The IVF marathon

A recent study from England published in the Journal of the American Medical Association has gained a lot of media attention because it addresses a question of how many cycles of In Vitro Fertilization a couple should attempt before finding success or succumbing to failure.  This study is notable because it follows over 150,000 UK women over a period of time from 2003 to 2012.  The large size of the study suggests that the findings could be applicable to the broader IVF population.  The most striking finding of the study was that success rates did not seem to drop dramatically until a fourth failed cycle and that pregnancies could be achieved up to the ninth attempt at IVF!  We know that this level of psychological, emotional and financial commitment required to continue along multiple IVF cycles is astounding!  

Media outlets have focused on the concept that IVF does not always work out the first time, and multiple cycles might be required.  While this is interesting, it is not necessarily ground breaking news.  We should be focused on improving the chances that we are successful in the first or second cycle and trying to avoid these "marathon" treatments.  Prior studies have demonstrated that the most common reason why patients drop out of treatment is the psychological and physical burden of IVF.  How can we limit this burden for our patients?  IVF can be an inefficient process as we are focused on obtaining multiple eggs and choosing the best embryo out of the bunch.  That embryo selection process is an essential component of helping couples be successful earlier in their treatment.  At RMANJ we have championed the use of extended embryo culture to grow embryos in the laboratory further so that their true reproductive potential becomes clear.  We have also pioneered the use of Comprehensive Chromosomal Screening (CCS) to choose embryos that have the correct genetic makeup and have the highest chances for success.  Our goal is to achieve a pregnancy in the shortest time possible, maximizing the reproductive potential of our couples.

At the end of the year, our IVF laboratory takes a break to prepare for a fresh start to the new year.  It is a good time to reflect on what we have accomplished and the work that lies ahead.  Like training for a marathon, it is essential that we prepare for the upcoming IVF cycles.  Our job is to prepare our patients for this journey and to set appropriate expectations.  Their focus should be on preparing their mind and body for the process ahead.  It is essential that our patients feel their best going into a treatment cycle.  I tell patients to focus on readying themselves by eating right, seeing a nutritionist, getting exercise, using alternative therapies like accupuncture and yoga to be ready for the road ahead.  Together our goal should be to train for that IVF marathon.  While not every IVF cycle turns out to be successful, we are fortunate that most of our patients are able to conceive eventually.  I hope that when this study is repeated again five years from now we can say that the time to pregnancy is shorter, that the heartache is less and that our successes have multiplied.  Until then, we will focus on making a difference one cycle at a time, one embryo at a time and one healthy baby at a time.

Genetic Counseling - Is it for me?

RMANJ has always been strong advocates for genetic counseling.  We believe that every couple looking to conceive should investigate whether they are at an increased risk to have a child with a genetic disorder.  In a short phone call or office visit, these risk factors can be identified and further investigated.  This means we can prevent or reduce your chances of having a child with a genetic disorder through the use of IVF and Preimplantation Genetic Testing.  See below for a nice FAQ modified from the National Society of Genetic Counselors...

1. Who should get genetic testing?

Patients who are looking to conceive should be offered preconceptualgenetic testing.  A consultation with a genetic counselor can identify whether the couple are at an increased risk for having a baby with a genetic disease and which tests should be offered.  Individuals with strong family histories of inherited diseases or specific cancers should also seek a consultation with a genetic counselor to see if there is a genetic cause.

2.    What conditions/diseases can be tested?

As the field of genetic medicine has evolved, our understanding of the genetic basis of diseases has increased exponentially.  Over 100 genetic diseases can be tested from a single tube of blood.  Many of these are extremely rare, however common diseases such as cystic fibrosis, tay sachs disease, fragile X syndrome and others are important to identify in couples seeking to conceive.  The BRCA genes are important causes for breast and ovarian cancer that can be identified.  There are other hereditary cancers which can also be identified.

