Practicing medicine for the past 30 years, I have developed an enormous respect for those things that happen to people that are beyond our control.  Sometimes, the issue of preventability is a gray one and defies definitive blame assignment.  Yet, when the dust settles there remain victims who are harmed for whom we are all sympathetic.  It is for this reason that we are compelled to do everything within our power to ensure that tragic errors do not occur.

Elsewhere in society there are potentially devastating outcomes to human error and, like in medicine, it may be difficult to unravel how much fault is from natural calamity and how much we could have avoided with more rigorous human controls.

Just over a week ago, the world was exposed to perhaps the worst of Mother Nature’s natural disasters: a severe earthquake with multiple aftershocks, followed by a massive Tsunami.  Aside from the horrendous devastation that took place in Japan, ongoing danger persists from damage to several nuclear power plants.  

These unintentional, uncontrollable catastrophes occur naturally and are arguably nobody’s fault.  And although some claim that nuclear power is dangerous because of the history of accidents like at Chernobyl and Three Mile Island, nuclear power plants continue to be constructed throughout the world because many perceive that the benefits of this alternate source of energy outweigh the risks.  We are assured by those responsible that these plants are safe even in the face of the worst disasters… until we learn they are not.

 It is our human condition to speculate how to prevent these complications from occurring.  In IVF, perhaps the greatest potential disaster we face is the mixing up of embryos.

 In February, 2009, a case of a mix-up of frozen embryos in a Michigan IVF program occurred to a couple who already had a set of twins as a result of a successful IVF.  Their embryos were mistakenly transferred into the wrong woman, who then carried the pregnancy and after delivery handed the baby back to his biological parents. Reports of the mix-up have triggered calls from some to make IVF illegal.  This sounds like the recent calls to decommission nuclear power plants and stop production of new facilities.

Mixing up gametes and embryos is tragic and society must do everything humanly possible to prevent it… except disallow the practice of IVF. As with other societal advances, accidents are rare but have 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 could sometimes been avoided. Sometimes, like the post-earthquake nuclear disasters in Japan, they are spawned by natural causes.  But other times, there is an element 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.

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 do occur rarely, usually because of a human slip. Rules are broken and mistakes result. When they do, hospitals review the procedures and protocols to better insure a sufficient system is in place to catch future errors before they effect 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 Michigan.

In our 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 double-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 repeatedly throughout the IVF process from retrieval through transfer. A similar system of double checks of patient and embryo identity exists for frozen embryo transfers as well.

In over 25 years of practicing IVF, my program has not mixed up gametes or embryos.

There are approximately 3 million babies born through IVF and only a few rare mix ups reported. Perhaps we don’t hear …or know…about every mix up. I’d estimate that less than 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.

When it comes to institutions whose impact on society is of such great magnitude, it is essential that governing regulatory agencies ensure that all possible checks and balances are in place to ensure the greatest degree of safety.  All involved must work hard to maintain the highest standards and then we can only pray that we have done everything possible so that such disasters never have such devastating consequences.

Two months ago I had my first IVF cycle & it did not work. I was wondering what common reasons there are a body would reject the 2 embryos that seemed to look good on the 3rd day?
A few years ago I had a healthy child that came naturally with out even trying. In the past 2 years I’ve had an ectopic pregnancy resulting in removing a tube as well as a miscarriage. It’s hard to understand why it was so easy to get pregnant naturally a few years back & why everything we have done since that time has not worked. Also, if a fresh embryo transfer didn’t work on day 3, would you recommend trying a frozen transfer or a fresh transfer again.

Still Not Pregnant

Dear Still Not Pregnant,

I often hear patients refer to a failed embryo transfer as an embryo rejection. I suppose it appears to make sense as the embryos that are being transferred appear completely normal. The disconnect between what appears to make sense and the reality of the procedure of IVF is that the creation of life is an enormously complex process truly beyond the level of human understanding.

Great strides have been made in the process resulting in pregnancy rates exceeding 60% for some groups. However, the apparent quality and grade of an embryo predicts the likelihood of a resulting pregnancy. It is far from guaranteeing a pregnancy. New tests for the viability of an embryo are being developed such as metabolomics and proteinomics. These assess an embryo by analyzing products of an embryo in culture. They will further the likelihood of achieving a pregnancy from a transferred embryo.

