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O-246 Wednesday, October 22, 2014 12:45 PM PREDICTORS OF LIVE BIRTH RATE (LBR) AFTER INTRAUTER- INE INSEMINATION (IUI) CYCLES. Z. Khan, E. P. Barnard, D. E. Morbeck, J. R. Jensen. Obstetrics & Gynecology, Mayo Clinic, Ro- chester, MN. OBJECTIVE: For patients undergoing fertility treatments, LBR is a more clinically relevant measure of successful outcome than clinical pregnancy rates (CPR). We report prognostic variables related to LBR after IUI cycles. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: All women undergoing IUI from 1/1/ 2005-12/31/2013 at Mayo Clinic, Rochester who gave IRB consent were included in the study. Information regarding ovulation induction (OI) proto- cols and semen parameters was collected. Regression models were utilized to identify independent factors associated with LBR. RESULTS: A total of 959 women who underwent 2605 IUI cycles were included. Overall 13.6% women had a positive pregnancy test. CPR and LBRs were 12.7 % (n¼332) and 9.5% (n¼248). Mean gestation age at delivery was 39.810.2 weeks. Women with successful live birth (LB) were younger; more of them used gonadotropins for OI and had hCG trigger compared to women without LB. They also used fresh semen sample for IUI and the sperm motility in the ejaculate (SME) as well as the inseminate (post wash) (SMI) was higher in this group compared to women without LBs. In the final multivariable model maternal age R38 years, stimulation protocol (oral agents vs. gonado- tropins), SME >40% and SMI >70% were independently associated with LB with adjusted odds ratios (95%CI) of; 0.43 (0.27-0.67), 0.74(0.06-0.53) vs. 1.51 (1.10-2.09), 1.87(1.04-3.69) and 1.92(1.11-3.59) respectively. No LBs were reported in women R43 years, where total motile sperm in the inseminate was <1 million, SME was <20% or SMI was <30%. CONCLUSION: Although clinically relevant to patients, IUI success as LBR is rarely reported. This large cohort reports maternal age, mode of stim- ulation for OI and sperm motility as important prognostic markers for LB af- ter IUI cycles. ART OUTCOME PREDICTORS - LAB II O-247 Wednesday, October 22, 2014 11:15 AM EPIGENETICS: ARE BABIES HEALTHIER CONCEIVED THROUGH IUI COMPARED WITH FRESH OR FROZEN IVF CYCLES? J. M. Bolnick, a A. D. Bolnick, a M. S. Estill, b M. P. Diamond. c a Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI; b Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI; c Department of Obstetrics and Gyne- cology, Georgia Regents University, Augusta, GA. OBJECTIVE: Assisted reproductive technologies have been implicated in adverse pregnancy outcomes. The available data lacks significance with po- tential risks of methylation alterations and genomic imprinting. Our objective was to compare epigenetic alterations in newborns conceived from infertile patients who underwent either in vitro fertilization (IVF) or intrauterine in- seminations (IUI) treatments. DESIGN: Laboratory investigation. MATERIALS AND METHODS: Three groups of infertile patients that underwent either IVF or IUI and delivered a viable infant were randomly chosen, Michigan Neonatal Biobank Bloodspots were obtained and deiden- tified, then placed into the appropriate intervention groups: IUI (N¼17), Fresh IVF embryo transfer(N¼38), and Frozen IVF embryo transfer(N¼38). DNA methylation profiles were obtained using Illumina Infinium Human Methylation 450 BeadChip system. RESULTS: Genders were identified utilizing Y chromosome probes. There were differences in methylation in male compared with female new- borns: IUI vs. Fresh (1378 to 2082), IUI vs. Frozen (1986 to 3661) and Fresh vs. Frozen (1613 to 2165). A number of genes were present in both the male and the female comparisons: IUI vs. Fresh (638 genes), IUI vs. Frozen (1252 genes) and Fresh vs. Frozen (720 genes). Of these genes, a subset showed the same pattern of methylation changes (hypo- or hypermethylation ) in both male and female comparison groups: IUI vs. Fresh (498 genes), IUI vs. Frozen (1052 genes), and Fresh vs. Frozen (559 genes) . Within these groups of genes that exhibited similar patterns, 90% were hypermethylated in the IUI vs. IVF and the IUI vs. the IVF Frozen groups, while 81% of the genes in the Fresh IVF vs. Frozen comparison were hypomethylated. Disease asso- ciation analysis, using Genomatix software GEPs, identified both Autism and Schizophrenia may be associated with either hypomethylation or hyperme- thylation changes found in IUI and IVF comparisons. CONCLUSION: Our data is consistent with an alteration of DNA methyl- ation profiles in babies conceived through IVF treatments compared with IUI. Furthermore the data suggests that embryo freezing may be associated with other changes in methylation status. Additional studies are required to ascertain the spectrum of effects and pregnancy outcomes on newborns conceived through ART. Supported by: This work was Supported in part by the WSU Ob/Gyn Research fund to MPD O-248 Wednesday, October 22, 2014 11:30 AM THREE DAY PROGESTERONE AREA UNDER THE CURVE: A BETTER TEST THAN PROGESTERONE ON THE DAY OF HCG? G. D. Royster, IV, a M. J. Hill, b S. M. Zarek, a A. H. DeCherney, a E. Levens, c E. Widra, c M. J. Levy. c a Program on Repro- ductive and Adult Endocrinology, National Institutes of Health, Bethesda, MD; b Reproductive Endocrinology and Infertility, Walter Reed National Military Medical Center, Bethesda, MD; c Shady Grove Fertility, Rockville, MD. OBJECTIVE: Elevated progesterone (P) on day of hCG trigger (P–hCG) has been associated with reduced ART pregnancy rates. However, less is known about the effect of persistently elevated P days before trigger. The Comparison of Successful vs. Unsuccessful IUI Outcome Live Birth (n¼248) No Live Birth (n¼2402) p-value Age 31.634.2 32.734.8 0.0002 Ovulation Induction with Oral Agents Yes 73(7.3) 927(92.7) No 175(10.9) 1430(89.1) 0.002 Ovulation Induction with Gonadotropins Yes 89(13.2) 588(86.9) No 159(8.3) 1769(91.8) 0.0002 hCG Trigger Yes 204(10.5) 1748(89.6) No 44(6.7) 609(93.3) 0.005 Semen Source Fresh 246(9.8) 2259(90.2) Frozen 2(2) 98(98) 0.009 Total Motile Sperm in Ejaculate 124.7113 120.7129.2 0.51 Motility of Sperm in Ejaculate 63.113.3 59.615.9 0.0001 Total Motile Sperm in Inseminate 5351 52.1160.3 0.81 Motility of Sperm in Inseminate 86.110.4 82.716.1 <0.0001 Numbers shown as: MeanStandard Deviation or Count(Percentage) FERTILITY & STERILITY Ò e85

