONTRACEPTION PRIOR TO IN VITRO FERTILIZATION (IVF) ADVERSLY AFFECTS FUNCTIONAL OVARIAN RESERVE AND OOCYTE YIELDS. N. Gleicher, H. Kubba, A. Weghofer. Center for Human Reproduction, New York, NY; Foundation for Reproductive Medicine, New York, NY; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT; Department of Obstetrics and Gynecology, Medical University Vienna, Wien, Austria. OBJECTIVE: Since short-term use of oral contraceptives (OCs) suppresses anti-M€ ullerian hormone (AMH) (Hum Reprod 2007; 22:3192-6), hormonal contraception (HC), likely, suppresses functional ovarian reserve (FOR), characterized by small pre-antral and antral follicles. Whether oocyte donors are on HC may, therefore, affect oocyte yields. DESIGN: Cohort study. MATERIALS AND METHODS: 32 oocyte donors underwent 39 IVF cycles (1 cycle, n ¼ 26; 2 cycles, n ¼ 5; 3 cycles, n ¼ 1) within maximally 100 days from initial physician interview, documenting contraceptive use and anti-M€ ullerian hormone (AMH). Oocyte yields were compared in 19 cycles on no HC (Group 1) and 20 cycles where donors were on HC. The latter was further subdivided into 7 with weak or no androgenic progestin (Group 2) and 13 with strong androgenic progestin (Group 3). All underwent routine IVF

FERTILITY & STERILITYÒ

cycle stimulation, using down-regulation with luteal phase agonist and gonadotropin stimulation of 150-300 IU. RESULTS: Time between last AMH and IVF cycle start for the whole study group was 69.4  20.5 days; mean age 24.2  4.0 years; mean AMH 4.5  1.8 ng/mL; and mean oocyte yield 14.8  5.6. Comparing donors off and on HC, mean ages were 23.4  4.6 vs. 23.2  2.3 years; mean AMH 4.6  2.1 vs. 3.8  1.4 ng/mL; mean oocyte yields 17.2  5.1 vs. 14.4  7.6. Oocyte yields in Groups 1-3 were in order: 16.2  6.0, 16.7  4.7 and 11.7  4.3 (P¼0.026, univariate analysis of variance); Groups 1 and 3 differed significantly (P¼0.024), a difference maintained after age adjustment (P¼0.032). CONCLUSION: This study strongly suggests that high androgenic HC exposure, indeed, suppresses FOR and impacts oocyte yields in IVF. Since OCs are routinely used in preparation for IVF, this may impact IVF outcomes in general, and especially in women with diminished ovarian reserve. At minimum, only low androgenic progestin HC should be utilized in association with IVF. Supported by: The Foundation for Reproductive Medicine and intramural research funds from the Center for Human Reproduction - New York.

O-283 Wednesday, October 19, 2011 11:45 AM PROSPECTIVE, RANDOMIZED STUDY OF PULSATILE GNRH THERAPY AND GONADOTROPINS TREATMENT (FSH+LH) FOR OVULATION INDUCTION IN WOMEN WITH HYPOTHALAMIC AMENORRHEA AND UNDERLYING POLYCYSTIC OVARY SYNDROME. S. Dubourdieu, T. Freour, L. Dessolle, P. Barriere. Medecine et Biologie de la Reproduction, Centre Hospitalier Universitaire de Nantes, Nantes, France. OBJECTIVE: Hypothalamic amenorrhea (HA) and polycystic ovarian syndrome (PCOS) are well-defined aetiologies of female infertility. Both can be associated in some women (HA/PCOS), but this has not been largely described. The ovarian hyperandrogenism in HA/PCOS is masked by suppressed hypothalamic-pituitary axis. Ovulation induction with FSH or hMG in HA/PCOS women often leads to inadequate ovarian response. The aim of this study was to compare pulsatile GnRH therapy and gonadotropins FSH + LH treatment for ovulation induction in HA/PCOS women. DESIGN: Prospective, randomized study. MATERIALS AND METHODS: We included 30 women with secondary amenorrhea associated with weight loss due to low dietary intake and/or intensive physical exercise, and PCOS according to Rotterdam criteria. They all had ovulation induction failure with clomiphene citrate and/or FSH alone and/or hMG. Computer-generated randomization list was used to choose between subcutaneous pulsatile GnRH therapy (15mg/pulse, every 90 min) or gonadotropins association (rFSH 75IU/L + rLH 75 IU/L daily injections).Treatment was initiated on day 2 of the cycle after progestin induced bleeding. Ovulation was triggered with hCG when one ovarian follicle reached 17 mm in diameter, and all women had luteal phase support (hCG injection 1500 IU every 72 hours, 3 times). RESULTS: Mean age, infertility duration, BMI, smoking status, baseline FSH, LH, E2, AMH, testosterone, stimulation duration were not significantly different in both groups. Ovarian response was adequate (mono or bifollicular) in 73.3% in the pulsatile GnRH group and 57.1% in the gonadotropins group. Clinical pregnancy rate was 50% in the pulsatile GnRH group and no evolutive pregnancy occurred in the gonadotropins group (one biochemical pregnancy). CONCLUSION: HA/PCOS is a specific subgroup of infertile women, in which pulsatile GnRH therapy can be used successfully for ovulation induction. The GnRH dose per pulse should be reduced compared with HA patients in order to prevent multifollicular ovarian response.

