Over 2 decades ago, ICSI (intracytoplasmic sperm injection) revolutionized the treatment of male infertility. The ICSI procedure involves injection of a single sperm into each egg at the time of IVF (in vitro fertlization). Before the development of ICSI, couples with sperm issues, what we call "male factor," had very low fertilization and pregnancy rates, even when undergoing IVF. Now a days, because of the use of ICSI, poor sperm quality is a very unusual reason for an IVF cycle to be unsuccessful or to blame for poor fertilization. Over concerns about potentially poor fertilization, many fertility centers have chosen to use ICSI routinely to ensure optimal fertilization even when the male partner's sperm is perfectly normal. At Princeton IVF, our philosophy has always been to allow fertilization to happen "naturally" in the dish when there is no history of sperm issues or poor fertilization. While ICSI had been shown to be quite safe, we feel that a more natural selection process makes more sense and research in the past has suggested that ICSI is only beneficial in male factor patients. A recent large-scale study recently published in the Journal of the American Medical Association has borne this out. ICSI when used in IVF cycles used in couples without sperm issues had lower fertilization and lower implantation rates than non ICSI cycles.
Could a cure for real cure for infertility be on the horizon? Today many causes for infertility can currently be successfully treated such fertility issues caused by damage to fallopian tubes, ovulation disorders, endometriosis and low sperm counts or motility. These treatments currently available to us include fertility drugs, insemination, surgery and IVF. However, there are still issues in assisting women have very few or no eggs left or men who produce no sperm at all. This is a particular problem for women since women produce all they eggs they will in a lifetime while still in their mother's womb, and by their mid 40s have hardly any normal eggs left. These couples can be successfully treated only with the use of donor eggs or sperm. While these donor procedures are often quite effective, the children who result from these pregnancies do not carry the DNA of one or both of the parents. This is a problem since most couples who seek out the help of a Reproductive Medicine specialist want their own genetic children. With our current state of reproductive science this may not be possible.
One potential way around this would be using stem cells in the lab using cloning technologies. A group of scientists at the Weizmann Institute in Rehovot, Israel and Cambridge in the UK have brought us a little closer to this cure, figuring out how to more efficiently get these stem cells to grow into cells that will eventually develop into eggs and sperm. Their findings were recently published in the journal Nature.
The researchers have yet to take the next step; producing eggs and sperm from these stem cells. While it may become technically feasible, besides the technical issues, there are ethical concerns, perhaps even greater than when IVF when first introduced to overcome before this proceeds. IVF was enormous breakthrough when it was developed, but it is still merely a replication of natural conception, albeit in a laboratory dish. If this next step is even possible, it could bring reproduction to entirely new level. These technologies may make it possible to have genetic children without ovaries, without testes and without age limits, shattering our concepts about parenthood, even more so than it is today. It is not clear if society is ready for this yet.
As we reported in our blog earlier this year, fertility specialists in Sweden transplanted uteri into women who were unable to carry a pregnancy to help them. They were presumably motivated by one of the remaining challenges in Reproductive Medicine, helping women who were born without a uterus, or have had their uterus removed or have severe scar tissue in the uterus making it difficult or impossible to carry a pregnancy. The only options for these couples until now has been to use a gestational carrier with IVF to carry the pregnancy for them, what most people think of as a “surrogate.” Picking up on research that began over a century ago, doctors in Sweden used modern surgical techniques and medications to enable transplantation of the uterus. There is now some good news on this front. One of these transplants in Sweden resulted in a healthy live birth. The pregnancy and birth were not without complications. The baby was born 9 weeks early and the mom developed pre-eclampsia, a serious condition in pregnancy also known "toxemia" whose symptoms include high blood pressure and swelling. The doctors are also unsure if the uterus will be usable for a second pregnancy. Still, this an exciting first in Reproductive Medicine.
