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Structural Issues

In vitro fertilization (IVF)

Home : Contents : Getting Pregnant—Infertility Solutions

Medical Help in Achieving Pregnancy: Infertility Solutions

Our prior article suggested that there are thousands of factors that can differ between couples and affect the amount of time it takes for them to get pregnant. Of necessity, an infertility work-up needs to focus on a limited number of factors that have a major impact.

There are two approaches to providing care for infertile couples. The first, more traditional approach, involves having all couples undergo a well defined battery of tests, attempting corrections of those factors which are abnormal, and then waiting for pregnancy to occur. We prefer a more interventional approach to infertility which individualizes the work-up depending upon a patient's history and physical exam. We may then use our increased understanding in the physiology of the reproductive process, to help cause pregnancy to occur more quickly then it would otherwise occur.

This approach is especially advantageous since many of our patients have subfertility on the basis of normal aging, as opposed to a pathological process like a pelvic infection. One hundred years ago most couples started their families in their teens or twenties. Many of our patients are waiting to start their families in their thirties or even forties. As a species we were designed to become less fertile as we grow older (*add link-thoughts on ovarian reserve). This is also true for other primate species. However, with medicine's increased ability to cure infectious diseases, as well as, other medical advances, women are living twice as long as they did a few centuries ago. We also live in a more complex world then our ancestors, and it makes sense for many to delay childbearing.

Researchers have observed a decrease in fertility that begins around age twenty-three, accelerates about age thirty-five and frequently is markedly impaired by age forty. Most women still intermittently ovulate at age fifty, but natural mechanisms make pregnancy at this age unlikely. The medical tools that we have available can overcome this decline in fertility. They work very well in a woman's thirties, but less well in her forties. Pregnancies after age forty-three with the woman's own eggs are rare.

Most couples can benefit from infertility care if they have not achieved pregnancy after one year without using birth control. After age thirty-five, undue delay of appropriate therapies may mean the difference between that couple ever having a baby, or never having a baby. After age thirty-five, therapy is appropriate after six months of trying to achieve pregnancy without success.


All infertility evaluations should utilize semen or sperm studies. In l998, almost any sperm specimen can be used to achieve pregnancy. Functional information about the sperm enables me to target or individualize a couples therapy. Sometimes the results of sperm studies will enable me to conclude that a number of traditional tests in the infertility work-up will add nothing to helping a particular couple achieve pregnancy. We view sperm specimens as being on a spectrum of fertility ranging from severely impaired to highly fertile. It is common that one of our therapies will help the sperm to work better and enable the couple to achieve pregnancy more quickly than otherwise. Semen studies that provide information about the relative fertility of sperm can only be obtained in subspecialty laboratories. Most regular laboratories and hospital laboratories that perform semen analysis provide very little useful information about the fertility of a sperm. This has to do primarily with the many changes that have occurred in the last twenty years with respect to evaluating sperm. It is also true because sperm are very difficult to evaluate. Information, even between good laboratories, is not completely interchangeable, and the physician ordering the test needs to be used to working with results from that laboratory.

Only a very small proportion of the sperm ejaculated into the vagina have a chance of getting into the female reproductive tract. The concentration of functional sperm that are likely to fertilize an egg is very important in terms of how quickly conception takes place. Most sperm are not capable of fertilizing an egg, even if the egg were right in front of it. A very fertile semen specimen has about 10% of its sperm that are likely to be functional.

One of the reasons that the male makes as many sperm as he does, is because it is difficult for him to make a very good one. The sperm creation process is an unusual process in which sperm are changed from normal appearing round cells to highly specialized sperm cells over the course of about eighty days. At least a hundred different genes produce chemical proteins in the right amounts, and in the right sequence, to repackage the sperm's DNA and remodel its cellular apparatus so that it can function like sperm.

