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Most Asked Questions
1. Age and fertility
A woman is born with all the eggs she is going to produce in her lifetime, an amount close to one million. By the time she starts to have menstrual periods, she still has between 400,000 and half a million. The human body uses about one thousand eggs a month, even though it may ovulate only one, many, or none (if the woman is pregnant or taking birth-control pills). Some 400 to 500 menstruations later, the egg supply is spent and menopause begins.
Not all eggs are equally fertile. The body utilizes the most fertile ones first, leaving those which are less viable for the later stages of reproduction.
Human fertility remains constant and even until the age of 34. Once that age is reached, a linear descent commences. Human fertility diminishes to 50% by age 40, and to 25% by age 43. The chances of conceiving, gestating and giving birth to a baby are almost nonexistent once the patient reaches age 46.
Pregnancy and live birth rates for ART cyles using fresh, nondonor eggs
or embryos, by age of woman, 2003
2. Risk of chromosome abnormalities
What is the probability of chromosome abnormalities, at a particular age?
When a sperm penetrates and fertilizes an ovum, the chromosomes in each join and mix in equal parts during the very first cellular division of the newly-formed embryo. As a woman becomes older, the probability of errors during fertilization and chromosome division increases, and with it, the incidence of babies with chromosome disorders. There are no maternal ages that are free of possible chromosome abnormalities in the baby, even so, the risk of anomalies is low in a woman's twenties and progressively higher as time goes by.
The risk for all chromosome abnormalities related to maternal age can be summarized as follows: 1% at age 35; 3% at age 40; and 7% at age 45.
Approximately one out of three abnormalities (1:3) are due to Down syndrome (Mongolism) in which the baby has an extra chromosome 21 (trisomy).
The risk of Down syndrome can be summarized approximately as (one third, by age, of all abnormalities): 1:300 at age 35; 1:100 at age 40; and 1:25 at age 45.
The table that follows presents the most precise figures of the incidence of Down syndrome during the second trimester of a pregnancy (the period at which amniocentesis is done) and at full term (delivery time). The difference is due to those pregnancies that end spontaneously, presumably due to an anomaly.
Age-based probability of Down syndrome
3. What Is Preimplantation Genetic Diagnosis?
Preconception genetic diagnosis (PGD) allows us to use just one cell of each eight-cell embryo (in the third day following fertilization) to analyze the chromosomes immediately and determine which embryos are free of predetermined genetic conditions (that is, are normal) and may be transferred into the mother two days later. The couples that may benefit from PGD are those where maternal age is an issue, or have a history of genetic disease in their families, or who have already given birth to an affected baby. The number of diseases that can be prevented by means of PGD nowadays exceeds 400 genetic and metabolic conditions, but as this number continues to increase, the total is practically unlimited. The advantages of PGD are that it offers the chance to begin a pregnancy with the probability that: the fetus is not going to be affected by a particular condition, it eliminates the transmission of a given gene to subsequent generations of the family, it avoids the stress related to uncertainty and possibly having to decide to terminate a pregnancy if the child turns out to be affected, and, it increases the chances of having a healthy birth. PGD is an alternative to both amniocentesis and placental biopsies (CVS, or “chorionic villi sampling”).
4. Preservation of fertility in cancer patients
One out of every 52 women develops some type of invasive cancer between birth and age 39. In the United States alone, more than 625,000 women are diagnosed with some form of cancer each year. The survival rate of cancer patients has increased dramatically due to new chemotherapeutic agents. One out of each 1000 people under 20 years of age are cancer survivors in the United States.
Chemo- and radiotherapy treatments pose a grave threat to ovarian function. These treatments reduce the number of follicles, or tiny eggs, that are present in the ovaries. Once the ovarian reserve is lost, reproductive failure and premature menopause ensue.
How Can Fertility Be Preserved in Cancer Patients?
Ovarian Inactivation: Gonadotropin-releasing hormone agonists (GnRH drugs), better known as Lupron or Zoladex, and to a lesser extent Depo-Provera and birth-control pills, induce inactivity in the ovaries which render the follicles more resistant to chemotherapy-caused damage. Before puberty the ovaries are more resistant to that type of damage. The use of Lupron before chemotherapy has been shown to protect ovarian function by 94%. On the other hand, 60% of patients who are not given these drugs suffer irreversible ovarian damage.
Embryo freezing: Patients can undergo in vitro fertilization treatments and the resulting embryos can be frozen for future implantation. This is the method that has yielded the best results. Frozen embryos can survive at least 5 years and possibly more. The disadvantage of freezing embryos is that it necessitates overstimulation of the ovaries before the IVF treatment, resulting in high levels of estrogens and other femenine hormones, which can exacerbate those cancers that are dependent on these hormones, such as breast cancer. The cancer treatment would have to be postponed several weeks while the IVF procedure takes place.
Freezing of ova: Patients who are unmarried, or who do not wish to store frozen embryos, have the possibility of freezing their eggs prior to eventual fertilization. Freezing of a woman's eggs is still an experimental form of treatment; fewer that 1,000 babies have been born in the whole world as a result of this procedure. It also requires IVF treatment involving hyperstimulation of the ovaries, as explained above. The life span of a frozen egg is not yet known; it is presumed to be quite limited. Frequently, the egg-freezing technique affects the genetic material and its potential for producing pregnancies at a future date. For this reason, it is still considered an experimental therapy, while scientific investigation proceeds.
