Despite setbacks, mom continues treatment, gets pregnant
At 6:15 a.m. on June 21, 2004, embryologist Wayne Caswell is riding west on the Long Island Expressway on his Kawasaki motorcycle. At the office of Reproductive Specialists of New York in Mineola, nine embryos are waiting for him in a petri dish the size of the top of a soda can. These embryos were created from eggs removed from Stacy Trebing's ovaries and fertilized with husband Steve's sperm.
At the laboratory, Caswell trades his leather jacket for blue scrubs. The hands that this morning tossed laundry into the dryer at home will now operate on embryos so small they can't be seen by the human eye.
Appropriately, Caswell's lab is stenciled with a playful ceiling border of sperm chasing an egg. The nine Trebing embryos are in an incubator that resembles a hotel room mini refrigerator. Caswell uses a tool that works like a miniature turkey baster to pick up embryo No. 1.
He transfers it to an individual dish and places it under a microscope. Through the lens, the eight-cell embryo looks like a soccer ball. It has a membrane, as if wrapped in plastic wrap. Caswell shoots a low intensity laser to burn a hole in the lining. Only then can he steal what he's after.
Scientists know an embryo can survive the loss of one cell. During routine in vitro fertilization, embryos are often frozen for future use. One or two cells may die in the thawing process, but a fully formed human being can still grow. Nature also causes some embryos to divide in two, forming identical twins.
Caswell can't talk while working -- because he literally uses his breath to blow and suck the cell off the embryo. He now uses two pipettes -- one to steady the embryo and the other to manipulate it. With his left hand holding the pipette to the embryo, the second pipette goes in his mouth like a straw.
Extracting cell from embryos
In a laboratory filled with sophisticated equipment, Caswell uses a low-tech process that's much like sipping a cocktail through a straw. He blows or sucks, easing the cell off the embryo. As he does, the cell stretches like a water balloon -- first round, then oval, until it breaks free from the others and returns to a circle.
When he gets to embryo No. 4, Caswell notes its beauty: evenly sized, good symmetry. On the other hand, embryo No. 8 is severely abnormal -- it has advanced to only two cells. Such embryos would be unlikely to survive on their own.
"I can't biopsy this embryo," Caswell says. "We didn't cause that. It's just inherent in the egg. Many patients think you've retrieved this amount of eggs, I should have this number of babies available. We're doing things to screen. We're doing things to select. But we're not doing things to fix."
Of the nine embryos, Caswell is able to remove a single cell off of seven for testing.
"Seven's not a bad number," he says.
Finding a match for Katie
The cells are deep frozen in tubes and put into a cooler to be loaded onto a routine flight at Kennedy Airport and flown to geneticist Mark Hughes at the Genesis Genetics Institute in Detroit. Hughes has been preparing for the cells' arrival for weeks, examining Steve's, Stacy's and Katie's DNA to make sure he can match the embryos correctly. Once the cells get to him, Hughes and his team will spend the next 19 hours performing preimplantation genetic diagnosis (PGD) to determine which of the seven cells are an exact human leukocyte antigen match for Katie. Those antigens are a code in the DNA that tells the body's immune system that other cells belong and are not foreign invaders. Having matching antigens would allow Katie's body to accept a sibling's bone marrow.
Two days after the embryos arrive in Detroit, Stacy is anxious, but excited. At noon, she is scheduled to have embryos that match Katie implanted into her uterus. Stacy had a dream last night that, of the seven embryos tested, one was viable. It was implanted and she got pregnant with a girl.
Steve won't be going with Stacy for the implantation. It's the height of the season for his party tent business and he's already scheduled to take a week off in July to go with the family to Camp Sunshine on the coast of Maine. The camp is for families with children who have life-threatening diseases, devoting a week, for instance, to leukemia and another to Diamond Blackfan anemia.
With the emotional boost of her dream, Stacy feels the day holds promise. On Father's Day the previous weekend, Steve's Aunt Kathy gave Stacy a candle with an angel on it. Hoping for the best, she and Steve lit it last night. As Stacy heads to Mineola, she knows only seven embryos were tested and the odds are one in four will be an exact match for Katie. That's disappointing to the Trebings, because 19 eggs had been harvested and 14 had fertilized into embryos immediately. The Trebings were surprised to learn that in the end they only had seven from which to choose. Dr. James Stelling, who heads the PGD division of Reproductive Specialists of New York, explained to them that this kind of attrition is normal and it's one reason doctors stimulate women's ovaries to mature multiple eggs in a cycle.
When Stacy arrives, she learns that the results aren't complete yet. They will wait another day.
In medical school at Stony Brook University, Stelling was one of the few people in his class who knew he wanted to become a fertility doctor.