Structural Issues

Most infertility evaluations should also involve an early assessment of the uterine cavity and tubes. Several "expert" groups have argued that the two most cost efficient tests in the routine infertility work-up are semen studies and the assessment of the uterine cavity and tubes. Previously, the most commonly used test for this is the hysterosalpingogram or HSG. This is done in the x-ray department of a hospital. It involves a pelvic exam in which radiopaque dye is injected into the uterus outlining the uterine contour and spilling out the tubes into the abdomen. This exam does cause some uterine cramping, but as long as the dye is injected slowly, most of my patients do not find it any more significant then the cramping which occurs during a period. In outlining the uterine cavity, the HSG may identify possible fibroids or polyps which can act like IUD's, and prevent implantation from taking place. It can also identify asymptomatic congenital abnormalities such as a septum, which can cause early miscarriages because the pregnancy has difficulty in establishing a connection to the mother's blood supply. It can also diagnose severe tubal damage commonly characterized by closed distended tubes.

More recently, there has been a greater focus on the uterine cavity.  Abnormalities here may contribute to difficulties in implantation.  Common gynecological conditions are associated with a high likelihood of abnormalities of the uterine lining such a polyps. For example, some studies suggest that endometriosis is associated with uterine polyps 40% of the time.  Chronic anovulation associated with irregular uterine shedding and prior pregnancy losses may also be associated with abnormalities of the uterine lining.  The best examination to evaluate the uterine cavity for polyps is the saline infusion sonohystogram, which is a transvaginal ultrasound using water to provide contrast in the uterus.

Most women with regular periods between twenty-six and thirty-two days ovulate monthly. Ovulation can be most easily confirmed in such women by obtaining a progesterone blood level approximately one week to the time of the expected period. A blood test taken at this time provides most of the useful information obtained from the more painful endometrial biopsies which are part of the traditional work-up.

A very common problem seen in the course of infertility care is that of chronic anovulation. This condition can result from a number of correctable hormonal abnormalities. Most commonly it is associated with a symptom complex that carries the label of polycystic ovarian syndrome. Such women will have menstrual irregularity, usually in conjunction with excess or undesired body hair growth usually on the abdomen, around the breasts or on the face. The condition is worsened by obesity. Unfortunately, the syndrome also involves metabolic abnormalities, and women afflicted by it will have difficulty in controlling their weight. There are health consequences, in addition to infertility, that patients need to be aware of. They include increased risk of diabetes and increased risk of endometrial cancer. From an infertility viewpoint, ovulation can be induced utilizing a number of different medications. There is also a surgical procedure, ovarian drilling, which can establish ovulation and help the patient achieve pregnancy.

The function of a women's immune system to allow a pregnancy to occur is quite complex and only partially understood. In patients who have had an evaluation suggesting no problems, and who have had a long history of subfertility, I become concerned about the possibility of autoimmune infertility. Evaluation is partially based on history. However, we have the ability to measure antibodies to proteins that are part of the developing placenta. In general, infertility patients are more likely to have these antibodies then fertile patients. Patients who have failed to get pregnant with utilizing in vitro fertilization are more likely to have these antibodies than other infertile patients. Several medical treatments for this problem are available. The most commonly used is directed at preventing these antibodies from binding to the placental tissue.

In general, infertility therapy should be started at a level that is most likely to overcome aspects of decreased function in the couple. Any therapy should be repeated for only a limited months or cycles. This is because, with respect to almost any therapy, most of the pregnancies that will be achieved due to the therapy will happen in the first four cycles. If pregnancy does not occur, therapy should become more sophisticated so that more of the normal reproductive process is bypassed. At the top of this chain of therapies are the advanced reproductive technologies. These include in vitro fertilization, ICSI and TESE.

