Irene Laffoon, a senior embryologist at The Center for Fertility and Reproductive Endrocinology at Magee-Womens Hospital of UPMC, demonstrates the daily evaluation of embryos that takes place in the lab. Projected on the screen is an eight-cell embryo.
By Pohla Smith Pittsburgh Post-Gazette
"How do you feel this morning?" Dr. Anthony Wakim asked the young woman waiting to donate eggs for a childless couple or two.
"I'm ready to rock," Ashley, a pretty 27-year-old from Westmoreland County, responded.
Dr. Wakim smiled. That was what he was hoping to hear: a confirmation that she had easily weathered the protocol of hormone shots used at the University of Pittsburgh's Center for Fertility & Reproductive Endocrinology at Magee-Womens Hospital of UPMC.
The protocol to prepare a donor's body for the harvesting of eggs, put in use five years ago, comprises 10 shots over nine days. The hormones given are follicle stimulating hormone (FSH), human chorionic gonadotropin (HCG) and a single shot of Lupron (leuprolide acetate), which suppresses the normal menstrual cycle.
It replaced a classic, widely used long protocol that included anywhere from 10 to 20 days of Lupron shots plus a course of FSH and then an injection of HCG.
At the Jones Institute of Reproductive Medicine of West Penn Allegheny Health System, an affiliate of the famed Jones Institute fertility clinic in Norfolk, Va., director Dr. Scott Kauma and his staff also use a different protocol than the classic procedure.
"In the past we maybe gave shots twice a day, now maybe once a day, the follicle stimulating hormone," he said. "That's usually given somewhere between eight and 10 days on average; it kind of depends on how a person responds. ...
"We don't use Lupron; we use ganirelix. That's only given for three to five days during the last days of stimulation." Ganirelix acetate is a newer drug.
The classic long course of Lupron, which shuts down the part of the pituitary gland that is responsible for the release of eggs from the ovaries, causes a kind of mini-menopause in the woman donor. Hot flashes are possible, but more worrisome is another possible complication called ovarian hyperstimulation syndrome.
Egg donor programs
Center for Fertility & Reproductive Endocrinology at the University of Pittsburgh: 412-641-7470
The Jones Institute of Reproductive Medicine of the West Penn Allegheny Health System: 1-888-313-6667
Reproductive Health Specialists: 412-731-8000
"It means the ovaries would stay big, [with] lots of cysts on them, and the cysts get bigger and bigger," Dr. Wakim said. He was referring to the follicles, also called cysts, that usually contain eggs. "Sometimes it's associated with fluid on the belly, fluid in the lungs, and if there's fluid coming out of the circulatory system, the blood will become thicker and there's a very high chance of having a blood clot," he added.
Fluid in the abdomen and in the lungs can cause difficulties with breathing and moving as well, he said.
Before the surgery, while discussing risks, Dr. Wakim proudly told Ashley that the clinic, which does 50 to 60 donor cycles a year, has not had one case of ovarian hyperstimulation syndrome since it changed its injection protocol. (Other risks are bleeding and infection, but he told Ashley the chance of bleeding is one in 5,000 and that she would be given antibiotics to guard against infection with her intravenous anesthesia.)
Dr. Wakim presented the university clinic's new protocol at a meeting of the European Society on Human Reproduction in Copenhagen, Denmark in 2005 and also co-authored and published an article on it with third-year fellow Dr. Teresa Erb. In the meantime, they undertook a study to compare pregnancy rates from before and after the change in protocol. That result was presented to the same European body at a meeting in Lyon, France in 2007: "We found there was no difference," Dr. Wakim said. A paper on that study has been accepted for publication in the journal Fertility and Sterility.
"I didn't invent this," Dr. Wakim said of the new protocol after completing Ashley's surgery. "I read about it many times before, but I've done this here routinely on all of our donors."
Dr. Kauma said his clinic, which only began doing egg donors about a year and a half ago and averages about 20 a year, has not had any cases of ovarian hyperstimulation either.
And that is as it should be, Dr. Wakim said.
"These are young women who are fertile," he said. "They're not here to get pregnant; they're here to help other people. So we have to make sure that the process is as easy to them as possible, so if they like it they could come back. Unlike with men [and sperm collection], it's not easy to get eggs."
Ashley will receive about $4,000 compensation for her time and travel. Return donors get up to $5,000. West Penn Allegheny's Jones Institute gives similar compensation.
"It's been pretty simple," Ashley said before Dr. Wakim arrived to start the surgical procedure. "You do shots. They're pretty painless. They aren't horrible."
Sometimes at night, she said, she felt a little bloated, "but no more than like when you eat too much ...
"You come in for ultrasounds and bloodwork. I think they schedule you every single day [of the shots] for it, but depending upon how your results come back they may not do bloodwork some days; they may not do ultrasound one day. I think I had two days off."
