We are approaching a time that freezing eggs will be a standard option for an IVF program much like Embryo freezing is today.  Despite the fact that hundreds of babies have been born apparently without an increase in defects or abnormalities, the American Society for Reproductive Medicine (ASRM) has proclaimed that Egg freezing is still considered experimental.

This is not just a scientific decision but is a philosophical and political one as well.  In the 1980’s, IVF was being performed likewise on an experimental basis.  Insurance companies denied that it had become standard of care until recently.  In fact, there are insurance providers who in an effort to deny claims continue to call IVF experimental despite the million babies already born without significant increases in abnormalities or defects noted.  However, the ASRM is afraid to push the envelope and take a risk that may make them appear to be promoting a procedure that could theoretically be associated with increased problems with the children created after egg freezing.

But why should we be interested in egg freezing anyway when we have IVF that is successful and known to be relatively safe after 33 years of experience?  The reasons are multiple.  A young woman who develops cancer and will have radiation therapy or chemotherapy that may affect her eggs or have her ovaries removed would with egg freezing have an option to preserve her fertility and still have her cancer treated.  In the past, the loss of a woman’s future ability to bear children was sometimes more emotionally depressing for her than the cancer itself.  The prospect of offering hope to such affected women is spreading throughout the community in part through the efforts of the Lance Armstrong Fund supported group, Fertile Hope.  They are attempting to educate not just affected individuals but oncologists and other physicians who come into contact with patients who may be able to take advantage of new IVF technologies to preserve their fertility while undergoing cancer treatment.

Another great potential use for frozen eggs is in the donor egg program.  Currently, our egg donors go through fresh IVF cycles coordinated in time with the recipients so that the eggs are fertilized fresh when they are retrieved.  This is highly successful in achieving pregnancies in approximately 80% of donations.  However, cycles can be delayed in trying to synchronize patients.   If programs can achieve similar success rates using frozen eggs it will allow recipient patients to choose donor eggs much like they select donor sperm today.

Yet, another benefit of the ability to bank frozen eggs is for women who either because of their career or lack of finding a suitable partner need to put off their childbearing until a time when they would otherwise put their future fertility at significant risk.  This is a more controversial use of this technology but a practical concern for countless women today for whom conceiving before age 35 is unrealistic.

Needless to say, egg freezing will be a great benefit for many when it becomes a safe acceptable IVF standard.  That time for consideration by patients is rapidly approaching and is something that the public needs to be made aware of.

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?

The case of a mix-up of frozen embryos in a Michigan IVF program in Feb. 2009 yet again became a media splash with the affected couple appearing on ABC News to promote their new book, “Misconceptions”.  The couple who already had a set of twins as a result of a successful IVF recounts a story about their experience including the fact that the frozen embryos were mistakenly transferred into the wrong woman.  This woman carried the pregnancy and after delivery handed the baby back to his biological parents.  Reports of the mix-up have triggered calls from a few to make IVF illegal.

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 strive to improve the safety of IVF, not eliminate it.

Many of the greatest advances have had tragic results, unintended accidents that should have been avoided. Usually, they are the result of human error often preventable with the institution of carefully designed safeguards with a system 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.

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.

Cardiac bypass surgery and other surgeries save lives and relieve suffering 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 rarely occur, usually because of a human slip. Rules are broken and mistakes result.  When they do hospitals review the procedures and protocols and insure a sufficient system is in place to catch errors before they have an effect on patient care.

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 the one in this case.

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 25 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 up. 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.

Successful IVF is dependent on many factors.  The quality of the egg and embryo, the placement of the embryo into the uterus and the environment surrounding implantation are all paramount to the ultimate goal of creating a pregnancy that leads to a live baby.

Typically, patients present with their own gametes so the genetics and pregnancy potential of the eggs and sperm is usually predetermined when patients first present to an IVF program.  As a specialist in REI and IVF, I have dedicated my career to optimizing those other factors that we may influence.

In the late 1990’s I recorded data on all my embryo transfers including distance the catheter tip was placed into the uterine cavity, number of cells and grade of the embryos, difficulty of the transfer, use of tenaculum etc.  I presented my results at the ASRM in 2000 that highlighted the two step transfer to the middle of the uterine cavity and replaced the tenaculum with a cervical suture when needed and this radically improved pregnancy rates.

