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?

Father Thomas Berg, Executive Director of the Westchester Institute for Ethics and the Human Person, said the recent case of a woman implanted with an embryo from another couple was the sort of “tragic mistake” that can happen” in “the unregulated world of IVF.” I agree that mixing up gametes and embryos is tragic and society must do everything humanly possible to prevent such a mix up except disallow the practice of IVF. As with other societal advances, accidents have rarely and unfortunately happened in the field of IVF but, weighed against the benefit of all the babies who otherwise would never have been born, we should improve the safety of IVF, not eliminate it.

Many of the greatest advances have had tragic results, ones that are unintended accidents that should have been avoided. Usually, they are the result of lapses in the most carefully designed safeguards of checks and balances.

Significant risk, including that of injury or death, is part of nearly everything we do in life today. The construction industry has always been plagued with accidental deaths. Not a bridge or a great high rise has been completed without misfortune. Do we stop construction? No, we ensure that all possible regulations that could protect those involved are in place and followed as strictly as possible to prevent further accidents.

In the Finance industry, society has recently suffered from scams, the worst being the Madoff ponzi scheme. Charities are facing potential ruin with significant direct financial and emotional impact on thousands of lives. Rules and regulations have been reviewed since and policies are currently changing to avoid such disasters from recurring.

Nuclear power is controversial because of the fear of accidents. Despite past accidents at Chernobyl and Three Mile Island, nuclear power plants continue to be constructed throughout the world because it is perceived that the possible benefits of this alternate source of energy outweighs the concerns for the risks.

People are electrocuted by power lines several times a year. Yet we do not consider living without electricity. We search for ways to make it safer to live without causing an accident.

Fast food leads to obesity and increased risks of developing heart disease. Yet we offer it in stores and restaurants because it’s a convenience many people are willing to accept, despite the obvious danger to their health.

Cardiac bypass surgery and other surgeries saves lives but, occasionally, patients intended to benefit are hurt or even killed accidentally. Rules and regulations are instituted to avoid problems such as performing the wrong operation on the wrong patient, using the wrong medication, operating on the wrong limb. Yet situations occur, usually because of a human slip. Rules are broken and mistakes result.

Just as we have safeguards in the operating room, we have them in place for identifying gametes and embryos with checks and balances that should prevent a mix up such as this one case in the news recently.

In the operating room, patients are identified while they are awake by the embryologist, nurse, physician and anesthesiologist by full name and birth date. As soon as the ovaries are aspirated, the eggs are identified and put in dishes with the patient’s full name and birth date on them. When the dishes are changed to replace the media, again matching names are put on the new dishes with a unique case number. A partner’s sperm specimen is labeled by him and processed in tubes labeled to match the partner’s name and the corresponding patient’s name and the case number. This is doubly checked with the patient’s record which will also reflect the unique case number. It is reviewed by two embryologists for accuracy prior to fertilization. Finally, when the embryo is loaded in a catheter for transfer, the identity of the dish from the embryo is checked by the physician, embryologist, nurse and the patient herself prior to the transfer being performed.

Every attempt is made to confirm the identity of the gametes and embryos throughout the IVF process prior to transfer. In 24 years of practicing IVF, my program has not mixed up gametes or embryos.

There are approximately 1 million babies born through IVF and only a few rare mix ups reported.

Perhaps we don’t hear about every mix ups? I’d estimate that between 1/50,000 and 1/100,000 pregnancies from IVF have occurred with some mix up in the embryo or gamete. When it occurs, it is tragic and requires the attention of our field and a refocus on those checks and balances we have in place to prevent such mishaps.

I work hard and I pray that we do everything possible so that this never happens again. The FDA regulates gamete donation. The New York State Department of Health regulates our labs and our operating rooms. These checks and balances are in place and are included in the monitoring performed by these agencies.

Perhaps, if the other states required as strict a monitoring to ensure their clinics and doctors are adhering to the necessary safeguards as well then the mix ups would not occur?

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Dr. David Kreiner is the Director of East Coast Fertility, a multi-office practice on Long Island, New York. You can learn more about Dr. Kreiner and his practice here.

Octomom was a result of IVF with an embryo transfer of six embryos. This far exceeds the number that the Society of Assisted Reproductive Technology (SART) has recommended as the limit. 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..

However, the Tunisian woman who is expecting six male and six female babies conceived using gonadotropins in combination with insemination. Unfortunately, one does not have the same control with insemination as you do with IVF. As many eggs as is stimulated by the gonadotropin injections can implant with intrauterine insemination (IUI) or without the benefit of retrieval of the eggs as one performs as part of the IVF procedure. With IVF one can limit the number of embryos transfered to a woman’s uterus. Insuance companies do not typically cover IVF but are more likely to cover IUIs. However, if one considers the cost of multiple pregnancy; including hospitalization for mother and babies born prematurely requiring the neonatal intensive care unit (NICU) and care for babies born handicapped, it would be a lot cheaper for insurance companies and employers, the government and society to cover IVF and have the control to prevent these high risk multiple pregnancies.

