Archive for IVF Treatment
The hormone testosterone is undoubtedly a major driving force when it comes to human function and endeavor. On the one hand it has led to bold initiatives that have resulted in human prosperity and achievement. On the other hand however, it has also prompted many ill-conceived and even foolish urges and actions that have ended in misfortune, heartache and even in disater.Similarly, when it comes to reproductive function testosterone effects have likewise been a mixed bag. Consider the following:
- Both male and female libido is in large part driven by testosterone. In the man, hypotestosteronism causes impotence and a lack of sex drive, while in the female, the production and the local release of testosterone by the ovaries also profoundly influences female libido.
- Neither ovarian follicle growth and development nor the production of estrogen could occur without the availability of the body’s own testosterone. The hormone is produced by the connective tissue (stroma) surrounding follicles from which it is delivered in a “bucket brigade” fashion to cells that line the inside of the follicle (granulosa cells). There, enzymatic digestion triggered by follicle stimulating hormone (FSH) converts testosterone to estrogen (mainly estradiol). This causes granulosa cells to proliferate, follicles to grow in size, and eggs housed in such follicles to undergo development and differentiation. At the same time, blood estrogen levels rise progressively. Thus, without access to ovarian testosterone, human reproduction would come to a halt.
However, it is also true that too much testosterone delivered to follicles (as commonly occurs in older women who have diminished ovarian reserve and women with polycystic ovarian syndrome or PCOS), can lead to exhaustion of granulosa cells, compromised egg development and poor egg and embryo quality. It is all about a delicate balance that involves regulation of ovarian testosterone production. Since this is regulated by luteinizing hormone (LH), it follows that when it comes to ovarian stimulation with fertility drugs, it is important to properly control (down regulate) the amount of LH administered and or produced immediately prior to and during stimulation.
- Everyone knows that male hormones (predominantly testosterone) act peripherally to increase muscle mass. Such peripheral activity is dependant upon the conversion of testosterone to a more active form known as dihydrotestosterone. This is why body builders use androgen type hormones (anabolic steroids) in order to maximize muscle growth, bulk and definition. But testosterone also suppresses body’s own pituitary LH which is necessary for adequate testicular sperm production which in turn results in reduced sperm production (spermatogenesis) and serves to explain why overuse of such synthetic, commercial products can lead to a reduction in sperm production and even to testicular atrophy. It is come as no surprise therefore, that many bodybuilders and other athletes who overindulge in the use of such synthetic hormones often end up with male infertility.
Another point of interest is that testosterone also works centrally at the level of brain synapses where it promotes libido (in both men and women) by being converted enzymatically to estrogen. Unfortunately, many synthetic commercially available androgen products (e.g. Dianabol) inhibit this conversion, thereby explaining why many athletes that use such products experience decreased libido.
Clearly, when it comes to treating women undergoing IVF (especially those with ovarian stromal overgrowth) it is important to maintain body’s own LH at a low level prior to and throughout the stimulation cycle. To do so it is necessary administer fertility drugs that are low in LH-like activity. Clomiphene citrate (Serophene) and letrozole (Femara) tend to cause the pituitary gland to release much LH while injectable gonadotropin fertility drugs such as Menopur and Repronex contain about as much LH-like activity as they do FSH.
Also, drugs like Lupron, Buserelin, Nafarelin and Synarel (agonists), elicit a profound increase of the body’s own (pituitary) LH. Thus when agonists are used they need to be administered several days before initiating stimulation so as to exhaust the woman’s own LH and allow the levels of this hormone to drop and thereupon be sustained at negligible concentrations before beginning stimulation. When the administration of agonists is initiated at the start of ovarian stimulation (microflare protocols), the LH levels rise rapidly, causing increased ovarian testosterone production at the very time that follicle and egg development starts. This has the potential of adversely affecting the quality of eggs in that cycle.
Also, since women with stromal overgrowth commonly have high LH activity, the use of protocols where an antagonist (Cetrotide, Ganirelix, Orgalutron) that blocks LH release is first administered 6-7 days after ovarian stimulation has been initiated, should in my opinion also be used with caution (especially in women with stromal overgrowth). The reason is that by the time LH release is controlled through their use, some degree of irreversible egg damage for that cycle might have already occurred.
One of the great travesties still being perpetuated by some doctors, is the indiscriminate administration of testosterone to infertile men in the erroneous belief that it will improve sperm production. Nothing could be further from the truth.
When it comes to reproduction, testosterone can truly be regarded as being the “root of both good and evil”. Its role in promoting reproductive objectives is indisputable but its therapeutic role can be fraught with hazard. It is as well that those desiring to conceive understand the dynamics involved in this delicate balance.
Posted on August 12, 2010 | Filed under IVF Treatment | Permalink
Hardly a month goes by without reading or hearing a media report of some or other catastrophe that a woman undergoing IVF has experienced. It was not long ago following the tragic death of the Saturday Night Live star Gilda Radner from ovarian cancer and the concern that it was her use of fertility drugs that caused or contributed to the disease. Then there were the numerous reports suggesting that babies born following IVF are at an increased risk of birth defects and of developing autism. Other reports have suggested that women receiving fertility drugs as part of an IVF procedure are invariably at serious risk of ovarian hyperstimulation with its sometimes life endangering complications. Most recently there was a report suggesting that the performance of intracytoplasmic sperm injection (ICSI) causes an increased risk of birth defects. Patients/couples seeking IVF treatment are highly vulnerable to alarmist reports, which in many cases, turn out to be “much ado about nothing.” Nevertheless, it is well to recognize that almost all patients/couples destined to undergo IVF will pose the question as to whether the process itself is safe for them and for their prospective offspring.
To start with, it is important to recognize that no medical intervention is totally devoid of risk. IVF is no exception to this rule. However, any decision regarding whether to proceed with a medical treatment must take the risk/benefit ratio into account. When it comes to IVF, the risks are not the same for all cases. Some patients/couples are at very low risk while others may be at higher risk. As with all medical procedures, it is essential to provide patients/couples with sufficient information with which to make an informed decision. Consider the following:
On average, women trying to conceive through IVF tend to be older. Accordingly, these women are thus more likely to have diseases such as hypertension and diabetes mellitus when they conceive. Both of these conditions can add a significant risk in any ensuing pregnancy. In addition, older women are more likely to have an anatomical reproductive disease such as uterine fibroids and/or endometriosis. Obviously, the greater the anatomical distortion, the more difficult it would be to access the ovaries or perform an embryo transfer, and accordingly, the greater the likelihood of causing bleeding and infection. Finally, there is the fact that babies born to older women are more at risk of chromosomal birth defects such as Down’s syndrome and of autism.
There is no doubt that the proliferation of IVF has been accompanied by a significant increase in the incidence of IVF multiple births, especially high-order multiples (triplets or greater) which in turn, leads to a much higher rate of premature births. These often have serious risks and consequences to the offspring as well as for the families.
Very young women and women who do not ovulate or who ovulate irregularly, are at a much greater risk of developing severe ovarian hyperstimulation syndrome following the administration of fertility drugs in preparation for IVF. Such complications can be life endangering if not managed expeditiously and properly.
Certain women are at an increased risk of developing blood clots during pregnancy as a result of an underlying condition known as thrombophilia. These clots can affect the placenta and so compromise growth and development of the baby. Sometimes clotting occurs in the deep veins of the lower limbs or pelvis. Such clots, should they become dislodged, can travel to the lung or brain with serious or even lethal consequences.
One important risk associated with IVF that is often overlooked is the fact that in some women, it causes such a degree of emotional destabilization as to unmask serious and often persistent psychological problems.
The question of course is whether such risks can be mitigated through preemptive prevention, evaluation, and management.
The performance of preimplantation genetic diagnosis can be used to assess the chromosomal genetic integrity of the woman’s eggs/embryos and can allow for the selective transfer of embryos that are free of chromosomal abnormalities. Once pregnant, timely performance of prenatal genetic testing through chorionic villus sampling (CVS) in the first trimester and amniocentesis early in the second trimester can detect chromosomal abnormalities that would warrant consideration of pregnancy termination. Unfortunately there is no prenatal test that can predict the subsequent occurrence of autism in the offspring, but this risk is small. It should, however, be discussed with older women who contemplate IVF.
Pregnancy induced complications such as preeclampsia and gestational diabetes are often predictable. Women that are markedly overweight, have a family history of diabetes, have polycystic ovarian syndrome (PCOS), etc., are more at risk of developing such complications during pregnancy. The performance of certain tests will go a long way towards identifying those women most at risk for developing such conditions. These include but are not limited to EKG, blood chemistry and a glucose tolerance test. The absence of any such predisposition in older woman significantly reduces there level of risk during pregnancy. In some cases, preemptive treatment, while not totally eliminating the risk of pregnancy-induced complications, can minimize it.
There is no doubt that IVF has caused a virtual explosion in the incidence of multiple births and that this represents the biggest risk associated with undergoing the procedure. Multiple births, especially high order multiples (triplets or greater) often times result in preterm deliveries. Premature babies in turn have a much higher mortality rate, and a large percentage of those that do survive arduous, prolonged and expensive treatment in neonatal intensive care units are left with long-term health problems that impact the quality of their lives, the lives of their caregivers, and society as a whole.
The main reason for high-order multiple IVF births is the transfer of multiple embryos at one time. Such practice (as evidenced by the recent “Octomom” experience) is irresponsible and inexcusable, given newer methods for identifying “competent” embryos. Newer genetic techniques such as the use of comparative genomic hybridization (CGH) to identify those embryos that are most likely to make a baby, now allow for fewer embryos to be transferred without compromising the chance of success. BUT it will take a long time for this new technology to gain a strong foothold – especially since it involves the additional cost associated with sophisticated genetic testing.
Severe ovarian hyperstimulation can be avoided through the use of a procedure known as “prolonged coasting” (see elsewhere) which completely eliminates the associated life-endangering risks.
Thrombophilia can be diagnosed through blood testing prior to the initiation of IVF. Appropriate treatment with high dosage folic acid and/or heparin (e.g. Lovenox, Clexane) starting as soon as pregnancy is diagnosed and continuing throughout gestation, will go a long way towards preventing related complications.
Finally, it is important not to ignore the emotional/psychological risks associated with IVF. It is my opinion that all patients need psychological support prior to and during IVF. While in most cases such support can be provided by a seasoned and well trained medical team of physicians and nurses, it is essential at all times to be on the lookout for those patients whose demeanor and behavior suggests severe emotional vulnerability. They should be referred for appropriate psychological counseling (and in some cases psychiatric treatment) prior to proceeding with IVF.
I wish to re-emphasize that IVF will never be a totally risk-free procedure. However, it is important to recognize that not all reports by sensationalistic media are necessarily valid. Often times the risks and complications that occur with IVF are related to the woman’s underlying health rather than to the process of IVF itself. As an example, after the Gilda Radner debacle, a large retrospective study undertaken and reported on in a highly prestigious medical journal concluded that fertility drugs increased the risk of ovarian cancer. This evoked such a degree of alarm that subsequently and for at least a decade, virtually every patient undergoing IVF required detailed advanced counseling and many IVF physicians even required that their patients sign a release form, exonerating them from any risk should ovarian cancer develop in the future.
Ultimately, after a few well conducted prospective studies showed that there was no association between the use of injectable fertility drugs and the subsequent development of ovarian cancer, things returned to normal. More recently, a similar alarmist publication suggested there was a link between the performance of ICSI and birth defects. Subsequent multicenter studies showed that it was not the performance of ICSI itself that caused the problem, but rather the underlying sperm dysfunction that mandated the treatment in the first place. These are but two of numerous examples that demonstrate how and why it is so important not to overreact when there is a media report of an adverse consequence associated with IVF.
Posted on August 3, 2010 | Filed under IVF Treatment | Permalink
I can hardly believe that it has been 32 years since the 1st successful IVF conception, (initiated by Patrick Steptoe, the father of human IVF) resulted in the birth of Louise Brown. Time has certainly flown.
I first met Patrick Steptoe in the very early 70’s when he was a visiting professor at the University of Cape Town, South Africa where I was a young professor. I was assigned the responsibility of chaperoning Dr. Steptoe around Cape peninsula and I got to know him quite well. When Dr. Steptoe, a passionate musician, met my wife Charlene, a professional stage actress, they immediately clicked. A friendship soon developed.