In recent years, Vitamin D has become the all the rage in medical research. It seems everybody these days is deficient in Vitamin D and a whole range of medical conditions from cancer to osteoporosis to reproductive issues have been potentially linked to insufficient Vitamin D. A recent study, which was in agreement several other previous studies, showed that women doing IVF with higher Vitamin D levels actually had significantly higher pregnancy rates than those who did not. While it is not clear at this time whether Vitamin D deficiency actually causes infertility or even whether supplementation will help couples conceive, it does suggest that maintaining healthy Vitamin D levels may contribute to good reproductive health.
With some states choosing to legalize marijuana, we hear very little of cannabis' effects on health, and even less on its impact on reproductive health. We have know for years that pot smoking can cause chromosomal breakage, and so for those couples trying to get pregnant, many reproductive specialists encourage both partners to quit when attempting pregnancy. Now, some new data out of the UK shows men who use marijuana are considerably more likely to have abnormally shaped sperm, Interestingly, in the same study, alcohol and tobacco did not. Since even in normal men, it is normal to have some proportion of misshapen sperm, this finding in itself is not enough information to say that marijuana causes infertility. Still, why take the chance? This is just another good reason to quit if you are planning to start a family in the near future.
Being that is National Infertility Awareness Month, this week seemed like an appropriate time to share this story. I recently attended a lecture given by one of pioneers in our field and one my personal mentors, Dr. Eli Adashi. The story he shared with the audience moved me and reminded us of our patients' suffering and why we do what we do. In the history books, when one looks at the breakthroughs in medical infertility treatment, the birth of the first IVF baby does and will stand out as one of the great milestones. The protagonists in the story that everyone knows are, Drs. Steptoe and Edwards, the brilliant gynecologist and scientist team, and of course, baby Louise Brown herself. But the popular narrative leaves out perhaps the most important character in this drama, Lesley Brown, the patient herself. Lesley was a reserved woman who never wanted attention but her delivery was one of the most famous events of the 20th century. She put up with repetitive surgeries and painful medical procedures knowing there was little chance they would work. When she did IVF with Drs. Steptoe and Edwards, she was basically (and knowingly) a human guinea pig. Nobody had any idea as to whether it could work, whether it was safe and if it did whether her child would turn out normal. On top of that she had to put up with moral outrage (and occasionally harassment) of those who opposed the very idea behind IVF. Without her bravery and perseverance, millions of couples would remain childless and millions of babies would never have had a chance at life. Lesley Brown passed away quietly in 2012 but the legacy she left has brought both hope and joy to millions.
Most Reproductive Medicine specialists know that our overweight patients often need higher doses of fertility medications, whether that is pills (clomiphene or Femara), or injections (Follistim, Gonal-F, Bravelle or Menopur). When we do IVF cycles, we also add a medication to prevent ovulation such as Lupron, Ganirelix or Cetrotide, and for the most part, the doses are not adjusted based on a patients weight. It turns out that doctors in Colorado looked at one of these drugs, Cetrotide (Cetrorelix) and found that overweight women actually metabolize the drug faster, meaning that the currently used dosing may not be sufficient in these patients. So, what does that mean? If the cetrotide does not last in the system long enough, premature ovulation may occur, and your IVF cycle could be cancelled. It may mean that we need to use higher or more frequent dosing in heavier women.
The Wall Street Journal recently published an article on one of the hot topics in Reproductive Medicine, Minimal stimulation IVF, also known as "Mini-IVF." This is IVF with very low doses of fertility drugs. It certainly sounds appealing, fewer drugs, fewer doctor visits, fewer side effects and less cost in order to have a baby. But, like most things in life, there is always a downside. Mini-IVF has significantly lower pregnancy rates than regular IVF. Does it work for some couples? Absolutely. Is the lower cost and hassle worth the lower chances for pregnancy? At this time, the jury is still out.