The dozen babies happened because the safer alternative, IVF was not performed. Gonadotropins without IVF are dangerously risky due to this lack of control over how many eggs may fertilize and implant. Society, the government and insurance companies in partnership with employers discourage IVF yet encourage gonadotropin therapy without the protection of IVF. They are at fault since they deny women coverage of IVF services. If IVF was covered by their insurance, physicians would not need to administer gonadotropins in such a dangerous and risky way. Perhaps gonadotropin treatment without IVF should be illegal or at least have very strict regulations regarding its use. Again, if IVF is a covered alternative who would not choose the safer more successful treatment?

That brings us to regulating how many embryos to transfer as Octomom went through IVF with transfer of six embryos. At East Coat Fertility, 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 for patients in the Single Embryo Transfer Program. In addition, patients may return for their frozen embryo transfers for free until a baby is born. Patients are encouraged by this program not to put all their eggs in one basket. Success rates with a fresh single embryo transfer with IVF at our program, is nearly 50%.

If IVF were a covered service as I recommend to avoid the dangers of uncontrolled gonadotropin use without IVF than we need to regulate how many embryos are transferred. The SART recommendations regarding the number to transfer should be law to prevent such aberrations as Octomom from happening. There is flexibility built into the recommendations taking into account critical factors such as patient age and embryo quality. One can even factor in past experience.

I believe it is not until we discourage the use of gonadotropins without IVF by offering IVF as a regulataed 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

Cryopreserved Embryos

At East Coast Fertility, we are realizing the Jones’ dream of safer, more efficient and cost effective IVF. By utilizing the ability to cryopreserve embryos in 2007, 61.5% (118/192) of patients under 35 were successful in having a live birth as a result of only one egg stimulation and retrieval cycle! In addition, because of our outstanding Embryology Laboratory, we are usually able to transfer as few as 1 or 2 high quality embryos per cycle and avoid risky triplet pregnancies. In fact, since 2002, the only triplet pregnancies we have experienced have resulted from the successful implantation of two embryos, one of which goes on to split into identical twins (this is rare!). By cryopreserving embryos in certain high-risk circumstances, we are able to vastly reduce the risk of ovarian hyperstimulation syndrome requiring hospitalization. At East Coast Fertility, safety of our patients comes first. Fortunately, our success with frozen embryo transfers is equivalent to that of fresh embryo transfers, so that pregnancy rates are not compromised in the name of safety, nor are the babies.

Today, as reported in the Daily Science: “The results are good news as an increasing number of children, estimated to be 25% of assisted reproductive technology (ART) babies worldwide, are now born after freezing or vitrification” (a process similar to freezing that prevents the formation of ice crystals).

The study, led by Dr Ulla-Britt Wennerholm, an obstetrician at the Institute for Clinical Sciences, Sahlgrenska Academy (Goteborg, Sweden), reviewed the evidence from 21 controlled studies that reported on prenatal or child outcomes after freezing or vitrification.

She found that embryos that had been frozen shortly after they started to divide (early stage cleavage embryos) had a better, or at least as good, obstetric outcome (measured as preterm birth and low birth weight) as children born from fresh cycles of IVF (in vitro fertilisation) or ICSI (intracytoplasmic sperm injection). There were comparable malformation rates between the fresh and frozen cycles. There were limited data available for freezing of blastocysts (embryos that have developed for about five days) and for vitrification of early cleavage stage embryos, blastocysts and eggs.

‘Slow freezing of embryos has been used for 25 years and data concerning infant outcome seem reassuring with even higher birthweights and lower rates of preterm and low birthweights than children born after fresh IVF/ICSI. For the newly introduced technique of vitrification of blastocysts and oocytes, very limited data have been reported on obstetric and neonatal outcomes. This emphasises the urgent need for properly controlled follow-up studies of neonatal outcomes and a careful assessment of evidence currently available before these techniques are added to daily routines. In addition, long-term follow-up studies are needed for all cryopreservation techniques,’ concluded Dr Wennerholm.

The use of frozen embryos has become a common standard of care in most IVF Programs. At East Coast Fertility we are able to keep multiple pregnancy rates down – by only transferring one or two embryos at a time – while allowing patients to hold on to the additional embryos that they may have created during the fresh cycle. It is like creating an insurance plan for patients. We developed a unique financial incentative program using the technology of cryo-preservation to encourage patients to transfer only one healthy embryo at a time. In order to ensure the best out come for mother and child – these special pricing plans take the burden off the patient to pay for the additional transfers and the cryo- preservation process. We have eliminated the cost of cryopreservation, storage and embryo transfer for patients in the single embryo transfer program. Thus, patients no longer have that financial pressure to put all their eggs in one basket! We truly believe we are practicing the most successful, safe and cost effective IVF utilizing cryopreservation.

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.