So, why am I mentioning this and what does it have to do with IVF? To me…everything because it literally opened the door for me, when 8 years later, he and Robert Edwards introduced human IVF. In fact, I vividly recall the day that Dr. Steptoe called my home to speak to my wife. He and Charlene were talking and at the tail end of the conversation when I got a few minutes to talk to him, he shared with me that he and Robert Edwards had after more than 100 unsuccessful attempts, succeeded in initiating the world’s 1st human IVF pregnancy. He suggested that I visit him in England, learn the technology and then set up an IVF program in the US where, at the time, there were only a handful of existing programs (today…almost 400).
So, off I went with Cliff Stratton PhD (a professor of embryology at the University of Nevada), to England. A few weeks later we returned and established the first private (non-university based) IVF program in the US. (Our 1st IVF babies were born less than 1 year later).
To be quite honest, establishing a “private” IVF program did not sit well with those of our colleagues who operated the other 3 (university-based) IVF programs in the US. The general feeling was that procedure was still in the research stage of development
and did not belong in the “private setting.” But we were lucky because we were able to turn to Dr. Steptoe and Robert Edwards who were very forthcoming and eager to help when we hit the inevitable bumps.
Dr. Steptoe went even further in assisting me getting my career in IVF launched. Often times when he was lecturing in the US, Canada and Asia, he would invite me along and introduce me to the powers that be, thereby affording me an opportunity to make scientific presentations. In this way, I was able to establish myself quite rapidly in what represented an emerging and exciting new field of medicine.
When I look back to where I started in 1982 and where we are today, I can hardly believe my good fortune in having known Drs. Steptoe and Edwards. I am in awe of how the field of assisted reproduction has evolved over a mere three decades.
Consider the following: When I started doing IVF and through most of the early 80’s, we had to harvest eggs from the woman’s ovaries by a surgical process known as laparoscopy. This required the introducing a “telescope”-like instrument through the belly button into the woman’s pelvis to visualize her ovaries and the follicles in them. Then through a separate puncture site, a needle was introduced into each follicle in turn, in order to aspirate the eggs that they contained. It was truly a cumbersome process – taking about an hour to perform – and it had to be conducted under deep general anesthesia. Moreover, post operative recovery was not a “picnic”. It was often a bumpy road. (By comparison, today when we do an
IVF egg retrieval we aspirate eggs from the follicles via a needle passed alongside a vaginally introduced ultrasound probe which allows clear visualization of the ovaries.)
This was also a time when most women received an oral medication, clomiphene citrate to stimulate the development of follicles and eggs in their ovaries. This yielded a low number of eggs and also created a less than ideal uterine environment for embryo implantation. I recall being one of the first in the world to switch from clomiphene to injectible fertility drugs (Pergonal and Humegon at that time). Our results immediately improved dramatically, allowing us to differentiate ourselves from the competition. It also heralded a major advance in the IVF arena, since injectible fertility drugs were found to be much more effective than clomiphene. As a foot note, it was around this time that I remember getting the idea that it might be possible by washing and preparing semen and then inseminating the enhanced sperm directly into the uterus and so improve results with artificial insemination (hitherto very poor). And so….the now common procedure known as Intrauterine Insemination (IUI) was born.
In the 80’s and early 90’s few people were performing in vitro fertilization in women over the age of 40 or for non tubal causes of infertility. The results were simply too poor, and with most IVF practitioners competing for business it was important to report the best possible outcome statistics. But the IVF field was growing as more and more physicians, both in the private and academic sectors, became captivated by the new technology and the promise it offered. Yet at that time IVF success rates were dismal, ranging from 5-10% per procedure, even in young women.
Then, in the mid 90’s, clinical researchers in Europe began reporting on a technique referred to as Intracytoplasmic Sperm Injection (ICSI) in cases of IVF of male infertility where results using conventional fertilization in the Petri dish had been dismal. With ICSI, a single sperm was injected into an egg to force fertilization. The success rate with IVF for male infertility shot up, to the point where they were comparable to cases of non-male factor.
I knew the researchers who had developed ICSI and contacted them. Within weeks I sent a team of embryologist to Europe to learn ICSI and upon their return, became among the first in the US to apply the technology in cases of male infertility. Today, we at SIRM, rather than fertilizing eggs conventionally in a Petri dish, prefer to perform ICSI across the board (for male factor and non-male factor cases alike). We (and other IVF programs) have found that routine ICSI improves fertilization rates as well as pregnancy rates without posing any significant risks to the offspring (read on ICSI elsewhere in this blog).
It was also in the latter part of the 90’s that everyone in the IVF field started moving away from using clomiphene to stimulate a woman’s ovaries for IVF, to injectable fertility drugs. Originally, these injectible fertility drugs (gonadotropins) were all derived from the urine of menopausal women which is rich in gonadotropins (active ingredients). Then, around the turn of the century came the widespread introduction of recombinant DNA, purified gonadotropin products such as Gonal F, Puregon and Follistim which have since all but replaced urinary-derived fertility drugs since they apear to be more effective ….to the great benefit of patients worldwide.
By the year 2000, the number of IVF programs in North America had risen to above 200in number and the quality of service had improved dramatically. Birth rates were now ranging between 20-30% per procedure with some programs reporting even higher results.
Unfortunately, the level of accountability in reporting IVF statistics did not keep pace with the evolution of the science and the technology. In fact, our governing body, the Society for Assisted Reproductive Technology (SART), that had been charged by central government with the responsibility of ensuring accurate reporting of success rates was unable to do so. This was largely because member programs were non-compliant and because SART lacked the will and the means to enforce compliance. This meant that, often unbeknownst to IVF patients, they could not rely on IVF outcome statistics reported by SART. Sadly even now , in this regard things have not changed . Yes, even mow in 2010 the so called “SART Report” that is supposed to accurately portray annual IVF outcome statistics on a dedicated website simply, regurgitates the IVF success rates reported to them anually by member programs without any audit or other verification of authenticity. Clearly this is something that must change… Consumers derserve more.
The most recent paradigm shift in the field of IVF occured with the emergence of genetic testing of eggs and embryos to identify those that are the most “competent” (i.e. the ones that have by far the greatest potential to propagate healthy pregnancies). Technologies such as comparative genomic hybridization (CGH) and polymerase chain reaction (PCR) now allow us to identify genetically “competent” embryos. The same technology also affords an opportunity to selectively freeze only the most competent eggs, opening the door to fertility preservation and egg banking.
Perhaps one of the most important benefits of CGH egg/embryo testing its use to select the most competent embryo for transfer, thereby promising a reduction in the risk of multiple pregnancies that cause much of the morbidity and mortality associated with IVF babies.
The changes that have occurred in the field of IVF over the last 32 years since Louise Brown was born would have been almost unimaginable to Dr Steptoe when he initiated all of this. For me, the 28 years that I have been involved in this medical field have been nothing short of a spectacular ride.
Yes indeed, things have come along way. Just consider the fact that IVF success rates which were under 5% in the early 80’s are now better than 50% per procedure in certain categories of patients. Then consider the introduction and the potential impact of CGH egg and embryo selection where the birth rate per single embryo transferred is now almost 70%. Now consider where we are likely to be headed with the emergence of applied genetic techniques that could have the potential to identify horrific life threatening diseases in advance.
No doubt, to Patrick Steptoe the consummate musician, this would have been “music to his ears”.
Posted on July 28, 2010 | Filed under IVF Treatment | Permalink
Ask virtually anyone about the indications for in vitro fertilization (IVF) and you will receive the answer hear that it is a procedure performed for the treatment of resistant infertility. While this is true for the vast majority of cases, it is not true for all. In fact, an ever growing number of women/couples are electing to undergo IVF for reasons other than infertility. Let us examine some of these reasons:
Fertility Preservation: The fast pace of the 21st century has catapulted women into the career building arena. Justifiably women of today often aspire to compete with men at the professional level. One of the disadvantages that they confront is the fact that in initiating having a family, it will often require interrupting their career path for a protracted period of time to give birth and then nurture their child(ren) through much of the formative years of childhood. Then, when they attempt to re-enter the workforce, they usually will find themselves having to play catch-up. While some can overcome this hurdle, the majority will find themselves severely disadvantaged by the interruption. Many will simply not be able to make up the lost ground. In the past, this factor has compelled many such women to delay having a family until they are older and have established themselves firmly in their career paths. However, the obvious problem in delaying having children is that advancing age inevitably decreases the ability to conceive, increases the risks of miscarriage and birth defects, and is associated with a growing risk of life-endangering pregnancy complications that can affect both mother and child.
The recent introduction of egg freezing, especially when genetic testing such as Comparative Genomic Hybridization (CGH) is used to select the best quality eggs for cryopreservation (vitrification) and storage (banking), now offers promise that women will be able to safely freeze their eggs and store them for use when they are ready to embark on having a family. By resorting to egg banking they are able to “stop the clock” and are afforded the opportunity to defer child bearing to a time of their choosing and with the man of their choice. Banking frozen eggs does however mandate that when the decision is made to have a baby, they will have to be thawed and fertilized before being transferred to the uterus…….. In other words, IVF will be needed. The emerging ability to freeze eggs has the potential of profoundly expanding the reproductive choices of women. It puts them back in the driver’s seat where they belong.
Fertility Rescue: In the past, women requiring surgery and/or chemotherapy for treatment of cancer often found themselves being propelled into a premature menopause with no hope of having a baby with their own eggs. The introduction of egg banking now affords such women the option of preserving their eggs before undergoing such treatment. In this way, once they have been cured, they have the opportunity to conceive using their own eggs. As with fertility preservation, the introduction of selectively banking CGH-tested eggs has vastly improved the efficiency of this process.
Embryo Banking: In this day and age, many couples who decide upon having a family find that they are not quite ready early on. Pressures in the workplace, financial considerations and even uncertainly regarding the stability of their relationship with their partner might justifiably drive them towards delaying building a family. Unfortunately, the biological clock cannot be reset, and for many such couples, the quality of their eggs will have declined by the time they decide to embark on family building…making it much more difficult for them to succeed. For such couples, the option of undergoing an egg retrieval, fertilizing their eggs, and then freezing (vitrifying) and banking the resulting embryos will provide a safe way to plan and time having babies. Again, the process would require IVF in spite of there being no fertility issue.
Same Sex Relationships: For same-sex male monogamous couples, IVF using donated eggs is one way to have a family. The use of a gestational surrogate and an egg donor is required in such cases. While this is of course a complex arrangement, it is far safer than the alternative, where a gestational surrogate is inseminated with a male partner’s sperm and ends up contributing her genetic package (in the egg) to the offspring. The latter situation is fraught with legal concerns regarding custody. One need only go back a few decades to recall the Baby M saga where the surrogate demanded custody of the child and a horrendous legal battle ensued.
For female same-sex couples, the options of undergoing artificial insemination using donated sperm is usually the first choice because it is less costly and is not likely to be subject to legal custody conflicts. However, for a growing number of these couples, there is a desire on the part of both that they contribute equally to the creation of the baby. In such cases, IVF is required because the process will of necessity require the harvesting of eggs from one partner and transferring the resulting embryos into the other.
Embryonic Stem Cell Technology: This is probably the most controversial of all applications of IVF. Here, in some cases of childhood disease, the use of embryonic stem cells might be the only hope of a cure. It is conceivable in such circumstances that the parents might elect to undergo IVF to gain access to embryos from which cells can be harvested for stem cell propagation and therapy to the afflicted child. It is also possible, subject to resolution of serious ethical, moral, religious and societal hurdles, that in the future, embryos might be generated specifically for the purpose of propagating stem cells for therapeutic use.
Clearly in the past, IVF was largely performed in reaction to a fertility problem but things are changing as the above article suggests. We are fast approaching a time where individuals/couples will choose proactively to undergo In Vitro Fertilization so as to secure their future child bearing potential, resolve lifestyle and career issues and/or address serious life threatening ailments.
Posted on July 20, 2010 | Filed under IVF Treatment | Permalink
An ever increasing number of women are deferring having babies until they have fulfilled career aspirations. Advancing age is associated with a progressive increase in the number of chromosomally abnormal (aneuploid) eggs and consequently a decline in egg “competence” (i.e., the ability to propagate embryos that can produce babies). Since it is predominantly the egg (rather than the sperm) that determines embryo “competence” it follows that as women get older, they experience an inevitable decline in reproductive performance which manifests in reduced fertility, as well as increased miscarriages and birth defects such as Down’s syndrome. Both are attributable to egg aneuploidy. It is therefore not surprising that the mean age of women seeking IVF services is also on the rise.
