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.
One of the chief concerns couples have is the about the safety of the procedures that fertility specialists use to help them achieve pregnancy, such as IVF (In vitro fertilization). Most of us in the field know that serious complications to the mother-to-be can occur but are quite rare. A recent study with the lead author from Emory University looked through nationwide database of IVF clinics across the country over the past 12 years, and confirmed that while IVF does entail risks for women, those risks are quire small.
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.
In recent years, endometrial scratching, irritating the endometrium (lining of the uterus) to help in making the womb more receptive for pregnancy has emerged as a new and unsual way to help couples get pregnant. Recently, a group from Turkey presented data at the American Society of Reproductive Medicine meeting suggesting that performing an endometrial biopsy prior to IVF can improve pregnancy rates in women undergoing IVF by about 20%. In fact over the years, seeming against common sense, there have been a number of studies suggesting that a biopsy and/or hysteroscopy may improve the chances for IVF success. At Princeton IVF, we have been using this technique for years, first in patients who failed cycles without any good explanation and then routinely in all our IVF patients. Although no one is quite sure why it helps, it is likely that the repair process from endometrial trauma helps to make the uterus more receptive to embryos.
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.
This sounds kind of odd. Why would fertility specialists use a drug intended to treat breast cancer patients to help couples conceive? To those in the field, the concept is nothing new. Clomiphene (Clomid) is a close relative of Tamoxifen, a drug used for years to prevent the recurrence of breast cancer. These drugs which block the action of the female hormone estrogen, cause hormone fluctuations that stimulate eggs to grow. Over the past decade, doctors have begun to use another breast cancer drug called Femara or Letrozole to treat couples in with infertility. Like tamoxifen, letrozole is used to prevent recurrence in breast cancer patients, and like clomiphene, it can also be used to stimulate ovulation (release of an egg). Until now, clomid has been the gold standard to help make women ovulate since it is relatively inexpensive and safe. Recently, however, a large study was published suggesting that letrazole may actually be more effective than clomiphene and result in fewer multiple births. Over time, it is likely that letrazole may replace clomiphene as a first line fertility drug.
Think going through fertility treatment today is stressful ? Imagine in a world in which everyone suffers from infertility, everyone needs donor embryos in order to get pregnant and there are not nearly enough embryos to around. Lifetime network plans to release a trailer for a series called the Lottery with just that story line. In the show, mankind faces extinction as no one is able to conceive and no babies are born. The only hope is in a small batch of embryos, the fate of which, and of mankind’s survival is left up to a lottery.
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.
Several months back, we reported in our blog that the authorities that regulate IVF and other fertility procedures in the UK were considering allowing IVF with mitochondrial transfer to move forward. Mitochondrial transfer is more popularly known as “three parent IVF,” because it involves three genetic parents: the woman who provides her chromosomes, the husband who provides his chromosomes and the donor who provides the mitochondria which contain their own DNA. The HFEA in the UK has now given the green light for tightly regulated research to proceed on mitochondrial transfer. So, now it is likely that fertility researchers in Britain will move forward and learn whether this technique can help couples with mitochondrial diseases.