3.    What criteria do experts use when referring patients for genetic testing?

Unfortunately, there is still some debate as to who benefits most from genetic testing.  At RMANJ, we offer every couple seeking to conceive the opportunity to speak with a genetic counselor who is best qualified to discuss which diseases a couple might be at risk to carry and what tests they should consider.  

4.    How can genetic testing help patients just by knowing that they’re carrying that gene?

If an Individual is found to carry a gene that predisposes them to a certain disease, such as cancer, early intervention may help prevent severe forms of the disease.  For couples looking to conceive, many of these conditions are Recessive, which means that they do not show symptoms of the disease but merely carry it.  Since we have two copies of each gene , a good copy can protect an individual and prevent disease.  When both members of a couple are carriers of a disease there is a 25% chance they will both contribute the bad copy to their child which will result in illness.  

A person’s risk for developing these diseases is specific based on their individual family history and ethnic background.  Speaking with a genetic counselor may help identify what diseases you may be at a higher risk to develop and any genetic testing which may help. 

If a couple is identified to be carriers of a recessive disease, In Vitro Fertilization with Preimplantation Genetic Diagnosis can virtually eliminate their chances of having a sick child.  In this process, sperm and eggs are brought into the laboratory and embryos are created which can then be tested to identify which embryos are healthy and which carry the disease.  PGD has made it possible to virtually eliminate these types of diseases when couples are properly screened and identified as carriers.

5.    What do genetics counselors do?

Genetic counselors are specially trained healthcare professionals with backgrounds in medical genetics and counseling.  These individuals can identifygenetic causes of diseases in indivuals presenting with a disease.  They can also identify families that carry a genetic disease or couples at high risk to have a child with a genetic disease.  Genetic counselors will speak with a patient, asking them questions about their family history and ethnic background to identify what they may be at risk to carry.  Genetic testing can be offered and genetic counselors will be able to counsel on what risk an individual carries for developing or passing on a genetic disease.

6.    Is genetic testing covered by health insurance?

Most health insurances cover basic genetic testing for couples seeking to conceive.  Each health insurance plan is different, so it is best to check with your provider.

7.    Does getting tested open a can of bad worms?

Part of ordering a test is knowing what do to with the results.  In some cases knowing you havea predisposition to a disease like cancer may cause psychological stress.  It also may prompt your physician to order extra testing which can be time consuming and expensive.  However, the potential upside for early detection of a disease or for preventing the birth of a child with a fatal genetic condition may outweight these risks.  It is a careful balance that should be considered but genetics are the future of medicine and will likely allow us to live longer, healthier lives.  

Fresh or Frozen?

In the last few days. much has been written about the lower success rates of using frozen donor eggs over fresh.  It is not surprising that fresh eggs have a significantly higher success rate.  Our group at RMANJ published a study on this several years ago looking at sibling oocytes from the same woman.  We demonstrated that the survival of frozen eggs was approximately 82% and that there were approximately one third fewer viable blastocysts.  These embryos were just as likely to have to the correct number of chromosomes and just as likely to result in a successful pregnancy.  Therefore, it is not surprising that frozen donor egg cycles are less successful - fresh eggs are more efficient at generating viable embryos, offering a better chance at pregnancy. 

However, after a few years of using frozen donor eggs, it is clear that they have their place.  Most egg banks provide their eggs in bundles of 6 or 8, thereby lowering the cost for the patient without insurance coverage.  For most patients, a treatment cycle with frozen donor eggs is half the cost of fresh donor eggs.  Even though we start off with fewer eggs, the majority of cycles result in one or two viable blastocysts.  This translates into pregnancy rates over 55-60% per transfer!  Perhaps more importantly is that couples can begin treatment almost immediately.  There are no wait list or schedules to coordinate.  A couple can order their eggs and begin treatment within weeks instead of months.  For some couples, this is an important distinction.  As little as 10 years ago, the concept of freezing oocytes was not possible with survival rates of 25 to 30%.  We should be celebrating the fact that frozen donor eggs have success rates that are similar, although not quite as good to fresh donor eggs!