Remember, that though an embryo may be otherwise viable it may still be abnormal genetically which will diminish pregnancy rates and usually result in miscarriage when implantation does occur. The likelihood of a genetically abnormal embryo developing increases especially as the age of the woman increases as well as with severely decreased sperm counts in the male.

The decision to go forward after a failed fresh transfer with a frozen transfer of sister embryos or a new fresh transfer should be individualized based on the quality and grade of the frozen embryos, the age of the woman, her

insurance coverage and her tolerance for the stimulation and retrieval as well as her motivation and patience. I recommend you have this conversation with your physician who can advise you better about your specific situation.

I wish you the best of luck!

It has been my experience as well as that of others in the field that many individuals conceived through gamete donation are curious about their donor and the donor’s other offspring. They may fantasize about their genetic parent and siblings. They are curious if they look like them and have similar behavioral traits. They want to know why their donor donated. They almost ubiquitously are curious to meet their donor whether they may want to have ongoing contact or not. The degree of interest is variable where some may simply be satisfied with a picture and information, others may feel comfortable with maintaining anonymity whereas still others feel a strong desire to physically meet their donor. These feelings typically change over time and may become more significant during certain stages of life, such as at the prospect of an individual starting their own family.

Donor conceived individuals may be looking to fill in the blanks in their identity. Rebecca Hamilton, conceived through donation, wrote in Behind Closed Doors: Moving Beyond Secrecy and Shame, edited by Mikki Morrissette, “It’s not a ‘Dad’ I’m after. I had a wonderful Dad who raised me. I’m not looking for a replacement. Nor, incidentally, is any other donor-conceived person I have ever met….Wanting to understand one’s genetic roots is a unique longing that remains no matter how great life is going on other levels.”

Universally, it appears that those individuals who were conceived through donation do not look at the donor as a parent. The donor does not replace the role of the parent. Instead having an open relationship with a donor can provide answers to questions many donor conceived individuals have about their own identity.

So how do I answer the question, “should I help my child find her donor?”

Professionals in the field tell us that based on research, developmental theory, and my own clinical experience, that it is best for parents to be honest with their children about their origins. In some cases I may recommend providing them with options for obtaining information about their donor. Although many sperm banks and egg donor agencies only facilitate anonymous donations. Some sperm banks offer the possibility of working with a donor who is willing to be identified to your child any time after your child turns eighteen. The sperm bank stores data and provides it upon request. Your adult child is the only one in control of this information. If she wants identity information, it is available for her. If she does not desire to know her donor’s identity, the information is never revealed.

However, it is most common at least in the Northeast that a definitive plan is not established at the outset for how a donor’s identity would be released. Most programs maintain strict anonymity. There is no guarantee that this information will be available for their child. A third party, which could be an agency, medical office, or attorney must obtain the information, and a formal contract, signed by the donor, must state when and how identity information will be released to the donor conceived individual.

Ultimately, as future parents it is vital to examine your feelings and concerns regarding disclosure of the donor’s identity. Disclosure of the donor’s identity may affect the donor conceived individual and his sense of self. Though the donor does not replace the parent there is potential for creating friction in the relationship. There is also the donor’s family to consider which will also be impacted by revealing one’s identity to the donor conceived individual. One must weigh the potential benefit of satisfying curiosities with the risk of causing harm to the relationship with the individual’s parents as well the risk of causing harm to the donor’s family.

I received this letter from a former donor egg recipient.  It made me think about what it might be like, years after the actual procedure for a child who grows up wondering about his/her donor parent.

Dear Dr. Kreiner,

I want to thank you and your wonderfully caring staff for all you did to help me have my daughter, Jessica.  There was not a moment that I did not feel supported during the process and for this I sing your praises constantly.

My daughter is truly a blessing and I will always cherish that you helped bring her into this world for me.

