- Email: [email protected]
The effect of early fetal losses on twin assisted-conception pregnancy outcomes
remained below 2% through 2004, then increased to 3% in 2005 and 7% in 2006. The proportion of all DO ETs that were eSET rose each year from 2% in 2002 to 18% in 2006. Pregnancy rates for auto eSET were 61% (68% in 2006) compared to 60% (61% in 2006) for transfers of 2 blastocysts. Pregnancy rates for DO eSET were 64% (67% in 2006) compared to 71% (67% in 2006) for transfers of 2 blastocysts. Only 1.4% of all eSET pregnancies were twins, compared to twinning rates of 51% for auto and 60% for DO pregnancies following elective transfer of 2 blastocysts. CONCLUSIONS: High implantation rates resulting from the transfer of 1 or 2 blastocyst stage embryos suggest that an increasing proportion of embryo transfers electively can be single. Implementation of this strategy in a large IVF program over the last 5 years through physician, staff and patient education of the risks and benefits has demonstrated that a reduction in multiple pregnancies is possible without a concomitant compromise in pregnancy rates. Supported by: None.
Monday, October 15, 2007 4:45 pm O-69 THE ART AND SCIENCE OF REPRODUCTIVE DONOR SCREENING: POOLED TESTING (PT) VS. INDIVIDUAL DONOR NUCLEIC ACID TESTING (ID NAT) AND FALSE POSITIVE TEST RATE. J. B. Gorlin, M. Janzen, J. VanHulzen. Donor Testing, Memorial Blood Centers, St. Paul, MN. OBJECTIVE: False positive test results can lead to a loss of thousands of dollars invested in stimulating an egg donor and recipient in assisted reproductive technology (ART) if results are received after stimulation has begun. This study reviews the impact of the requirement for ID NAT negative for hepatitis C (HCV) and HIV as opposed to pooled testing (PT). NAT testing is currently performed in pools of 24 (Roche) or 16 (GenProbe) on blood donors, which decreases cost and risk of false positive testing. Because vendors only submitted blood donor data the FDA approved pooled testing only for blood donors and individual donor testing is required for other donor types. In the event of a positive pool, the individual components are tested, giving an opportunity to rule out false positive initial tests. This pool resolution algorithm does not exist for an ID-NAT positive result. DESIGN: A retrospective analysis of the rates of false positive tests of reproductive donors during pooled testing and ID NAT were compared. MATERIALS AND METHODS: From 1/05 through 4/07 we tested over 9,000 reproductive donors. All tests since 12/05 were tested in individual donor format following the 2005 ASRM meeting. RESULTS: Over 2000 donors were tested as pools and false positive rates of 0.09% for HIV & HCV were observed. For ID NAT (>7000 donors) false positive rates of 0.32% (HIV) and 0.38% (HCV) were about 4 times higher (Student’s T test P<0.01) CONCLUSIONS: ID NAT will inevitably result in a higher false positive rate. Pooled testing can rule out false positives, whereas the initial positive is the test of record in ID NAT. Solutions include allowing PT (which would require test manufacturer submission to FDA), or ensuring that tests are done prior to initiation of a cycle. The recent ‘‘FDA guidance for industry: Eligibility determination for donors of human cells, tissues and cellular and tissue-based products (HCT/Ps)’’ (2-27-07) specifically allows testing %30 days prior to retrieval for oocyte donors and %7 days for semen donors (p.28). Testing early ensures that a false positive is received prior to stimulation saving dollars. Automatic reflex testing of an alternate sample in the event of discordant results ( þ NAT but EIA) does not eliminate the positive test of record but helps donor counseling and prevents expensive & unnecessary medical referrals. We encourage FDA to work with industry to facilitate a re-entry algorithm for donors with false-positive ID NAT results, analogous to those available for blood donors. Supported by: None.
D. A. Grainger, J. E. Stern, N. Klein, M. I. Cedars. School of Nursing & Health Studies, University of Miami, Coral Gables, FL; Biostatistics, University of Michigan, Ann Arbor, MI; Obstetrics and Gynecology, University of Kansas Medical School, Wichita, KS; Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Hanover, NH; Seattle Reproductive Medicine, Seattle, WA; Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, CA. OBJECTIVE: To evaluate the effect of first trimester fetal losses (spontaneous or iatrogenic) on gestation, birthweight, and birthweight-for-gestation (Z-scores) in twin births from assisted reproductive technology (ART). DESIGN: Retrospective analysis of twin live births in the 2005 SART database, including autologous and donor oocytes and embryos. MATERIALS AND METHODS: The study population included 9,996 twin pregnancies, categorized by number of fetal hearts initially identified on early ultrasound as two, or three or more. Birthweight Z-scores were calculated to evaluate adequacy of weight-for-age. Maternal characteristics and pregnancy outcomes were compared between groups using c2 and Student’s t tests; binary logistic regression was used for dichotomized outcomes, controlling for maternal age, primigravidity, oocyte or embryo state, history of prior term birth, and newborn genders, with the group with two fetal hearts on early ultrasound as the reference. Data below are presented as means standard deviations (SD), percents, or as adjusted odds ratios (AOR) with 95% confidence intervals. RESULTS: See table below.
