5. Egg Fertilization
Numerous eggs are fertilized in the lab, usually with her own eggs and her partner’s sperm, but occasionally with either donor eggs or donor sperm, as discussed after the list of these steps.
6. Intracytoplasmic Sperm Injection (ICSI)
In many cases, a fine needle is used to insert the sperm “directly into the egg, as discussed in the IVF and the Use of ICSI section later on.”
7. Preimplantation Diagnosis
The resulting embryos are often examined through sophisticated tools that ultimately screen for those that are free of chromosomal defects. Variations of these techniques are discussed here.
8. Embryo Transfer
One or more of the embryos are returned to the uterus through a narrow catheter inserted through the cervix, where they will hopefully succeed in implanting and ultimately lead to the birth of a healthy baby.
9. Pregnancy Testing and Confirmation
About two weeks after the transfer, a blood test will be taken to confirm pregnancy. If it’s positive, an ultrasound will be performed several weeks later.
IVF and the Use of Donors
If men are infertile or unable to use their own sperm for whatever reason, donor sperm are often used with either artificial insemination or IVF. If women are unable to use their own eggs (usually due to their diminished ovarian reserve), they can use IVF with donor eggs from other women who are often younger. These eggs are fertilized with their partner’s sperm and placed in their uterus in the same way that traditional IVF works. Both sperm and eggs can be chosen from donors with similar physical attributes as well as the same ethnic and religious backgrounds as those of the couple wishing to conceive.
With this option, even women with a poor ovarian reserve are often able to experience the joys and bonding of a normal pregnancy and delivery. You can choose to receive the egg of a screened but anonymous donor, or even use the eggs of a close relative or friend. Of course, there are profound implications to the procedure. Besides the obvious issue of the child not being biologically related to you, there are other factors to consider. For example, would you be comfortable if the child carries your partner’s genes but not yours? And would you want to tell your child? Ultimately, the option is very promising, but not one that should be taken lightly.
Couples can also use donor embryos, which are already carefully screened for both physical attributes and potential problems. One of the benefits of choosing this route is that it might be more psychologically appealing, since both partners would know that the child isn’t biologically related to either of them, so it might feel more equitable. In addition, it’s more affordable, because it doesn’t involve as many steps as traditional IVF. Finally, many couples may feel better knowing that they have chosen an embryo from a couple who clearly wanted to be parents and went to great lengths to achieve that goal.
Copyright © David Horsey, Seattle Post-Intelligencer.
IVF and the Use of ICSI
Intracytoplasmic sperm injection (ICSI) is a procedure in which a single sperm is inserted directly into the ova through the assistance of high-tech instruments. One of the advantages of ICSI is that the healthiest-looking sperm can be selected for the process. After fertilization is achieved, the newly created embryo is placed in an incubator for about 2 to 4 days before it is inserted back into the woman’s uterus.
ICSI was initially developed for those conditions in which the man’s sperm is severely compromised, or had been unable to fertilize an egg in previous IVF attempts. But now at least half of all IVF procedures incorporate it, regardless of what the actual cause of the infertility. The rationale is that since IVF success rates appear to be higher with it, its use could spare couples the emotional and financial burden of additional IVF attempts.
IVF and the Use of Preimplantation Diagnosis Technologies
More than half of all embryos produced during IVF are chromosomally abnormal, and thus often incapable of successfully implanting in the endometrium. This explains why doctors used to return five or more embryos to the woman’s uterus, with the rationale that maybe one or two would ultimately implant. Yet, as you know, sometimes three, four, or even all five would take, dramatically increasing the risk to both the mother and her babies.
Today, however, there are a variety of sophisticated and improving technologies that allow doctors to choose the healthiest embryo of the group to return to the womb. The most important and widely known of these is Preimplantation Genetic Diagnosis (PGD). This involves an intensive examination of the newly formed embryo at the cellular level, specifically to look for the genetic markers of various diseases such as cystic fibrosis and muscular dystrophy, which could cause problems both in pregnancy and beyond.
While PGD is a remarkable technology that can improve the odds for women suffering from recurrent miscarriages, it’s quite expensive, and moreover, it does not necessarily improve the pregnancy rate among women as a whole. (Indeed, one metastudy found that live birth rates overall actually declined, likely due in large part to the invasiveness of the embryonic biopsy, which is a part of this process.)
A similar technology with a slightly different goal is Preimplantation Genetic Screening (PGS). This procedure is focused not so much on any specific diseases, but rather on filtering out embryos that have an abnormal number of chromosomes—a condition which is also called aneuploidy. This is crucial since an abnormal number greatly increases the risk of both birth defects and miscarriage. (As you hopefully remember, a healthy embryo should have 23 pairs of chromosomes.)
As with PGD, PGS is a procedure that appears to be getting better, with its proponents claiming that it now results in significant improvements in the live birth rate. But again, it can add several thousand dollars to the cost of IVF, and as of this writing, there haven’t been enough studies on the newest version to see how well it’s truly working (the latest generation of PGS involves testing on 5-day-old embryos with over 100 cells, whereas previously, testing was done on 3-day-old embryos containing only 8 cells).*
There are two other related technologies that have emerged over the last few years and will likely become much more widely used in the years ahead. One is next-generation DNA sequencing (NGS), which is also used to count the number of chromosomes that a preimplanted embryo has. Sophisticated DNA sequencing machines are used for the task, which can make this technology both faster and cheaper than PGS or PGD, while still being as accurate.