O-284 Wednesday, October 19, 2011 12:00 PM EMBRYO COHORT SIZE DOES NOT AFFECT EUPLOIDY. B. Kaplan, H. Danzer, M. Glassner, M. Opsahl, J. Cohen, S. Munne. Reprogenetics, Livingston, NJ; Fertility Centers of Illinois, Highland Park, Highland Park, IL; ART Reproductive Center, Beverly Hills, CA; Main Line Fertility and Reproductive Medicine, Bryn Mawr, PA; Northwest Center for Reproductive Sciences, Kirkland, WA. OBJECTIVE: Chromosome abnormalities cause the failure of a high proportion of embryos to implant or reach term. A correlation between follicular

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response and cohort size could indicate that ovarian reserve is correlated with egg or embryo quality and euploidy. The goal of this study was to determine the frequency of euploidy in cleaved embryos as well as blastocysts across maternal age groups according to the cohort size. DESIGN: Retrospective multicenter study. MATERIALS AND METHODS: Ovarian stimulation protocols varied and were clinic-specific. More than 60 clinics were included in this study. Preimplantation genetic diagnosis was performed by array Comparative Genomic Hybridization (aCGH) following day-3 biopsy (649 cycles) or day-5 (blastocyst) biopsy (124 cycles). A total of 5435 day-3 embryos and 701 blastocysts were biopsied. Based on reanalysis of non-replaced embryos (n ¼ 221), the technical error rate of aCGH was 3% for day-3 and 0% for day-5 biopsied embryos. RESULTS: See table:

% Euploid Embryos According to Maternal Age and Cohort Size # embryos in cohort day-3 biopsy 1-4 5-7 8-10 >10 day-5 biopsy 1-4 5-7 8-10 >10

egg donor

<35

35-39

40-42

>42

50% 40% 65% 47%

43% 38% 35% 47%

18%* 26% 28% 32%*

17% 15% 15% 16%

6% 5% 8% 8%

50% 70% 73% 58%

55% 66% 64% 57%

50% 44% 50% n/a

36% 38% 36% n/a

20% 23% n/a n/a

* P<0.05 CONCLUSION: The results do not support the notion that larger cohorts of embryos or aggressive stimulation regimes produce chromosomally inferior embryos. Furthermore, a smaller cohort of embryos reduces the absolute number of normal embryos available for fresh/frozen-thawed transfers while reducing the cumulative chances of pregnancy. Increasing the cohort size when possible, combined with comprehensive chromosome assessment and embryo selection followed by high yield freezing or vitrification procedures may optimize single embryo transfer and increase cumulative pregnancy rates.

O-285 Wednesday, October 19, 2011 12:15 PM THE PREGNANCY AND NEONATAL OUTCOME FOLLOWING OVULATION INDUCTION WITH AROMATASE INHIBITOR LETOROZOLE AND CLOMIPHENE CITRATE. Y. Nakajo, Y. Fukuda, Y. Sato, S. Suzuki, T. Takisawa, K. Kyono. Kyono ART Clinic, Sendai, Miyagi, Japan. OBJECTIVE: To evaluate the pregnancy and neonatal outcome after ovulation induction with aromatase inhibitor letorozole or clomiphene citrate (CC). DESIGN: A prospective, randomized study. MATERIALS AND METHODS: The study included couples directed for IVF/ICSI treatment to the IVF unit at Kyono ART clinic, Japan, from May, 1995 to December, 2010. The couples, who all gave written, informed consent to undergo this method, were divided into two groups. (letorozole and CC). Letorozole at a dose of 5 mg/day or CC at a dose of 100mg/day was given to patients on days 3-7 of menstrual cycles. Patients were treated with hMG or FSH or a combination of the two each day, starting from day 8. GnRH antagonist (Cetrotide 0.25mg/day) was administered when the dominant follicle reached 14 mm in diameter. Ovulation was triggered with urinary hCG. We compared the result of assisted reproductive technology (ART) and neonatal conditions with letorozole and with CC. RESULTS: The clinical pregnancy rate was significantly higher in the letorozole group in comparison to the CC group. There were no differences in the results of other ART and neonatal outcomes between the two groups (Table 1). CONCLUSION: Aromatase inhibitors and CC resulted in favorable pregnancy and neonatal outcomes, and indicated that children were growing normally. It is shown that the two medicines are safe for mothers and fetuses.

