Highlights of the 15th Annual In Vitro Fertilization and Embryo Transfer-A
Comprehensive Update-2002 Meeting, Santa Barbara, California (Part I)
By David R. Meldrum, M. D.  

The 15th Annual In Vitro Fertilization and Embryo Transfer Comprehensive Update, July 14-17 2002 was again a huge success with well over 200 attendees from around the U.S. and the world.  Reproductive Partners’ Dr. David Meldrum has directed this postgraduate course in conjunction with the Office of Continuing Medical Education, UCLA School of Medicine each year since 1987.  The course owes its success to the large number of top-quality speakers, each an authority in his or her particular field.  Most IVF programs in the U.S. make a point of having someone attend at least every couple of years.  Since each year some applications are turned away, the conference is limited to those actively working in the field.  

STIMULATION PROTOCOLS

Dr. Meldrum (Reproductive Partners Medical Group, Southern California) began the meeting with a review of standard ovarian stimulation regimens.  The long GnRH agonist regimen using Lupron is the most common method of ovarian stimulation, yielding more eggs, reduced cancellation, and a higher pregnancy rate.  It is very commonly combined with an oral contraceptive (OC) lead-in, to avoid cysts and to minimize menopausal symptoms prior to the rise of estrogen.  Dr. Meldrum emphasized that with some regimens, particular involving OC, the levels of LH can be excessively suppressed.  Addition of human menopausal gonadotropins to the FSH can improve cycle outcomes.

Dr. Francois Olivennes (Hospital A. Beclere, Clamart, France) spoke about the new GnRH antagonists.  These agents can be given for a very short duration late in ovarian stimulation thus reducing the number of injections.  The ovarian response is lower and the rate of ovarian hyperstimulation is correspondingly reduced.  Their value hinges on whether success rates are equivalent to GnRH agonists and whether the approximately 20% lower success rate is related to a direct effect on the uterine lining or to other factors such as lower LH levels or simply that these regimens require more experience on the part of physicians.  By avoiding ovarian suppression, GnRH antagonists may prove to be ideal for poor responders.  Early in the reported studies there was not an appreciation of the differences in the ovarian response.   Estradiol levels rise more quickly, causing some clinicians to reduce the gonadotropin dose.  The marked reduction of endogenous gonadotropins when the antagonist is begun dictates that the exogenous dose should generally be maintained. 

Dr. William Schoolcraft (Colorado Center for Reproductive Medicine, Englewood, Colorado) discussed the role of LH in ovarian stimulation in more detail, again emphasizing that for certain regimens, the addition of LH will improve outcomes.  Recombinant pure FSH has generally been a great advance, but LH is also probably important to full developmental competence of the eggs.  Currently this is supplied by using hMG.  In the future, recombinant LH or a very small daily dose of hCG may be a more consistent way of supplying LH actively.

Dr. Richard Scott (Reproductive Medicine Associates of New Jersey, West Orange, New Jersey) spoke on reserve testing and stimulation of the poor responder.  He emphasized the value of the basal follicle count in predicting outcome in addition to day 3 FSH and the clomiphene challenge test.  When the resting follicle count is less than 4, all outcomes are markedly reduced.  The two most common regimens for poor responders are “mini-dose Lupron” and Antagon (GnRH agonist).  There is no clear advantage of one versus the other with experience to date.

SELECTION OF PROCEDURE

Dr. Bill Yee (Reproductive Partners Medical Group, Southern California) spoke on the GIFT procedure (gamete intrafallopian transfer), emphasizing its role in particular circumstances.  GIFT has been particularly successful with donor sperm, probably because of a more consistent fertilization than with infertile husbands sperm.  When embryo transfer continues to be difficult in spite of cervical dilation and ultrasound-guided transfer and the male factor is fairly normal, GIFT may be an excellent choice.  Finally, the trend has been toward higher results with GIFT for women over age 42, although no well-controlled study has been done comparing IVF and GIFT in this age group.

Dr. Gabriel Garzo (Reproductive Partners Medical Group, La Jolla, California) spoke on gestational surrogacy and mainly emphasized the complexity of this process and that surrogate agencies vary considerably in quality.  Patients should be referred to physicians who do surrogacy and are familiar with agencies that do this well, rather than to choose the agency from the Internet or other promotional materials.

Dr. Joseph Gambone (UCLA School of Medicine, Los Angeles, California) discussed uterine factors.  The data on fibroids and IVF clearly shows reduced outcome with submucosal fibroids distorting the cavity.  There are reports finding and not finding a reduced outcome with intramural (in the uterine wall) fibroids.  It would seem prudent to consider removal of large intramural fibroids particularly since this may also reduce miscarriage. The data on polyps is scant since they are generally removed.  The consensus is that all except very small polyps (e.g. less than 5 mm) should be removed before IVF.

LABORATORY TECHNIQUES

Dr. Kwang-Yul Cha (Pochon CHA University, Seoul, Korea) reviewed the subject of human egg and ovarian tissue freezing.  There have been fewer than 50 pregnancies worldwide with freezing of human eggs.  The latest results by Dr. Cha’s group in 34 cycles showed that 69% of eggs survived freezing, 72% of those fertilized, and of 28 women undergoing transfer of an average of 4.5 embryos, the delivery rate was 25% (21% of cycles).  The low implantation rate (6% per embryo) shows the low efficiency of this technique.  The results do confirm that it is a reasonable method for cancer patients prior to chemotherapy or radiation.  Work on ovarian tissue freezing is much more preliminary with no reported pregnancies as yet.

Dr. Mike Wilson (Reproductive Resource Center, Overland Park, Kansas) spoke about results in a program that has done 5-day (blastocyst) culture in all IVF patients.  Pregnancy rates improved with a reduction of the number of embryos transferred.  Unresolved issues are whether the low rate of monozygotic (identical) twinning with 5-day culture is a reason to not offer it routinely, and whether there are women whose embryos do not survive to day 5 that could have conceived with day 3 transfer.  Freezing of blastocysts has been more variable but is improving.  It is interesting that the implantation rate with transfer of embryos that did not reach the blastocyst by day 5 is not markedly reduced.  Another important question to be resolved is whether assisted hatching can help those more advanced embryos to implant.

In a debate between embryologists, Lucinda Veeck, MLT, DSc (hon)  (Cornell University Medical Center, New York, New York) reviewed the factors that can enable the selection of the best embryos for transfer on day 3.  The simplest and most reliable method aside from the morphology of day 3 embryos is identification of early cleavage to the two-cell stage.  Excellent results can be obtained with transfer of two day 3 embryos and freezing of cleavage stage embryos is well defined. Dr. David K. Gardner (Colorado Center for Reproductive Medicine, Englewood, Colorado) took the position that the best embryos can be identified on day 5, thus allowing transfer of only two embryos in all women under age 40.  Freezing results at the blastocyst stage are less consistent but are rapidly improving.

Both debaters appeared to agree that as sequential media continue to improve with consistent quality control and as blastocyst freezing continues to improve, that ultimately extended culture might become routine.

All in all, the meeting was a great success.  This conference is unique in the world in having such a large number of speakers who are leaders in the field each indicating the methods associated with optimal results at each step in this complex process.  The U.S. has become a clear leader in IVF success in the world.  There is little doubt that this conference and its excellent faculty have played a significant role in that regard.

The next issue of Reproductive Times will feature Part II of the Highlights of the 15th Annual In Vitro Fertilization and Embryo Transfer-A Comprehensive Update-2002 meeting including sections on male factor, preimplantation genetics and improving IVF success.