Like most Reproductive Medicine practices, we perform what we refer to as "Third Party Reproduction" meaning we use donor sperm, donor eggs, gestational carriers for couples who need these procedures. One of the problems with the use of an egg and sperm donors or surrogates and gestational carriers, is that using them can be rather pricey. A lot of effort is required to make sure all parties involved are protected medically and legally, and so many patients may be tempted to do this at home without medical intervention. This story of a "Turkey Baster" do it yourself surrogacy from the UK illustrates why it is so important not to try this at home.
For most couples going who use assisted reproduction, one of the foremost concerns they have is about the health of the children they will hopefully deliver. While there are some concerns about the risks of birth defects and other complications of pregnancy in IVF babies, little was known about how these children do long term. Now, there is some promising long term data coming from Melbourne, Australia that suggests IVF kids do just fine as they grow into adulthood, with generally similar quality of life, health and educational achievement to normal conceived children.
With government agencies in the US and UK, considering allowing the use "cloning" technologies to prevent the transmission of mitochondrial disease, nuclear transfer has become a hot topic in Reproductive Medicine. As discussed in our prior blog post, IVF is used to obtain eggs from both the intended mother and an egg donor, and the nucleus of the egg (which contain the mother's genetic material) is transferred into the donor egg (which contains healthy unaffected mitochondria). British authorities have now issued a draft guidance document recommending letting research proceed on mitochondria donation. What will the USFDA recommend and will this type of research to help couples with mitochondrial diseases move forward? Only time will tell.
Most of the genetic material in our cells is contained in the chromosomes which we inherit as a mixture from our mothers and fathers, but not all of it. A small amount of DNA is found in the mitochondria, the little structures in our cells that act like batteries. The only way to prevent the transmission of the genetic diseases of the mitochondria to date in couples who wants their own genetic children has been through the use of donor egg IVF. The problem is with donor egg is that the baby receives no genetic material from the the mother, and that only way around that problem would be to move the nucleus (which contains mom's genetic material) from the mother's egg into a donor egg. That process is called nuclear transfer and was banned by the US government because it involves cloning technologies. Now the FDA is considering lifting the ban to allow research into IVF with nuclear transfer for mitochondrial diseases. If successful, this would create babies with 3 genetic parents for the first time, a genetic mother, a genetic father and a mitochondrial mother. Quite a bit to ponder.
The use of Preimplantation Genetic Testing (PGD) enables fertility doctors to screen embryos for genetic diseases such as Cystic Fibrosis or Sickle Cell Anemia, permitting couples at high risk to avoid transmitting these diseases onto their children. PGD is done as part of an IVF cycle. A biopsy is taken when the embryo reaches the 8 cell or the blastocyst stage, and tested for the specific gene we are concerned about. This same technology can also be used to test for genes that do not necessarily cause a disease but put an individual at risk for other serious diseases. One such genetic mutation, called the BRCA 1 and 2 gene, puts affected women at very high risk for developing breast and ovarian cancer. The risk of developing these cancers in affected women is so high that many women (such as Angelina Jolie) chose to have their breasts and/or ovaries surgically removed just to prevent cancer. Since we know the genetic sequence of the BRCA mutation, it is possible to screen embryos for it, and prevent transmitting the gene onto one's daughters. This article in the Wall Street Journal tells the story of a family who decided to go that route.
We know that in normal fertile couples it takes an average of 3 months to conceive. We also know that in successful IVF programs, most embryos will never implant. Even when genetic testing is performed on the embryos to eliminate the most common cause of IVF failure, 30% of embryos will still not stick. So, is the embryo sending some sort of message to the uterus that is OK to allow implantation or not? Researchers from the UK, discovered that embryos produce an enzyme called trypsin that facilitates the implantation process, but that embryos which are genetically abnormal produce less trypsin. This may be a way that embryos tells the uterus whether it ok to allow implantation. Perhaps a better understanding of this process may help develop ways to make IVF more successful.