The woman’s age, largely through the effect it has on her eggs, determines both her natural fertility potential as well as her ability to achieve success following In Vitro Fertilization. But age can also impact on the woman’s ability to successfully complete a pregnancy as well as the health of the baby she gives birth to.
Older women (reproductively speaking) – especially those over the age of 39 – are much more likely to have underlying medical conditions such as diabetes, hypertension, coronary and cerebral vascular disease as well as an increased potential to develop thromboembolism. For this reason it is advisable that such women routinely undergo detailed screening before embarking on a journey to achieve a pregnancy. A full physical examination as well as pap smears, pelvic ultrasound and tests such as EKG, chest X ray, blood urea/electrolytes/creatinine/lipid profile/thrombophilia panel/liver enzymes as well as a glucose tolerance test should be done. Women who pass such testing often are not that much more at risk at developing pregnancy-induced complications such as preeclampsia, placental abruption, gestational diabetes, and pre-term delivery than are their untested counterparts. Their babies are also far less likely to be low birth weight and/or to suffer maternal age-related complications such as autism and intrauterine growth retardation.
It is unfortunate that older women only come to realize their predicament when they are already confronted with the ravages of the biological clock. At that point, most will be faced with only two options. The first is to attempt to have a baby using their own eggs; the second, to consider In Vitro Fertilization with eggs derived from young donors and which are less likely to be chromosomally abnormal. Consider the fact that at age 35, about 2 in 3 eggs are aneuploid, at 40 the chances are about 6 in 7, and at 45 years, more than 9 in 10 are “incompetent.”
Obviously, most women would far prefer to have a baby using their own eggs than those of an egg donor. In fact, in my experience, most couples will push to at least have one attempt with their own eggs before going to IVF-egg donation — even those who also have severely diminished ovarian reserve and have little chance of achieving a pregnancy with their own eggs, whether or not IVF is used. They simply have a need to reach “closure” before moving on. Not only is this understandable, but it is their right to make such a decision, which their IVF doctor should not deny them simply on the grounds that it will lower his or her statistics. It should be the patient’s choice to make, provided that there is no medical reason to believe that either the IVF process or an ensuing pregnancy will place the patient in harm’s way. It is our responsibility as IVF physicians to disclose all information necessary to patients that will enable them to make informed choices, not to dictate those choices to them.
Egg donation is the preferred treatment for all women with depleted ovarian reserve (regardless of their age) as well as for women over the age of 43 years (regardless of their ovarian reserve). The chance of a woman of 43 years or beyond having an IVF baby with her own eggs is well under 10% per attempt. Thus, any such woman desiring to use her own eggs should be informed of this fact. If, in spite of this information, she still chooses to proceed, and is physically and mentally healthy enough to do so, she should be afforded the opportunity to try. I will never forget a patient who came to me at the age of 47 years demanding to do IVF with her own eggs. In spite of my protestations, she ultimately prevailed and we embarked upon what I then considered to be an exercise in futility rather than fertility. It took several attempts but she did conceive and her healthy little boy that she delivered (my Godson) at age 48, currently bears my name. While this serves to remind us that no matter how clever we think we are…. “man proposes while G-d disposes” it should not and does not suggest a change in policy with regard to the age beyond which a woman should preferably choose to use an egg donor.
I’m often told by older women that the reason they are reluctant to use an egg donor is that this would deny them the ability to have their own biological child. My routine answer in such cases is that the woman who gives birth is by definition the biological parent. No man can bear a child and thus he can only be a genetic contributor….never a biological parent under the former definition. Under normal circumstances the woman is both a genetic contributor and a biological parent. Thus, giving up the genetic component by using donated eggs still enables the woman to share her biological contribution with her partner as a genetic parent and together with him to create a nuclear family.
There have been several important recent advances in the field of advanced assisted reproduction that provide attractive options to women who anticipate to, or find themselves already in a situation where they seek to have a child at a later age. These are the following:
- Customizing ovarian stimulation: As women get older, so do their ovaries. In the process, they respond differently to standard, “recipe” protocols of ovarian stimulation. What works in the younger woman does not necessarily work in an older woman or in a woman with diminished ovarian reserve. In such cases, protocols of stimulation need to be customized to meet individual needs. To the developing follicle and egg in such women, the biggest enemy is overexposure to LH-induced testosterone, which compromises egg development and increases the risk of egg aneuploidy. In such women, it is important to avoid protocols that either deliver too much LH (fertility drugs such as Repronex and Menopur have too much LH-like activity) or that cause the release of too much LH (“flare” protocols or the administration of Clomiphene and/or Letrozole). Ideally, in such women who undergo ovarian stimulation, LH concentrations should be kept low prior to and during the stimulation. My preference is to prescribe what we call agonist/antagonist conversion protocol (A/ACP) with or without estrogen priming. Having said this, it is important to note that even the ideal protocol cannot counter the inevitable increase in egg aneuploidy that occurs with advancing age. All it can do is avoid compromising the ovarian environment during ovarian stimulation and further prejudice egg quality.
- Blastocyst transfers: A blastocyst is an advanced embryo that contains more than 100 cells. It takes 5-6 days for healthy embryos to reach this stage. Those that do not make it are almost invariably aneuploid and not worthy of transfer. Those that do make it are more likely to be (but certainly not always) chromosomally normal. Thus, other than convenience, there is little reason to transfer earlier cleaved (day 2-3) embryos. Furthermore, by taking embryos to the blastocyst stage it is possible to improve the “efficiency” of the IVF process. With few exceptions, I recommend this to my patients.
- Vitrification (ultra rapid egg/embryo freezing): Conventional (slow freezing) causes ice crystals to form in the cells and so damages them. That is why in the past, IVF success rates using frozen eggs or embryos have been much lower. With vitrification, the rate of freezing occurs 600 times faster, thus avoiding ice crystal formation. As a result, eggs and embryos so frozen are virtually as viable as are their fresh (unfrozen) counterparts. In addition, more than 95% of embryos and eggs will survive thawing following vitrification.
- Embryo banking: Since older women often produce few eggs/embryos per cycle and a small percentage of these are likely to be “competent” there is often an advantage in performing several egg retrieval procedures sequentially (over several months) in order to stockpile as many embryos as possible. In this way, the woman can prolong her own reproductive potential by subsequently transferring 1 or more embryos to her uterus at a time.
- Genetic embryo selection: We recently introduced Comparative Genomic Hybridization (CGH) as a method for identifying chromosomally normal eggs and embryos. This process now allows us to selectively transfer only embryos that are chromosomally normal or are derived from CGH normal eggs. When we transfer such embryos, the baby rate per embryo is dramatically improved, and when we vitrify eggs that are CGH normal, the baby rate per frozen egg is at least 7-fold greater than when non-genetically tested eggs are used. CGH may well turn out to be a “game changer” in IVF, but in the case of the older women considering embryo banking, it has a special significance. In such cases, it is possible to provide the older women with more confidence that her vitrified, CGH tested, banked embryos have a high potential to propagate viable babies regardless of her age.
In cases of IVF with egg donation, CGH affords the opportunity to store only “competent” embryos and then to transfer only 1 or 2 at a time (at a later date). This avoids the risk of high order multiples (triplets or greater) and at the same time facilitates convenience in that the woman does not need to synchronize her cycle with that of her chosen donor.
Another advantage of this method is that it allows younger women to bank their eggs for future dispensation. This is especially advantageous for young women embarking on a career and who know that by interrupting their career path through having a baby, they might fall behind in the opportunities otherwise available. In other words, women who intend to delay child bearing can stop the biological clock by selectively banking their genetically tested eggs. We call this Fertility Preservation (FP). It has been estimated that the demand for FP is probably 7 or 8 times larger than for IVF.
Egg freezing also opens the door to donor egg banking. We hope soon so establish the world’s first genetically tested egg bank – wherein we will compile a large selection of CGH tested donor eggs. What this will do is allow women/couples to choose one or more eggs (based upon their need and preference) for thawing and transfer without having to embark in a detailed complex and tedious donor selection process. It will shorten the time involved in an ovum donor cycle, will improve success rates per embryo transferred (and thus reduce multiple birth rates) while drastically reducing the cost of service in the US.
Older women face two opposing situations. The first is that as they get closer to the menopause, diminishing ovarian reserve will inevitably lead to a reduction in the availability of their eggs. The second is that as they get older, the quality of their eggs will decline at an ever increasing rate. Thus, time becomes their enemy. On the other hand, once a decision is made to go to egg donation, the issues of both egg quality and ovarian reserve fall away. The only area of concern that remains is their ability to safely complete a pregnancy. It is this grappling with the decision as to whether they should use their own eggs or go to egg donation that often creates the greatest amount of torment. It is our responsibility to help them navigate this journey, and in doing so, it is often necessary to seek the assistance of qualified counselors, psychologists and sometimes even psychiatrists. As advising IVF physicians it is also important to avoid allowing personal preferences and prejudices to cloud our judgment.
As physicians who have taken the Hippocratic Oath, it is our responsibility to try our best to “avoid doing harm”. Thus, it is essential to fully evaluate all patients we treat. When it comes to IVF where we actively induce a condition that if misdirected can indeed cause harm it becomes even more important to thoroughly evaluate our patients in advance of treatment. And in the case of older women who, when it comes to pregnancy, are even more vulnerable and at potential risk this becomes even more of an imperative.
Posted on July 13, 2010 | Filed under IVF Treatment | Permalink
Fewer than 150,000 IVF procedures (out of a pool of more than 1.5 million women/couples that are believed to be in need of IVF) are currently performed yearly in the United States. In other words, fewer than 10% of patients who need IVF gain access to this treatment. The number of procedures performed barely scratches the surface of the demand. At the same time most of the more than 360 programs in this country are grossly underutilized.
One half of all the IVF procedures in the United States are probably performed in fewer than 40 programs, with the remainder divided among the rest of the clinics. Since some larger programs are doing more than 1,000 procedures a year that means that others are performing far fewer than 100. Yet no one can gain optimal expertise doing so few procedures per year. Nor can smaller programs afford to incorporate many important technologic advances in the field. It is also impossible to develop meaningful statistics, let alone confidently report them, when they are based on such small numbers of cases per clinic.
The fact that only about one in ten women who need IVF actually undergo the treatment bears is largely due to two factors: First, most women/couples who are in need of IVF often find themselves being prescribed other lesser such as reproductive surgery and intrauterine insemination that do not offer them a reasonable prospect of success. Second, since only about 20% of American women/couples have insurance that covers IVF, such expensive treatment often represents an out of pocket expense that is unaffordable to most.
The fact that even in this the “era of Viagra” many insurance companies still reimburse for procedures such as penile implants done in cases of male impotence, and yet the same providers refuse to cover infertility, is an embarrassment. Perhaps, the predominantly older male executives of these insurance companies view male impotence as a life?endangering condition and a couple’s desire to have a baby, as a vanity….Talk about a “double standard!” Also, many insurance companies cover relatively ineffectual surgeries to unblock Fallopian tubes, and in some cases for fertility hormone therapy and intrauterine insemination, but not IVF procedures. They do so either through ignorance, naivety or in the hope of avoiding or deferring IVF, probably as a cost-cutting strategy …yet another example of a “double standard”. After all, if they recognize the need for infertility treatment and are willing to pay for some forms of therapy, the only plausible explanation for denying coverage for IVF which is far more likely to be successful, is to cut their expenses and bolster profit. Americans deserve better.
Insurance companies would no doubt argue that they are reluctant to pay for IVF treatment for two basic reasons. The first is the unacceptably high cost associated with caring for mothers and babies compromised as a result of the very high incidence of IVF-multiple pregnancies (especially triplets or greater). The second is that IVF statistics currently reported annually by the Society for Assisted Reproductive Technology are delivered unaudited and unaccredited. While most IVF programs are honest in the reporting of there statistics, this not true for all, giving some credence to the claim by insurance providers that without access to valid outcome statistics they are unable to determine the cost of doing business.
So should Federal or State government mandate that insurance companies pay for all IVF? Some states already do, but this has led to internal cost-cutting trends that can prejudice standards of care. So, I personally do not favor mandatory regulation. I do, however, strongly advocate independent accreditation of all IVF programs. All United States IVF programs should submit their statistics on quality of service for review by an impartial accrediting agency. There are strong incentives for IVF programs to participate in such accreditation, including the argument that, (provided accreditation is accompanied by a forced limitation in the number of embryos transferred so as to reduce the incidence of multiple births), insurance companies should start stepping up to the plate when it cones to covering IVF .