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Abstracts

Table1 letorozole No. of oocyte pick up 821 cycles Maturation rate (%) 77.7 (3225/4152) Fertilization rate (%) 68.7 (2217/3225) Blastocyst formation 42.3 ( 566/1339) rate (%) Clinical pregnancy rate 22.3 (207/ 929) (%)/embryo transfer No. of ongoing 38 pregnancies (n) Abortion rate (%) 32.9 (68/207) No. of births (n) single:95 twin:5 Average birth single:2910  435 weight (g) twin:1929  299 Deformed child (n) 1*

CC 912 81.4 (2067/2538) 71.4 (1476/2067) 42.9 ( 313/ 699)

NS NS NS

15.5 ( 113/ 731)

P¼0.0005

35 31.9 (36/113) single:39 twin:3 single:3017  458 twin:1941  178 0

NS NS

* trisomy 21 (Down syndrome)

O-286 Wednesday, October 19, 2011 12:30 PM CAN DOPAMINE AGONIST CABERGOLINE REDUCE OVARIAN HYPERSTIMULATION SYNDROME IN ART TREATMENT CYCLES? A PROSPECTIVE RANDOMIZED STUDY. H. Amir, D. Yaniv Kovalski, A. Amit, F. Azem. Racine IVF Unit, Lis Maternity Hospital, Sourasky Medical Center, Tel Aviv, Israel. OBJECTIVE: To examine whether dopamine agonist reduces OHSS in high-risk patients undergoing ART and to analyze whether cabergoline administration, affects the outcome of ART. DESIGN: We designed a prospective randomized study to evaluate the potential of cabergoline to decrease the incidence of OHSS in high-risk patients undergoing ART. MATERIALS AND METHODS: Forty patients with oestradiol concentrations over 4000 pg/ml on the day of hCG administration were evaluated. They were randomized into two groups: group A (n ¼ 20) received oral cabergoline 0.5 mg/day for 8 days beginning on the day of hCG, and group B (n ¼ 20) control. Women were monitored at the day of hCG, at the day of embryo transfer (ET) and 7 and 12 days after ET. We used transvaginal ultrasound to measure ascites. To evaluate hemoconcentration we measured hemoglobin, hematocrit, and leukocyte count. Liver and renal functions were analyzed to ascertain the severity of the syndrome. Prolactin levels were also measured. RESULTS: Ascites was significantly lower at the day of ET (P ¼ 0.04), day 7 (P ¼ 0.029) and day 12 (P ¼ 0.039) after ET in group A as compared with control. No significant differences (P>0.05) were found between the groups in prolactin, hemoglobin, hematocrit, leukocyte, liver and renal functions. Emergency room visiting (P ¼ 0.95) and hospitalization (P ¼ 0.32) rates were without statistical differences between the groups. The incidence of moderate OHSS (established on ascites) was 17% in group A and 47% in the control (P¼0.035). No difference was detected between the groups in fertilization (P ¼ 0.6), implantation (P ¼ 0.1) or pregnancy (P ¼ 0.2) rates. CONCLUSION: Our data support the use of cabergoline in the management of high-risk patients undergoing ART, in order to provide better clinical control of ovarian response and consequently a reduction of the risk of OHSS, with no deleterious effect on ART outcome.

O-287 Wednesday, October 19, 2011 12:45 PM INTERMEDIATE AND NORMAL SIZED CGG REPEAT ON THE FMR1 (FRAGILE X) GENE DOES NOT AFFECT OVARIAN RESPONSE IN OOCYTE DONOR. J. Llacer, B. Lledo, J. Guerrero, J. A. Ortiz, J. Gimenez, R. Bernabeu. Instituto Bernabeu, Alicante, Spain; IB Biotech, Alicante, Spain; NEOGINFER, Alicante, Spain. OBJECTIVE: The goal of this study is investigated whether CGG repeats on the FMR1 gene have predictive value for ovarian response to stimulation with gonadotropins during an oocyte donors programme. DESIGN: We evaluate the ovarian response to gonadotropin in oocyte donors with different CGG repeats on the FMR1 gene in normal range.

Vol. 96., No. 3, Supplement, Sepetmber 2011