My son is starting his second year residency in obstetrics and gynecology. He, like I was 30 years ago, is turned on by reproductive medicine and enjoys performing gynecologic surgery. When I decided then to specialize in reproductive endocrinology and infertility (REI) I was looking forward to being on the frontier of fertility medicine. The details of Reproductive physiology were being unraveled in real time and IVF had just reported its first successful pregnancies. In those days, microsurgery of the fallopian tubes was commonly performed by REIs as well as endometriosis and fibroid surgery.

During my fellowship, surgery was a huge part of my training. I travelled to Nashville to train with one of the world’s experts in laser laparoscopy. I practiced my tubal microsurgery skills weekly on anesthetized rats in a plastic surgical lab. I assisted on reproductive surgery several cases every week throughout my fellowship.

Myself and other fellows performed research on basic reproductive physiology questions that had yet to be worked out. Personally, my interest was polycystic ovarian disease and its relationship to weight gain. I studied male hormone production in the ovary and the adrenal gland before and after significant weight loss. I discovered that there was an inverse relationship between weight loss and male hormone production and that this was mediated through insulin. These were exciting times. If only we had metformin back then, I would have proven that in addition to weight loss, we could decrease insulin levels and therefore male hormone levels with metformin.

Today, discoveries in reproductive physiology are much more esoteric than it was when I was a fellow. Reproductive surgery, in particular tubal microsurgery and laser laparoscopy for endometriosis and adhesions is usually replaced with in vitro fertilization (IVF) which has become so much more successful, less invasive and therefore a preferable option. Most causes of infertility, if they are not successfully treated with ovulation induction and intrauterine insemination (IUI) can be overcome with IVF.

In the 1980’s when I was a fellow, IVF was grossly inefficient and we had to transfer multiple embryos to achieve a pregnancy. Consequently, triplets and quadruplets were not rare occurrences. In many programs, they constituted over 10% of all pregnancies. Today, we can often transfer one embryo at a time minimizing the risk of multiple pregnancies. We can freeze excess embryos so many patients need go through only one stimulation and retrieval and still have multiple transfers providing them with an excellent chance of conceiving a baby from their efforts.

Today, we get excited about advances in preembryo genetic screening and diagnosis and contemplate the current and future potential of eliminating hereditary medical disorders. This involves highly trained laboratory personnel who perform the latest technologic advances. In 2010, the REI, in general is removed from a hands on involvement with the frontiers of Reproductive Medicine and instead works like a film producer gathering his team including these lab personnel, nurses, etc and directing them as to how to approach his patients’ fertility problems. It used to be that he used the microscope and laser laparoscope to perform the tubal and endometriosis surgery. The IVF retrieval and transfer were new procedures that were still being perfected.

Today, they are the routine cases performed daily by the REI.

My son looks at the REI of today as a doctor who starts his day with 1-2 hours of ultrasound that is part of the daily ovulation monitoring for IUI and IVF. Many REIs no longer perform more surgery than hysteroscopy and occasional laparoscopy or myomectomy in addition to their retrievals. These are all considered routine procedures now. The current frontier in infertility is limited pretty much to the laboratory. Though many of us consider ourselves expert in stimulations, retrievals and transfers and while we know we make a significant difference in our patients’ outcomes our work does not appear or feel as glamorous as it once did. Perhaps, he will decide, as I did, that the pleasure in helping women build their families is sufficient reward. Or perhaps, this Nintendo generation, will seek a more apparently exciting lifestyle. How about that Robotic surgery?

According to the Center for Disease Control, reported in the same NY Times issue, thousands of premature deliveries would be prevented resulting in a $1.1 Billion savings if elective single embryo transfer was performed on good prognosis patients. That brings us to regulating how many embryos to transfer as Octomom went through IVF with transfer of six embryos. At East Coat Fertility, we make it cost neutral to transfer only one embryo at a time by offering free cryopreservation, free embryo storage and free embryo transfers until a patient achieves a live birth, all for the cost of a single IVF cycle. Patients are encouraged by this program not to put all their eggs in one basket. Success rates with an elective fresh single embryo transfer with IVF at our program, is 50% and with subsequent frozen embryo transfers it is over 64%. It is possible that East Coast Fertility is the only center in the country doing this. That is the shame of it.