I believe that until IVF programs become accountable and submit to a full and transparent accreditation process that verifies their IVF success rates, we will not achieve universal insurance reimbursement for IVF. As a result, the remaining 90% of couples who need this treatment will continue to be left out in the cold. And why should the size of the pocket book determine the ability to have a family?
I firmly believe that accountability and legislation should go hand in hand. Neither approach would be entirely successful alone. But it will not be easy to accomplish these changes. Convincing insurance companies that it is in their own best interests to fund IVF performed by accredited programs will be a long, slow process. And until there is more accountability by individual IVF programs, insurance companies forced to fund procedures with widely varying outcomes might be expected to lobby for repeal of mandatory reimbursement laws.
Under such a system, IVF programs might submit to an ongoing process of peer review. Participating programs would register each prospective patient with the accrediting body prior to initiation of treatment. A patient code number could ensure confidentiality, and registration of the patient with the society would guarantee proper data interpretation. New programs that initially submit themselves for accreditation could have 12 months to demonstrate an ability to meet “acceptable” operational and outcome standards. Programs wishing to apply for accreditation after the first year could submit to a similar prospective evaluation or may elect to undergo a detailed retrospective audit according to the standards set forth by the accrediting body’s peer?review committee. Instead of eliminating marginal IVF programs (which might otherwise occur under government?mandated regulation), such an accrediting body would set an example and would even help struggling programs upgrade their standards and performance in the area of high?tech infertility treatments. Each accredited program would undergo an annual peer review to become re-accredited. This would provide an ongoing assurance of proficiency to the consumer and to the referring doctor, and would also give each program important feedback regarding its own performance.
I further anticipate that participation in such an accrediting process would snowball as IVF programs become convinced that accreditation would be in their own best interest for the sake of insurance reimbursement, and to forestall mandatory regulation by federal or state governments.
Ultimately, consumers can control the debate. They may have to band together to make their voices heard against the forces of the marketplace, but they can bring about change. Now is the time for IVF consumers to be outspoken. If they don’t participate in the campaign to put the IVF house in order, they will have only themselves to blame if progress towards insurance reimbursement comes slowly. One of the most promising lobbying avenues would be to join one of the infertility support groups, both to become more informed, and to speak with a louder voice before the medical profession, legislative groups, and the insurance industry.
It is time for consumers to marshal their buying power to demand that these “Four A’s” in the field of high?tech infertility management are met:
Accreditation of IVF programs
Accountability by the medical profession with regard to providing validated statistics or a track record, and instilling rational expectations in infertile couples who seek their advice.
Availability and access to the consumer of state?of?the?art standards of care.
Affordability of services to all those in whom they are indicated.
Posted on July 7, 2010 | Filed under IVF Treatment | Permalink
An ever increasing number of American women first seek IVF treatment in their late 30’s or early 40’s.This trend is in large part due to the fact that more and more women are choosing to defer childbearing until they have fulfilled their career aspirations. While such deliberate deferment is understandable, it nevertheless poses significant problems, because women in their late 30’s and early 40’s have about one half the chance of having a baby following IVF than do women in their early to mid 30’s. There are two primary reasons for this:
First is the fact that advancing age beyond 35 years is accompanied by an inevitable and progressive increase in chromosomal egg abnormalities (aneuploidy) which lead to “incompetent” embryos that cannot propagate viable pregnancies. That is why we see a profound and steady decline in IVF success rates as well as an increase in chromosomal miscarriages and birth defects such as Down’s syndrome with advancing maternal age.
Second, as women get older, there occurs a progressive decline in their ovarian egg supply. This so-called “diminished ovarian reserve” (DOR) results in less eggs being accessible via egg retrieval and consequentially, fewer “competent” embryos available for transfer to the uterus.
Most women/couples would like to have more than one child. This desire is no less prevalent in older women. However, by the time the older woman decides to do IVF, goes through the process successfully, has a baby, completes breastfeeding, and thereupon re-establishes regular menstruation in order to try for another IVF baby, a period of 2-3 years will have elapsed. While such a hiatus would usually be of little consequence to a young woman, for an older woman such a delay could seriously impact her “biological clock” so as to drastically reduce her chance of having another baby with her own eggs.
Egg/embryo banking offers a potential solution for older women and those with DOR who wish to minimize the relentless effect of the biological clock. The process involves undergoing several IVF stimulation/egg retrieval procedures in relatively quick succession, and then freezing/banking all viable embryos for future dispensation, rather than having them transferred to the uterus immediately. Such embryo “stockpiling” would literally stop the biological clock in its tracks, allowing for the subsequent elective thawing of one or two frozen embryos at a time in future frozen embryo transfer (FET) cycles. This process would avert the risk of progressive declining egg/embryo “competency” over time.
The concept of embryo banking/stockpiling would not have been feasible even 5 years ago, since it was not until quite recently that we became able to reliably identify chromosomally normal (“competent”) embryos for selective banking. Embryo freezing technology has also evolved dramatically over that time. Just a few years ago, the freezing process took a serious toll on embryos, severely damaging up to 50% of them in the freeze/thaw process. But that was then…Today, through the adaptation of comparative genomic hybridization (CGH) technology to egg and/or embryo selection we are able to much better identify “competent” embryos for banking and stockpiling. In addition, the recent introduction of much improved egg/embryo freezing through ultra-rapid cryopreservation (i.e. vitrification) eliminates most of the potential damage incurred to “competent” embryos during the freezing and thawing process. In fact, in IVF centers of excellence, the frozen embryo transfer (FET) process using vitrified/thawed embryos now yields the same IVF success rate as when fresh embryos are transferred!
These innovations (CGH and Vitrification) have not only made embryo banking/stockpiling feasible, but have rendered the approach a most appealing option for older women and women with DOR who seek to undergo IVF using their own eggs.
This having been said, CGH is not an indispensable part of embryo banking. The process can be done without it. But, given the inevitability of an age-related increase in the incidence of chromosomal abnormalities in the egg/embryo, it would be impossible for patients to know whether they have stored “competent” embryos and which ones to transfer to the uterus for the best chance of success when the time comes.
I want to emphasize that CGH does not improve embryo quality. It is an efficiency tool that allows us to select “competent” embryos for transfer and thereby dramatically improve the baby rate per embryo transferred. It is also well to bear in mind that aneuploidy not only reduces the chance of a successful pregnancy but it is also the cause of miscarriages and many birth defects (e.g. Down’s syndrome). Thus CGH embryo selection not only improves IVF success (per embryo transferred), but it also reduces the incentive to transfer multiple embryos at a time, thereby virtually eliminating the occurrence of high-order multiple pregnancies (triplets or greater).
Proudly, we at SIRM were the first to introduce CGH embryo selection into the clinical IVF arena. Since then, we have reported hundreds of successes using this approach, which is finally starting to gain wide acceptance in the IVF field. We were also among the first in the United States to supplant conventional egg/embryo freezing with “vitrification.” It is against this background that we now provide selective embryo banking/stockpiling to an ever increasing number of older women and women with DOR. We have already witnessed the profound benefits of such an approach.
Finally, embryo banking/stockpiling would also have appeal to younger women who plan on deferring having children until later in life – or who want to at least have the option available, should their life/career path so dictate. Even some fertile women for whom IVF would otherwise not be necessary could fall into this category.
Through our technology and package pricing, we at SIRM have attempted to make this approach relatively accessible to those that need or desire access to this advantage.
Posted on June 29, 2010 | Filed under IVF Treatment | Permalink
It is only through propagation of our biological offspring that we as humans can leave a lasting legacy of our existence. Perhaps this explains why the desire to have children is a basic human instinct and why an inability to achieve this goal (infertility) often leads to considerable psychological and social strain. Infertility evokes a strong sense of failure, loss and helpless leading to one of life’s most distressing crises.
According to an article published a few years ago in the Journal of Philosophy, Science and Law: “Seven out of ten children and young adults with cancer can be cured. Accordingly, by the end of this decade, an estimated one in two hundred and fifty adults will be survivors of childhood cancer.” Unfortunately for many of them, one of the long-term risks of treatment is infertility
Many cancer chemotherapy and/or radiation regimens that are directed at the reproductive organs will render the patients infertile. It is argued by some that cancer survivors should be so grateful as to ignore the “inconvenience” of having been rendered infertile by the treatment they underwent — that the burden of post-treatment infertility pales in significance when compared to the long term and often life-endangering complications associated with radiation and chemotherapy. Moreover, those who make this argument often take the position that such patients could always have a baby through using donated eggs or sperm. But this dispassionate attitude ignores the fact that most people crave having their own biological children.
In the last decade, the advances in Reproductive Technology have made it possible for cancer patients to have their sperm or eggs collected and cryopreserved (frozen) for post-recovery dispensation. For males, the collection and cryopreservation of sperm specimens is quite uncomplicated and efficient, while for females gaining access to eggs for cryopreservation is significantly more involved and costly. It requires the prior administration of fertility hormones for more than a week followed by a surgical procedure (egg retrieval), performed under local or general anesthesia.
The recent introduction of a procedure known as in vitro maturation (IVM), where the woman has her eggs harvested without having to undergo prior hormonal stimulation, would simplify the procedure of egg collection for cryopreservation. It would shorten the delay in starting cancer therapy and would reduce the cost associated with egg banking. The bad news is that as yet, the efficacy of the IVM process in securing viable eggs for banking is by no means established.
Another troublesome problem is the fact that conventional egg banking has until recently been much of a hit-and-miss proposition. The baby rate per frozen egg has hovered around 3-4%….hardly sufficient to give a woman confidence that that her banked eggs will ultimately produce a baby for her. This low yield per frozen egg is the reason that most egg banks advise women to freeze a large numbers of eggs (15-20) in advance of undergoing cancer therapy in order to provide reasonable level of confidence that banked eggs will ultimately produce a baby. Sadly, ignorance of this reality has led many women to freeze eggs with only a false sense of expectation that by doing so, they will ultimately be able to be mothers.
A recent major advance promises to change all this. It involves a genetic test [comparative genomic hybridization (CGH)] that selectively identifies those eggs that are most likely to make a baby. In fact, a CGH selected frozen egg yields a baby rate of 27%, which is eight-fold higher than previously attainable. As such, the selective banking of 4-6 such “competent” eggs should provide a far greater level of confidence and offer particular promise for young female cancer victims scheduled to undergo chemotherapy/radiotherapy.
Another obstacle to fertility preservation via egg freezing is that cancer patients rarely have the luxury of time to undergo these procedures. Additionally, some patients (e.g. young women with estrogen-receptor-positive breast cancer), the use of fertility hormones might be contraindicated for medical reasons, due to the potential for increasing the rate of cancer cell growth. This is perhaps where IVM, once the technology matures, could provide a significant advantage.
Then there is the issue of financial cost of fertility preservation. Insurance companies and government payers rarely cover the costs. While the freezing and storage of eggs is not that much more expensive than the analogous service for sperm, the costs associated with the ovarian stimulation, egg retrieval, and anesthesia can be considerable – and in the current economic environment must be totally borne by the patient and/or her family.
The bottom line is that technology is indeed available to help cancer patients preserve the option of having biological children. Since we now have the know-how to preserve human gametes (eggs and sperm), the preservation of fertility for cancer patients should become a standard service available to all those in need of it, rather than a “luxury” reserved only for those who can afford it. Unfortunately, major challenges remain that prevent this from becoming a reality.
Posted on June 21, 2010 | Filed under IVF Treatment | Permalink
I’m pleased to announce that in addition to my blog, we have created a forum for the other Sher Institute physicians, embryologists and clinical staff to post their articles and insights. You can find it at:
www.haveababy.com/infertilityblog
Dr. Tortoriello has written the inaugural post on Minimal Stimulation IVF. Please feel free to visit and post your comments and suggestions on what topics you would like to see addressed.
- Geoff Sher
Posted on June 16, 2010 | Filed under IVF Treatment | Permalink
Sadly, in spite of major advances in the treatment of infertility, one the biggest challenges that remains is the reluctance on the part of many men to confront their role in the infertility equation. It is still somewhat common to have a woman arrive for an infertility consultation without her partner. Thus, at this time of “Men’s Health Month”, it is appropriate to make men aware of the indispensible nature of their contribution to, and participation in the evaluation and management of infertility.