The other one is a new imaging technology designed to take time-lapse images of the preimplanted embryo from the time of conception to just before transfer, and, as with the other technologies above, the ultimate goal is to ensure selection of the healthiest possible embryo. There are currently two variations: one is the EmbryoScope, which basically functions as a type of IVF incubator with a built-in camera. The other is the Eeva test (for Early Embryo Viability Assessment).
Both are noninvasive and use sophisticated software to monitor various parameters for embryo health. Again, though, there are few studies as of this writing that can confirm their effectiveness in raising pregnancy and live birth rates. But regardless, and as with all these new technologies, you should always ask your clinician to explain their pros and cons for your particular condition.
IVF and the Next Potential Breakthrough
Finally, it’s worth noting here that with continued advances in biotechnology, some scientists believe we will one day reach the point where all ovulatory drugs will be unnecessary, since it will be easier to retrieve immature oocytes directly from the ovaries through a procedure using fine-needle aspiration. They would then be matured in vitro before being fertilized through standard IVF. Indeed, this type of in vitro maturation (IVM) is already available at certain clinics.
However, it’s expensive and its success rates appear to still be well below those of IVF using eggs stimulated through traditional ovulatory drugs. In addition, as of this writing, the technology is still only recommended for women with cer
tain disorders, such as PCOS, those at risk for ovarian hyperstimulation syndrome, and those with estrogen-sensitive cancers. Nevertheless, IVM is a technology with great potential in the years ahead, and so I encourage you to keep current on it if you are considering IVF.
TREATMENT OPTIONS FOR WOMEN WITH PCOS
As women’s health conditions go, PCOS can be one of the most emotionally painful because, in addition to all of the overt symptoms and health risks that women with this condition may experience, they may also face serious challenges in trying to get pregnant. In fact, PCOS is one of the most common causes of female infertility. The good news, though, is that most women with this condition can get pregnant even with their own eggs, if given the right fertility treatment.
While PCOS is a significant health concern affecting so much more than just fertility, the reason it poses such a serious impediment to getting pregnant is the adverse effects of the polycystic ovaries themselves. In addition, women with PCOS often tend to:
•Stop maturing eggs at the earliest stage of development, so they rarely ovulate or have normal cycles. Instead, they develop multiple small cysts on the outer capsule of the ovaries that are technically “preantral follicles” (not to be confused with “prenatal”). They are usually discovered by clinicians during an ultrasound, and are often referred to as a “string of pearls” for the way they appear on the ovary (see picture here in the color insert).
•Have long intervals of time between menses, which, technically, are often not even true periods, which, as you know by now, is the bleeding that occurs about 12 to 16 days after ovulation.
•Have long cycles of sporadic patches of eggwhite, so they may feel they are constantly on the verge of ovulating (but a lack of a thermal shift confirms that they actually don’t).
•Have abnormal ovulations if they do indeed ovulate, both in terms of the development of the egg as well as the corpus luteum.
•Have an increased risk of endometriosis, further compounding their chances of infertility.
Finally, you should also be aware that women with PCOS rarely benefit from ovulation predictor kits, since they produce numerous spikes of LH during their anovulatory cycles, and this often renders the kit results invalid.
THE GOOD NEWS: PCOS AND THE VARIOUS OPTIONS FOR GETTING PREGNANT
As mentioned in Chapter 8, it’s crucial that a woman’s treatment plan be individualized for her specific genotype, age, and hormone levels, even though for all the treatment options the primary goal is to induce a healthy ovulation. You may have already read about some of the treatments listed below in that chapter, but some will be different in the context of trying to get pregnant:
Natural Hormone Balance
Before trying any of the following treatments, you will probably want to do all you can to take control of your PCOS through the natural methods discussed in Chapter 9, because, in addition to being healthier for you all around, they don’t have any side effects.
Metformin (Glucophage)
This drug is an insulin-sensitizing medication that can be very effective in helping women with PCOS to develop more regular ovulatory cycles, but it can have quite a few side effects, including fever and back pain.
An Ovulatory Drug Such as Clomid or Letrozole
If Metformin doesn’t help a woman to ovulate on her own, she will usually be prescribed a drug such as Provera to induce a “period,” after which she can start taking an ovulatory drug such as Clomid or Letrozole, usually beginning on about Day 3 of the new cycle. Letrozole seems to work better for women with PCOS.
However, PCOS patients must be treated extremely carefully, because they have so many immature follicles that they need to avoid ovarian hyperstimulation syndrome, where too many eggs mature simultaneously. They are therefore usually given the least amount of ovulatory drug possible, gradually increasing the dosage until they eventually respond and release an egg. In fact, because of this risk, all women who are prescribed these strong ovulatory drugs should confirm with their doctors that they don’t have PCOS before they take them, to better control for ovarian hyperstimulation.
