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Achieving Pregnancy Using Fresh Versus Cryopreserved Semen for Donor Insemination

Achieving Pregnancy Using Fresh Versus Cryopreserved Semen for Donor Insemination. Blood Products Advisory Committee, 12/14/01 Emmet J. Lamb, M.D. Professor of Gyn- Ob, Emeritus Stanford University, Stanford, California. Indications in 2001 for donor insemination .

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Achieving Pregnancy Using Fresh Versus Cryopreserved Semen for Donor Insemination

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  1. Achieving Pregnancy Using Fresh Versus Cryopreserved Semen for Donor Insemination Blood Products Advisory Committee, 12/14/01 Emmet J. Lamb, M.D. Professor of Gyn- Ob, Emeritus Stanford University, Stanford, California

  2. Indications in 2001for donor insemination • Azoospermia or severe oligospermia • ICSI not available • No sperm • Not successful • Too Costly • Genetic problem of male • No male partner

  3. Variables that improve fecundity Stratify in analysis • Azoospermic Male • Young female • Normal female • Parous female • Short duration infertility • First cycle

  4. Donor selection Fertile High motile sperm count Good cryosurvival Fresh sperm Cryopreservation Methods Sperm preparation Insemination Methods Ovulation monitoring Cervical mucus and BBT Urinary LH Pelvic ultrasound Ovulation enhancement Clomiphene Gonadotropins Variables that can be changed to improve fecundity

  5. Comparing Fecundity • Cycle fecundity • Total pregnancies / Total cycles of exposure • Assumes constant hazard rate. • Easy calculation • Easy explanation • Close to reality • Kaplan Meier survival analysis • Cox proportional hazard regression analysis

  6. Fresh versus thawed semenMeta-analysis of cycle fecundity

  7. Meta-analysisSummary Statistics • Total subjects 23,374 • Summary odds ratio 0.62 (0.43 to 0.90) • 2p Fresh v. Thaw 0.011 (Z= -2.55) • Heterogeneity, Q 129 (Tau sq= 0.42)

  8. Fresh versus Thawed SemenCumulative Meta-analysis

  9. Cycle fecundity with donor frozen semen in clomiphene or unstimulated cycles O’Brien in Cochrane Library, 2001

  10. Frozen Semen • Lower fecundity = more cycles • More drop-outs • Fewer children • Greater use of limited resources • More multiple pregnancies if gonadotropin stimulation used to compensate for lower fecundity

  11. The use of frozen semen to avoid HIV transmission • Stanford University School of Medicine • Michael Payne • Health Research and Policy • Douglas Owens • Internal Medicine and HRP • Emmet Lamb • Gynecology and Obstetrics

  12. Methods of study • Gauge health benefit in terms of QALYs gained • Assign quality-adjusted utility to health states • Calculate quality-adjusted life expectancy • Discount utilities at 3% • Gold, et al. Cost-effectiveness in Health and Medicine. Oxford University Press , 1996

  13. Markov model • Events unfold over time at fixed intervals -- insemination cycles • Cohort of 80,000 women • Monthly cycles (insemination) up to 12 • Yearly follow-up for a lifetime • Two treatment options • Frozen semen. Donor screened twice with EIA • Fresh semen. Donor screened once with EIA.

  14. Probability of Transmission of HIV-1 by insemination Product of two elements: • Probability of infection from 1 insemination with an infected donor • Probability of an infected donor • Sum of two elements • Missed by EIA: Prevalence of HIV X (1-sensitivity) EIA • In window and not “False” Positive : Prevalence of window donors X specificity

  15. Heterosexual transmission • Uninfected partners of infected men • Per episode risk = 1 in 500 to 1 in 1000 • Mastro & Kitayaporn. Aids Research & Human Retroviruses 1998;14 (Suppl 3):S223-7 • Royce, Sena, Cates, Cohen. New Engl J Med 1997;336:1072-8

  16. Valleroy. FDA BPAC, 12/14/01 Payne, Owens, Lamb. In review 2001.

  17. Prevalence of donors in the window period • 50,000 new HIV cases in males • 35,000 high risk. • 8,750 (25%) escape screen (by self selection, history, STD tests) • + 8,750 high risk • + 15,000 low risk • = 23,750 infected potential donors Peterson, et al Transfusion 1994;34:1721 CDC HIV/AIDS Surveillance Report 1997

  18. Prevalence of donors in the window period • 23,750 potential donors / 12 months = 1,980 per month • X 3 months window period • = 5,940 per year • About 1 in 10,000 of the 65 million males of reproductive age -- 0.0091% • US Department of Census. Statistical Abstract of United States 1997. Tables 14,169,170

  19. Outcomes if All 80,000 Inseminations Were Fresh

  20. Outcomes if All 80,000 Inseminations Were Fresh Mean Fresh Frozen Difference Number of insemination cycles 3.83 4.33 -0.51 Life years after age 30 44.597 43.601 -0.004 Discounted QALYs 21.02 20.95 0.07

  21. Donor inseminationMicromorts from HIV-1 Howard RA. Intn J Tech Assessment Health Care 1989;5:357

  22. Annual Risks at Home Stallings & Paling. Obstet Gynecol 2001;98:345-9

  23. Annual Micromorts at Home

  24. OB-Gyn Risks Stallings & Paling. Obstet Gynecol 2001;98:345

  25. Micromorts from Gyn Surgery

  26. Conclusions • The risk of using fresh semen in donor insemination is quite small, in the range of risks we accept on a daily basis. • The reward, higher fecundity, is substantial. • Informed patients may reasonably accept the risk in order to get the reward.

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