One third of infertility is due to the man, one third the woman and the remaining third, a combination of both partners. With male factor infertility playing such a large role and about 10% of men having some degree of sperm dysfunction, the unwillingness on the part of many men to step up to the plate and confront their role in this equation is a matter of concern. Perhaps this reluctance to confront their reduced procreative ability is centered on an ill-conceived notion that male infertility equates with reduced virility. This is certainly not helped any by the fact that most reproductive research has in the past been conducted by men.
It was not until the last quarter of the 20th century that significant scientific attention was paid to the evaluation and treatment of the infertile male. Not only was the understanding of male infertility poor, but to make matters worse, there was no reliable treatment available. Procedures such as artificial insemination (intrauterine insemination or IUI) hardly improved success rates, (especially when used in cases of moderate or severe male infertility), surgeries such as varicocelectomy to remove a collection of varicose veins around the testicles was rarely of benefit and the use of fertility drugs to enhance the production of sperm was poorly understood and thus mostly futile.
Then came the introduction of In Vitro Fertilization (IVF) and with it, a new found ability to successfully treat several, hitherto intractable causes of female infertility (tubal blockage and severe endometriosis, etc.). IVF sparked a hope that it would also benefit treatment of male factor infertility. Alas, this was not to be, because the same factors that prevented sperm from fertilizing an egg in the woman’s body similarly compromised the process of fertilization in a Petri dish.
But all this was soon to change. The advent in the early 90’s of Intracytoplasmic Sperm Injection or ICSI which involves the injection of a single sperm directly into each egg to fertilize it, was to revolutionize the treatment of male infertility. ICSI soon found its rightful place in the growing infertility therapeutic armamentarium… to the point that today, this approach is used with considerable success to treat more than 90% of male infertility. What is more, reported pregnancy rates achieved by this method of fertilization are as high as those obtained using conventional IVF performed in cases of non-male-factor infertility.
There have also been major advances in the ability to enhance sperm production through the use of selective therapies in men with reduced sperm function due to hormonal factors. In addition, the use of antioxidant and vitamin therapies with male fertility blends such as ProXeed or Proceptin have been shown to improve sperm function in certain cases. Additionally, surgical removal of early spermatozoa from the testicle – called Testicular Sperm Extraction or TESE (with subsequent performance of ICSI) has assisted in achieving success in men who are not capable of ejaculating any sperm at all.
The first step in addressing male infertility is to obtain a detailed history and then to perform a basic computerized semen analysis so as to assess sperm structure and function. From the history, factors that might have compromised testicular sperm production can often be identified. Relatively common causes of the latter include failure of both testicles to have descended into the scrotum at the time of birth, childhood testicular infection with viruses such as mumps, testicular trauma or injury during childhood or early adulthood, exposure to radiation or chemotherapy for cancer, and toxicity from heavy metals such as lead or mercury that could injure the sperm bearing tissue in the testicles.
Then there are those cases where the man’s brain and the pituitary gland (a small gland that hangs beneath its base) fail to adequately stimulate the testicles to produce sperm. In most such cases, the diagnosis can be made by testing blood levels of testosterone, Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). In some cases, the underproduction of FSH and LH will be apparent and readily amenable to treatment with medications that reverse this effect. In other cases, a high concentration of these hormones will point to (usually) irreversible, permanent damage.
It remains a fact that unless moderate or severe male infertility can be reversed through simple medical or surgical intervention, treatment will be unsuccessful without access to In Vitro Fertilization (IVF) with ICSI. Perhaps this post will help persuade men to take a more active role in the evaluation of infertility.
For those men/couples who have not been evaluated for male factor issues, SIRM is now offering a free semen analysis at any of our offices. I encourage you to contact your nearest SIRM office to take advantage of it.
Posted on June 16, 2010 | Filed under IVF Treatment | Permalink
Sadly, in spite of major advances in the treatment of infertility, one the biggest challenges that remains is the reluctance on the part of many men to confront their role in the infertility equation. It is still somewhat common to have a woman arrive for an infertility consultation without her partner. Thus, at this time of “Men’s Health Week”, it is appropriate to make men aware of the indispensible nature of their contribution to, and participation in the evaluation and management of infertility.
One third of infertility is due to the man, one third the woman and the remaining third, a combination of both partners. With male factor infertility playing such a large role and about 10% of men having some degree of sperm dysfunction, the unwillingness on the part of many men to step up to the plate and confront their role in this equation is a matter of concern. Perhaps this reluctance to confront their reduced procreative ability is centered on an ill-conceived notion that male infertility equates with reduced virility. This is certainly not helped any by the fact that most reproductive research has in the past been conducted by men.
It was not until the last quarter of the 20th century that significant scientific attention was paid to the evaluation and treatment of the infertile male. Not only was the understanding of male infertility poor, but to make matters worse, there was no reliable treatment available. Procedures such as artificial insemination (intrauterine insemination or IUI) hardly improved success rates, (especially when used in cases of moderate or severe male infertility), surgeries such as varicocelectomy to remove a collection of varicose veins around the testicles was rarely of benefit and the use of fertility drugs to enhance the production of sperm was poorly understood and thus mostly futile.
Then came the introduction of In Vitro Fertilization (IVF) and with it, a new found ability to successfully treat several, hitherto intractable causes of female infertility (tubal blockage and severe endometriosis, etc.). IVF sparked a hope that it would also benefit treatment of male factor infertility. Alas, this was not to be, because the same factors that prevented sperm from fertilizing an egg in the woman’s body similarly compromised the process of fertilization in a Petri dish.
But all this was soon to change. The advent in the early 90’s of Intracytoplasmic Sperm Injection or ICSI which involves the injection of a single sperm directly into each egg to fertilize it, was to revolutionize the treatment of male infertility. ICSI soon found its rightful place in the growing infertility therapeutic armamentarium… to the point that today, this approach is used with considerable success to treat more than 90% of male infertility. What is more, reported pregnancy rates achieved by this method of fertilization are as high as those obtained using conventional IVF performed in cases of non-male-factor infertility.
There have also been major advances in the ability to enhance sperm production through the use of selective therapies in men with reduced sperm function due to hormonal factors. In addition, the use of antioxidant and vitamin therapies with male fertility blends such as ProXeed or Proceptin have been shown to improve sperm function in certain cases. Additionally, surgical removal of early spermatozoa from the testicle – called Testicular Sperm Extraction or TESE (with subsequent performance of ICSI) has assisted in achieving success in men who are not capable of ejaculating any sperm at all.
The first step in addressing male infertility is to obtain a detailed history and then to perform a basic computerized semen analysis so as to assess sperm structure and function. From the history, factors that might have compromised testicular sperm production can often be identified. Relatively common causes of the latter include failure of both testicles to have descended into the scrotum at the time of birth, childhood testicular infection with viruses such as mumps, testicular trauma or injury during childhood or early adulthood, exposure to radiation or chemotherapy for cancer, and toxicity from heavy metals such as lead or mercury that could injure the sperm bearing tissue in the testicles.
Then there are those cases where the man’s brain and the pituitary gland (a small gland that hangs beneath its base) fail to adequately stimulate the testicles to produce sperm. In most such cases, the diagnosis can be made by testing blood levels of testosterone, Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). In some cases, the underproduction of FSH and LH will be apparent and readily amenable to treatment with medications that reverse this effect. In other cases, a high concentration of these hormones will point to (usually) irreversible, permanent damage.
It remains a fact that unless moderate or severe male infertility can be reversed through simple medical or surgical intervention, treatment will be unsuccessful without access to In Vitro Fertilization (IVF) with ICSI. Perhaps this post will help persuade men to take a more active role in the evaluation of infertility.
For those men/couples who have not been evaluated for male factor issues, SIRM is now offering a free semen analysis at any of our offices. I encourage you to contact your nearest SIRM office to take advantage of it.
Posted on June 14, 2010 | Filed under IVF Treatment | Permalink
Procreation – and with it the ability to achieve immortality by living on through one’s children – is one of the most insatiable human needs. This strong natural urge exerts tremendous pressure on couples unable to have a baby. And the pressure to reproduce becomes increasingly acute as couples grow older and become more aware of their own mortality. The introduction of In Vitro Fertilization (IVF) more than 30 years ago has made parenthood possible for millions who otherwise would never have been able to conceive.
The biggest decision an infertile couple will ever make in regard to IVF is whether or not they really want to become parents. An IVF procedure requires an enormous emotional commitment at each level of the program, whether or not IVF is successful. This has a permanent impact on the couple. Because the toll can be so great, both partners must be committed to supporting each other from the very beginning.
The IVF process is stressful and since in general per egg retrieval, there is at least as great a chance of not being successful, it is essential for IVF patients and their partners to be realistic about the prospects – to be guardedly optimistic but to prepare themselves emotionally so that they are not overwhelmed by failure in case IVF does not succeed. Both partners should be prepared to respond to a variety of emotionally stressful demands as they undergo IVF, including:
- Dealing with general stress “baggage” (shame, guilt, anxiety, depression, anger) they bring into the program because of their long?standing battle with infertility
- Following new procedures; interacting with a strange and sometimes impersonal clinical staff, and perhaps with a constantly changing cast of characters
- Living in an unfamiliar environment: many couples will travel from another state or country to undergo IVF in a good program. This encompasses a different daily schedule, time?zone changes, and separation from their normal support network
- Coping with the unpredictable emotions that the fertility drugs trigger in the woman
- Reacting to family and marital stress, which may be heightened by the constant need for mutual support
- Managing the financial aspects of the procedure
Couples react to the demands of IVF in strikingly different ways.
One expectant mother found that the stimulation phase of her second IVF treatment cycle (her first cycle had ended in an ectopic pregnancy) was the most stressful:
“One of the most difficult things I went through was the roller?coaster ride
waiting for the estradiol level. Would it be high enough? Would I have enough
eggs? Would I have to be on another day of fertility injections? It was really
the most exhausting part of the entire process.”
The mother of a one?month?old IVF son also found the waiting to be most trying:
“The expectation between each step was difficult for me. But waiting for the
pregnancy test?that was the hardest part!”
In contrast, the mother of IVF triplets said:
“I was at the point of giving up, and then found new hope through IVF. I was so
excited and exhilarated through the whole process that the time just flew by.”
Having a baby should represent the “icing on the cake;” the couple’s relationship should represent the “cake” itself. IVF often imposes significant stress on a relationship. It is thus very important that couples undergoing IVF be made aware of this fact and counseled that they should not lose sight of the other aspects of their relationship.
One nurse?coordinator reminds her patients to…
” ‘Lighten up’ a bit by writing prescriptions for candlelight and wine.”
The father of triplets, meeting with a group of other IVF couples, commented:
“All of us have one thing in common?we’ve been through the highs and lows of
IVF. My wife and I represent the high! But it wasn’t always easy for us. I
can’t emphasize enough how important it is for everyone to keep their chin
up through the whole procedure.”
Another man, holding his one?month?old son in his arms, added:
“I would encourage everyone definitely to maintain a positive attitude. The
hardest part of the whole procedure is dealing with failures. It’s inevitable
that when the first IVF attempt fails you just stop wanting to try because you
don’t want to fail again. If you could just keep it in perspective and know IVF
is a trial?and?error scientific procedure and sometimes you just have to expect
problems that will help a great deal.”
It is important for couples to realize that there is little the woman can do to influence outcome following IVF in either a positive or negative way. Women often tend to blame themselves when they get a negative result. This is almost always unfounded and counterproductive, but it is also unfortunately relatively inevitable. Appropriate counseling and a good emotional support system can go a long way toward minimizing this misperception.
Proper emotional preparation and mutual support throughout the treatment cycle will help both partners cope more effectively with the physical demands on the woman. And they should keep in mind that once the pregnancy is confirmed, the remainder of the gestational period will probably vary little from pregnancies experienced by all other expectant women.
The financial risk in IVF is great, but the return can be priceless. That is why it is so important for each couple to be absolutely sure of their willingness and financial ability to make such an investment before they attempt IVF. Yet more and more couples are willing to make the financial commitment. Why? When asked if he and his wife had difficulty deciding whether to undergo IVF given its cost and uncertain outcome, one new IVF father responded:
“Well, when you really want children you set your priorities. We think babies
are more important than fancy vacations or a sailboat. We were able to budget
for IVF. But we’re sorry that insurance doesn’t usually cover it because a lot
of people just can’t spend $10,000 or so to go through these procedures.”
