By David R. Meldrum, M.D.
Because of our many years of work in IVF and our excellent results, we commonly have patients self-referred and sometimes referred by other IVF programs. Many of these couples have experienced reduced embryo quality in their previous cycles. Poor embryo quality is a problem that frequently repeats itself in each cycle, although sometimes changes can be made in the management of the ovarian stimulation and laboratory techniques that can improve embryo quality or assist the implantation of sub-optimal embryos.
Short sperm-egg incubation:
In the fallopian tube, the human egg is exposed to a very small number of sperm. In in-vitro fertilization, very high concentrations of sperm are placed around the eggs. We know that sperm release substances such as free oxygen radicals that are harmful to eggs, and that the sperm penetrate the egg within a very short time. Studies have shown improvement in embryo quality by incubating the eggs with sperm for only one or two hours, rather than overnight which has been the classic technique since IVF first began.
Culturing embryos in groups:
Embryos produce factors that help embryo growth. Studies of mouse embryos have shown that embryos grow better in smaller volumes of fluid or in groups. Although there are no definitive studies in humans, culturing embryos in groups or individually in small drops of culture medium under oil may increase the exposure of the embryo to factors that are thought to promote or improve embryo growth.
Culture of embryos under reduced oxygen:
The concentration of oxygen in the fallopian tube is equivalent to a 5% concentration rather than the 21% that is present in air. However, the most common culture condition used for IVF is room air. This is in part because the use of 5% oxygen is more complicated. In addition, until recently there has not been any proof in the human that embryo growth is improved in the presence of the lower oxygen concentration. In a study of in vitro embryo growth to the blastocyst stage, it has recently been found that there are significantly more cells in the inner cell mass (which ultimately forms the fetus) when the lower oxygen concentration is used.
We have been using this technique and have found that more three-day embryos are developed beyond the eight-cell stage than we ever saw with room air. This technique requires a special incubator that drives down the oxygen concentration by adding more nitrogen. Besides the increased expense of the new incubators, the process uses more nitrogen tanks. It also requires more incubators because of the cooling which occurs with each door opening. However, we have been convinced enough of its benefits to now use it routinely.
In vivo, the embryo develops in close contact with cells lining the fallopian tube. In vitro, cells surrounding the embryo are removed to check for normal fertilization, and the embryos are cultured in contact with only culture medium and a plastic dish. Over the last several years, studies have shown that when embryos are cultured along with various types of cells, embryo morphology can be improved.
The most convenient source of cells is from the follicle. The mature egg is surrounded by tissue called cumulus. The cells making up the cumulus have been shown to have a beneficial effect on embryo morphology. With cumulus co-culture, a piece of cumulus is taken from around a mature egg and kept in culture to place with the embryos after the fertilization check. One minor drawback of cumulus co-culture is the small chance of losing an embryo which becomes adherent to the cumulus.
Embryos with poor morphology usually have varying degrees of fragmentation. These fragments are from damaged cytoplasm extruded from the cells of the embryo. Animal studies have suggested that the fragments themselves further reduce embryo viability. The fragments can be removed at the time assisted hatching is done, provided the removal itself would not damage the embryo.
Embryos with reduced morphology have lower metabolic activity and may not be able to thin out the shell (zona pelucida) and escape (hatch) from the zona. By making an opening in the zona with a tiny pipette and an acidic solution, the ability of the embryo to hatch, and therefore implant, is enhanced.
In a very selected group of women with multiple cycles of IVF with recurrent poor embryo quality, a research group in New Jersey has taken cytoplasm from donor eggs and has injected it into each infertile woman’s egg. Embryo quality was improved, and the pregnancy rate was increased compared to women with multiple failed cycles.
There has been a lot of controversy regarding possible consequences of mixing cellular material from two individuals, and an increased incidence of chromosomal abnormalities occurred in a small group of women having the procedure. We currently do not advise use of this technique outside of a very strictly controlled research protocol.
We now recognize that the quality of a woman’s embryos varies from woman to woman almost as much as sperm quality varies among different men. Women with poor embryo quality have a reduced prognosis with IVF. The above techniques can be used to try to improve their embryo quality, and thus maximize the chance for a successful outcome.
Reproductive Partners Introduces
At Reproductive Partners, we believe in success. Our expert physicians and staff are dedicated to using our knowledge and skills to maximize the chances of achieving the dream of having a baby. With well over fifteen years of experience, we anticipate that a couple capable of getting pregnant with IVF will have a good chance to succeed within three completed cycles of IVF. The SUCCESS PROGRAM is based on this philosophy. It’s designed to help take advantage of that important third cycle, if it’s needed.
Reproductive Partners SUCCESS PROGRAM is really very simple. You are eligible if you do not have insurance coverage for IVF, pay the full Global Rate for each of two complete IVF cycles at Reproductive Partners, and transfer all embryos from those cycles, including frozen embryos, without achieving a viable12 week pregnancy. Your third IVF cycle at Reproductive Partners for the same category of Global Rate and procedures will be provided free for all the same procedures covered under the Global Rate in the first two cycles.
There are no age limits, no higher up-front fees, no payments for the second cycle until the first is completed, no mandatory procedures like hysteroscopy or IVIG injections and no arbitrary cancellations. If we determine that you are a candidate for and complete at least two cycles of IVF you may participate in the program. We expect our patients to succeed, and when success does not come quickly, we will go the extra mile for you.
All frozen embryos must be transferred without achieving a viable 12-week pregnancy before you will be eligible for the third cycle. If a viable 12-week pregnancy is achieved within the first two cycles, including the use of frozen embryos, couples will not be entitled to a free third cycle. If three cycles are necessary, all must be completed in an 18-month period. You have 18 months from the start of birth control pills or Lupron in the first cycle, to the start of the third cycle. All fees for each “paid” cycle must be paid in advance.