(Republished with permission from the St. Louis Post-Dispatch. This article originally ran in the Science & Medicine section on Thursday, July 27, 2006)
By Tina Hesman Saey
Fertility treatments are all about the timing.
Laura Schroeder, 36, of O’Fallon, Mo., and her husband, Jim, bent their daily schedules to make sure Laura got injections of an ovary-stimulating hormone at exactly the right time.
That’s why the couple packed up their needles and snuck away to a bathroom during a holiday at Plaza Frontenac, and the reason Laura pulled into an elementary school parking lot on her way home from a float trip. The couple estimates that in two years of trying to have a baby, Laura took about 2,000 shots of hormones and blood thinners.
But a discovery made in a Washington University laboratory could greatly reduce the number of hormone shots needed and the inconveniences associated with them.
A Dutch company, Organon, announced this week that it would begin the final phase of clinical trials to test a long-lasting form of a hormone that stimulates ovaries to release eggs.
The company says that a single shot of the hormone can last for a week. That means a woman preparing for artificial insemination or egg harvesting for in vitro fertilization would need one shot a week instead of the typical daily injections for seven to 10 days. In extreme cases, some women inject themselves with ovary-stimulating hormones for up to 20 days.
“It’s kind of cruel. They’re pincushions for two to three weeks,” said Dr. Kelle H. Moley, a reproductive endocrinologist at Washington University.
The new hormone is part of a trend toward making fertility treatments more patient-friendly, she said.
The company plans to test the long-lasting hormone against daily injections in 1,700 women worldwide, said Eric Hoomans, a company spokesman. If it proves as safe and effective, Organon can apply for FDA approval to market the product in the United States. The process could take years.
The potential market for the new hormone is large. In the United States, about 6.1 million women ages 15-44 have fertility problems. About 20 percent seek treatment.
Many use injections of a follicle-stimulating hormone. The hormone can help women ovulate, increase the efficiency of artificial insemination, or produce eggs for in vitro fertilization, said Dr. Marc Fritz, chairman of the practice committee of the American Society for Reproductive Medicine.
In 2003, women in the United States went through 100,891 in vitro fertilization treatments, or cycles, according to the Centers for Disease Control and Prevention. A woman may go through more than one cycle in a year. No statistics were available for how many women may use the hormone to aid ovulation or artificial insemination.
The company acknowledges that the weekly hormone shot may not be for everyone. Women who are very sensitive to the hormone could be susceptible to overstimulation. Overstimulating the ovaries can lead to too many eggs being produced, too rapid egg production – which can mean poor quality – and in the most severe cases, death for the woman.
Daily injections allow doctors to control hormone levels precisely to make sure eggs develop properly, Fritz said. The inability to adjust a woman’s hormone levels could be a drawback to the new hormone, he said.
The new hormone was discovered in Irving Boime’s laboratory at Washington University nearly two decades ago. Boime and his colleagues study how a family of hormones that includes the follicle-stimulating hormone are made and how the proteins function.
For instance, follicle-stimulating hormone lasts for only a short time in the body, but a similar hormone made in the placenta sticks around longer. The difference between the two proteins is that the placenta hormone contains a sugar-studded tail. Snipping the tail off cuts the protein’s life span in half.
Boime reasoned that if removing the tail could shorten the amount of time one hormone stays in the body, perhaps adding the tail could lengthen the time another protein sticks around. His colleagues tacked the tail onto the follicle-stimulating hormone. The tail didn’t alter the hormone’s function but increased its longevity two to three times.
Washington University patented the new hormone in 1991. Organon researchers, who collaborated with Boime, recognized the hormone’s potential, Hoomans said. The company bought the rights to develop the hormone into a consumer product even before Boime and colleagues at Stanford University showed in animal studies that the hormone could stimulate ovaries for a week with only a single injection.
Taking and timing daily injections is stressful, Laura Schroeder said. A single in vitro fertilization cycle may last two months or more, starting with six weeks of daily injections to shut down the ovaries and let them rest, then two weeks of daily shots of the follicle-stimulating hormone to ripen the eggs combined with ultrasounds every other day to monitor the progress, surgery to remove the eggs for fertilization and more shots of another hormone called progesterone to prepare the uterus to receive implanted embryos.
“It all ends with one draw of blood to tell if you’re pregnant or not. If it’s positive, everything’s great, but if it’s negative, then everything you went through is for nothing,” said Laura Schroeder, who gave birth to twins in December 2004. “It’s mentally, physically, emotionally and financially completely draining.”
Eliminating several days’ worth of shots would ease some of the stress, she said. “I could definitely see a benefit.”
Timeline of a fertility drug
1988 — Washington University researchers led by Irving Boime develop a long-lasting form of follicle stimulating hormone, a hormone used to induce ovaries to make eggs.
1991 — Washington University patents the hormone and sells a license to Organon, a Dutch company that makes fertility treaments
1992 — Boime and collaborators at Stanford University show with animals studies that a single shot of the new hormone can stimulate ovaries for a week. The normal form of the hormone must be injected every day.
2000 — Organon begins human clinical trials
2003 — The first report of a baby born after stimulation with the hormone in clinical trials
2006 — Organon announces Phase III clinical trials. This is usually the final stage of clinical tests before seeking market approval for a drug.