The uterine environment has been optimized through screening for anatomic issues in the uterine cavity with a hydrosonogram to identify polyps, fibroids and scar tissue that may impede implantation.  Hormonally, we have supplemented patient’s cycles with progesterone through both vaginal and parenteral (intramuscular) administration as well as estrogen that we monitor closely after embryo transfer and make adjustments when deemed helpful.

The greatest improvement in pregnancy rates for the past several years however has been due to a Culture Revolution in IVF that is the media environment bathing and feeding the embryos.  All these advances have had a great impact on IVF success rates to the point that 50% of retrievals will result in a pregnancy.  Unfortunately, older patients and some younger ones have yet to share in this success.

Many IVF programs have reintroduced the concept of utilizing a co-culture medium to improve the quality and implantation of embryos. Co-culture is a procedure whereby “helper” cells are grown along with the developing embryo. Today, the most popular cell lines include endometrial cells (from the endometrium, or uterine lining) and cumulus cells from women’s ovaries.  Both cell lines are derived from the patient, thereby eliminating any concerns regarding transmission of viruses. Endometrial cells are much more difficult to obtain and process, while cumulus cells are routinely removed along with the oocytes during IVF retrieval.

Cumulus cells play an important role in the maturation and development of oocytes.  After ovulation cumulus cells normally produce a chemical called Hyaluronan.   Hyaluronan is secreted by many cells of the body and is involved in regulating cell adhesion, growth and development. Recent evidence has shown that Hyaluronan is found normally in the uterus at the time of implantation.

Co-culture of cumulus cells provides an opportunity to detoxify the embryo’s culture medium that the embryos are growing in and produce growth factors important for cell development.  This may explain why some human embryos can experience improved development with the use of co-culture.

Preparation of co-culture cells starts with separation of the cumulus cells from the oocytes after aspiration of the follicles. These sheets of cells are washed thoroughly and then placed in a solution that permits the sheets to separate into individual cells.  The cells are then washed again and transferred to a culture dish with medium and incubated overnight. During this time individual cells will attach to the culture dish and create junctions between adjoining cells. This communication is important for normal development. The following morning, cells are washed again and all normally fertilized oocytes (embryos) are added to the dish. Embryos are grown with the cumulus cells for a period of three days to achieve maximum benefit.

Performing co-culture of embryos has improved implantation and pregnancy rates above and beyond those seen with the IVF advances previously described. More importantly, it promises to offer advantages for those patients whose previous IVF cycles were unsuccessful.

Pre-embryo genetic screening (PGS) was developed to help weed out embryos containing inherited metabolic disorders and genetic abnormalities prior to implantation. It was thought that PGS could be used to minimize the risk of miscarriage and perhaps even increase live birth rates in older women IVF undergoing .

We have thus far been disappointed in our results obtained using the FISH technique, the procedure performed for PGS for the past decade and a half. But an alternative new technology that was recently developed makes me very excited about PGS once again: Array Comparative Genomic Hybridization (aCGH).

ACGH is a technique actually applied to detect deficiencies and excesses of genetic material in the chromosomes. DNA from a test sample and a normal reference sample are labeled using colored fluorophores that hybridize to several thousand probes. These probes are created from most of the known genes of the genome and placed on a glass slide.

The differential color of the test compared to the normal sample DNA reflects the amount of DNA in the test specimen. It can pick up monosomies, trisomies or significant deletions on an embryo’s chromosomes.

The first baby born from this procedure was in September 2009 to a 41-year old woman. When aCGH is performed on a Blastocyst biopsy, it is effective in screening out mosaicism (mixed cell lines in the same organism). ACGH is 20 percent more sensitive than the best FISH assays with an error rate of two to four percent. Fifty percent of the embryos tested were normal with pregnancy rates exceeding Blast transfers without aCGH screening.

So, who could benefit from using this new technology?

1. Patients with repeat miscarriages can eliminate up to 90 percent of their miscarriages.

2. Older patients who naturally have a higher percentage of genetically abnormal embryos may now screen for and only transfer their normal embryos.