Because of the emotional, physical, and financial toll exacted by IVF, it is preferable that no one undertake a one?shot attempt. If a couple can only afford one treatment cycle, IVF is probably not the right procedure for them. After all, there is only about one chance in three that IVF will be successful?and a tremendous letdown if it fails.
I believe it is unreasonable to undergo IVF with the attitude that “if it doesn’t work the first time, we’re giving up.” In vitro fertilization is a gamble even in the best of circumstances. But statistically speaking, the couple who have selected a good IVF program are likely to have a better than 70% chance if they undergo IVF three times, as long as their gametes can fertilize, and the woman is under 40 with a normal uterine cavity and a proper hormonal environment.
Unfortunately, some people will ultimately be unsuccessful. Repeated IVF failures and disappointments can exact such a financial and emotional toll as to become counterproductive and destructive on relationships. There is a time to stop trying. Couples trying to have a baby should always examine the option of adoption which can be very rewarding because it addresses both fertility as well as a social need. In my opinion, it is rarely advisable to undergo IVF repeatedly without there being a well defined and potentially remediable cause for failure.
One woman (who eventually adopted a newborn boy) described her disappointment over three failed IVF procedures:
“It’s very difficult to deal with. You go into any of these procedures with the
expectation they will work. Somehow we are raised in our society to think that
it’s not whether you are going to have children, but how many do you want? We
plan for our car, and we plan for our house?and assume that the children are
going to come. And when they don’t, it’s devastating. You are basically out of
control of your own body. There is nothing that you can do to make the egg and
sperm unite.”
Couples who choose to undergo IVF should realize from the outset that the inability to become pregnant should never be considered a reflection on them as individuals. They should view the entire procedure with guarded optimism but nevertheless must be emotionally prepared to deal with the ever?present possibility of failure.
Posted on June 7, 2010 | Filed under IVF Treatment | Permalink
There is currently a lively media debate raging on whether a woman’s age, sexual orientation, marital status or economic strength should influence her eligibility to undergo advanced fertility treatments such as IVF. Perhaps not surprisingly, the most vociferous opposition has come from those who already have children of their own, from women who in spite of (often repeated attempts at) fertility treatments have failed to conceive and from those who for whatever reason have chosen not to have children.
Discrimination on the basis of the woman’s age:
Those who speak out against older women (over the age of 50 years) embarking on a quest for parenthood usually parents use two arguments to support their position. The first is that pregnancy carries with it such significant, incremental age-related medical risks to both mother and baby that it is inordinately dangerous for older women to conceive and accordingly that any medical interventions aimed at propagating conception would verges on being morally and ethically reprehensible.
The second argument relates to parenting risks. The argument advanced is that with progressive aging, older women will lack the physical ability to share in the common formative physical activities with their offspring, and that the emerging generation gap would ultimately become so wide as to compromise child rearing and finally, that there would be a greater risk of the child being orphaned at an early age without having fully benefited from parenting.
1. Age-related medical risks: It is indeed indisputable that in general, pregnancy in older women is associated with increased risk to both mother and baby. Pregnancy-induced complications (e.g. preeclampsia, gestational diabetes, intrauterine growth retardation, premature separation of the placenta, preterm delivery, low birth weight, dysfunctional labor and caesarean section) are all far more likely to occur in older women. However, this risk can be mitigated by in advance identifying those older women who are most predisposed to developing such complications.
The following assessments in advance of pregnancy would allow for screening out those women who for medical reasons should not undergo fertility treatments:
§ Tests of cardiovascular status include physical examination, effort EKG , blood lipid-profiling and Chest X-ray
§ Predicting the risk of gestational diabetes through glucose tolerance testing and blood insulin levels
§ Assessing the risk of preeclampsia by testing liver enzymes, blood BUN, electrolytes and creatinine and through advance evaluation for hereditary blood clotting; tendencies (thrombophilia)
§ Evaluation of the integrity of the woman’s reproductive apparatus through physical and pelvic ultrasound examinations
§ Tests for blood diseases such as severe anemia, lymphoma and leukemia include a complete blood and platelet count, measurement of the blood sedimentation rate, iron and folic acid levels as well as selective evaluation of women of African extraction for Sickle Cell disease and those of Asian and Mediterranean extraction for Thalassemia
§ Psychological screening
When women so deemed to be at risk are selectively precluded from proceeding, the physical risk of age-related complications can be minimized.
2. Parenting risks: The common argument made is that the mother might either not live long enough or because of age-related maladies, might not be able to afford her child all the benefits of parenting. I would argue that less than 5 decades ago the average lifespan of women was in the mid-70. Today through women commonly live into their eighties. While it is true that advancing age might well compromise the ability to fully participate in some physical activities with their children, other advantages that age brings to child rearing such as enhanced wisdom, and a greater likelihood of financial and marital stability as well as preservation of the nuclear family, would in my opinion more than offset any disadvantages. Rather such age-related benefits might better prepare children for the real challenges of life in the 21st century. But surely the same parenting concerns should apply to men becoming fathers at an older age. Singling out women in this regard represents a double standard and is somewhat sexist, in my opinion.
Discrimination on the basis of sexual preference:
Over the last 29 years I have been instrumental in assisting more than 100 same sex couples have IVF babies and I can truly testify that in my experience they have usually turned out to make exemplary parents. This has especially been the case with same-sex female couples who often have more stable and lasting relationships than do male counterparts. Frankly, in my opinion, same-sex couples who decide to have a family together often give the issue much more sober consideration than is the case for many heterosexual couples. It is almost as if, given the hitherto non-legally binding relationship that “gay couples” have to live with, they recognize the complexity and gravity of the road they are embarking on and as such, take the step to IVF (or other forms of fertility enhancement) much more seriously.
I recently had the great privilege of attending the Bar and Bat Mitzvahs sponsored by the parents of a set of IVF twins. Also attending the festivities was single gay gentlemen whom I had helped have a daughter through use of an egg donor and gestational carrier. With him was his beautiful 11 year old daughter. He and I spoke about his relationship to her and I also spent time talking to his daughter, the love of his life. The joy that these two beautiful people had brought into each other’s lives was obvious. His love and adoration for her and hers for him was absolutely indisputable. Similar encounters that I have had with many same-sex IVF parents and their children over the years has left me realizing that sexual orientation is irrelevant when it comes to parenting. It does not leave the children confused about their own sexuality. An individual’s sexual identity and orientation is probably well established in early childhood. In the final analysis what matters is love and commitment between two people choosing to have a family. Not their sexual orientation.
Discrimination on the basis of marital status:
While there can be little doubt that children born to single parents are often disadvantaged through absence of a nuclear family setting. In addition, it is a reality that in these harsh economic times, it often takes two bread winners in a family to get by…let alone provide the where with all to support the needs of a child. This having been said, the fact remains that the modern institution of marriage is under siege, with more and more couples choosing to cohabit without “tying the legal knot”. This inevitably has led to a steady rise in the number of babies being born out of wedlock as well as ever increasing number of unmarried individuals and couples being diagnosed with infertility and seeking medical assistance to have a baby….and the number is expected to continue to rise. This is a reality that cannot be ignored or wished away. To turn our backs on such women/couples would be unthinkable, in my opinion.
Discrimination on the basis of Economic status:
I strongly protest the notion that anyone has the right to deny an individual or couple the right to have a family through medically assisted reproduction purely on the basis of the economic status of the prospective parent(s). After all, this never comes into the equation with natural, non-assisted reproduction. So why should it apply when it comes to assisted reproduction. Needless to say, there is a need and an obligation to counsel the economically disadvantaged who seek infertility treatment as to the short and long term financial consequences of having a child. Of course a legitimate question arises as to who should pay for the often expensive advanced fertility treatment needed in such cases. That is a different matter altogether. It is up to individual societies to determine how far the obligation to subsidize such medical benefits should go.
I have long held that it is not the role of a physician to dictate medical treatment to patients. I also believe that we have no right to deny access to advanced fertility treatments purely on the basis of a woman’s age, marital status, sexual orientation or the size of her pocket book. Rather, it is our role is to provide sufficient information to allow patients to make their own informed choices. Thereupon, provided that doing their bidding does not conflict with our own ethical/moral stance, and ever conscious of the tenant of the “Hippocratic Oath”, that binds physicians to “do no harm”, we are obligated to provide optimal medical care.
Posted on June 3, 2010 | Filed under IVF Treatment | Permalink
There is currently a lively media debate raging on whether a woman’s age, sexual orientation, marital status or economic strength should influence her eligibility to undergo advanced fertility treatments such as IVF. Perhaps not surprisingly, the most vociferous opposition has come from those who already have children of their own, from women who in spite of (often repeated attempts at) fertility treatments have failed to conceive and from those who for whatever reason have chosen not to have children.
Discrimination on the basis of the woman’s age:
Those who speak out against older women (over the age of 50 years) embarking on a quest for parenthood usually parents use two arguments to support their position. The first is that pregnancy carries with it such significant, incremental age-related medical risks to both mother and baby that it is inordinately dangerous for older women to conceive and accordingly that any medical interventions aimed at propagating conception would verges on being morally and ethically reprehensible. The second argument relates to parenting risks. The argument advanced is that with progressive aging, older women will lack the physical ability to share in the common formative physical activities with their offspring, and that the emerging generation gap would ultimately become so wide as to compromise child rearing and finally, that there would be a greater risk of the child being orphaned at an early age without having fully benefited from parenting.
1. Age-related medical risks: It is indeed indisputable that in general, pregnancy in older women is associated with increased risk to both mother and baby. Pregnancy-induced complications (e.g. preeclampsia, gestational diabetes intrauterine growth retardation, premature separation of the placenta, preterm delivery, low birth weight, dysfunctional labor and cesarean section ) are all far more likely to occur in older women. However, this risk can be mitigated by in advance identifying those older women who are most predisposed to developing such complications.
The following assessments in advance of pregnancy would allow for screening out those women who for medical reasons should not undergo fertility treatments:
§ Tests of cardiovascular status include physical examination, effort EKG , blood lipid-profiling and Chest X-ray
§ Predicting the risk of gestational diabetes through glucose tolerance testing and blood insulin levels
§ Assessing the risk of preeclampsia by testing liver enzymes, blood BUN, electrolytes and creatinine and through advance evaluation for hereditary blood clotting; tendencies (thrombophilia)
§ Evaluation of the integrity of the woman’s reproductive apparatus through physical and pelvic ultrasound examinations
§ Tests for blood diseases such as severe anemia, lymphoma and leukemia include a complete blood and platelet count, measurement of the blood sedimentation rate, iron and folic acid levels as well as selective evaluation of women of African extraction for Sickle Cell disease and those of Asian and Mediterranean extraction for Thalassemia
§ Psychological screening
When women so deemed to be at risk are selectively precluded from proceeding, the physical risk of age-related complications can be minimized.
2. Parenting risks: The common argument made is that the mother might either not live long enough or because of age-related maladies, might not be able to afford her child all the benefits of parenting. I would argue that less than 5 decades ago the average lifespan of women was in the mid-70. Today through women commonly live into their eighties. While it is true that advancing age might well compromise the ability to fully participate in some physical activities with their children, other advantages that age brings to child rearing such as enhanced wisdom, and a greater likelihood of financial and marital stability as well as preservation of the nuclear family, would in my opinion more than offset any disadvantages. Rather such age-related benefits might better prepare children for the real challenges of life in the 21st century. But surely the same parenting concerns should apply to men becoming fathers at an older age. Singling out women in this regard represents a double standard and is somewhat sexist, in my opinion.
Discrimination on the basis of sexual preference:
Over the last 29 years I have been instrumental in assisting more than 100 same sex couples have IVF babies and I can truly testify that in my experience they have usually turned out to make exemplary parents. This has especially been the case with same-sex female couples who often have more stable and lasting relationships than do male counterparts. Frankly, in my opinion, same-sex couples who decide to have a family together, often give the issue much more sober consideration than is the case for many heterosexual couples. It is almost as if, given the hitherto non-legally binding relationship that “gay couples” have to live with, they recognize the complexity and gravity of the road they are embarking on and as such, take the step to IVF (or other forms of fertility enhancement) much more seriously.
