Embryo Implant Successes Linked to Drug Treatment : Medicine: Pregnancy rates nearly double in fertility experiment. Results could represent a long-sought breakthrough in solving antibody problem, doctors say.

By SHARI ROAN

Dec. 13, 1994 12 AM PT

TIMES HEALTH WRITER

Doctors using a mixture of aspirin and the blood-thinning drug heparin report that they may have found a way to nearly double the chances that a large class of infertile women undergoing in vitro fertilization can achieve a successful pregnancy.

The doctors, led by Dr. Geoffrey Sher of the Pacific Fertility Medical Center in San Francisco, achieved a 49% “viable pregnancy” rate in a group of 169 women. The women were treated with the medications and underwent one cycle in an attempt at in vitro fertilization, or IVF.

The new treatment, reported in the December issue of the Journal of Human Reproduction, appears to represent an important advance in a field that has been stymied for years by the failure of most IVF embryos to be successfully implanted in the mother’s womb.

“Given our findings, it is indeed possible that the long-awaited breakthrough in achieving significantly improved success rates with (IVF-embryo transfer) might well have arrived and that a 50% birth rate per embryo transfer could become routine in many IVF centers of excellence,” the authors said.

The key to success, the authors said, was first identifying women who tested positive for antibodies--called antiphospholipid antibodies--that are thought to interfere with the implantation of embryos. The antibodies were found to be much more common in women with pelvic disease, such as abnormal tissue growth or surgical scars. This could be part of the reason that such women have difficulty becoming pregnant, they indicated.

Normally, women with pelvic disease who undergo IVF in a high-quality clinic have a 27% chance of becoming pregnant, according to one independent expert who reviewed the study for The Times.

But when they are treated with the aspirin-heparin combination, that figure jumps to 49%. A “viable pregnancy” in the study was defined as a live birth or evidence of a fetal heartbeat using ultrasound monitoring.

Other infertility specialists, however, said the results need to be widely replicated before predictions can be made on the significance.

“The 49% success rate represents a single set of data,” said Dr. Joel Batzofin, of the Huntington Reproductive Center in Pasadena. “If others can corroborate the findings, I think it will become more important.”

The London-based Journal of Human Reproduction is edited by the co-creator of IVF, Dr. R. G. Edwards, who commented: “It’s a very important paper, indeed. But in our field, when people publish a paper of some significance, you often get headlines and then (the experiment) can’t be repeated. So we will have to wait for that. But I think it will be repeated quickly. Everyone will want to do these trials. It will generate a lot of enthusiasm.”

Infertility specialists are able to produce embryos in 80% of all IVF cycles, capitalizing on such recent advances as the ability to inject a single poor-quality sperm into the center of an egg to produce a healthy embryo.

But the vast majority of all embryos fail to implant after being transferred to the uterus. Only 16.8% of women whose eggs are retrieved during an IVF attempt actually take home a baby nine months later, according to the American Society for Reproductive Medicine.

“Implantation is the great frontier. It is the area that has to be improved if IVF success is to go up,” said Dr. Michael A. Feinman, director of the Pacific Fertility Center in Westlake Village and a co-author of the paper.

Researchers have long suspected that the mother’s age, the condition of the embryo and other factors may be responsible for the high rate of failure. However, Sher’s study explored another potential factor: antibodies produced by the mother that repeatedly interfere with the embryo’s implantation.

According to this theory of repeated miscarriages, some women produce antiphospholipid antibodies, which are thought to cause platelets to form around the developing placenta, cutting it off so it fails to implant.

“For many, many years, these antibodies have been linked to (miscarriage). That is well-accepted science,” said Feinman. “We reasoned that it might happen in IVF patients . . . like a mini-miscarriage.”

In the first part of the study, Sher established that antiphospholipid antibodies appear to be especially prevalent in women who have pelvic damage from infection, surgery or endometriosis, a disorder that causes abnormal tissue growth in the uterine lining. Just over half (53%) of the women with pelvic damage tested positive for the antibodies, compared to 14% of the women without pelvic damage.

Sher then assigned 365 women with pelvic disease into various treatment groups.

Of 169 women who had antiphospholipid antibodies and were treated with aspirin and heparin, 49% reportedly achieved a viable pregnancy after one IVF cycle, compared to a 16% rate for similar women who were not treated.

Of 171 women who tested negative for the antibodies, none were given the medications and 27% achieved a viable pregnancy. That figure is typical of women with pelvic disease who undergo IVF.

The daily treatment consisted of low-dose aspirin, taken orally, and two heparin shots. Women began the medications at the beginning of the IVF cycle, and those who became pregnant continued therapy through the first trimester. According to Sher, the aspirin and heparin fight the antibodies and prevent clotting that can cut off implantation.

The treatment is safe, said Feinman.

“Heparin does not cross the placenta. Aspirin in high doses can cause problems (such as bleeding) late in the pregnancy. But we are using minimal doses and stopping it well before then,” he said.

An average of four embryos were transferred per IVF cycle in all groups. About 20% of the pregnancies involved multiple births, which is typical of IVF cycles in which several embryos are transferred in one womb, Feinman said.

Based on the results, Sher said he now recommends that all women undergoing IVF because of pelvic damage be tested first for antiphospholipid antibodies. Besides aspirin and heparin, other researchers are exploring the use of another medication, intravenous immunoglobulin, as an agent to retard the antibodies, he noted.

The improved understanding of how and why an embryo implants could have far-reaching effects for all types of infertility treatment--not just IVF, said Chicago infertility specialist Alan Beer, who pioneered the theory of antibodies as a cause of miscarriage.

“We have always wanted to know: Are some women already primed and ready to reject the baby? What (Sher) did was screen all these individuals looking for the type of immunity, called autoimmunity, that can retard the development or ‘stickingness’ of the embryo--and that when you offer this treatment you double the success rate,” he said.

“It’s a potentially very significant contribution,” said Dr. Carolyn Culam, director of Reproductive Immunology at the Genetics and IVF Institute in Fairfax, Va. “The advantage of this type of work is it provides one marker to identifying individuals in whom you can at least try to enhance the implantation rates,” she said.

Other infertility specialists expressed cautious optimism.

“The numbers are fairly good-sized for sample groups, but they are not huge,” said embryologist David Hill of the Center for Reproductive Medicine at Century City Hospital. “This data is a good start. But let’s see how it pans out as we go along,” he said.

Sher also cautioned that anatomical defects and infectious organisms can also prevent successful implantation, and the aspirin and heparin treatment does not address those problems.

Embryo Implant Successes Linked to Drug Treatment : Medicine: Pregnancy rates nearly double in fertility experiment. Results could represent a long-sought breakthrough in solving antibody problem, doctors say.

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