Freezing of ovarian tissue: Ovarian tissue is obtained by laparoscopy-guided biopsy. These tissues, or the complete ovary, can be frozen for future use. Ovarian tissue can be obtained from unmarried women, before or after puberty. It is obtained via a simple surgical procedure and it does not delay cancer treatment. It is, however, still experimental. How long the frozen tissues remain viable, and if many eggs are lost due to freezing, remains to be determined. Once the cancerous condition has been overcome, these tissues could be retransplanted into the patient to restore her hormonal and ovarian function. However, if there are tumors that have invaded the ovarian tissues, there exists a risk of reintroducing tissue with cancerous cells. Freezing ovarian tissue is the method that offers the most promising alternative for preserving fertility in cancer patients.
Patients whose ovaries are no longer functional can receive eggs or embryos donated by another couple. Some patients who undergo cancer treatments are advised not to become pregnant, for fear of a relapse, or that extensive chemotherapy could affect the baby. Embryos created from a woman's own genetic material could be gestated by another patient (a surrogate mother) thus giving her the chance to have her very own descendants. It remains to be seen if and when reproductive cloning will become an alternative in the future.
Studies have shown that 57% of female cancer patients did not receive information about the risk of infertility and reproductive failure as a consequence of the treatments. Physicians who treat this patient population have a duty to make them aware of the consequences and guide them toward alternatives that will minimize the risk.
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Fertile Hope
5. Advances in Reproductive Medicine
In May of 2007, the first baby born in Puerto Rico as a result of IVF celebrated her 21st birthday. A treatment that used to be considered experimental has become, nowadays, practically an everyday procedure that achieves success levels never before seen. New developments and discoveries are opening doors to unprecedented treatments and positive outcomes.
Reproductive science has focused on achieving ever-higher rates of embryo implantation. Ovulation stimulation protocols using agonist and antagonist drugs, together with ultra-pure recombinant gonadotropins, allow us to develop mature eggs with a greater degree of fertilization potential and better embryo quality and implantability. Optimal conditions for cellular cultures in the lab have resulted in a greater number of embryos reaching blastocyst stage. We do the majority of embryo transfers on the fifth day after aspiration of ova (retrieval of eggs) because the pregnancy rate is higher with blastocysts.
The development of the uterine endometrium has been the object of a great deal of attention, both to foster greater receptivity and to enhance implantation potential. The replacement of estrogen and progesterone after ovulation maintains a delicate balance between these two hormones, necessary to bring the endometrium to its ideal phase for implantation. The embryo is implanted during one of only two specific days, and any minimal changes in endometrial readiness affects receptivity of the embryo. An evaluation of the endometrium allows us to tailor therapies to each individual patient, inasmuch as hormonal requirements vary from one person to another. At the molecular level, the level of integrins can be evaluated. These are binding molecules that form the adhesive links between the embryo and the endometrium. An absence of integrins is an impediment to implantation and the start of a pregnancy.
Guided by ultrasound, embryo transfer can be carried out with much greater precision, allowing us to deposit the embryos in the optimum location within the uterus, using an echogenic catheter. Assisted eclosion (also called assisted zona hatching, to aid the embryos emergence from its protective outer layer) to increase the probability of implantation is routinely done by creating an opening in its enveloping tissues (zona pellucida).
The treatment of male infertility has also improved considerably, especially since the creation a procedure known by the acronym ICSI, for IntraCytoplasmic Sperm Injection. When the husband has either a low sperm count or low sperm motility, his sperm can fertilize the egg by means of ICSI. In cases where sperm are not present in the semen (azoospermia or total absence of sperm), non obstructive or after surgical vasectomy, sperm can be obtained by testicular biopsy (TESE). These techniques make it possible to need only one sperm to fertilize each egg. The average female patient produces 11 eggs during an IVF treatment cycle, which means that a man needs fewer than a dozen sperm to be able to father a child.
More recent advances enable us to determine the chromosomal health of the embryos before pregnancy. Preimplantation genetic diagnosis (PGD) allows us to use just one cell of an eight-cell embryo to analyze the chromosomes immediately and determine which embryos do not have predetermined genetic conditions (that is, are normal) and could be transferred to achieve a healthy child. The couples that may benefit from this analysis are those who are older, those who have a history of genetic disease in their families, or who have already given birth to an affected baby. The number of diseases that can be prevented by means of PGD nowadays includes more than 400 genetic and metabolic conditions, but as this number continually increases, the total is practically unlimited.
One of the areas of greatest medical advance today is the preservation of fertility. Statistically, one out of every 52 women develops cancer before the age of 39. Chemotherapy and radiation treatments frequently cause sterility. The preservation of their reproductive potential is exceedingly important for these patients. Cryopreservation or freezing of embryos has been taking place for many years now. More recent techniques include the freezing of ova (eggs) or ovarian tissue, or both. Although still experimental, ovarian tissue can be transplanted back into the patient once she has been cured of cancer, reestablishing her fertility and hormonal function.
Early attention to all fertility-related conditions increases the probability of achieving pregnancies. Patients are encouraged to seek the professional help of medical specialists who are certified in infertility and reproductive endocrinology. We have been pioneers in IVF in the U.S. for the past 24 years, the last 22 of these in Puerto Rico, and our medical practice is exclusively dedicated to helping couples make their cherished dream of becoming moms and dads come true.
Pedro J. Beauchamp MD, FACOG, FACS, REI
Amaury J. Llorens Martinez MD, FACOG, REI
(Article published in Buena Salud magazine)