Gonadotropins
If women are still unable to ovulate, they are often prescribed a gonadotropin, which is more potent and produces larger numbers of follicles, but poses an even higher risk for ovarian hyperstimulation. For this reason, most clinics will only prescribe these meds in combination with IVF, so that they can be monitored carefully and have only one or two embryos returned to the woman’s uterus.
Ovarian Drilling and Ovarian Wedge Resection
As also mentioned in Chapter 8, these two archaic-sounding treatments can actually be surprisingly effective for women with PCOS. In fact, some physicians believe that either ovarian drilling or ovarian wedge resection should be the first treatment tried if drugs alone don’t work, though naturally, others feel it should be the last (alas, as you’ve seen, such is the nature of modern medicine). The theory behind each is that by removing a portion of the ovary, the androgen-producing follicles are diminished, thereby allowing for more normal cycles and ovulation. In addition, women opposed to IVF on religious grounds may find these procedures more acceptable.
Ovarian wedge resection is rarely performed anymore because it used to have a high adhesion rate, and thus was widely seen as too risky a procedure. However, a growing number of surgeons are now being trained to use this technique with a very low adhesion rate. This can make it a preferable surgery, since it helps women to ovulate on their own while also addressing so many of the debilitating health effects of PCOS. If interested in pursuing this option, I encourage you to contact the Pope Paul VI Institute for the Study of Human Reproduction in Nebraska for a list of the surgeons they have trained in this procedure.
In Vitro Fertilization (IVF)
IVF, in conjunction with one or more of the ovulatory treatments listed above, tends to be quite successful for most women with PCOS. However, there are those who have a particular genotype who unfortunately tend to have a much lower success rate. These women tend not to be overweight, and may not even demonstrate signs of excessive androgens or other characteristics that are typically associated with PCOS. Yet they still develop polycystic ovaries at a younger age, so they deplete their ovarian reserve earlier, leading to premature ovarian aging.
THE MAN’S FERTILITY WORKUP
When people think of fertility problems, they tend to think of it as primarily a woman’s issue. But, as you know by now, fertility problems affect men and women equally. The reason a man should be tested first is that his own workup is fairly simple, cheap, and hardly uncomfortable! The foundation is the semen analysis, which is easily obtained by having the man ejaculate into a cup.
Remember that even though the analysis is usually referred to as a “sperm count,” the expression is somewhat misleading. The count is only one facet of the whole analysis. As discussed in Chapter 3, the key to judging a man’s fertility is not so much to look at the total number of sperm per ejaculate, but rather the total number of those sperm that are of normal shape and motility.
Based on that analysis, a physician will be able to tell you whether your partner’s sperm count is considered normal or subfertile. If the analysis shows a low count, he would likely have at least one more analysis performed a few weeks later in order to verify the results.
One additional investigation that is often done with the sperm sample is the sperm penetration assay, or the hamster egg penetration test (yep, hamster!). It’s done to determine the fertilizing capabilities of a man’s sperm. As the name implies, the sperm is placed immediately next to hamster eggs to see whether they can penetrate them, since such penetration generally correlates with how well sperm can penetrate human eggs.
Like any test, though, it’s definitely not perfect. In fact, 5 to 10% of men whose sperm do not “pass the test” are still able to eventually impregnate their partners. And likewise, some men whose sperm do fine in the test are still unable to fertilize their partner’s eg
gs. For this reason, some in the field believe it’s a waste of money because it doesn’t impart any additional information that isn’t already available through a sperm analysis. However, it’s considered fairly standard in a fertility workup, and should be taken for what it’s worth.
Finally, many clinics now offer exams that test for the chromosomal integrity of sperm. The most common one is the sperm DNA integrity assay (SDIA). This test is more likely to be performed if the semen analysis itself is abnormal, or in cases of unexplained infertility, but otherwise the test does not reliably predict treatment outcomes and is not widely recommended for routine clinical use.
Depending on the results of the semen analysis, the physician may perform a variety of other procedures. These include a physical exam to look for varicoceles, prostate problems, or testicular anomalies, as well as blood tests to ascertain hormone levels. In addition, the doctor may need to take semen cultures to determine the presence of sperm clumping (agglutination) or genital tract infections, as well as X-rays of the sperm-producing tissues. Once the source of the problem is identified, there may be a variety of treatments possible.
Correcting the Man’s Basic Underlying Problem
As with women, the man’s fertility may be improved simply by changing diet and eliminating the consumption of caffeine, nicotine, recreational drugs, and alcohol. Some people believe that acupuncture and naturopathic treatments as well as nutritional supplements may also be useful. Still, men facing infertility problems usually have a variety of overlapping symptoms that require medical intervention. While fertility specialists generally view male infertility as easier to detect but more difficult to cure than its female counterpart, it’s also true that some of the more prevalent problems can be successfully treated.
In addition, various techniques have been designed to extract sperm from the vas deferens, the epididymis, and even the testicles themselves, allowing them to be used with ICSI (discussed earlier). This essentially bypasses virtually all forms of male infertility, though it must obviously still be used in conjunction with IVF. In any case, male infertility may be due to problems relating to any combination of the following:
Taking Charge of Your Fertility Page 25