We informed Jessica about her genetic parentage a few years ago with the help of a psychologist who saw my husband and I first and then with Jessica for two or three more visits.  I thought it went well.  Jess seemed to understand that we loved her and that Russ and I were truly her father and mother and I cannot say that our relationship had changed in any significant way since then.

However, Jessica is now 14 years old and has recently been asking me about what I know about her genetic mom which is how she referred to her.  I, took offense to her use of the term ”mom” and immediately corrected her, saying “you mean donor, honey”.  This started a huge argument and has created a tense rift that still exists.  I know that she has been doing research to identify her donor including calling your program.  I don’t know what to do.  Did we make a mistake by telling her?  Should we seek out the donor and ask if she is willing to reveal herself to my daughter?  Is it even legal or moral for us to ask?  Should we tell my daughter that it is not possible to identify her and just leave it like that?  I am afraid not to try as it seems to be so important to her and if I appear to be resisting she will get angry with me again.

What should we do Dr. Kreiner?

Still thankful but with some remorse,

Former donor egg recipient

I have been involved in these donor egg cases since 1985 and this type of question is rare for me to receive but now I wonder if that is because patients do not feel close enough to me to discuss these problems years after my services have been performed.

It is not uncommon for potential donor egg recipients to say to me ”I’m not going to tell my child about the donor. I’m going to carry him. I’m the mom”.  We have always recommended that parents disclose that they had utilized donation to their child since it is thought that honesty is better than trying to shoulder “the big lie” which ultimately would be found out and lead to much larger problems.
If you are planning to build a family with a sperm or egg donor, you may be thinking about these very issues. Many patients believe that by disclosing their child’s donor origins will damage the parent-child bond that is so precious to them. They fear that a genetic connection to a donor could trump their relationship with their child. Most commonly, my patients plan to tell their child about the donor but want the donor’s identity to remain anonymous. They worry that an identified donor could disrupt the integrity of their family by inserting herself or himself into it.

Professionals in the field of infertility tell us that patients who need help to have a child often feel vulnerable and may view donors as threatening.

To Disclose or Not to Disclose That is The First Question

Unlike heterosexual couples, same sex couples and single individuals understand that from the moment they decide to build their family that they require assisted reproduction. These families openly disclose their children’s donor origins because it is the only way to explain their conception and birth.  Inevitably, the children look at other families around them and wonder if they have a mommy or a daddy.   It does not appear that disclosure in these cases has a negative impact on the families.

However, the heterosexual couples seek assistance only after failed attempts to have a child on their own and sometimes even after multiple IVF attempts using the woman’s own eggs.  These couples typically experience incredible loss, frequently feel inadequate, and often become clinically depressed. Assisted reproduction with outside help with their family building was not something they ever imagined. Many feel a sense of shame that may add additional motivation to keep the donor parentage a secret from their child. We are told by those professionals in the field who study this that many former donor recipients turned parents fear their child will see the donor as the “real” mom or dad and believe they are preventing potential problems by keeping the secret from their child.

Interestingly, many individuals who are the result of gamete donation report feeling like they don’t fit in with their families. I have heard that when they ultimately are informed of their donor origin that it often makes sense to them and not infrequently is received by the child with a degree of relief to explain their uniqueness from their family.  Sometimes donor conceived individuals inadvertently learn about their origins under less than ideal circumstances such as from a family friend or relative. Nondisclosure, in these cases, usually undermines trust and honesty within a family and may lead to psychological harm.

Professionals studying donation tell us that when children have been told about their donor origins, they are typically accepting of the recipient moms and dads. In fact, it appears that when children learn of their donor origins at a young age, they are more likely to have a more positive experience. Their donor conception is integrated from the beginning into their life story.   It becomes who they are at an early stage when they develop their own identity and sense of self.  Individuals told later in life are more likely to have more negative feelings about their donor conception than those told earlier. They may become angry about being deceived and often feel betrayed by the very people they thought were the most trustworthy in their lives, their moms and dads.  Hence, disclosure at an early age is recommended by professionals studying this issue.

I will address the question of disclosing the identity of the donor in my next blog.