3. Patients who want to maximize their success with a single embryo transfer.

4. Patients who have experienced repeat implantation failure can be screened for genetically abnormal embryos.

This technology is available for about the same cost as the FISH procedure yet, since it is performed on a Blastocyst, it is safer with less effect on the integrity of the embryo and without significant risk of wrongly identifying abnormal embryos. A concern with FISH is that embryos identified as abnormal can actually result in a normal fetus. This risk is practically eliminated with aCGH and is another reason making it more successful.

I expect PGS will now become a commonly used addition to standard IVF to promote more successful single embryo transfer, improve success in older patients, eliminate miscarriages and treat patients with repeat implantation failure.

We are approaching a new era in IVF. Brace yourselves for a thrilling ride into IVF’s future.

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.

IVF

After eggs are retrieved, they are transferred to the embryology laboratory where they are kept in conditions that support their needs and growth. The embryos are placed in small dishes or tubes containing “culture medium,” which is special fluid developed to support development of the embryos made to resemble that found in the fallopian tube or uterus. The dishes containing the embryos are then placed into incubators, which control the temperature and atmospheric gasses the embryos experience.

A few hours after eggs are retrieved, sperm are placed in the culture medium with the eggs, or individual sperm are injected into each mature egg in a technique called Intracytoplasmic Sperm Injection (ICSI) (see below). The eggs are then returned to the incubator, where they remain to develop. Periodically over the next few days, the dishes are inspected so the development of the embryos can be assessed.

The following day after eggs have been inseminated or injected with a single sperm (ICSI), they are examined for signs that the process of fertilization is underway. At this stage, normal development is evident by the still single cell having 2 nuclei; this stage is called a zygote. Two days after insemination or ICSI, normal embryos have divided into about 4 cells. Three days after insemination or ICSI, normally developing embryos contain about 8 cells. Five days after insemination or ICSI, normally developing embryos have developed to the blastocyst stage, which is typified by an embryo that now has 80 or more cells, an inner fluid-filled cavity, and a small cluster of cells called the inner cell mass.

It is important to note that since many eggs and embryos are abnormal, it is expected that not all eggs will fertilize and not all embryos will divide at a normal rate. The chance that a developing embryo will produce a pregnancy is related to whether its development in the lab is normal, but this correlation is not perfect. This means that not all embryos developing at the normal rate are in fact also genetically normal, and not all poorly developing embryos are genetically abnormal. Nonetheless, their visual appearance is the most common and useful guide in the selection of the best embryo(s) for transfer.

In spite of reasonable precautions, any of the following may occur in the lab that would prevent the establishment of a pregnancy:

- Fertilization of the egg(s) may fail to occur.
- One or more eggs may be fertilized abnormally resulting in an abnormal number of chromosomes in the embryo; these abnormal embryos will not be transferred.
- The fertilized eggs may degenerate before dividing into embryos, or adequate embryonic development may fail to occur.
- Bacterial contamination or a laboratory accident may result in loss or damage to some or all of the eggs or embryos.
- Laboratory equipment may fail, and/or extended power losses can occur which could lead to the destruction of eggs, sperm and embryos.
- Other unforeseen circumstances may prevent any step of the procedure to be performed or prevent the establishment of a pregnancy.
- Hurricanes, floods, or other ‘acts of God’ (including bombings or other terrorist acts) could destroy the laboratory or its contents, including any sperm, eggs, or embryos being stored there.

Quality control in the lab is extremely important. Sometimes immature or unfertilized eggs, sperm or abnormal embryos (abnormally fertilized eggs or embryos whose lack of development indicates they are not of sufficient quality to be transferred) that would normally be discarded can be used for quality control. You are being asked to allow the clinic to use this material for quality control purposes before being discarded in accordance with normal laboratory procedures and applicable laws. None of this material will be utilized to establish a pregnancy or a cell line unless you sign other consent forms to allow the clinic to use your eggs, sperm or embryos for research purposes. Please indicate your choice below:

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.

Success varies with many factors. The age of the woman is the most important factor, when women are using their own eggs. Success rates decline as women age, and success rates drop off even more dramatically after about age 37. Part of this decline is due to a lower chance of getting pregnant from ART, and part is due to a higher risk of miscarriage with increasing age, especially over age 40. There is, however, no evidence that the risk of birth defects or chromosome abnormalities (such as Down’s syndrome) is any different with ART than with natural conception.

