Latest multiple birth has fertility centers pondering ethical issues
Latest multiple birth has fertility centers pondering ethical issues
Should caregivers influence parental decisions?
The McCaughey septuplets, the world’s first surviving set of seven babies born at the same time, recently celebrated their first birthday on the "The Oprah Winfrey Show" with Barney the TV dinosaur, Sesame Street’s Elmo, and well-wishers from around the world. But not everyone who tuned in was in the mood to celebrate.
"You see all of the this, and the babies seem to be healthy, and you feel happy for [the parents], but it makes you wonder what happened," says Edward L. Marut, MD, medical director of the fertility program and in vitro fertilization center at Highland Park (IL) Hospital.
Marut, along with several fertility specialists across the country, have followed with a keen interest the McCaughey case and, more recently, the birth last month of the Lewis octuplets in Houston. One Lewis baby died several days later.
According to experts, high-order multiple births (more than four babies) are extremely rare and, in most cases, are preventable through scrupulous monitoring of women during pregnancy. Because of the likelihood that such babies will be born extremely prematurely and their mothers will experience health complications, occurrences such as these should be seen as tragic failures of medical treatment and should provoke an examination of what went wrong, they say.
"I view [high-order] multiple pregnancies as a disaster for the most part, even if some of them do end up with reasonably good results," concurs Eli Reshef, MD, director of the Bennett Fertility Center at Integris Baptist Medical Center in Oklahoma City.
As newer and more powerful fertility drugs are developed and become available to a wider number of physicians and facilities, questions about their ethical use will continue to arise, predicts Marut. (For information on conception following in vitro fertilization, see news brief, p. 24.)
"Fertility [as a specialty] isn’t treated as seriously. Someone who is not an oncologist is not going to do cancer stuff, but everyone likes to dabble in fertility because they figure there isn’t a downside. Now we are seeing the downside," Marut explains.
Knowing where the risks are
The occurrence of multiple pregnancies is a possibility with any type of assisted reproductive technology, both with the use of fertility drugs alone, known as ovulation induction (OI), or with OI in combination with in vitro fertilization (IVF).
Most of the higher-order multiple pregnancies, however, result from OI alone because it is harder to control, says Reshef. With IVF, a limited number of embryos will be returned to a woman’s uterus for possible implantation.
These are among the guidelines developed by the Birmingham, AL-based American Society of Reproductive Medicine, which the Bennett center and several others use:
• in women under age 35, three or fewer embryos should be used;
• in women 35 to 40, four embryos can be used;
• in women over 40, the number is negotiable, based on several factors.
"These are guidelines we use, but they are not set in stone," Reshef continues. "There are other factors to consider besides age — such as the quality of the embryos right before transfer, the desire of the couple — all of these things are blended together to reach a decision."
Usually, staff will transfer no more than five embryos to a given patient, he says. This means that a patients may end up with quintuplets, but it is not very likely.
"In the cases with all of the controversy, the multiple-pregnancy births, these resulted from non-IVF procedures," he notes. "Under those circumstances, you have less control as to how many eggs will fertilize and how many will end up in the uterus."
According to Reshef, the risk of a multiple pregnancy is between 20% and 25% with OI alone and between 35% and 40% with IVF. However, most multiple births are twins and triplets. The incidence of multiple pregnancies with more than three fetuses is dramatically higher for patients undergoing OI alone.
Reshef and other fertility specialists say OI patients usually are intensively monitored by checking blood levels for estrogen and ultrasound monitoring of ovarian stimulation to determine the risk of ovarian "hyperstimulation." Hyper stim ulation can result in too many eggs maturing in the ovaries and can cause deadly health complications for the mother.
"However, even the most objective medical criteria can fail to detect an impending multiple-multiple pregnancy," he relates.
Reshef says he was tempted to criticize the physician handling the McCaughey case but held his tongue. "It’s a good thing I did," he notes. "Six months later, I got quintuplets." That patient was well within the clinical range deemed safe to proceed with fertility treatments. However, the result was a quintuplet pregnancy.
Such unexpected occurrences also can occur with IVF, says fertility specialist Andrew Toledo, MD, a physician with Reproductive Biology Associates in Atlanta. For one of his patients, for example, he inserted four embryos in the uterus, and one later divided.
"Two of the girls are identical twins," he says. "The chances of that happening were extremely rare. I told the mother she should buy a lottery ticket. But it is possible."