At RMANJ we have sought to provide a multitude of options for our patients who wish to conceive.  The concept of frozen donor eggs has evolved over time and clearly has its place.  Moving to donor eggs is a difficult decision and one that many couples agonize over.  It is essential that couples understand their reproductive options and choose the treatment that maximizes the potential use of their emotional, psychological and financial resources.  

Too Much of a good Thing

As you might have heard, the Gardner quadruplets were delivered yesterday nearly 2 ½ months premature (http://www.cnn.com/2014/12/29/living/feat-ivf-mom-gives-birth-quads/index.html?hpt=hp_c3_ ).  While we certainly wish this family the best, babies born before 30 weeks have a tough start and will likely spend several weeks in Neonatal Intensive Care.  There has been a  lot of publicity surrounding this particular couple’s infertility struggle which culminated in a quadruplet pregnancy after two embryos were transferred and both split during IVF.  This is an extremely rare occurrence and hopefully the outcome will still be good for this family. 

Having twins after IVF is not a rare occurrence and often leads to similar premature deliveries.  These pregnancies aren’t followed by national media outlets because they happen too often.  The Gardner’s story should serve to highlight the problem of multiple pregnancy from multiple embryo transfer.  In years past, the ability to select which embryo(s) might deliver a healthy baby was poor and in order to compensate, doctors transferred multiple embryos, hoping that at least one might stick.  Sometimes, more than one implanted and IVF became synonymous with multiple pregnancy.  In recent years, better embryo culture and selection with the help of Comprehensive Chromosomal Screening has made single embryo transfer a viable option.  At RMANJ we have transferred one embryo in nearly 2/3 of our IVF cycles in 2014.  This means that we have helped reduce the burden of prematurity from twin pregnancies for our families.  It also means we have work to do to get that remaining third of our cycles to use one embryo at a time. Our medical and research staff will be working hard throughout 2015 to improve our ability to select and transfer one embryo at a time.  We won’t rest until the dream of a single embryo transfer and a single healthy baby becomes a reality for all our patients.

A new paradigm for IVF with single embryo transfer

Our group has been advocating the use of comprehensive chromosomal screening for some time.  

Here's a link to an interview I did discussing how CCS can improve the efficiency of single embryo transfer, thereby reducing the burden of twins...  hopefully we can make this the standard of care and get more patients pregnant with one healthy baby at a time....

High Pregnancy Rates with Single Embryo Transfer and Chromosome Screening @molinath http://t.co/iHxenI4sg8 via @sharethis

— RMANJ (@RMANJ) December 18, 2014

Happy Holidays!

The holiday season always gives time for reflection.   Looking back on the year I am always astonished at the number of new patients I've seen (over 300!) and the number of pregnant patients sent off to their obstetrician (over 50%)...  This year I am fortunate enough to receive many holiday cards from current and former patients.  It may seem like a small gesture, but the fact that these patients felt it was important to include me in their list of holiday greetings is important.  I am reminded of the incredible impact we have on a couple's life, allowing them to become a family.  It's amazing to see these children grow knowing that I played a small part in the prologue to their story.  

Happy holidays to all my current and former patients.  Thank you for allowing me to participate in the beginning of your small miracles.  Here's to a great 2015 with many new challenges ahead!

RMANJ 15th Anniversary

Last month, we celebrated the 15th anniversary of Reproductive Medicine Associates of New Jersey.  Hard to believe that the organization has grown so much in just 15 years. The initial beginnings of our practice when Dr. Bergh, Dr. Drews and Dr. Scott embarked on their journey was as a small group.  Now we have grown to an organization of 15 doctors and more than 200 staff.  We are dedicated to providing the best reproductive health care possible.  Our educational and research missions have converged on our fellowship and we have had some of the most productive fellows train with us over the past few years.  It is our hope that we will continue to set the pace for infertility care.  For one night last month, we all came together and celebrated the fact that we have the best job around.