Predictors of live birth rate (LBR) after intrauterine insemination (IUI) cycles

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Page 1: Predictors of live birth rate (LBR) after intrauterine insemination (IUI) cycles

O-246 Wednesday, October 22, 2014 12:45 PM

PREDICTORS OF LIVE BIRTH RATE (LBR) AFTER INTRAUTER-INE INSEMINATION (IUI) CYCLES. Z. Khan, E. P. Barnard,D. E. Morbeck, J. R. Jensen. Obstetrics & Gynecology, Mayo Clinic, Ro-chester, MN.

OBJECTIVE: For patients undergoing fertility treatments, LBR is a moreclinically relevant measure of successful outcome than clinical pregnancyrates (CPR). We report prognostic variables related to LBR after IUI cycles.

DESIGN: Retrospective cohort study.MATERIALS AND METHODS: All women undergoing IUI from 1/1/

2005-12/31/2013 at Mayo Clinic, Rochester who gave IRB consent wereincluded in the study. Information regarding ovulation induction (OI) proto-cols and semen parameters was collected. Regressionmodels were utilized toidentify independent factors associated with LBR.

Comparison of Successful vs. Unsuccessful IUI Outcome

Live Birth (n¼248) No Live Birth (n¼2402) p-value

Age 31.63�4.2 32.73�4.8 0.0002Ovulation Induction with Oral AgentsYes 73(7.3) 927(92.7)No 175(10.9) 1430(89.1) 0.002Ovulation Induction with GonadotropinsYes 89(13.2) 588(86.9)No 159(8.3) 1769(91.8) 0.0002hCG TriggerYes 204(10.5) 1748(89.6)No 44(6.7) 609(93.3) 0.005Semen SourceFresh 246(9.8) 2259(90.2)Frozen 2(2) 98(98) 0.009Total Motile Sperm in Ejaculate 124.7�113 120.7�129.2 0.51Motility of Sperm in Ejaculate 63.1�13.3 59.6�15.9 0.0001Total Motile Sperm in Inseminate 53�51 52.11�60.3 0.81Motility of Sperm in Inseminate 86.1�10.4 82.7�16.1 <0.0001

Numbers shown as: Mean�Standard Deviation or Count(Percentage)

RESULTS: A total of 959 women who underwent 2605 IUI cycles wereincluded. Overall 13.6% women had a positive pregnancy test. CPR andLBRswere 12.7% (n¼332) and 9.5% (n¼248).Mean gestation age at deliverywas 39.8�10.2 weeks. Women with successful live birth (LB) were younger;more of them used gonadotropins for OI and had hCG trigger compared towomen without LB. They also used fresh semen sample for IUI and the spermmotility in the ejaculate (SME)aswell as the inseminate (postwash) (SMI)washigher in this group compared towomenwithoutLBs. In thefinalmultivariablemodel maternal ageR38 years, stimulation protocol (oral agents vs. gonado-tropins), SME>40% and SMI>70% were independently associated with LBwith adjusted odds ratios (95%CI) of; 0.43 (0.27-0.67), 0.74(0.06-0.53) vs.1.51 (1.10-2.09), 1.87(1.04-3.69) and 1.92(1.11-3.59) respectively. No LBswere reported inwomenR43years,where totalmotile sperm in the inseminatewas <1 million, SME was <20% or SMI was <30%.

