Showing posts with label Improving Implantation Rates. Show all posts
Showing posts with label Improving Implantation Rates. Show all posts

Thursday, March 5, 2009

First the biopsy, then the baby



A common medical procedure may be the key to helping couples who've had no luck with artificial insemination and IVF. Could a common uterine biopsy make pregnancy "stick" for women having trouble conceiving? A small but growing number of couples are embracing an unusual use of biopsies during infertility treatments in the belief that they may help increase the chances of a successful pregnancy.

In a handful of small studies, biopsies of the endometrium, the lining of the uterus, which are usually performed as a diagnostic tool to sample tissue and test for infections, disease or other problems, have been found to boost the pregnancy rates of women who had tried in-vitro fertilization and failed to become pregnant.

One Toronto couple credits the procedure with the first successful pregnancy in 10 years of trying. After 11 artificial inseminations and two IVFs proved fruitless, Roslyn and Howard Kaman had experienced the gamut of failure, from miscarriages to ectopic pregnancies. They had opted to try adoption when they read an article about a lecture at Toronto's Weizmann Science Canada by an Israeli researcher, Nava Dekel.

In 2003, Dr. Dekel found that 45 women who had undergone a uterine biopsy during the menstrual cycle before undergoing IVF had almost twice the rate of pregnancies and births compared with a control group of 89 women. In 27.7 per cent of the women in the biopsy group, the embryo transfer was successful.

The IVF worked for just 14.2 per cent of the control group.

The Kamans wrote to Dr. Dekel, and she connected them with the fertility clinic in Israel that had performed the procedures. Doctors there sent the couple a detailed protocol, which involved three separate biopsies on particular days in the cycle just before an IVF treatment. The Kamans' Toronto fertility specialist, Fay Weisberg, agreed to try it.

Ms. Kaman became pregnant on the first IVF cycle after the procedure and baby Hannah is now three months old.

"I still can't believe it. I think I will go through my whole life and not believe we were successful," says Ms. Kaman, 41.

While broader research is being conducted to confirm the role these biopsies may be playing, anecdotal evidence is starting to mount suggesting that the disruption of the uterus somehow leads to the successful implantation of an embryo. Some practitioners say they'll wait for randomized trial results before they start offering biopsies to IVF patients.

Togas Tulandi, a McGill University medical researcher, is hoping to figure out what role the biopsies might play, if any, in the successful pregnancies of women like Ms. Kaman. He is in the midst of conducting a large randomized study (he hasn't yet reached his goal of 162 participants) and says that if the biopsies are working, the mechanism may be akin to tilling the soil before you plant a tulip bulb.

"Maybe this slight injury to the endometrium makes the environment for implantation better," he says. "If we can prove that it works, we can do it routinely."

Since the procedure carries little risk, other than discomfort and a very small chance of infection or injury to the uterus, many fertility doctors are already incorporating it into their practices. While it is not listed on her menu of services at the First Steps Fertility clinic where she is medical partner, Dr. Weisberg says she now offers it to most of her patients who have failed to conceive with IVF and for most patients before they undergo a frozen embryo transfer.

"I suspect that it will probably soon be a routine for all patients undergoing IVF."

The only reason it's not routine is a paucity of large studies and the fact that it's painful and uncomfortable for most women, she says.

Although she can't unequivocally say whether the biopsies are effective - "the women end up being their own control" - Dr. Weisberg has a hunch that they work.

It could have something to do with increased blood flow, or the way in which the proteins in the uterus heal, she says. "I do believe something changes deep down."

And she's not worried about a stampede for the procedure on the part of desperate couples.

"Not to be cavalier, but this is a procedure already being done on younger women for bleeding of the uterus and other problems," she says. "It's easy, quick, but painful. There's no anesthetic. You can go right back to work."

Other specialists take a more cautious approach. Fertility expert Arthur Leader does not offer it to patients at the Ottawa Fertility Centre where he practises. Until a randomized study such as Dr. Tulandi's can prove that women undergoing these biopsies have a better chance of getting and staying pregnant, "the precautionary principle should apply," he says. "You shouldn't do it until a benefit has been shown."

He points out that there have been many other treatments, including low-dose Aspirin, a blood protein called albumin and a diabetes drug called metformin, that were believed to help women conceive and were routinely prescribed but which, after much study, proved either to do harm or have no effect. And, as far as Dr. Leader is concerned, "No good is harm."

For couples who end up with a healthy pregnancy after uterine biopsies, it's hard not to credit the procedure for their little bundles of joy. Still, Ms. Kaman says that even though she suspects the treatment did work, there may have been some luck involved. When she imagines trying for a second IVF baby, "part of me thinks lightning's not going to strike twice with us."

Anatomy of a biopsy

An endometrial biopsy is performed by inserting a suction catheter through the vagina and cervix, into the uterus. The end is pressed up against the uterine wall where it cuts away a small sample of the lining tissue.

Because of any number of factors, an embryo may not be able to attach itself to the cells that make up the lining of the uterus.

After the biopsy is taken, some researchers and fertility experts believe that the slight damage caused to the wall of the uterus makes it a better environment for implantation, whether because of increased blood flow, the healing process or some other factor.

Tuesday, February 24, 2009

Blastocyst transfers in older women

A large retrospective study has yielded information on the optimal number of blastocyst stage embryos to transfer on day 5 or 6 in women aged 38 years or older.

Specialists in a Writing Group convened by the USA’s Society for Assisted Reproductive Technology conducted the study, based on data collected by the society between 2000 and 2004. The data related to a total of 5,569 day 5 and day 6 embryo transfers in women aged 38 or older who were undergoing their first assisted reproductive technology cycle. These 5,569 transfers led to 1,667 deliveries.

The researchers used both univariate and multivariate logistic regression to model the probability of delivery, twins, and higher-order multiples based on certain patient characteristics. These were age, the number of embryos transferred, the maximum follicular phase FSH level, the number of oocytes retrieved, cryopreservation of excess embryos, and the use of ICSI.

In their new paper in the current issue of the journal Fertility and Sterility, the researchers report the findings of their analyses. In women aged 38 or 39 years, there was an increase in delivery rates when two embryos were transferred, compared with when one embryo was transferred. Transferring more than two increased the rate of multiples but not delivery.

In women aged 40 years, transferring up to three embryos increased the delivery rate without increasing the multiple rate. In women aged 41 or 42 years, the delivery rate plateaued after the transfer of three embryos, but the twin rate continued to increase.

In the paper, the researchers draw their findings together in order to present the following recommendations on the suggested number of embryos to transfer on days 5 and 6 to minimize the risk of multiples in patients undergoing their first cycle:

Number of oocytes <10 and no cryopreservation:

Maternal age 38 years: 2 embryos.
39 years: 2.
40 years: 2-3.
41-42 years: 3.
43-44 years: 3.

Number of oocytes 10 or more, and/or use of cryopreservation:

Maternal age 38 years: 1-2 embryos.
39 years: 1-2.
40 years: 2.
41-42 years: 2-3.
43-44 years: 3.

Discussing their findings, the researchers note that these recommendations of course “do not represent strict guidelines” but do represent an analysis of outcomes from a large national US dataset. They write: “From this analysis, it appears that, in patients aged 38 to 39 years who are considered candidates for blastocyst transfer, delivery rates can be maximized while minimizing multiple pregnancy rates by transfer of no more than two blastocyst stage embryos.”

The researchers acknowledge that different laboratories can have significantly different stimulation protocols, indications for blastocyst stage transfer, and classifications of embryo morphology, and point out that these differences were not taken into account in the data analyzed and presented.

Source: Fertility and Sterility 2009;91:157-66