Single Embryo Transfer: In the News

I am happy to see that single embryo transfer is gaining more and more notice in the popular press.  We have known for years that one embryo gives you the best chance for one baby at a time.  The "cost" of twins in terms of bedrest, prematurity and other complications is too high.  Our colleagues in Europe have known this for years...  It's about time we caught on.  I just hope that the American consumer mentality will accept the compromise in success rates that comes with single embryo transfer.  Hopefully the general public will agree that the "goal" of infertility treatment should be one healthy baby at a time!

The Co$t of IVF

I am fortunate enough to work in a really great infertility practice.  Our group has a large research division and remains committed to pushing the envelope and setting the standards for infertility treatment.  There are always research studies available to our patients which usually allow them to participate in treatments designed to improve their chances for having a successful pregnancy.  This is truly translational research, designed to bring laboratory advances directly to the bedside, improving patient outcome.  

Recently, we launched our nextgen study looking at next generation DNA sequencing as a more efficient method to perform Comprehensive Chromsomal Screening of embryos.  As part of the study, patients receive most of their care during an IVF cycle for free.  There are strict requirements to qualify for the study that many patients will not meet.  For patients with no insurance coverage, this type of study, which does not come around often, is their only opportunity to have In Vitro Fertilization.  Clearly, this has me thinking more and more about the cost of IVF.  Yes, there is a financial toll that IVF takes.  A recent New York Times article highlighted the lengths that one couple went through to make their miracle dream come true, and the massive debt that they accumulated.  It is clear that the financial burden of IVF looms large.  However, there is an emotional price that so many patients pay

Many infertility patients are completely overwhelmed and exhausted by the process of attempting to conceive.  Frequent doctors visits and the up and down roller coaster of each month waiting for that positive pregnancy test only to be disappointed again takes its toll.  There are studies that show an increase in divorce among couples undergoing fertility treatments. While some of that may be related to partners that discover they feel differently about how far they are willing to go to conceive, the stress of frequent visits clearly plays a role.  

Our practice has refocused our efforts to care for the emotional and physical needs of our patients with our collaborative wellness program.  Patients can benefit from nutrition counseling, yoga, acupuncture and support groups.  Preparing for IVF is like training for a marathon and it is important to get your mind and body into the best shape possible.  There will be hills and valleys throughout any IVF cycle and training yourself to be prepared is important.  IVF has a cost that is both financial and emotional, but the reward on that investment is priceless when it succeeds.  At the end of the day, advances in our understanding of human reproduction are allowing most couples to be successful.  So don't forget to invest in a little hope along the way.  

One or Two?

There’s been a lot of press the past few weeks about single embryo transfer. Single embryo transfer is not anything that’s new. Europeans have been advocating single embryo transfer for almost a decade. In The USA, around 10% of IVF cycles utilize single embryo transfer. My OB colleagues who deliver babies would agree that the biggest complication that arises after infertility treatment is as a result of twin pregnancy. Twins had become so commonplace that we no longer turn a head when we see a stroller with twins in the grocery store or the shopping mall. It is true that most of these pregnancies result in healthy babies, although there are often complications along the way. Twin pregnancies are harder on moms, harder on babies and harder on the obstetrician to care for them.

Having one baby at a time sounds great, but the best way to accomplish this in infertility treatments like IVF is to transfer only one embryo at a time. This sounds perfectly plausable in theory, but single embryo transfer results in fewer pregnancies after IVF. Transferring two embryos gives us more positive pregnancy tests. Unfortunately, it’s a big reason the twin rate is so high. Triplets and quadruplets are fairly rare after IVF because putting back more than 2 or 3 embryos is rare. Yet, putting back two is pretty standard and sometimes both stick.

Why has it taken so long for physicians and patients in our country to accept single embryo transfer? This is America and everybody wants bigger and better. We simply won’t tolerate a lower chance of “success”. The key here is of course how you define success. “Success” is not simply a positive pregnancy test. “Success” is not a 24 week twin delivery that results in months and months of neonatal intensive care. Success should be defined as the birth of a single healthy baby.

