September 3, 2006, Updated September 12, 2012

Two recent studies by Israeli teams provide some very good news for women who are experiencing difficulty getting pregnant or are prone to miscarriages. In one study conducted at the Weizmann Institute, biopsies performed on women with fertility problems led to some extremely surprising results, when the biopsies themselves appeared to increase fertility.

In the second study, a team of Israeli researchers from the Hadassah Medical Center discovered that the immune system plays a major role in fetal development and pregnancy, with important implications for conditions that cause pre-eclampsia and miscarriages.

More than six million American women and their partners experience infertility, according to the American Society of Reproductive Medicine. Of those, about 5% choose in-vitro fertilization treatment. According to the latest statistics, the success rate for IVF is similar to the 20% chance that a healthy, reproductively normal couple has of achieving a pregnancy that results in a live born baby in any given month.

Prof. Nava Dekel of the Weizmann Institute’s Biological Regulation Department, led a team of Weizmann researchers and colleagues from the Kaplan Medical Center that earlier this year investigated a protein they suspected plays a role in the implantation of a fertilized egg in the uterus.

“Our research is trying to look for the expression of different genes and proteins in the menstrual cycle which could be used to increase the chances of fertilization,” she told ISRAEL21c. “We were looking for one specific protein and in order to take sample throughout the menstrual cycle, we had to take biopsies of 12 patients.”

The team’s research went according to plan and they found evidence pointing to the protein’s role. The surprise came soon after:

“All 12 women had a long story of failure with IVF treatment, but after the biopsies were performed, 11 of the 12 women became pregnant during the next round of IVF,” said Dekel.

Dekel and her team decided to delve further into the unexpected results.

“We decided to conduct a larger study of this phenomenon, and enlarged the group to 140 women. We explained the goals of the study, and 50 of them volunteered to have the biopsies. The rest were used as a control group,” she said.

The results showed that the women who underwent the biopsies had a success rate of pregnancy double than the women who underwent the standard IVF treatment without biopsy. In other words, having a biopsy doubled a woman’s chances of becoming pregnant.

According to Dekel, the biopsy treatment is now used as routine protocol included in the IVF unit at Kaplan, as well as at Wolfson and Assaf Harofe hospitals. She’s confident that it will soon become standard practice in US hospitals.

“I’m sure there’s already pressure from the patients – in today’s day and age with everyone having access to the Internet and the research, it’s very easy for a patient to read a study, show it to their doctor, and day ‘this is what I want,'” she said.

Not content to let biopsies be the end-all of her study, Dekel said she’s continuing research to get to the bottom of the mystery. She suggested that some form of distress, in this case a biopsy procedure, provokes a response that renders the uterus more receptive to implantation.

“We’re trying to find the molecular basis or the mechanism that is enabling this increase in the pregnancy rate. We’ve analyzed samples of women that underwent the treatment, looking for the expression of genes that may be responsible for change in the uterine tissue.”

Both animal studies and human clinical trials are now being conducted to identify genes that may play a role in this process.

“Since I’m a researcher and not a physician, I’m more interested in understanding the mechanism. Once we understand which molecule is responsible, we can develop a specific treatment, perhaps an injection, that will remove the need of the biopsy.”

This study is conducted by Dekel and Drs. Yael Kalma and Yulia Gnainsky (former and present post-doctoral fellows, respectively), in collaboration with Drs. Amichai Barash and Irit Granot of the In Vitro Fertilization Unit of the Kaplan Medical Center Obstetrics and Gynecology Department.

In the other Israeli study, which also has upended conventional wisdom, researchers at the Hadassah Medical Center in Jerusalem have discovered that the immune system’s primary function as a destroyer of foreign invaders is complemented by an ability to build as well.

This previously unknown function plays a major role in fetal development and pregnancy, with important implications for conditions that cause pre-eclampsia and miscarriages. Their breakthrough findings were published in Nature Medicine.

“Our research revealed that Natural Killer (NK) cells of the immune system are positive regulators of human cells, in addition to their well-known killing activity that eliminates infected cells, tumor cells and foreign bodies,” said Prof. Simcha Yagel, a senior physician in the Department of Obstetrics and Gynecology at Hadassah University Hospital-Mt. Scopus. “This positive regulation stimulates the immune system to secrete special growth factors and triggers the tremendous uterine blood vessel widening necessary for the growth and development of the placenta. We know now that without this positive regulation, the placenta does not develop properly”.

Yagel, along with Professors Ofer Mandelboim and Dr Jacob Hanna, of the Lautenberg Center for General and Tumor Immunology in the Hebrew University-Hadassah School of Medicine, and Dr. Debra Goldman-Wohl of the Department of Obstetrics and Gynecology Hadassah University Medical center and discovered this significant – and previously unknown – feature, using both cellular and molecular biology to advance their understanding of the maternal-fetal interaction and the role of the immune system.

“Now that we have proven this, we’re in an excellent position to find a means to enhance the activity to those cells, and we’re continuing research to that goal,” he told ISRAEL21c.

“What we have learned about the immune system will have significant impact on many aspects of problematic pregnancies as well as the In Vitro Fertilization (IVF) process. In the future our research may help us remedy or prevent these conditions,” he said.

“The placenta is the connection between the mother and the fetus. If the placenta does not develop properly, it impedes implantation of the fetal cells”, he explained. “Shallow fetal cell implantation is a hallmark of pre-eclampsia, a condition that develops in late pregnancy caused by vascular problems of the placenta. Our discovery could potentially lead to treatment that reduces the incidence of pre-eclampsia, a condition that affects seven percent of all pregnant women and may have therapeutic implications on recurrent miscarriage,” he says.

“In the next stage of our research, we will continue to explore the precise immune receptors for a better understanding of how they function, and ultimately, how they can help ensure healthy babies.”

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