Meeting spotlight: ASRM 2000

By Chidem Kurdas, Senior Associate Editor

The scientific program at the 56th Annual Meeting of the American Society for Reproductive Medicine covered a wide range of topics, including the latest research on endometriosis, breast cancer, new birth control methods, and genetic testing. Here are some highlights.

Why some breast Ca defies tamoxifen

While tamoxifen inhibits most breast cancer cells (which are illustrated at right), it may stimulate some cancer cells, argued Kathryn B. Horwitz, PhD, from the University of Colorado Health Sciences Center in Denver. In a series of experiments reported at the ASRM meeting in San Diego, Dr. Horwitz showed that "coregulatory proteins" found in the cell nucleus control the steroid receptor response to hormones. In particular, two coregulatory proteins, SMRT and hN-CoR, repress the agonist action of tamoxifen, so that when high levels of these proteins are present, the drug behaves as an antagonist and has the desired effect on breast cancer.

But when a cell has an insufficient supply of coregulatory proteins, this cancer drug stimulates tumors instead. "Tamoxifen can be either a super agonist or a strong antagonist," Dr. Horwitz said. "These coregulatory proteins determine the difference."

She also emphasized the key role of ovarian estradiol and progesterone production in the development of most breast cancers. The disease "has nothing to do with breasts and everything to do with the ovaries," she declared, and pointed out that women whose ovaries are removed at a young age have a very low rate of breast cancer.

Novel approaches to contraception

In two studies, a transdermal patch that delivers 150 µg of norelgestromin and 20 µg of ethinyl estradiol was found to be at least as effective in suppressing follicular development as some common oral contraceptives.¹ One trial involved 32 centers while the other included 12 centers and contraceptive effectiveness was determined via U/S measurements of mean follicular diameters. The birth control patch was more effective in a 20 cm² size than in 10- and 15-cm² sizes and a single patch was worn for 7 to 10 consecutive days.

Another direction in contraception research is to develop IUDs that do not cause excessive or breakthrough bleeding but that still match the high degree of effectiveness of existing IUDs. Antiprogestin-releasing IUDs prevented withdrawal bleeding and inhibited endometrial development in monkeys, according to a study done at the Oregon Primate Research Center.² The authors conclude that antiprogestin-releasing IUDs can act locally to inhibit the effects of both estrogen and progesterone on the endometrium and may be a highly effective, bleeding-free form of contraception.

Embryo testing reduces chromosomal abnormalities and miscarriages

A study of 101 babies and 51 viable fetuses in IVF pregnancies where embryo biopsy and aneuploidy testing had been performed showed a twofold reduction in cases of trisomy, compared with the incidence that would be expected in the absence of embryo screening.³ The parents of these infants had previous IVF failures, spontaneous abortions, or trisomic conceptions, and many of the women were over age 35. With these risk factors, a 2.5% rate of aneuploidy was expected, but only 1.3% was found. The authors caution that even with preimplantation genetic testing, "prenatal diagnosis is still recommended since errors still occur."

In another study involving some of the same researchers, spontaneous abortions significantly decreased after preimplantation translocation testing for 54 couples in which one partner carried a chromosome abnormality.⁴ Several testing methods were used, including chromosome-painting probes in polar bodies and subtelomeric, enumerator, or breakpoint-spanning probes in blastomeres. Favorable pregnancy outcomes depended strongly on 50% or more of the implanted embryos being chromosomally normal.

New drug for endometriosis in the works

Abarelix Depot, a sustained-release GnRH receptor antagonist, suppresses LH, FSH, and estradiol production in women with endometriosis pain and is well-tolerated, a preliminary trial showed.^5,6 Abarelix did not cause the hormonal surges associated with GnRH agonists. The study concludes that, "By providing rapid, reversible, and prolonged inhibition of LH, FSH and E₂ production, avoidance of hormonal flare and sustained activity, Abarelix Depot offers a potential therapeutic advance in clinical conditions where GnRH agonists are currently in common use." Presenter Shekman L. Wong, PhD, Amgen Inc., Thousand Oaks, Calif., said the drug is also being investigated as a treatment for prostate cancer, because it suppresses testosterone through a similar mechanism.

Avoiding multiple births

Efforts to bring down the rising numbers of triplet and higher-order multiple pregnancies include the use of algorithms to tailor the number of transferred embryos to each woman's circumstances and investigating the transfer of only two embryos rather than three or more. In one study involving oocyte donation cycles, pregnancy rates were similar for women who received two embryos and those who received three.⁷ Nearly 12% of the second group had triplet pregnancies. "Reducing the number of embryos transferred in oocyte donation cycles can virtually eliminate the incidence of triplet pregnancies without significantly lowering the overall pregnancy rate," the authors conclude.

Assisted reproductive technology procedures, however, are not the only cause for multiple births—ovulation induction drugs are also responsible. Another study found that lowering peak serum estradiol level thresholds in ovulation induction cycles may reduce the incidence of higher-order births but would also significantly lower pregnancy rates.⁸ These researchers question "whether any stimulation criteria for gonadotrophins cycles can be devised which offer reasonable pregnancy rates and a low high-order multiple pregnancy risk." They suggest IVF be considered earlier in infertility treatment algorithms.

Commenting on various presentations on ways to prevent multiple pregnancies, Philip McNamee, MD, President of the Society for Assisted Reproductive Technology, stated, "This kind of research points out ways to help all our patients have the children they want, one at a time."

REFERENCES

1. Pierson RA, Archer DF, Moreau M, et al. A contraceptive patch is significantly more effective than oral contraceptives in suppressing follicular development. Fertil Steril. 2000;74:S70.

2. Nayak NR, Slayden OD, Chwalisz K, et al. Antiprogestin-releasing intrauterine devices: a novel approach to endometrial contraception. Fertil Steril. 2000;74:S70.

3. Munne S, Magli C, Jones A, et al. Babies born after embryo biopsy and aneuploidy testing. Fertil Steril. 2000;74:S50.

4. Munne S, Escudero T, Sandalinas M, et al. Translocation testing prior to embryo transfer. Fertil Steril. 2000;74:S51.

5. Wong SL, Dmowski WP, DePaoli A, et al. Comparative pharmacodynamic effects of Abarelix Depot-F vs. Lupron Depot in women with endometriosis-associated pain. Fertil Steril. 2000;74:S118.

6. Wong SL, Dmowski WP, DePaoli A, et al. Pharmacokinetics of Abarelix Depot-F by subcutaneous injection in women with endometriosis-associated pain. Fertil Steril. 2000;74:S185.

7. Licciardi A, Berkeley S, Noyes N, et al. A two- vs. three-embryo transfer: the oocyte donation model. Fertil Steril. 2000;74:S58.

8. Gleicher N, Oleske D, Tur-Kaspa I, et al. Criteria for the prevention of high order multiple births following ovulation induction with gonadotrophins. Fertil Steril. 2000;74:S90.

 

Chidem Kurdas. Meeting spotlight: ASRM 2000. Contemporary Ob/Gyn 2000;12:66, 71.