Highlights of the 15th Annual In Vitro Fertilization and Embryo Transfer-A
Comprehensive Update-2002 Meeting, Santa Barbara, California (Part II)
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. 

MALE FACTOR

Dr. Peter N. Schlegel (Cornell University Medical Center, New York, New York) outlined the clinically relevant evaluation of the infertile male.  Men with non-obstructive azoospermia (absent sperm) or severe oligospermia (very low [<5 million/ml] sperm counts) should have a karyotype.  Men with congenital absence of the vas or unexplained epididymal obstruction should have cystic fibrosis testing on the female partner, since not all mutations in such males are identifiable.  Men with non-obstructive azoospermia should have Y chromosome deletion testing.  AZF b and a deletions are associated with a very low chance of sperm retrieval.

He reviewed the published literature on malformation rates after IVF or ICSI.  A large amount of available data suggests no increase of abnormalities with these techniques except about a 0.6% increase of sex chromosome anomalies.  Most of these are probably due to an increased rate of sex chromosome anomalies in men with very low sperm counts.  There may be a very small increase due to ICSI.  However, since these anomalies are not severe, it is unclear whether ICSI alone should be an indication for prenatal genetic screening.

Dr. Gianpiero Palermo (Cornell Medical College, New York, New York) reviewed results of over 6000 ICSI cases from Cornell.  There was no observed increase of anomalies, including sex chromosome anomalies with ICSI compared to regular IVF and follow-up of children at 3 years has been normal.  A higher incidence of chromosome anomalies has been observed with “rescue ICSI.”  It appears to be best to perform ICSI whenever reduced fertilization is a concern, and to not perform ICSI after fertilization has failed.

Dr. Peter Schlegel (Cornell University Medical Center, New York, New York) spoke on sperm retrieval techniques.  Testes biopsy is generally done with obstructive azoospermia (OA) to confirm normal sperm production.  It is not necessary in non-obstructive azoospermia (NOA) since it is poorly predictive of finding sperm with microdisection.  In OA, sperm can be retrieved by percutaneous epididymal sperm aspiration (PESA) or percutaneous testes biopsy.  Microsurgical epididymal sperm aspiration (MESA) has the advantage of providing sufficient sperm for multiple IVF attempts.  For NOA, microdisection is able to find isolated functional tubules, allowing minimal removal of tissue and preservation of the vascular supply of the testes.  AZFa or AZFb Y-chromosome  microdeletions are associated with a very low chance of sperm retrieval in men with NOA.  Sperm retrieval attempts should be separated by at least 6 months in NOA to allow full recovery of testicular function.  In NOA, frozen testicular sperm often do not survive freezing/thawing.  Repeat TESE even in the most experienced hands only achieves sperm retrieval in 80% of men with successful retrieval previously.  Men with prior chemotherapy or irradiation have about a 45% sperm retrieval rate.  One should wait at least one year before TESE/ICSI.

PREIMPLANTATION GENETIC DIAGNOSIS

Dr. Mark Hughes (Wayne State University School of Medicine, Detroit, Michigan) spoke on preimplantation genetic diagnosis (PGD).  Many single gene defects can now be screened for using PGD.  Because of the very exacting work involved, it makes sense to have a limited number of large laboratories around the country that can do the analysis and provide the results in time for morula or blastocyst transfer.

Dr. William Schoolcraft (Colorado Center for Reproductive Medicine, Englewood, Colorado) spoke on “A Clinician’s Perspective” regarding preimplantation genetic diagnosis (PGD).  One of the main areas of controversy has been the role of aneuploidy (abnormal chromosomes) testing in improving implantation and reducing miscarriage, for example, in older women.  In very experienced hands, testing of a blastomere (single cell from an embryo) for numerical abnormalities of multiple chromosomes has increased pregnancy and reduced miscarriage.  There are about 10% of embryos where the result is not definitive and in 10-20%, an abnormal cell may be obtained from a normal embryo.  Until wider experience has shown clear benefits this technique should be considered experimental.

IMPROVING IVF RESULTS

Dr. Richard Scott (Reproductive Medicine Associates of New Jersey, West Orange, New Jersey) spoke on immunologic testing before IVF.  The current consensus is that there is no apparent value to testing for antiphospholipid antibodies, antithyroid antibodies, or natural killer cells before IVF.  There is no demonstrated benefit of treatment with intravenous immunoglobulin or leukocyte immunization therapy (LIT).  The FDA has indicated that LIT is experimental and requires FDA approval of any protocol.

Dr. Dominique de Ziegler (Hopital de Nyon, Nyon, Switzerland) spoke on uterine factors in implantation.  Out of this complex and elegant presentation, the work on the association of excessive uterine contractions with reduced cycle outcome perhaps deserves the most attention.  A reduction of uterine contractions could be the principle mechanism whereby optimal transfer technique improves implantation.

Dr. Bill Yee (Reproductive Partners Medical Group, Southern California) spoke on the negative effect of a hydrosalpinx on IVF outcome.  Clearly the presence of a hydrosalpinx reduces IVF success by about 50% and salpingectomy or a tubal interruption procedure raises success to normal.  There may be a minor negative effect of salpingectomy on ovarian response.  It is not clear whether surgery is helpful in women without an ultrasound visible hydrosalpinx.  There are conflicting data on whether drainage of a hydrosalpinx can improve IVF outcome.

Dr. Gabriel Garzo (Reproductive Partners Medical Group, La Jolla, California) spoke on the luteal phase and transfer technique.  Luteal phase support is advised for GnRH agonist and antagonist cycles.  There is some recent support for the use of luteal phase estrogen.  Ultrasound-guided transfer has been shown to improve the pregnancy rate in multiple randomized studies, although one can criticize the control groups regarding the use of a mock transfer, use of optimal transfer technique and whether a full bladder technique was used.  Empirically once the UTZ-guided technique is adopted, it is difficult not to become convinced of its value.

Dr. Joseph Gambone (UCLA School of Medicine, Los Angeles, California) spoke on fertility drugs and ovarian cancer.  The most recent studies have been very reassuring in not showing a significant impact of fertility drugs; although clearly, having not delivered a baby and infertility both increase ovarian cancer risk.

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.