Before he had his own three children, he might have balked at what the Trebings are doing. But the worry over an ill child hit home when one of his children was born with glaucoma that threatened her vision and required 16 operations. He knows the agony of wanting to heal your child.
"If you asked me 10 years ago if I thought it was a good idea to genetically test embryos to see if one was a bone marrow match for a current child, I would have considered it an ethical debate," he says. "Because you're creating life to serve a purpose outside of just being a baby. Now that I have kids, I wouldn't debate it at all. I would do it in a second. I would do whatever I could."
Embryos tested for disease
Hughes tested the embryos for Diamond Blackfan anemia in his Detroit laboratory, and none of them has the disease. One of a geneticist's worst fears is to tell parents an embryo is disease free and later find out it's not. These results confirm Katie's disease is a spontaneous mutation, a random occurrence that didn't come from either parent. This meant any future children they had wouldn't have an inherited risk of Diamond Blackfan anemia. Hughes wanted to ensure the Trebings weren't so-called gonadal carriers, who have the mutation in their reproductive organs instead of their DNA.
As far as the delay in getting the results of the antigen match from Detroit, Stelling's attitude is no news is good news. But Stacy's worried.
"Will waiting another day affect the viability of the embryos?" she asks.
"Only if they start to hatch," Stelling says. This is when the embryo lining breaks open completely so the cells can multiply more rapidly. "I'd rather it hatch in you, where it's used to hatching." If the embryo hatches outside the body, doctors worry about it forming twins.
The more days that pass before the embryos are implanted, the more they weaken. After too many days, the embryos will try to attach to the petri dish, sensing it is a uterus. Eventually, they will perish. Also, Stacy's uterus is expecting an embryo. If one doesn't arrive, she will menstruate.
Just one is a match
The next morning, Stacy's back. Only one embryo of the seven is a match for Katie, but it isn't one of the thriving ones.
"We're going to implant that embryo and give it a chance," Stelling says.
Caswell joins Stelling at Stacy's bedside. "It hasn't really grown," he says of the matching embryo. "That's not great, but it has a chance."
Stacy tries to pin a number on it. "Ten percent chance?"
"Yeah," Caswell says. "It may do better in the uterus than it does in the lab. It's worth a transfer."
Stacy's disappointed and she calls Steve, who's in the Hamptons putting up a tent for a graduation party.
"There's only one match and it's not a good one, but they're putting it in anyway," Stacy says, her eyes tearing.
"All we need is one," Steve says.
When Stacy is back in bed, Stelling sits down beside her. "Three embryos are growing well today," he says. "But they're not the match. Do you want me to freeze them?"
"No," Stacy says. "Dr. Hughes talked about donating them to research."
Later, the embryos were found to have deteriorated too much to be donated to research and had to be discarded.
In the procedure room, Stelling inserts a catheter into Stacy's uterus. Embryologist Michael Perretti slides the embryo down it like a ball down a tube. They wait 30 seconds for it to settle.
"See that whiter spot right about there?" Stelling tells Stacy, directing her attention to the ultrasound screen. "That's the fluid that has the embryo."
"I think I can, I think I can," Stacy chants.
It's 9 p.m. a few days later, and after Steve and Stacy put Calvin and Katie to bed, Stacy lays out a hypodermic needle on the kitchen counter and retrieves an ice cube from the freezer.
Steve ices her lower back below the waist to help numb the coming pain. Stacy must now endure 10 weeks of shots to her buttocks. Steve jabs Stacy with a long, thick needle filled with hormones to help the body nourish a pregnancy. Stacy feels reassured that Steve plays on a dart team in East Islip. Transferrable skills, she jokes.
In early July, the Trebings learn Stacy isn't pregnant. The weak embryo didn't take. They would have to start all over again.
Message from a parent
Undeterred, they head to Camp Sunshine. Because Diamond Blackfan is so rare, this will be the first time the Trebings will speak in person to other parents who have been through the same medical and emotional roller coaster. Approximately 40 Diamond Blackfan anemia families from across the country attend the camp.
While the children spend the day at supervised activities such as swimming, baseball and arts and crafts, parents attend lectures on the latest treatment and research. It's at one of those sessions that Stacy and Steve are handed a five-page letter written by the mother of a 12-year-old Diamond Blackfan patient who had attended camp two years earlier.
On the top, in capital letters, is typed: "THINK TWICE BEFORE HAVING A BONE MARROW TRANSPLANT."
Just reading the first paragraph sickens Stacy. By the end of the letter, she's sobbing.
"Our son, Keir Zangrando, had been transfusion dependent with Diamond Blackfan anemia since he was 51/2 weeks old," began Wendy Zangrando of Ohio. "He died on Wednesday, November 19th, 2003, of complications stemming from a bone marrow transplant that was supposed to have cured him. He was 12 years old."