Success rates vary with the number of embryos transferred. However, transferring more embryos at one time not only increases the chance of success with that transfer, but will also increase the risk of a multiple pregnancy, which are much more complicated than a singleton pregnancy. The impact of the number of embryos that are transferred on success rates also varies with the age of the woman.

Pregnancy complications, such as premature birth and low birth weight, tend to be higher with ART pregnancies, primarily because of the much higher rate of multiple pregnancies. Nationally, in 2002-2003 about 30% of ART deliveries were twin deliveries, versus 1-2% of spontaneous pregnancies. The risk of pregnancy containing triplets or more was 6% in 2003.

As women get older, the likelihood of a successful response to ovarian stimulation and progression to egg retrieval decreases. These cycles in older women that have progressed to egg retrieval are also slightly less likely to reach transfer.  The percentage of cycles that progress from transfer to pregnancy significantly decreases as women get older.  As women get older, cycles that have progressed to pregnancy are less likely to result in a live birth because the risk for miscarriage is greater.  This age related decrease in success accelerates after age 35 and even more so after age 40.  Overall, 37% of cycles started in 2003 among women younger than 35 resulted in live births. This percentage decreased to 30% among women 35–37 years of age, 20% among women 38–40, 11% among women 41–42, and 4% among women older than 42.  The proportion of cycles that resulted in singleton live births is even lower for each age group.

The success rates vary in different programs in part because of quality, skill and experience but also based on the above factors of age, number of embryos transferred and patient population.  Patients may also differ by diagnosis and intrinsic fertility which may relate to the number of eggs a patient may be able to stimulate reflected by baseline FSH and antral follicle count as well as the genetics of their gametes.  These differences make it impossible to compare programs.

Another factor often overlooked when considering one’s odds of conceiving and having a healthy baby from an IVF procedure is the success with cryopreserved embryos.

Thus, a program which may have a lower success rate with a fresh transfer but much higher success with a frozen embryo transfer will result in a better chance of conceiving with only a single IVF stimulation and retrieval.  Success with frozen embryos transferred in a subsequent cycle also allows the program to transfer fewer embryos in the fresh cycle minimizing the risk of a riskier multiple pregnancy.  It may be more revealing to examine a program’s success with a combination of the fresh embryo transfer and frozen embryo transfers resulting from a single IVF stimulation and transfer.  For example, at East Coast Fertility, the combined number of fresh and frozen embryo transfers that resulted in pregnancies from January 1, 2005 to April 2006 was.  The number of retrieval during that time was.  The success rate combining the fresh and frozen pregnancies divided by the number of retrievals was 77.2%.  The high frozen embryo transfer pregnancy rate allowed us to transfer fewer embryos so that there were 0 triplets from fresh transfers during this time.

What can I do to increase my odds?

Patients often ask if there are any additional procedures we can do in the lab that may improve the odds of conception.  Assisted hatching is the oldest and most commonly added procedure aimed at improving an embryo’s ability to implant.  Embryos must break out or hatch from their shell that has enclosed them since fertilization prior to implanting into the uterine lining.  This can be performed mechanically, chemically and most recently by utilizing a laser microscopically aimed at the zona pellucidum, the shell surrounding the embryo.  Assisted hatching appears to benefit patients who are older than 38 years of age and those with thick zonae.

Recently a protein additive called “Embryo glue” was shown to improve implantation rates in some patients whose embryos were transferred in media containing “Embryo glue”.  Time will tell if the adhesive effect of this supplement is truly increasing success rates and warrants wide scale use in IVF programs.

Embryo co culture is the growth of developing embryos is the same Petri dish as another cell line.  Programs utilize either the woman’s endometrial cells obtained from a previous endometrial biopsy or granulosa cells obtained at the time of the egg retrieval from the same follicles aspirated as the eggs.  Growth factors produced by these endometrial and granulosa cell lines diffuse to the developing embryo and are thought to aid in the growth and development of the embryo.  It appears to help patients who have had previous IVF failures and poor embryo development.