CONCLUSION: Although clinically relevant to patients, IUI success asLBR is rarely reported. This large cohort reports maternal age, mode of stim-ulation for OI and sperm motility as important prognostic markers for LB af-ter IUI cycles.

ART OUTCOME PREDICTORS - LAB II

O-247 Wednesday, October 22, 2014 11:15 AM

EPIGENETICS: ARE BABIES HEALTHIER CONCEIVEDTHROUGH IUI COMPARED WITH FRESH OR FROZEN IVFCYCLES? J. M. Bolnick,a A. D. Bolnick,a M. S. Estill,b

M. P. Diamond.c aDepartment of Obstetrics and Gynecology, Wayne StateUniversity, Detroit, MI; bCenter for Molecular Medicine and Genetics,Wayne State University, Detroit, MI; cDepartment of Obstetrics and Gyne-cology, Georgia Regents University, Augusta, GA.

OBJECTIVE: Assisted reproductive technologies have been implicated inadverse pregnancy outcomes. The available data lacks significance with po-

FERTILITY & STERILITY�

tential risks of methylation alterations and genomic imprinting. Our objectivewas to compare epigenetic alterations in newborns conceived from infertilepatients who underwent either in vitro fertilization (IVF) or intrauterine in-seminations (IUI) treatments.DESIGN: Laboratory investigation.MATERIALS AND METHODS: Three groups of infertile patients that

underwent either IVF or IUI and delivered a viable infant were randomlychosen, Michigan Neonatal Biobank Bloodspots were obtained and deiden-tified, then placed into the appropriate intervention groups: IUI (N¼17),Fresh IVF embryo transfer(N¼38), and Frozen IVF embryo transfer(N¼38).DNA methylation profiles were obtained using Illumina Infinium HumanMethylation 450 BeadChip system.RESULTS: Genders were identified utilizing Y chromosome probes.

There were differences in methylation in male compared with female new-borns: IUI vs. Fresh (1378 to 2082), IUI vs. Frozen (1986 to 3661) and Freshvs. Frozen (1613 to 2165). A number of genes were present in both the male

and the female comparisons: IUI vs. Fresh (638 genes), IUI vs. Frozen (1252genes) and Fresh vs. Frozen (720 genes). Of these genes, a subset showed thesame pattern of methylation changes (hypo- or hypermethylation ) in bothmale and female comparison groups: IUI vs. Fresh (498 genes), IUI vs.Frozen (1052 genes), and Fresh vs. Frozen (559 genes) . Within these groupsof genes that exhibited similar patterns, 90% were hypermethylated in theIUI vs. IVF and the IUI vs. the IVF Frozen groups, while 81% of the genesin the Fresh IVF vs. Frozen comparison were hypomethylated. Disease asso-ciation analysis, using Genomatix software GEPs, identified both Autism andSchizophrenia may be associated with either hypomethylation or hyperme-thylation changes found in IUI and IVF comparisons.CONCLUSION: Our data is consistent with an alteration of DNA methyl-

ation profiles in babies conceived through IVF treatments compared withIUI. Furthermore the data suggests that embryo freezing may be associatedwith other changes in methylation status. Additional studies are required toascertain the spectrum of effects and pregnancy outcomes on newbornsconceived through ART.Supported by: This work was Supported in part by the WSU Ob/Gyn

Research fund to MPD

O-248 Wednesday, October 22, 2014 11:30 AM

THREE DAY PROGESTERONE AREA UNDER THE CURVE: ABETTER TEST THAN PROGESTERONE ON THE DAY OFHCG? G. D. Royster, IV,a M. J. Hill,b S. M. Zarek,a

A. H. DeCherney,a E. Levens,c E. Widra,c M. J. Levy.c aProgram on Repro-ductive and Adult Endocrinology, National Institutes of Health, Bethesda,MD; bReproductive Endocrinology and Infertility, Walter Reed NationalMilitary Medical Center, Bethesda, MD; cShady Grove Fertility, Rockville,MD.

OBJECTIVE: Elevated progesterone (P) on day of hCG trigger (P–hCG)has been associated with reduced ART pregnancy rates. However, less isknown about the effect of persistently elevated P days before trigger. The

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