I recently had the great privilege of attending the Bar and Bat Mitzvahs sponsored by the parents of a set of IVF twins. Also attending the festivities was single gay gentlemen whom I had helped have a daughter through use of an egg donor and gestational carrier. With him was his beautiful 11 year old daughter. He and I spoke about his relationship to her and I also spent time talking to his daughter, the love of his life. The joy that these two beautiful people had brought into each other’s lives was obvious. His love and adoration for her and hers for him was absolutely indisputable. Similar encounters that I have had with many same-sex IVF parents and their children over the years has left me realizing that sexual orientation is irrelevant when it comes to parenting. It does not leave the children confused about their own sexuality. An individual’s sexual identity and orientation is probably well established in early childhood. In the final analysis what matters is love and commitment between two people choosing to have a family. Not their sexual orientation.
Discrimination on the basis of marital status:
While there can be little doubt that children born to single parents are often disadvantaged through absence of a nuclear family setting. In addition, it is a reality that in these harsh economic times, it often takes two bread winners in a family to get by…let alone provide the where with all to support the needs of a child. This having been said, the fact remains that the modern institution of marriage is under siege, with more and more couples choosing to cohabit without “tying the legal knot”. This inevitably has led to a steady rise in the number of babies being born out of wedlock as well as ever increasing number of unmarried individuals and couples being diagnosed with infertility and seeking medical assistance to have a baby….and the number is expected to continue to rise. This is a reality that cannot be ignored or wished away. To turn our backs on such women/couples would be unthinkable, in my opinion.
Discrimination on the basis of Economic status:
I strongly protest the notion that anyone has the right to deny an individual or couple the right to have a family through medically assisted reproduction purely on the basis of the economic status of the prospective parent(s). After all, this never comes into the equation with natural, non-assisted reproduction. So why should it apply when it comes to assisted reproduction. Needless to say, there is a need and an obligation to counsel the economically disadvantaged who seek infertility treatment as to the short and long term financial consequences of having a child. Of course a legitimate question arises as to who should pay for the often expensive advanced fertility treatment needed in such cases. That is a different matter altogether. It is up to individual societies to determine how far the obligation to subsidize such medical benefits should go.
I have long held that it is not the role of a physician to dictate medical treatment to patients. I also believe that we have no right to deny access to advanced fertility treatments purely on the basis of a woman’s age, marital status, sexual orientation or the size of her pocket book. Rather, it is our role is to provide sufficient information to allow patients to make their own informed choices. Thereupon, provided that doing their bidding does not conflict with our own ethical/moral stance, and ever conscious of the tenant of the “Hippocratic Oath”, that binds physicians to “do no harm”, we are obligated to provide optimal medical care.
Posted on June 2, 2010 | Filed under IVF Treatment | Permalink
At a recent meeting of the International Society for Autism Research (INSAR) on Thursday, May 20, 2010, a few papers were presented suggesting that in vitro fertilization is associated with an increased risk of autism in offspring. The world wide alarm that this evoked amongst infertile couples is understandable and is reminiscent of a similar “panic attack” that was sparked by a publication in the prestigious New England Medical (NEMJ) in the 90’s which suggested that the use of fertility drugs increased the risk of ovarian cancer. This study was seriously flawed in that it: a) was retrospective, b) failed to evaluate the effect of infertility itself, on the incidence of ovarian cancer c) did not adequately correct for the age of the women, d) failed to take into account family history, e) did not carefully consider the clinical cause of infertility and, f) did not account for the effect of ethnic/racial influences. It was not until a decade or so later, following completion of several international studies in Australia, Europe, Israel and the United States that the findings of the original study were finally negated. However, by that time the message had unnecessarily traumatized an already vulnerable infertile community and created pandemonium amongst medical care givers.
The data reported at the INSAR meeting on IVF and Autism is interesting, but anecdotal. As with the original study reporting an increase in ovarian cancer in women taking fertility drugs this study was also retrospective in design, thereby introducing recall and participation bias. The sample size was also small. The reported incidence of autism in IVF babies versus the control; group was also very small. In addition the incidence of autism is known to be more common in babies born to older mothers and also in low birth weight offspring both of which are collectively and individually much more common in IVF. Thus the occurrence of autism in IVF babies most likely is related to the “type of woman” who undergoes IVF rather than to IVF treatment itself.
It would be no surprise to wake up one morning (soon) to learn of a study that links IVF treatment and fertility drugs to an increase in the incidence of breast cancer. After all, breast cancer occurs more commonly in women who have reached the 2nd half of their reproductive lives while breast cancer becomes more prevalent as the woman gets older. Also breast malignancy is more common in women who are overweight infertility, while such women are also more likely to have hormonal dysfunction causing infertility that might ultimately necessitate IVF. Finally, breast feeding somewhat protects against breast cancer and of course, infertility, precludes or delays the ability to breast feed.
To conclude that situations associated with infertility and the need for IVF are also associated with an increased incidence of breast or ovarian cancer would be reasonable. However, to go a step further and suggest that infertility treatments increase the risk, is in my opinion without foundation at this time.
*Autism is a neurological, developmental disorder characterized by deficiencies with social interaction, verbal and nonverbal communication, and dysfunctional interests and behavioral patterns.
Posted on May 21, 2010 | Filed under IVF Treatment | Permalink
One of the advantages of infertility treatment is that it focuses the woman on the imminence of conception and thus provides a unique opportunity for both partners to optimize their health, as well as the health of their potential offspring.
The objective of pregnancy should be to maximize the quality of life after birth. Since most women do not plan for and are unaware of when they conceive they seldom modify or, adjust their lifestyles to prepare for this the most important event in determining the well being of their future offspring. Undoubtedly, embryonic and fetal growth are highly susceptible to nutrition and lifestyle choices around the time of implantation and through the first 12 weeks of pregnancy (the 1st trimester). Many women are unaware that they have conceived until around the 5th or sixth week, a time period when the early embryo is most vulnerable to environmental influences, especially to aberrations in blood flow, metabolic influences, a dysfunctional hormonal environment, and to the toxic effects of tobacco, alcohol and “recreational” narcotics.
While isolated poor health choices are not as detrimental to the developing conceptus as protracted exposures to an adverse environment, there are certain things that a woman can do to prepare for conception, improve her fertility potential, and optimize the quality of life after birth should she conceive:
1. Institute a balanced diet and nutrient supplementation, and maintain a healthy body weight.
A balanced diet should incorporate high protein and moderate carbohydrate intake. Fresh fruits and vegetables and modest meat consumption is advisable. The ideal calorie intake is around 2,500 calories per day.
It is advisable for the woman contemplating having a baby to start taking vitamins in preparation for pregnancy. Adequate supplementation with preparations that contain Vitamins A, B-complex, C and D as well as iron and folic acid is important. Folic acid consumption deserves special mention because it reduces the risk of neural tube defects in the baby. Vitamin D (daily consumption should range from 400-1000 IU per day) is also very important as more than half of pregnant women are deficient. This vitamin protects against the development of certain malignant diseases, helps reduce the risk of hypertension and diabetes mellitus, and helps prevent osteoporosis by improving calcium and magnesium absorption. In addition, Vitamin D may lower the incidence of type 1 diabetes.
There seems to be a trend emerging for women who are trying to conceive to take “Chinese herbs.” I’d like to go on record as saying that while some of these might indeed be helpful, there is no scientific data to support there being any real benefit. Of greater concern is the fact that little is known about the ingredients present in some of these preparations. As a result, there is not only no assurance that they are helpful, but a possibility that some might even be harmful. In my opinion, simply passing the use of “Chinese herbs” off by saying “they won’t do any harm” is an oversimplification and could be potentially dangerous.
More recently, the use of DHEA as an attempt to improve egg quality has come in to vogue. I personally consider this to be potentially harmful – especially in women who are in their 40’s and beyond, as well as women with diminished ovarian reserve. In such cases, I believe that this male hormone, by being converted to more potent androgens such as testosterone, could even compromise egg and embryo quality. Supplements such as pycnogenol, myo-inositol, carnitine, DHA (note: this is not the same as DHEA) and co-enzyme Q might be beneficial but the benefits still remain unproven. However, I doubt that their use would be harmful.
2. Maintain a healthy body weight and BMI
Being either overweight (BMI over 30 kg/ml) or underweight (BMI less than 18.5>
Polycystic ovarian syndrome (PCOS) a condition that is often characterized by a high BMI and is commonly associated with insulin resistance, infertility and dysfunctional or absent ovulation. PCOS represents a classic example of how excessive body weight might complicate conception and pregnancy. It should be borne in mind that it is inadvisable to attempt weight loss during pregnancy, thus the emphasis falls on trying to achieve a normal BMI prior to conception.
It is also harmful for women contemplating pregnancy to be underweight, because such women are more likely to experience nutritional deficiencies that might deprive the developing conceptus of the nutrients necessary for healthy growth and development. In addition, underweight women are also more susceptible to pre-term labor, compromised placental development (placental insufficiency) with intrauterine growth retardation, and low birth weight babies.
Exercise Regularly
Women preparing for pregnancy should initiate a disciplined and regular exercise regimen. This will help them maintain an optimal body weight, strengthen the cardiovascular system and reduce stress. I advise women contemplating a family to join a health fitness club so as to ensure a safe and structured exercise program. The regimen should be modified during pregnancy.
Women undergoing ovarian stimulation should avoid “high impact aerobic exercise” while undergoing treatment. It should go without saying that exercise must be avoided around the time of ovulation or egg retrieval and until a pregnancy is confirmed by ultrasound or discounted through blood testing. Once pregnant, the exercise regimen should be modified to exclude “high impact aerobics” and the woman should be advised not to try and push herself beyond her tolerance level. Simply stated, pregnancy is not the time to push for that “extra lap” or “extra set “ that could establish a relatively anaerobic state that might compromise oxygen and nutrient delivery to the developing baby.
3. Avoid smoking, excessive alcohol use and/ or “recreational drugs”
It goes without saying that smoking is a no-no! Cigarette smoke harms egg and sperm development. On the other hand, alcohol in small amounts is probably not that harmful when preparing for pregnancy. However, it is important to emphasize that alcohol, along with all non-prescription drugs not given under proper medical supervision, should be avoided following conception and throughout pregnancy. There is irrefutable evidence that alcohol and tobacco use during pregnancy can and do adversely effect fetal growth and development. Drugs such as methamphetamines, speed, cocaine and narcotics such as oxycontin, vicodin, etc. are all positively harmful and should under NO CIRCUMSTANCES be taken without a prescription and medical supervision.
4. See your primary care physician to ensure your health care is current
It is important to be up-to-date with pap smears, mammograms and annual physical examinations. In the same vein, women preparing for pregnancy should make sure that, if required, they have been properly immunized against German measles (rubella) more than 8 weeks prior to conception, against Chicken Pox (varicella) and vaccinated against influenza – especially during the flu season. It is also advisable to be checked for rarer but serious viral conditions such as hepatitis B, hepatitis C and HIV, all of which have the potential to infect the developing baby. That is not to say that if a woman has had one of these infections she cannot have a baby. Rather, she should be made aware of the fact that there are associated risks, and these should be explained to her and be taken into consideration before conceiving.
Another condition that can be screened for is the presence of the Cystic Fibrosis gene, where the risk of being a carrier is approximately 4%. Both partners should be checked for this gene, which, if present in the man and the woman, places any offspring at serious risk. The same consideration is applicable with regard to identifying conditions such as Sickle Cell Disease or traits which are most commonly seen in people of African descent, and Thalassemia, which is most commonly seen in individuals of Mediterranean extraction. Then there is the increased risk of Tay Sachs Disease, especially in individuals of Jewish Ashkenazi extraction.
5. Prioritize medications taken prior to pregnancy
It is very important to weigh the cost-benefit ratio of taking any medications prior to or during pregnancy. Please refer to the following link, which provides “FDA ratings for prescription drug use during pregnancy, active ingredients in common over-the-counter drug products.” The classifications showed range from Category A (safest drugs) to Category X where fetal anomalies are prevalent with use. Most of the drugs prescribed prior to conception or in pregnancy and which most physicians feel relatively comfortable recommending, fall into Categories A and B. Category C drugs need further consideration. It should be clarified here that women who have certain chronic health conditions will often need to continue taking their medications, even though they might not ordinarily be recommended. Examples where this might apply include seizure disorders, disease such as ulcerative colitis or Crohn’s Disease, tuberculosis, and bipolar disorders. It is important to confer with your physician if you are taking maintenance doses of any medication while contemplating a pregnancy.