One of the most fascinating things about practicing Reproductive Medicine in an ethnically and religiously diverse area is learning to understand the value systems that our patients bring to the table when they come to seek out fertility treatment. Some faiths such as Roman Catholicism reject Assisted Reproduction as a separation between reproduction and intimacy and others such as Judaism encourage it emphasizing the importance of the biblical commandment "to be fruitful and multiply." Sunni Islam permits assisted reproduction but forbids the use of donors or gestational carriers. The most fascinating and perhaps most paradoxical is that of Shia Islam, the predominant religion in Iran. Most of the world views the Islamic Republic of Iran as one of the most brutal and intolerant in the world, yet when it comes to Assisted Reproduction, it is actually one of the most open minded. As pointed out in an Op-Ed in the Pittsburgh Post Gazette, Iran's Shiite theocracy allows relatively unrestricted access to ART and IVF, including the use of egg and sperm donation, a practice forbidden in most of the Middle East. Iran, in fact, now has over 70 clinics, luring patients from Sunni countries that forbid the use of donation.
It has been known for some time that couples suffering from infertility, including those who get pregnant using assisted reproductive techniques such as IVF, are more likely to have complicated pregnancies.: more high blood pressure, diabetes, miscarriages, preterm births and likely birth defects as well. This is true even with singleton pregnancies. What is not so clear is why this is so. Is it the patient population? Women who have infertility tend to be older and have more medical and metabolic problems. Is it the fertility medications such as clomid and injectables? Is it something in the process of IVF or IUI that causes problems? Researchers at Cedars Sinai Hospital in Los Angeles have received a large grant from the National Institute of Child Health and Development to help study the molecular events the underlie an early pregnancy after IVF. They will be looking at both genetics (the DNA in the chromosomes) and epigenetics (changes in gene expression that occur outside the chromosomes) to try to discover an explanation for these problems
Researchers at the National Institutes of Health, looked at the effects of obesity on sperm quality. They determined that men who were overweight (high BMI) or has a high waist circumference had significantly lower sperm counts and significantly low semen volumes than men of normal weight. Other semen parameters such as motility (percent swimming), morphology (percent normal shaped) and DNA fragmentation (proportion of sperm with normal DNA) interestingly were unaffected.
Many IVF and fertility practices such as ours use a procedure called PICSI to help certain couples where we are concerned that there may be a problem with sperm quality even when fertilization is succesful with ICSI. PICSI relies on placing the sperm on a field hyaluronic acid and having the embryologist determine whether sperm are able to bind to it. Sperm which are immature or otherwise abnormal are less likely to bind to the hyaluronic acid, and so sperm which do bind to it are used for the injection into the egg for ICSI. We and others have found that it may help certain couples who have failed ICSI cycles or had miscarriages from ICSI cycles. However, to date there are no large studies yet showing how effective it is, so researchers at the University of Leeds in the UK have initiated a large study to determine this.
Since its start on the fringes of medicine, In Vitro Fertilization (IVF) has resulted in an estimated 5 million births worldwide as announced at the American Society for Reproductive Medicine and International Federation of Fertility Societies this week. The biggest reason for the sudden explosion in IVF babies increased demand in developing countries such as China who now have access to modern medical care including fertility treatment. There are now more children born through IVF than the population of some countries. That's pretty remarkable for something that 35 years ago was not readily accepted by society. Click here for more from the article in USA Today.
Coenzyme Q-10 is a naturally occurring chemical found in the parts of the cells (mainly the mitochondria) that produce energy, and is thought by some to be helpful for certain diseases such as cancer, heart disease and some neurologic diseases. A recent study suggests that using Coenzyme Q-10 as part of IVF (In vitro fertilization) may increase the percentage of embryos that are genetically normal. We know that genetically abnormal embryos (which is actually most embryos transferred) explain most IVF failures and miscarriages, so anything that might increase the number of generically normal embryos may improve a couple's odds for success. A word of caution: this study is too small to draw any conclusions. Further research is needed to determine if Coenzyme Q10 is effective or not.