TABLE
# Fetal Hearts
Two
Threeþ
P Value
No. pregnancies Maternal Age (yrs) Length of gestation (weeks) % 22–32 weeks % 33–36 weeks % R 37 weeks Mean Twin Birthweight (grams) Mean Twin Pair Birthweight Z-score Either Twin Birthweight Z-score <1.96 (%) Either Twin Birthweight Z-score <1.96 (AOR) Gestation 22–32 weeks (AOR) Gestation 33–36 weeks (AOR) Gestation R37 weeks (AOR)
9,295 34.5 5.2 35.4 2.8
701 35.9 4.8 34.9 3.0
<0.0001 <0.0001
14.7 55.2 30.1 2,381 541
20.4 54.8 24.8 2,246 568
<0.0001 <0.0001 <0.0001 <0.0001
0.40 1.00
0.49 0.87
0.015
8.4
10.7
0.030
1.00 (Reference) 1.41 (1.01–1.97)
0.044
1.00 (Reference) 1.51 (1.11–2.05)
0.009
1.00 (Reference) 1.30 (1.01–1.67)
0.039
1.00 (Reference) 0.71 (0.56–0.91)
0.005
CONCLUSIONS: Early fetal loss in pregnancies that result in a twin live birth is associated with significant increased risks for lowered birthweight, shortened gestation, and reduced birthweight-for-age. Since first trimester multiple fetal hearts are more common in ART pregnancies, this factor may help explain their greater risk for reduced birthweight and shorter gestations. Supported by: A SART Writing Group paper.
Monday, October 15, 2007 3:15 pm OUTCOME PREDICTORS-CLINICAL: ART ABSTRACTS Monday, October 15, 2007 3:00 pm O-70 THE EFFECT OF EARLY FETAL LOSSES ON TWIN ASSISTEDCONCEPTION PREGNANCY OUTCOMES. B. Luke, M. B. Brown,
S26
Abstracts
O-71 INTRAFOLLICULAR ANTI-MULLERIAN HORMONE (AMH) LEVELS POSITIVELY CORRELATE WITH FOLLICLE SENSITIVITY TO FOLLICLE STIMULATING HORMONE (FSH) AND ARE ELEVATED IN POLYCYSTIC OVARY SYNDROME (PCOS). D. A. Dumesic, T. G. Lesnick, J. Booher, A. Wong, G. D. Ball, D. H. Abbott. National Primate Research Center, University of Wisconsin, Madison, WI; Department of OB/GYN, University of Wisconsin, Madison,
Vol. 88, Suppl 1, September 2007
Monday, October 15, 2007 4:45 pm O-69 THE ART AND SCIENCE OF REPRODUCTIVE DONOR SCREENING: POOLED TESTING (PT) VS. INDIVIDUAL DONOR NUCLEIC ACID TESTING (ID NAT) AND FALSE POSITIVE TEST RATE. J. B. Gorlin, M. Janzen, J. VanHulzen. Donor Testing, Memorial Blood Centers, St. Paul, MN. OBJECTIVE: False positive test results can lead to a loss of thousands of dollars invested in stimulating an egg donor and recipient in assisted reproductive technology (ART) if results are received after stimulation has begun. This study reviews the impact of the requirement for ID NAT negative for hepatitis C (HCV) and HIV as opposed to pooled testing (PT). NAT testing is currently performed in pools of 24 (Roche) or 16 (GenProbe) on blood donors, which decreases cost and risk of false positive testing. Because vendors only submitted blood donor data the FDA approved pooled testing only for blood donors and individual donor testing is required for other donor types. In the event of a positive pool, the individual components are tested, giving an opportunity to rule out false positive initial tests. This pool resolution algorithm does not exist for an ID-NAT positive result. DESIGN: A retrospective analysis of the rates of false positive tests of reproductive donors during pooled testing and ID NAT were compared. MATERIALS AND METHODS: From 1/05 through 4/07 we tested over 9,000 reproductive donors. All tests since 12/05 were tested in individual donor format following the 2005 ASRM meeting. RESULTS: Over 2000 donors were tested as pools and false positive rates of 0.09% for HIV & HCV were observed. For ID NAT (>7000 donors) false positive rates of 0.32% (HIV) and 0.38% (HCV) were about 4 times higher (Student’s T test P<0.01) CONCLUSIONS: ID NAT will inevitably result in a higher false positive rate. Pooled testing can rule out false positives, whereas the initial positive is the test of record in ID NAT. Solutions include allowing PT (which would require test manufacturer submission to FDA), or ensuring that tests are done prior to initiation of a cycle. The recent ‘‘FDA guidance for industry: Eligibility determination for donors of human cells, tissues and cellular and tissue-based products (HCT/Ps)’’ (2-27-07) specifically allows testing %30 days prior to retrieval for oocyte donors and %7 days for semen donors (p.28). Testing early ensures that a false positive is received prior to stimulation saving dollars. Automatic reflex testing of an alternate sample in the event of discordant results ( þ NAT but EIA) does not eliminate the positive test of record but helps donor counseling and prevents expensive & unnecessary medical referrals. We encourage FDA to work with industry to facilitate a re-entry algorithm for donors with false-positive ID NAT results, analogous to those available for blood donors. Supported by: None.