In vitro fertilization (IVF)

In vitro fertilization involves stimulating a woman's ovaries with FSH containing medications to cause multiple follicles to develop. It is necessary to work with multiple follicles because of the intrinsic inefficiency in the human reproductive process. In order for the eggs to develop optimally the woman also needs to be treated with another medication (often a GnRH agonist) which will prevent her from producing hormones that might damage the eggs. When the eggs are likely to be mature the woman would then take a medication to cause the chromosomes to divide within the egg and for the egg to become free of its attachment within the follicle. Eggs are then removed from the woman in an office procedure and identified in the laboratory. The husband's sperm is processed and the eggs are then inseminated with the number of sperm thought likely to optimize the potential for fertilization. Three days later some of the embryos are transferred back to the woman's uterine cavity. Depending on the patient's age usually three or four embryos are transferred. Excess embryos are usually frozen for additional tries at getting pregnant without the patient having to go through the whole hormonal treatment process. An important feature of IVF is that the sperm and the egg choose each other. The sperm has to be biologically competent to fertilize the egg and based on our understanding of this process, most sperm are not able to do this.

In the event that the husband does not produce sperm that are likely to fertilize the egg, a variation of IVF referred to as ICSI can be undertaken. With ICSI, the sperm are processed and an individual sperm is captured and injected into each mature egg. ICSI enables many couples who would have previously had no chance of pregnancy, to achieve pregnancy. The process is, however, much less natural then IVF and should only be used when required.

An even newer technique is that of TESE. This can be used to achieve fertilization and pregnancy in a couple when the man produces no sperm in his ejaculate. In order to undertake TESE a testicular biopsy has to be performed on the husband. The tissue is evaluated and about 60% of the time, developing sperm can be found in small areas. Processing the tissue to locate this sperm is very time consuming, but these testicular sperm perform almost as well as normally ejaculated sperm with ICSI.

The egg is contained in a protein shell called the zona pellucida. This shell is a barrier to sperm and is part of why so much is required of a sperm in order to fertilize an egg. In the normal situation after fertilization takes place an embryo divides inside the zona pellucida. The embryo within the zona pellucida is free floating within the uterus for three to four days. The embryo must break out of the zona pellucida in order to attach to the mother and become a pregnancy. We believe that the primary mechanism by which women become less fertile as they get older is because they have difficulty breaking out of the zona pellucida. If a patient is undergoing in vitro fertilization or its variants, we can enhance the ability of the embryo to implant in many cases by partially dissolving the shell around the embryo prior to transferring the embryo back. This micro operative procedure is referred to as assisted hatching. It has been shown to enhance the pregnancy rate in many situations including that of the woman being above age thirty-eight.

Most of the patients I see only desire to achieve pregnancy using their own eggs and sperm. However, there is a well defined role for using both donor eggs and donor sperm. Using donor sperm is a relatively simple technology that has been with us for more then thirty years. It is a much less expensive approach to achieving pregnancy then IVF with ICSI. The key problem with using donor sperm is not the technology, but rather the psychology. The couple has to come to terms with the idea of using donor sperm. Donor sperm is collected and processed by a relatively small number of sperm banks in the United States. The standards of these sperm banks follow are quite stringent and the use of donor sperm is much safer then it has ever been in the past. Donor eggs are much more difficult to obtain. Many programs recruit donors in order to help their patients who either do not produce eggs or whose eggs are unlikely function because of their age. The donor has to undergo the IVF procedure and usually the donors are well compensated for doing this. The approach that our program has taken is to utilize shared donor eggs. This is a situation in which a patient who is usually young and needs IVF in order to achieve pregnancy, is willing to undergo an ovulation induction which is paid for by an older recipient patient who needs donor eggs. When the eggs are obtained they are divided between the recipient and the donor and fertilized with each of the recipient and donor's husband's sperm before transfer.

The field of reproductive technology is moving at a break neck pace. Different practices are incorporating different aspects of this new technology into their practices. For many problems there is no right way of doing things. Rather, there are justifiable ways of doing things and choices are made based on underlying practice philosophies. The patient should seek out those practices with philosophies most consistent with their desires and comfort.