Fertility treatment without IVF is even more hazardous since as many eggs that are developed with treatment may implant and lead to a hazardous multiple pregnancy. In a perfect world, where a patient’s welfare was put before insurance companies, IVF would be a covered service for all people, and the use of fertility medications in an uncontrolled IUI cycle would not be used anymore. In this perfect world, we would also regulate how many embryos are transferred. It is time to put our professional recommendations of the Society of Assisted Reproductive Technology (SART) into law. There is flexibility built into the recommendations taking into account critical factors such as patient age, embryo quality and past experience.

It is not until we discourage the use of gonadotropins without IVF by offering IVF as a regulated covered alternative will we eliminate risky multiple pregnancies. Until then, all of us including society, the government, insurance companies and employers are to blame for letting these dangerous multiple pregnancies occur.

Patients often seek my help, desperate to try In-Vitro Fertilization (IVF) after having a previous cycle cancelled at an outside clinic. These patients stimulated with fewer follicles and therefore due to their lower pregnancy expectations were not allowed to proceed. We presented our data on IVF performed on patients with 3 or fewer follicles at the American Society for Reproductive Medicine (ASRM) (insert hyperlink to www.asrm.org) in 2008. Our pregnancy rate was 15% for this group. Though this is admittedly low, for those who were successful in having a baby using their own eggs it was felt by them to be miraculous because they were either not allowed to cycle at other centers or had their cycles cancelled.

We counseled them regarding their lower odds for success but some elected to give it a try. Previously, most of these patients were offered Intra-Uterine Insemination (IUI), a much less successful option that does not affect the programs reportable pregnancy rates.

Unlike most other fields in medicine, IVF results are subject to public reporting since the passage of the Wyden Bill in 1992. The intent of the CDC (Center for Disease Control) report and SART (Society of Reproductive Technology) report was to help infertility patients by informing them of the relative success of different IVF programs. Unfortunately, what sometimes creates the best IVF statistical outcomes in pregnancy rates is not always what is in the best interest of the mother, child, family and society. Now that prospective patients are comparing pregnancy rates between programs there is a competitive pressure on these programs to produce the best reportable rates. This means that patients with lower odds of success are less likely to be offered IVF retrievals and are diverted to IUIs or donor egg cycles.

The high order multiple birth rate was also fueled by competition in the field to have the highest success rates. The Wyden Bill results in competitive pressure to transfer more embryos to increase pregnancy rate as reported. Despite the fact that there is evidence that a program can achieve similar live birth rates by transferring a single embryo each time, the Wyden Bill creates a disincentive to do so. It is no surprise that the clinics with the highest success rates have also had the highest triplet rates. Live birth rates are reported per fresh cycle and those from subsequent frozen embryo transfers are not included. It is true that live birth rates are reported for frozen embryo transfers separately but again it is per transfer motivating programs to transfer multiple embryos to enhance their success rates. If live birth rates were reported per fresh IVF stimulation and retrieval (that part of IVF with risk) including those conceived from subsequent frozen embryo transfers then programs would be likely to provide the less risky option of single embryo transfer to patients.

William Petok, Ph.D the Chair of The American Fertility Association’s Education Committee reported on Single Embryo Transfer (SET) “Single Embryo Transfer: Why Not Put All of Your Eggs in One Basket?” He stated that “at the ASRM meeting in November of 2008 … data was reported that looks favorably at SET. A Center for Disease Control researcher said that although multiple rather than single embryo transfer for in-vitro fertilization is less expensive in the short run, the risk of costly complications is much greater. Universal adoption of single embryo transfer would cost patients an extra $100 million to achieve the same pregnancy rates as multiple embryo transfer, but this approach would save a total of $1 billion in healthcare costs.”

The risks of prematurity and pregnancy complications are far higher in multiple pregnancies than in singleton pregnancies. The financial and emotional costs to families and society are enormous. These multiple pregnancies result in much longer hospitalizations, NICU admissions, complications resulting in handicapped children and occasionally death. They often do not have a happy end including increasing the incidence of divorce. So does it not behoove insurance companies to make IVF available in such a way that encourages SET? Should not the government enforce the recommendations of SART regarding the number of embryos to transfer?