Boy's sister was a match
The letter explained Keir had been lucky enough to have an exact-match sibling -- his sister, Emma. Emma wasn't an IVF/PGD baby -- the Zangrando's second and only other child turned out to be a match for her brother.
When Keir was 10, in the summer of 2002, the Zangrandos attended Camp Sunshine. There, doctors encouraged them to do a bone marrow transplant on Keir before he got much older, because the younger the child, the better the odds of survival.
Keir entered Cincinnati Children's Hospital Medical Center in August, 2003, for the transplant. While there, he developed veno-occlusive disease, which can be caused by the chemotherapy drug busulfan, a drug Katie also would get if she had a bone marrow transplant. Veno-occlusive disease causes clotting in the veins of the liver, all but shutting it down. Another drug, defibrotide, which had yet to be approved by the federal Food and Drug Administration, might have been able to treat the disease, but it was only available at a small number of hospitals participating in a study of its safety and efficacy. Children's Hospital wasn't one of them, Wendy Zangrando wrote.
While he seemed to recover, Keir quickly got an infection followed by pneumonia. He soon became so sick that only medications were keeping him alive.
"Finally, on November 19th, we had them stop giving him epinephrine and dopamine, the two drugs that were helping keep him alive by keeping his blood pressure normal," Keir's mother wrote. "We spend a lot of time second-guessing ourselves. Before all this, Keir was very healthy and hardly ever got sick, not even a cold, so we feel what happened to him was really radical.
"I think because DBA is so rare, and there aren't many sibling donors, there just aren't enough DBA patients having bone-marrow transplants for there to be reliable statistics . . . If the bone-marrow transplant had worked, we'd be telling everyone to do it. But this is our story."
Before leaving camp, every word of the letter on their minds, Stacy and Steve make a decision: they will continue to try for a third child who could be Katie's donor. They could decide later whether to go through with the bone marrow transplant.
In mid-August, back to square one, Stacy and Steve head to Stelling's office for another egg retrieval.
Steve is exhausted. Days before, his company pitched tents for a $25,000-a-plate fundraiser for presidential candidate John Kerry in the Hamptons at the home of Darren Star, the producer of "Sex and the City." He is asleep when Stelling tells Stacy he was able to retrieve 28 eggs. When Steve's sperm is mixed with the eggs, 23 fertilize.
The day of the biopsy of this group of embryos falls on Aug. 21. But Caswell, who was to remove the cells for shipment to Detroit, is in the hospital with gastrointestinal problems. And embryologist Perretti has his son's birthday party.
The embryos can't wait.
So Stelling brings in an embryologist from Maryland, who retrieves 22 cells from the 23 embryos and sends them to Hughes for testing -- three times more than the first round. Of the 22, 15 are found to be good enough to be tested as matches for Katie. Of those 15, eight are growing well enough in the lab to be implanted, if the testing in Detroit shows they are matches.
But only two match, numbers 19 and 21. Stelling implants both.
"Black jack," Steve says.
Katie is on steroids
Amid all this activity, there is still Katie's health to worry about.
By now, Katie is 18 months old and she's had 23 blood transfusions. Each one is only a temporary fix to counter the Diamond Blackfan anemia -- each transfusion depletes itself in three to four weeks.
Doctors decide to try the second Diamond Blackfan treatment option on Katie -- liquid steroids taken orally -- to see whether that could spur her body to generate red blood cells and eliminate the need for transfusions.
Very soon, side effects of the steroids cause Katie to be cranky and hungry. Dr. Jeffrey Lipton, Katie's Diamond Blackfan doctor at Schneider Children's Hospital in New Hyde Park, had predicted Katie would demand hot dogs at seven in the morning and Cheerios at eight at night, and that her weight would quickly increase by 20 percent.
On top of these changes, follow-up blood tests at Stony Brook University Medical Center show Katie's hemoglobin has changed only slightly, meaning the steroids aren't doing much. The doctors had hoped for what is called a reticulocyte count -- or retic count -- increase of up to 4 percent. Katie's didn't even approach .05. A retic count is a way of measuring increased production of young red blood cells.
Rapid iron buildup
That news was bad enough. But another setback comes out of nowhere: iron appears to be building up very rapidly in Katie's liver.
On earlier monitoring tests, Katie's ferritin level, a measure of the body's total iron content, had been approximately 1,000, still not alarmingly high. Normal for someone Katie's age is under 400. This time Katie's ferritin is 4,471. Lipton had been talking about starting Katie on the drug Desferal, which would pull some iron out of her system and allow her to get rid of it when she urinated, the process called chelation. He starts Katie on the drug immediately.