In America we are consumers and we are inundated every day with the consumer mentality. There is no doubt that everybody wants to be successful and they want the best chance at pregnancy. But sometimes patients view themselves as a customer purchasing a product rather than as a patient coming to a physician for treatment. The biggest obstacle I face to single embryo transfer is the couple sitting across the table from me who are weighing the risk of a twin pregnancy with the potential improvement in success. Time and time again I hear patients say that they would rather have two embryos transferred because it improves success and they just can’t bear the thought of another negative pregnancy test.

In the field of reproductive endocrinology we have struggled for years to better identify which embryos are most capable of resulting in a healthy baby. In the last five years the technology of bioinformatics and molecular genetisc have been combined to develop the ability to genetically screen embryos prior to transfer. Our group at RMANJ has pioneered the use of comprehensive chromosome screening (CCS) to better identify embryos which are more likely to result in a baby. Last year we published a trial where we demonstrated that a single genetically screened embryo could result in as many healthy babies as to untested embryos. In the coming years scientists will expand our ability to screen embryos by adding metabolic markers and using time lapse imaging to better identify embryos that grow at the right pace. As science and technology expand our knowledge, the chances for success with a single embryo will increase dramatically and it should become the standard of care. For now, I am happy to be ahead of the curve, leading the way and pushing forward. My patients who have one healthy baby at a time are happy too.

Donor Eggs: Are they for everyone?

A recent conversation…

I sat with a couple this week and we discussed a recent failed cycle of In Vitro Fertilization due to poor egg and embryo quality. We discussed the use of donor eggs and they looked at me as if I had told them we were going to fly her to the moon to dig up eggs to get pregnant with.

“You can do that?” she said.

“We do it all the time.” I responded. “and not just our clinic, it happens thousands of times each year.”

“What crazy medications do I have to take for it to work? Won’t my body reject it?” She was aghast.

I smiled. “Nope.. just estrogen and progesterone.. your uterus is a very welcoming place. The beautiful thing is that your pregnancy would be like any other. Actually it would be healthier than if you had been pregnant with your own egg since it is a younger, healthier egg. Not even your obstetrician would know it was a donor egg”

It sounds like science fiction to most people, but it happens all the time. When women are conceiving well into their forties, a good majority are using the technology of donor eggs to have healthy pregnancies that result in healthy babies.

An article published in the Journal of The American Medical Association yesterday entitled “Trends and Outcomes for Donor Oocyte Cycles in the United States, 2000-2010" has grabbed my interest. The article reports on the outcomes of donor egg cycles for the past decade. In case you did not know, a woman is born with a fixed number of eggs which are used over the course of her life until there are none left and menopause ensues. As many of my patients can attest to, the decline in fertility happens many years before menstrual cycles cease as the quantity and quality of eggs decreases. For women whose eggs are no longer of the caliber to result in a healthy pregnancy, science has developed the ability to take another woman’s eggs, fertilize them with the male partner’s sperm and return these embryos to the recipient’s uterus with minimal medication to help them stick.

What strikes me is that in 2010 over 18,000 donor egg IVF cycles were performed in this country, accounting for roughly 11.5% of IVF cycles in the United States. The findings of the study also confirm that donor eggs are more likely to result in a healthy pregnancy. In fact, when donor oocytes are combined with extended embryo culture (growing to day 5/6) and single embryo transfer, outcomes are best. In our own practice, we have pushed the envelope by moving all transfers to day 5/6 and by encouraging single embryo transfers for most of our patients. It is reassuring to see that we are ahead of the curve!

Don’t get me wrong — no one walks in to my office demanding to use donor eggs. For most couples, it is an option of last resort when all else has failed. Couples who face this situation should know that they are not alone — it is happening all around them. Furthermore, they should be reassured that outcomes are good, and maybe even better than if they had conceived with their own, lower quality egg. At the end of the day, the goal of infertility treatment is a healthy baby. Donor eggs are not the first step, but for many it is the best option. I’d be willing to be that for almost all couples, once they are holding that baby in their arms, all regrets and trepidation melt away.