The Joneses had just moved to Norfolk after a forced retirement at Johns Hopkins and hadn’t finished unpacking when the greatest fertility event of all time hit the news. Patrick Steptoe and Robert Edwards had succeeded in Great Britain with creating a new life through a process they called In Vitro Fertilization that the media had termed “test tube babies”.

I had the great fortune to study REI (reproductive endocrinology, infertility) with the Joneses and Zev Rosenwaks in Norfolk from 1985-1988. In 1988, I started IVF on Long Island which was successful then in about 25% of cases. In 1990, I met Dr. Robert Edwards who impressed me with his wit, his charm as well as his great intellect. I told him about my softball team named East Coast IVF that Dr. Edwards found particularly amusing. After all the scientific and political challenges he overcame to successfully achieve a live birth through IVF, he was struck by the irony that IVF had become routine as a commonplace alternative for those with difficulty building their own families.

Today, IVF is now successful 50% of the time. Four million babies have been born who if not for the technology of IVF would not be here today. What a remarkable testimony to his scientific accomplishments. Dr. Edwards truly deserved the Nobel Prize for developing this technology that led to the creation of so many lives.

As someone who owes his career to the man I am forever grateful and to those who have been touched through the birth of one of the 4 million we owe him much more than we can ever give.

The old fertility legend about a couple who had failed fertility treatments, adopts a baby and then all of a sudden gets pregnant is one we have all heard.

In fact, as a practicing reproductive endocrinologist over the past 25 years, I have experienced this with some of my own patients.

Those stories have led us to believe that it takes longer for women with high stress levels to conceive. Unfortunately, there has not been much research on this. Until now, the best evidence for the benefit of stress reduction comes from the wellness center at Boston IVF where they had shown higher IVF success rates for women who were involved in their Mind Body program.

Latest Research on Stress and Fertility

A new study in the current issue of the ASRM journal Fertility and Sterility (the primary research outlet for our national fertility society) lends credence to a link between stress and fertility. In the study, 274 British women, ages 18 to 40 years old, were examined to determine if using fertility-monitoring devices would improve their chances of conception.

They were followed for six menstrual cycles or until they got pregnant, whichever came first. On Day Six of each cycle, saliva samples were collected. Researchers measured their levels of alpha amylase and cortisol, two substances that reflect how the body reacts to stress.

Pregnancy rates were compared in women with the highest concentrations of alpha amylase in their first cycle to women with the lowest levels of the stress hormone marker. It was found that over the six-month period, the group of women with the highest alpha amylase (and hence stress) were 12 percent less likely to conceive than women with the lowest.

Cortisol levels were not associated with the women’s chances of conceiving. The alpha amylase and cortisol reflect two different components of the stress response and don’t necessarily correlate well. Alpha amylase reflects the “fight-or-flight” response to immediate stressors.

To confirm these findings, the research team conducted a larger and longer study of women trying to conceive. Evidence from these trials suggests that stress-reduction techniques can improve pregnancy rates in couples who use in vitro fertilization and related methods.

Applying the Findings

With such findings it appears that patients would benefit if they enroll in various stress reducing programs when trying to conceive. Mind-body programs, support groups, acupuncture and massage apparently offer the greatest benefit.

As a practitioner in the field of infertility for 25 years, I endorse these adjunctive therapies for my patients undergoing treatment, with the goal of reaping the fertility enhancing benefit of stress reduction before we submit them to multiple treatment cycles.

IVF’s Early Years

Practicing reproductive medicine during the ’80s was like having a new love or beginning a new romance — all of it seemed liked a miracle, and everything was about helping patients get pregnant using this new technology and educating the world about what was now possible. This was an exciting time, and the 15 percent pregnancy rate was achieved by transferring six embryos at a time.

But our excitement was often tempered by the consequence we experienced with many high order multiple pregnancies. Unfortunately, these were often complicated and did not always end well. Aside from pregnancy and neonatal complications, many of the marriages also suffered. It was hard to balance a new family’s anticipation and heartfelt joy with the sometimes painful and unforeseen consequences — babies who suffered and families that fell apart.

Sometimes beginnings are like that. They start off so bright, and then they get tempered.