Preventing the dilemma
Patients undergoing OI go through two major steps in each cycle of treatments. A dose of fertility drugs is administered, such as clomiphene citrate (Clomid) or one of the newer recombinant DNA drugs such as Lupron, to stimulate the ovaries. Then, when the physician determines via ultrasound that the ovaries have several mature follicles, a dose of the hormone HCG is administered to trigger the release of the eggs and allow fertilization.
During this time, the patient’s blood estrogen levels are monitored. A very high level indicates hyperstimulation, says Reshef, and the cycle should be halted. This is done by withholding the "trigger shot," he says, estimating that about one in 10 cycles are canceled at his center.
Most fertility centers and specialists have additional criteria for determining when a given cycle has the potential to produce a multiple pregnancy. An ultrasound showing too many eggs developing in the ovaries is the most common.
"Most of us look at estradiol levels between 1,000 and 2,000 pg/mL and between four to six preovulatory follicles," Toledo says. "You can’t see the oocyte on ultrasound. A preovulatory oocyte is usually somewhere between 14 and 20 mm in size. You want to see the majority of follicles you are monitoring above the size of 14 mm, with most of the follicles in that range, not a lot of teeny tiny follicles."
Start slowly and be patient
Marut counsels patience when using OI, particularly in younger patients, by starting with small doses of the fertility drug and gradually increasing the dose until the desired range of mature follicles is seen on ultrasound.
"I may be aiming at one egg per cycle extra, so I should not see [the number of mature follicles] jump from one to five or one to six, which is what happens, I think, when these things get out of control. Moving very gradually and very conservatively, I tell people it might take three or four cycles for it to work," he says, noting that in his practice he has not seen a quadruplet pregnancy result from OI in the past 10 years.
Although their fertility programs operate under certain guidelines, ultimately the patient’s decision is final when it comes to determining how many embryos to transfer or whether to continue a cycle of drugs, say Toledo and Reshef.
"We don’t have a policy that says, If this happens, we must go to [selective] reduction’ or If this happens, the cycle must be canceled,’" Toledo says. "What we will do is give our best recommendation. Now, obviously, if there is huge risk to the patient’s life, we are not going to do that, going back to the Hippocratic oath."
However, Marut says the physician often must be firm and take some of the decision- making responsibility away from the prospective parents.
"There are really two points along the way [with patients undergoing OI]," he advises. "One is the starting point where we sit down and talk specifically about the injectables we will be using and saying, Here’s what can happen.’ We can’t tell them they won’t get quadruplets, only that the chances are very tiny, and here are the percentages. Then you say, But, if that does happen, would you have a reduction?’ If they say, no,’ that’s fine. I respect their beliefs. But, I am going to treat them much more conservatively than if they would be willing to have a reduction."
If he sees on an ultrasound that a patient’s ovaries have so many follicles developing that a quadruplet or greater pregnancy is possible, he would be unwilling to proceed with the cycle if the patient were not willing to consider selective reduction, Marut says.
"I don’t blame people because their beliefs dictate to them that they shouldn’t do a reduction," he explains. "They shouldn’t do it. But if you get in there ahead of time [before a pregnancy occurs] and say, Well this looks like it could be a jackpot, what are you going to do?’ And, they say, Well we’d just let nature take its course, leave it up to God’s will or whatever,’ then I’d have to say, It’s looks like you’re not going to get pregnant this time.’
"You must make the judgment that is in the best interest of the patient," he adds. "If they get ticked off and leave, fine. But the last thing you want is someone who is going to jeopardize their own health because they don’t understand the risks."
Recommended reading
• Phillips DF. Reproductive medicine experts till an increasingly fertile field. JAMA 1998; 280:1,893-1,895.
• Annas GJ. The shadowlands — secrets, lies, and assisted reproduction. N Engl J Med 1998; 339:935-939.
• Templeton A, Morris JK. Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N Engl J Med 1998; 339:573-7.
Sources
• American Society of Reproductive Medicine. World Wide Web: http://www.asrm.com.
• Edward L. Marut, MD, Medical Director, Highland Park IVF Center, Highland Park Hospital, 718 Glenview Ave., Highland Park, IL 60035.
• Eli Reshef, MD, Integris Health, Inc., 3300 NW Expressway, Oklahoma City, OK 73112-4418.
• Andrew Toledo, MD, Reproductive Biology Assoc iates, 5505 Peachtree-Dunwoody Road NE, Atlanta, GA 30342-1705.
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