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CURRENT CLINICAL RESEARCH INVESTIGATIONS

1. Efficacy of Frozen IUI Ready Specimens 
2. Donor Fecundity in Sperm Banking
3. Transferred Embryo Cell Number as a Predictor of IVF Success
4. Blastocyst Transfer, Extended Embryo Culture
5. in vitro Maturation of Oocytes
6. Ovarian Cryopreservation

Research activities involving our faculty and staff in the andrology field have centered on improving the pregnancy rates associated with sperm banking and insemination with donor sperm.  In the late 1980s (Wolf, Patton), we described improved results when intrauterine rather than intracervical placement of sperm was employed.  Then in 1988 it was mandated that all donor sperm had to be quarantined for at least 6 months and the same donor retested to prove he was HIV non-reactive before the semen could be used.  This meant that all semen had to be frozen for the 6 month quarantine period.  The use of fresh donor semen was no longer warranted. However, frozen semen is not as effective as fresh semen.  In response we described an improved method for freezing sperm that could be applied to routinely processed or intrauterine insemination-ready samples, (Larson JM, McKinney KA, Mixon BA, Burry KA, Wolf DP: An intrauterine insemination-ready cryopreservation method compared with sperm recovery after conventional freezing and post-thaw processing. Fertil Steril 68(1):143-8).  Since sperm used for insemination must be washed free of the seminal medium, laboratories froze the semen first then washed after thawing.  In other words, instead of freezing semen and isolating sperm after thawing, sperm could be isolated from semen first and frozen such that no after thaw processing was required. 

This work set the stage for women to receive donor sperm inseminations in their physician's office as processed samples could be shipped and used without the need for additional processing.  We have more recently (Wolf et al) described the pregnancy rates associated with the use of this new IUI-ready method compared with the conventional approach of freezing semen and processing sperm for use after thawing.  Pregnancy rates as high as 36% were associated with the use of IUI-ready sperm in a prospective trial. 

 In addition to seeking improvements in the preservation and use of donor sperm, we have studied sperm donor screening and donor sperm performance in IUI.  Thyer described a retrospective evaluation of donor performance and concluded that future donor fecundity could be predicted after 15 inseminations.   Equally important was the discovery that some donors were associated with relatively low fecundity rates.  This conclusion is not surprising but sperm banks do not currently provide information on the relative fecundity of banked donors, a service that is potentially very beneficial to the consumer. 

In an effort to be proactive in donor screening, Navarette described the potential use of the optimized sperm penetration assay to differentiate between low and high fecundity donors.  In other words, it seems that sperm functional quality is more important than the quantity of thawed donor sperm used in an insemination to achieve a pregnancy.  We have noticed that some donors achieve a pregnancy much sooner than others even if the number of sperm delivered per IUI is less. This is an interesting possibility and we are now evaluating its proactive use.  We are beginning to screen our donors with this process to remove (cull out) any donors’ semen that looks good under the microscope after thawing (high number of motile sperm) but will not likely produce a pregnancy.  This means that the frozen semen that we store and release is more likely to achieve a pregnancy in fewer cycles. 

In ART (Assisted Reproductive Technology) related research, the lab director and his staff have been instrumental in perfecting and evaluating protocols used in IVF and in laboratory accreditation and the credentialing of laboratory personnel (reference to two books edited by DPW).  Recent publications involving both laboratory and clinical staff describe the incorporation of a blastocyst embryo transfer program into our IVF routine, (Patton PE, Sadler-Fredd K, Burry KA, Gorrill MJ, Johnson A, Larson JM, Wolf DP: The development and integration of an extended embryo culture program. Fertility Sterility 72:418-22), the use of extended culture with cryostored embryos, (Gorrill MJ, Kaplan PF, Patton PE, Burry KA:Initial experience with extended culture of cryopreserved embryos. Am J Obstet Gynecol. 180: 1472-4) and the appropriate steps to be taken in screening potential egg donors, (Gorrill MJ, Johnson LK, Patton PE, Burry KA: Oocyte donor screening: the selection process and cost analysis, Fertility and Sterility 2001, 75:2 : 400-404). Oocyte maturation has also been an area of interest and studies have been conducted in the monkey (Alak et al,  Smith et al) in an effort to perfect protocols for clinical use.  Dr. David Lee, the newest addition to our academic staff, also has an interest in ovarian cryopreservation and the in vitro maturation of oocytes.  We have been active in developing insights into the mechanisms underlying ovarian stimulation, again with experimentation in the rhesus monkey, with collaborators at the Oregon Regional Primate Research Center (Zelinski Wooten).  We have just completed another book, published by Humana Press, on the ARTs, co-edited by Drs. Wolf and Zelinski-Wooten with chapters on embryo transfer (Burry), reproductive potential evaluation (Patton), satellite IVF (Gorrill), the ARTs in non-human primates (Ouhibi et al) and human cloning (Wolf).

The director of the laboratory, Dr. David Battaglia, is advancing the technologies involving oocyte and ovarian freezing. In March of 2004 he was featured in the Portland Monthly as one of "Portland's Best Doctors" (445Kb pdf). The article relates an unusual clinical situation in which he was able to turn a negative into a positive outcome by applying insights gained from his research. 

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