The Middle Years—Safer and Not So Sexy

Thankfully, I am now in the “middle years,” of IVF which is so much more successful and no less a miracle. We can attain pregnancies in greater than 60 percent of retrievals for women under 40. These rates are accomplished while transferring one, two or, at most, three embryos at a time. Cryopreservation, or freezing embryos, has also improved our pregnancy rates per retrieval, giving us multiple opportunities to get a patient to conceive from a single IVF stimulation and retrieval.

The middle years of IVF are not like the beginnings of a romance — this is the wood chopping time. The freshness of the technology has worn off, and the focus on making the treatment affordable, accessible and safe may not seem as sexy. But it is the middle years of any pursuit — whether it is marriage, raising a child or practicing medicine — in which the gold is often mined.

A Time for Reason, Not Headlines

The middle years of my practice mean we are making an effort to encourage safer single-embryo transfer and avoid risky multiple pregnancies. We introduced a program in 2007 at East Coast Fertility for patients who transferred one embryo at a time, offering free cryopreservation, storage and frozen embryo transfers until a live baby was born.

Still, patients don’t commonly choose single-embryo transfer. They haven’t seen what I have seen — they still believe that the technology will some how fail them, that IVF won’t work. But from our experience, similar to others’, there was no significant difference in pregnancy rates between patients who chose to transfer one embryo vs. those who chose to transfer two embryos.

While there was a trend toward higher rates for the two-embryo transfer group, it was practically eliminated when frozen embryo transfers were added. These groups were age-matched with no difference except for a 40 percent twin rate and one triplet in the two-embryo transfer group, compared to the single-embryo transfer group in which no twins were created.

It is hoped that these results will encourage a higher percentage of patients with a good prognosis to transfer a single embryo, which is the safer option.

The middle years of practicing reproductive endocrinology captivate my heart. It is a time for reason — not headlines. And for me that is just perfect.

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.

Many husbands pride themselves in their new found skill with mixing medications and administering injections for their wives. It helps many men who are used to caring for their wives to be in control of administering the medication for them. Successful IVF then becomes something he’s has played a very active role in and related better to the experience, his wife and the resulting baby.

Despite a lack of prior experience, most people can learn to prepare and administer the medication. Whether it is the feeling of “playing doctor” or the knowledge that he is contributing significantly in the process and supporting his wife, most men relate that giving their wives the injections was a positive experience for them and for their relationship.

Along the same line of thinking, accompanying your wife at the time of embryo transfer can be most rewarding. This can be a highly emotional procedure. Your embryo/s is being placed in the womb and at least in that moment many women feel as if they are pregnant. Life may be starting here and it is wonderful to share this moment with your wife. Perhaps you may keep the Petri dish as a keepsake as the “baby’s first crib”. It is an experience a husband and wife are not likely to forget as their first time together as a family. I strongly recommend that men don those scrubs, hats and booties and join their wines and partners as the physician transfers the embryos from the dish into her womb. Nine months later do the same at delivery for memories that last a lifetime.

Thankfully, today IVF is so much more successful and we can attain pregnancies in greater than 60 percent of retrievals for women under 40. These rates are accomplished while transferring one, two, or at most three embryos at a time. Cryopreservation, or freezing embryos, has also improved our pregnancy rates per retrieval giving us multiple opportunities to get a patient to conceive from a single IVF stimulation and retrieval.

In an effort to encourage safer single embryo transfer and avoid risky multiple pregnancies, we introduced a program in 2007 at East Coast Fertility for patients who transferred one embryo at a time. For these patients we offered free cryopreservation, storage and frozen embryo transfers until a live baby was born.
Still, patients don’t commonly choose single embryo transfer. From our experience, similar to others’, there was no significant difference in pregnancy rates between patients who chose to transfer one embryo vs. those who chose to transfer two embryos. There was a trend, however, towards higher rates for the two-embryo transfer group that was practically eliminated when frozen embryo transfers were added. These groups were age matched with no difference except for a 40 percent twin rate and one triplet in the two-embryo transfer group compared to the single-embryo transfer group in which no twins were created.

It is hoped that these results will encourage a higher percentage of good prognosis patients to transfer a single embryo, which is the safer option.