D. A. Grainger, J. E. Stern, N. Klein, M. I. Cedars. School of Nursing & Health Studies, University of Miami, Coral Gables, FL; Biostatistics, University of Michigan, Ann Arbor, MI; Obstetrics and Gynecology, University of Kansas Medical School, Wichita, KS; Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Hanover, NH; Seattle Reproductive Medicine, Seattle, WA; Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, CA. OBJECTIVE: To evaluate the effect of first trimester fetal losses (spontaneous or iatrogenic) on gestation, birthweight, and birthweight-for-gestation (Z-scores) in twin births from assisted reproductive technology (ART). DESIGN: Retrospective analysis of twin live births in the 2005 SART database, including autologous and donor oocytes and embryos. MATERIALS AND METHODS: The study population included 9,996 twin pregnancies, categorized by number of fetal hearts initially identified on early ultrasound as two, or three or more. Birthweight Z-scores were calculated to evaluate adequacy of weight-for-age. Maternal characteristics and pregnancy outcomes were compared between groups using c2 and Student’s t tests; binary logistic regression was used for dichotomized outcomes, controlling for maternal age, primigravidity, oocyte or embryo state, history of prior term birth, and newborn genders, with the group with two fetal hearts on early ultrasound as the reference. Data below are presented as means standard deviations (SD), percents, or as adjusted odds ratios (AOR) with 95% confidence intervals. RESULTS: See table below.
TABLE
# Fetal Hearts
Two
Threeþ
P Value
No. pregnancies Maternal Age (yrs) Length of gestation (weeks) % 22–32 weeks % 33–36 weeks % R 37 weeks Mean Twin Birthweight (grams) Mean Twin Pair Birthweight Z-score Either Twin Birthweight Z-score <1.96 (%) Either Twin Birthweight Z-score <1.96 (AOR) Gestation 22–32 weeks (AOR) Gestation 33–36 weeks (AOR) Gestation R37 weeks (AOR)
9,295 34.5 5.2 35.4 2.8
701 35.9 4.8 34.9 3.0
<0.0001 <0.0001
14.7 55.2 30.1 2,381 541
20.4 54.8 24.8 2,246 568
<0.0001 <0.0001 <0.0001 <0.0001
0.40 1.00
0.49 0.87
0.015
8.4
10.7
0.030
1.00 (Reference) 1.41 (1.01–1.97)
0.044
1.00 (Reference) 1.51 (1.11–2.05)
0.009
1.00 (Reference) 1.30 (1.01–1.67)
0.039
1.00 (Reference) 0.71 (0.56–0.91)
0.005
CONCLUSIONS: Early fetal loss in pregnancies that result in a twin live birth is associated with significant increased risks for lowered birthweight, shortened gestation, and reduced birthweight-for-age. Since first trimester multiple fetal hearts are more common in ART pregnancies, this factor may help explain their greater risk for reduced birthweight and shorter gestations. Supported by: A SART Writing Group paper.
Monday, October 15, 2007 3:15 pm OUTCOME PREDICTORS-CLINICAL: ART ABSTRACTS Monday, October 15, 2007 3:00 pm O-70 THE EFFECT OF EARLY FETAL LOSSES ON TWIN ASSISTEDCONCEPTION PREGNANCY OUTCOMES. B. Luke, M. B. Brown,
S26
Abstracts
O-71 INTRAFOLLICULAR ANTI-MULLERIAN HORMONE (AMH) LEVELS POSITIVELY CORRELATE WITH FOLLICLE SENSITIVITY TO FOLLICLE STIMULATING HORMONE (FSH) AND ARE ELEVATED IN POLYCYSTIC OVARY SYNDROME (PCOS). D. A. Dumesic, T. G. Lesnick, J. Booher, A. Wong, G. D. Ball, D. H. Abbott. National Primate Research Center, University of Wisconsin, Madison, WI; Department of OB/GYN, University of Wisconsin, Madison,
Vol. 88, Suppl 1, September 2007