On Aug. 30, a nurse comes to the Trebings' house to show them how to use the Desferal pump, which is about the size of an eyeglass case. Katie will need to be on the pump 10 hours a night, five days a week.
It's evening, so Steve and Stacy wake Katie. The pump's needle is inserted into her thigh and she screams.
Looking for some measure of hope the future might be different from the present, Stacy takes a home pregnancy test.
It responds with a very faint line.
Stacy takes Katie and older brother Calvin with her to Stelling's office for her official pregnancy blood test.
"Did you cheat?" the nurse asks.
"Yes! Two nights ago. It was pretty faint."
"I really think it's going to be positive," the nurse says as she draws Stacy's blood.
By 11:30 a.m., Stacy can't bear the waiting anymore. She calls Stelling's office for the results.
"We did it!" the nurse says
"Woo-hoo!" Stacy yelps. She calls Steve at his office.
"You're going to be a daddy again," she says.
But Stacy has to take a follow-up blood test in two days, to make sure the pregnancy is progressing normally. After that test, she meets Steve and their kids at Steve's parents' beach house on Fire Island. Steve is nervous about the test results.
Stacy tells him she doesn't know them yet. Steve heads to the beach to swim, but an uneasy Stacy calls Stelling's office, only to be told her pregnancy hormone levels haven't doubled as they should have.
Stacy goes out to the beach and breaks the news to Steve. This is the nightmare he's been worrying about -- that Stacy might miscarry.
"It better stay," he says. He leans down and kisses Stacy's stomach. "Come on, baby," he urges.
The next week, Stacy's hormones have rebounded. In fact, doctors briefly think both embryos might have taken and produced twins. But follow-up ultrasounds show Stacy is pregnant with one baby.
By late September, Stacy has come to hate steroids, which Katie has been taking for six weeks. She feels she's poisoning her daughter. Calvin doesn't understand why his sister is hitting and biting him. Stacy knows strangers see Katie's chubby face as she's giving her daughter another ice pop, and she's certain they're thinking, "You shouldn't be feeding this kid."
While Katie waits to see Dr. Lisa Mueller, her hematologist at Stony Brook, she's eating chicken nuggets from McDonald's. She weighs 28 pounds, six pounds more than she weighed five weeks ago when she began taking steroids. Normally, she would have gained half a pound in that period. She is now in the 50th percentile in height for her age and in the 75th percentile for weight.
"She's going to blow up," Stacy jokes, and indeed Katie looks like her skin is a dress that's two sizes too small.
"Hey Katie bug," Mueller says as she enters the exam room. Right away, Stacy wants to know the plan for taking Katie off steroids.
But Mueller doesn't want to wean her yet. There is still time for it to kick in, she says."I know you don't have hope," she says. "But I still hope she'll respond." Mueller orders Katie's blood tested again. Katie is already crying in anticipation.
Instead of her usual rendition of "Barbara Ann," Stacy sings, "Who Let the Dogs Out?" to distract Katie from the prick of the needle.
Stacy again steers the conversation toward weaning Katie.
"I know you don't like my plan," Mueller insists. "But I think that we should try. It's only two more weeks of suffering."
Stacy has to wait for the retic count before she and Katie can go home. When she hears it -- just .1, still practically non-existent -- it's the final straw.
"What's this doing? Really? Really?" Stacy says. She is uncustomarily agitated and belligerent. "I hate this drug. It's a terrible drug. I don't want to be six months down the road saying we didn't really give it a shot, but I really don't think it's doing anything. I don't care what she looks like. It's how she feels. It's all right that she looks like a balloon. I'm sorry, I don't mean to give you a hard time. But they're not doing anything. She's miserable."
Mueller sticks to her guns; she'd rather see Katie respond to steroids than put her life at risk during a bone marrow transplant. She doesn't say what's in her mind: "When Katie's lying in the hospital having a bone-marrow transplant and is potentially fighting a life-threatening infection, I want to know I did everything I could."
Katie is taken off steroids
That night, Stacy and Steve decide to wean Katie off steroids. Feeling guilty, Stacy e-mails Katie's Diamond Blackfan doctor, Jeffrey Lipton, for his opinion. He e-mails her back that in all likelihood, if Katie hasn't responded yet, she probably won't.
But now, with steroids off the table, it's either back to monthly blood transfusions -- or moving ahead to a future bone marrow transplant from the new baby.
After her next appointment at Reproductive Specialists of New York, Stacy learns from one of Stelling's partners, Dr. Kristen Cain, that the baby is growing normally and she can go on to her regular obstetrician for the remainder of her pregnancy. Stacy pulls the doctor into a hug. Tears drip down her face.
"How do you thank someone for giving you a child to save your other child?" she says.