At ECF, we have, since 2006 offered our Single Embryo Transfer program to cover the financial cost for transferring one embryo at a time. For the fee of one IVF cycle, we offer free cryopreservation, embryo storage and unlimited frozen embryo transfers until a patient achieves a live birth.

We offer MicroIVF, minimal stimulation IVF, for $3900, less than the cost of 2 IUIs with three times the success rate and ¼ the risk of hyper stimulation syndrome. Since minimal stimulation does not result in as many eggs, many programs are uncomfortable offering it and therefore lowering their reported pregnancy rates.

If we are going to report pregnancy rates with IVF as is required by the Wyden Bill, let us put all programs on the same playing field by enforcing the number of embryos to be transferred and promoting minimal stimulation IVF as a safer and more efficient treatment than IUI.

The Wyden Bill without the teeth to regulate such things as the number of embryos transferred and reporting success per stimulation and retrieval and not by isolated embryo transfer does more harm than good. Let us support efforts to reduce the number of embryos transferred by removing the added costs to the patient of cryo-preservation, storage and subsequent frozen embryo transfers and by absorbing them ourselves as a profession. This will go a long way in eliminating multiple birth pregnancies, and will do the right thing for the patients, their families and for society. It’s time for us doctors to “Man Up”.

Dr. Panayiotis Zavos

Source: www.ivf.net

Fertility doctor denounced for claims of human cloning

First Octomom and now this. I get the impression there are fertility specialists out to ruin the reputation of IVF for the rest of us. In the case of octomom, there is some question as to how the patient was counselled. We focus on high success with least risk as possible. It is unfortunate that a few others aspire to something other than their patient’s best interests. It is very difficulty for a fertility specialist to deal with patients who insist on using up all their embryos in one attempt. We share with the patient a desire not to discard embryos but retain responsibility for not allowing for potentially dangerous outcomes.

Cloning is an ethical dilemma yet to be solved by society. Until then we do not participate in cloning since we are unsure whether to do so is ethically sound. Benefits of modified forms of cloning have been proposed. Multiplying high quality embryos in patients would theoretically increase their success rates. Women who had poor quality eggs (cytoplasm) could have their nuclei transplanted into the egg of a healthy young woman. Again, theoretically, this can improve success rates. Another proposed clinical use is to produce tissue for transplantation say in a child with cancer who requires chemotherapy.

The form of cloning that usually comes to mind however, is the creation of an identical being whether it be to replace a loved lost child or in our common vernacular a “minime”. It is this possible use of the technology that causes almost universal disdain in our society. We have yet to figure out whether there is a place for any of the aforementioned forms of cloning that is potentially more palatable.

IVF, is a clinically useful form of technology that is allowing for greater than 40,000 more babies to be born each year who may otherwise never have been given life. But, as with all technology there are risks and potential downsides that need to be considered. Today, cloning as well as high ordered multiple embryo transfers moves the IVF technology beyond our comfort zone with our assessment of the potential risks and downsides. Let us not distort the relative benefit vs. risk of IVF technology by wrongfully applying it to cloning or high order multiple embryo transfer.

Nadya Suleman

The American public has been stunned by the news of a mother of six giving birth to octuplets. This shocking news is compounded by the stories broadcast by the mass media regarding the woman’s family situation and that she used IVF for these pregnancies.

Physicians have known for many years the dangers of multiple pregnancies and have worked steadily to formulate evidence‐based guidelines for the number of embryos to transfer in IVF cycles. The current rate of triplets in IVF cycles nationally has dropped in 2005 to only 2% of cycles. At East Coast Fertility our triplet rate has been below 1% since 2002 and not one of these occurred from transfer of more than 2 embryos. In fact a financial incentive is offered to patients to transfer a single embryo. Cryopreservation of embryos is offered for free as well as storage for up to 1 year. In addition, up to 3 frozen embryo transfers are offered for free until a baby is born. Patients are encouraged by this program not to put all their eggs in one basket. Unfortunately, this was not the case for this woman. Success rates with IVF, especially, in the good prognosis patients exceed 50% even when 1 or 2 embryos are transferred. It is hard to imagine a situation where it would make sense to take such an extraordinary risk like was done in this case in California.

We should keep this case in mind when considering how many embryos to transfer. It is rarely worth the risk to put more embryos back when one can alternatively keep the embryos in frozen storage until a patient is ready to conceive again.