But long before the shots there are some basic qualifications: "First of all it's age," said Dr. Wakim's Pitt colleague Dr. Joe Sanfilippo. "We don't let them come in if they're 32 and three months. Our lower limits would be 21."
The local Jones Institute affiliate has the same age requirements.
"I always say that the orchestra leader is the age of the egg," Dr. Sanfilippo said. "If the egg is 25 years old vs. 40 years old, there's a dramatic difference, and so fertility goes best with a relatively younger age."
But the qualifications for being a donor go much deeper than age. At the university clinic, a 15-page egg donor profile includes such questions as the prospective donor's hair and eye color and the physical characteristics of her grandparents, parents and siblings. There are queries about her talents and skills and about her sexual and medical histories. Then there are philosophical questions about egg donation ranging from "Who owns the eggs you are donating?" to "If frozen embryos result from the procedure, who owns them?" to "Would you be willing to meet the child/children in the future if they wanted to know about their genetic roots?"
While waiting to go back to the surgical suite, Ashley was asked if she has any curiosity about who will receive her eggs.
"No, not really," she said. "You think about it, but it's just good to know you're helping someone. Like today I'm thinking she has to be really excited this is happening. ...
"To me, it's like donating blood. It's just your cells."
Women like Ashley come to the city's two donor programs in many ways. Ashley heard about it at work, where a total of four colleagues have become donors, two of whom have donated twice.
"We advertise and by word of mouth," Dr. Kauma said. "I know [the ad] goes on if you pick up on our phone [hold] system. We send some [ads] out to our OB/gyn doctors for their waiting rooms; some go in local papers."
Dr. Sanfilippo also cites word of mouth "because our program is on the map;" referrals from a relative or friend of a patient who wants a child; and ads in City Paper. Another big source is "very savvy, Internet-savvy, sophisticated individuals who really want to help a couple. We get a number from Internet research."
Ashley was wheeled into the surgical suite, and nurse anesthetist Sylvia Bernassoli has started her on the light sedation known as twilight sleep. Ms. Bernassoli will talk to her throughout the approximately half-hour procedure and she will respond -- "I could lie here all day," she slurs when asked if she is comfortable -- but she will have no memory of the conversation or the procedure.
While Ms. Bernassoli continued to sedate Ashley, Dr. Wakim inserted a speculum and flushed her vaginal area with a liter of saline solution. Then he inserted an instrument called a transvaginal ultrasound probe; it has a sheath containing a long needle on top of it. The ultrasound showed him follicles on the ovaries that he hoped would contain eggs.
While watching the sonogram, Dr. Wakim pierced follicles and used the needle to aspirate the fluid out of them and into plastic tubing that carried it into test tubes. Nurse Hope McCall kept track of the aspirations, telling him when the fluid stopped flowing and at what level in the tube. She then passed the tubes on to embryologist Irene Laffoon, who looked at the follicular fluid under the microscope and announced the number of eggs, if any, in each tube.
The process continued, with Dr. Wakim aspirating all but a couple of small follicles that lay perilously close to an artery. He passed on them because of the danger of nicking an artery for what might be no or immature eggs and moved on to the other ovary.
Ms. Laffoon still was counting eggs when Dr. Wakim removed the ultrasound probe and needle and Ms. Bernassoli began to awaken Ashley, who wouldn't be fully conscious for about a half-hour.
By then the count would be complete: Ashley donated 23 eggs.
"Not all of the eggs that we get are going to be mature," Dr. Wakim said after the surgery. "Usually 80 to 81 percent are mature, and about 80 percent of those will fertilize if the sperm is OK -- that's another story.
"Not all of the fertilized eggs become embryos. They stop [dividing] or there are problems with mitosis and stuff like that and not all of those are equal in quality. We say 'quality,' but what we're looking at is how many cells did that embryo divide into over a certain period of time."
The eggs will sit for several hours in a medium under cultured oil. Then approximately 75,000 sperm will be introduced to each egg.
About 18 hours later, they will be assessed for fertilization. On day three, two of the embryos will be implanted in the prospective mother by the process called in vitro fertilization.
"Our pregnancy rate is approximately 65 percent," said Etta Volk, the university program manager and an embryologist. "That's outstanding and we're extremely proud of that. That puts us ahead of the national average. That's a hard number to get hands around but is somewhere between 40 and 50 percent."
Dr. Kauma declined to give a specific percentage for the Jones affiliate, saying "most programs, including ours, do very well with donor eggs and certainly a good program should have over 50 to 60 percent pregnancy rates."
Other embryos from Ashley's donation might end up frozen, giving the couple another chance if the first transfer doesn't work or providing opportunities for a second or maybe even a third child. They also might go to a second couple.
"Embryos freeze extremely well," Dr. Sanfilippo said.
Indeed they must.
In Dr. Wakim's office is a wall covered with the pictures of babies and older children who were conceived through the in vitro or donor programs. One of these children was born nine years after her embryo was frozen.