6. Reduce stress and optimize mental health
Without exception, women experiencing infertility will experience stress. The longer they have been trying unsuccessfully to conceive and the older they are (and thus more likely to be confronted by a rapidly advancing biological clock), the more important it becomes to find an effective method of stress reduction. As stated above, getting moderate exercise and joining an infertility support group as well as establishing a very healthy and open relationship with her partner will go a long way toward reducing stress. Intense exercise or alcohol use as stress remedies are not recommended. Other helpful ways to address the problem are yoga classes, Pilates, gardening, massage therapy, taking walks and acupuncture.
Above all, taking the time to concentrate on personal needs is vital. Getting adequate sleep (8 hours per night), rest, and quiet time are also important.
Posted on May 19, 2010 | Filed under IVF Treatment | Permalink
A trend has emerged where more and more couples are choosing to delay having children because of financial and career-related reasons. For a woman, such a decision carries with it an ever present risk that when she ultimately decides to have a baby, she might find herself unable to conceive.
It is an undeniable fact that a woman’s fecundity (the ability to conceive per month of trying) declines in her mid 30’s and then falls off precipitously after 40. Unfortunately, most women/couples do not realize that there could be a price to pay for delaying starting a family. Clearly, aspiring parents need to understand this reality so that they can make informed choices when it comes to planning their family.
Upon becoming aware of the impact of the biological clock, many women/couples become desperate and look to in-vitro fertilization as a solution. For women approaching their 40’s, a achieving a pregnancy without help or through the use of fertility drugs and/or intrauterine insemination offers less than a 5% per month chance of having a baby. Given such relatively poor odds many such women, for good reason, turn to IVF as it can significantly improve the chance of becoming pregnant before time runs out. However IVF is certainly not a panacea.
Regardless of the method used to achieve a pregnancy, older women inevitable will have to confront the following hurdles:
- A progressive and accelerated decline in egg quality
- A progressive decline in the number of eggs they will be able to produce in response to fertility drugs (as evidenced by rising FSH , and declining AMH and Inhibin B levels
- A marked increase in the miscarriage rate, which could be as high as 60% by age 45.
- An increased risk of chromosomal birth defects such as Down’s Syndrome which reaches 1 in 30 by age 45.
Another factor to be considered is the fact that many women trying to start a family at an older age would often like to have more than one baby. In such cases, they will need to come to terms with the fact that by the time they have had their first child and have breastfed for a year or so, 2-3 critical years will have been lost, making the likelihood of having another baby (even through IVF) much less probable.
It is important to recognize that the main reason for declining fertility with age relates to a progressive and inevitable decline in the chromosomal integrity of a woman’s eggs as she advances beyond her mid 30’s and into her 40’s. The simple fact is that there is no medical remedy for this problem. As an example; at 30-35 years about 40% of a woman’s eggs are chromosomally normal. At 40, less than 20% are likely to be normal, while by age 45, well under 10% are chromosomally intact. The good news is that a chromosomally normal egg is just as likely to propagate a healthy embryo/baby regardless of the age of the egg provider. A chromosomally normal egg from a woman of 45 probably has the same chance of producing a healthy baby as does a normal egg taken from a 25 year old.
Recently, the introduction of comparative genomic hybridization (CGH) enables us to identify chromosomally “competent” eggs or embryos. Such normal embryos transferred to the uterus of a healthy woman would propagate a healthy baby i.e., about 60% of the time, regardless of the age of the “egg provider.”
What is embryo banking/stockpiling all about? We recently began offering women the opportunity to freeze/store and then stockpile/bank their CGH-normal embryos for future dispensation. To do this, they undergo multiple IVF procedures that each proceed through fertilization of their eggs. The resulting embryos are then biopsied and allowed to progress to the blastocyst stage (the most advanced preimplantation stage of embryo development), whereupon they are vitrified (ultra-rapidly frozen) and then banked.
Several such cycles are conducted in the hope of stockpiling a number of advanced embryos (blastocysts) for later use. Once the last cycle of embryo banking is completed, the biopsied samples derived from all surviving blastocysts are subjected to genetic (CGH) testing only once, thereby minimizing cost that otherwise would have had to be incurred were CGH testing were to be performed after each procedure.
Selective banking of genetically tested embryos in women for whom the end of their reproductive careers is in sight, dramatically expands reproductive choices available to them. First, it allows them to have more than one baby without the ever-present fear that by the time they have had the first one they might not be able to have another. Second, for women who are only interested in having one baby, it establishes realistic and rational expectations of success versus failure, and thus will help them decide when it is time to stop doing IVF, adopt, or go to egg donation. Simply stated, it establishes either a favorable resolution or closure.
It behooves all individuals/couples who are intent upon having a family to be aware of the fact that a woman’s biological clock cannot be reset. It is relentless, merciless and unforgiving. It is also well to bear in mind that a woman’s fertility potential can suddenly decline over a few years – both due to, or independent of, advancing age. While the threat of declining fertility is greatest in the late 30’s and early 40’s, it could just as easily occur in younger women. Because of this reality, women of reproductive age are well advised to undergo hormonal and physical assessments of their fertility potential every few years and to increase the frequency in their mid-30s.
Posted on May 12, 2010 | Filed under IVF Treatment | Permalink
In more than 25% of early pregnancies, there will be some vaginal bleeding. About one half of these end up in miscarriage. In the remaining half, the bleeding subsides and the pregnancy continues to evolve, such that most will culminate in a healthy live birth. In less than 2% of cases of such bleeding, the cause is hydatidiform mole (molar) pregnancy. This is a benign tumor of the root system (trophoblast) of the embryo which under normal conditions develops into the placenta that connects the baby to the mother. With molar pregnancy, the roots of the trophoblast (chorionic villi) undergo cystic degeneration and when the woman bleeds, these cystic structures are passed in dark blood, giving rise to the common description of “white currants floating in red currant jelly”. Hydatidiform mole occurs in about one out of 2,000 pregnancies and is approximately twice as common in women of Asian extraction.
In non-molar pregnancies, an inevitable miscarriage usually presents with flattening or declining blood pregnancy hormone (i.e. hCG) levels. Conversely, with hydatidiform mole the blood hCG concentration is usually very elevated (well above the expected concentration) and continues to rise. In addition, the woman will often experience exaggerated pregnancy symptoms (e.g. pernicious vomiting, frequent urination and bloating) and lower abdominal cramping. On examination, she will often be found to have a markedly elevated blood pressure (early “toxemia”). Upon abdominal or vaginal examination, her uterus is commonly enlarged beyond that which can be explained on the basis of the duration of the pregnancy. Ultrasound examination usually (but not invariably) reveals a hazy, so-called “snow storm pattern” and the absence of a conceptus. There are two types of hydatidiform mole:
- Complete
- Partial
1.Complete Hydatidiform Mole: Like normal pregnancies, the complete mole has 46 chromosomes (two sets of 23), i.e., it is diploid. However, unlike with normal fertilization where one set of chromosomes comes from the mother and the other set from the father, both sets of chromosomes come from the father in the case of a complete molar pregnancy. This results from duplication of a sperm’s chromosomes after it has fertilized an “inactive egg”. Since an embryo that has a YY karyotype is not viable, the chromosome gender of the complete molar pregnancy is invariably XX (female).
Accordingly, with IVF, if one avoids transferring an embryo that by preimplantation genetic diagnosis (PGD) is found to be female (XX), and selectively transfers only male (XY) embryos, the possibility of a complete molar pregnancy can be virtually eliminated. A complete molar pregnancy can result from fertilization of an “inactive egg” by 2 separate spermatozoa. Injection of a single sperm by intracytoplasmic sperm injection (ICSI) prevents the latter from occurring altogether.
2.Partial (placental) molar pregnancies: These are usually triploid [i.e. their cells contain three sets of (23 each) chromosomes]. Thus with partial moles the sex chromosome configuration will be XXY or XYY. Partial Hydatidform molar can therefore be avoided through selectively transferring embryos where triploidy has been excluded through PGD.
Treatment of molar pregnancies: More than 80% of molar pregnancies are benign (noncancerous). Treatment involves complete emptying of the uterus as soon as the diagnosis is made – even in cases where a spontaneous passage of the molar tissue appears to be complete. The reason is to avoid the development of an invasive mole (where the uterine wall is permeated by remaining tissue), and to limit the development of choriocarcinoma (where the molar tissue becomes malignant). In the vast majority of properly managed cases however, outcome after treatment is usually excellent. In cases where the beta hCG level fails to drop appropriately fowing evacuation of the uterus, chemotherapy will usually be curative. Close follow-up with serial quantitative blood hCG testing, ultrasound and/or Magnetic Resonance Imaging (MRI) is essential. After successful treatment, the woman must use very effective contraception for at least 6 to 12 months, so as to avoid pregnancy in order to allow for proper follow-up.
While Molar pregnancy is not commonly seen in patients undergoing IVF, it does occur and the vigilant doctor should always be on the look-out for it. As indicated, in cases where a woman seeking IVF has a family history of the condition or has had a prior molar pregnancy herself, PGD can provide an efficient way to all but prevent this condition from occurring.
Addendum: Choriocarcinoma is a very malignant tumor that invades the uterus and can spread rapidly via the blood system to bone, lungs, brain and other sites. Fortunately this cancer does respond well to hysterectomy, removal of ovaries plus aggressive chemotherapy.
Posted on May 4, 2010 | Filed under IVF Treatment | Permalink
National statistics indicate that as many 4 million of an estimated 35 million cohabiting heterosexual couples in the United States are infertile (i.e. unable to conceive within a year of trying). Saturday, April 24th, marked the start of National Infertility Awareness Week (NIAW), which is intended to make aspiring parents aware of their vulnerability when it comes to fertility and the need to take charge of their reproductive options.
Most individuals and couples take their fertility for granted, believing that upon trying, they will easily and readily conceive. After all, their parents and friends seem to experience no difficulty in getting pregnant, so why should they? Nothing could be further from reality! The truth is that fertility potential in fact can vary widely from one couple to another with some conceiving right off the bat while others are unable to do so after at least a year of consistent trying (this is infertility by definition). The need for early and regular assessments of fertility potential is even more essential for women than for men, as all women will inevitably experience diminishing “fertility potential” with advancing age. This decline usually starts after age 35 but it many cases, it can and indeed does begin much earlier.
The causes of infertility are diverse and are more or less evenly divided between the female and male. Blocked or damaged fallopian tubes, endometriosis, uterine implantation problems (usually due to anatomical disease or immunologic factors), and advancing age associated with declining egg quality, are among the commonest causes of female infertility.
When it comes to the man, blockage of the sperm ducts, reduced testicular function due to environmental toxins, radiation, chemotherapy, heavy metal poisoning, delayed descent of the testicles into the scrotum and varicocele, are among the commonest causes of male infertility. In addition, many (if not most) of reasons for male infertility are as yet “unexplained”. Because of ignorance, vanity, machismo, or denial, most men fail to see a physician for reproductive evaluation without being prompted. As a result male infertility is more likely than female infertility to go undetected for long periods of time.
As stated above, there is a wide diversity in “fertility potential” among couples and individuals. It is therefore advisable that those contemplating having a baby undergo a thorough reproductive assessment sooner rather than later in their relationships. Moreover, such evaluations should ideally be repeated every few years.
A woman’s egg quality/competence declines beyond her mid 30’s, as does her ovarian reserve (the number of eggs she is able of producing per cycle). In some cases it falls off much sooner. Thus, while young women usually have the time to address fertility issues, this is not invariably the case. The earlier they become aware of a possible problem, the more time they will have available to address and correct it before potentially irreversible egg quality issues deny them the opportunity to do so effectively.
The egg (rather than the sperm) is the main determinant of post-fertilization embryo competence and overall reproductive potential, and egg quality inevitably is linked to the woman’s age. At 30 years old, about 40% of a woman’s eggs are genetically normal. At 35 years…..about 25%, at 40 years …about 15%. Beyond the mid forties, probably no more than 10% are capable of making a baby. Moreover, the closer the woman gets to the menopause, the fewer viable, competent eggs she is capable of yielding (we refer to this as diminishing ovarian reserve). It follows that age and proximity to the menopause need to be carefully monitored. Diminishing ovarian reserve can be detected from rising blood follicle stimulating hormone (FSH)levels, declining Inhibin B levels and declining Anti-Mullerian Hormone levels early on in the menstrual cycle.
While most American women will experience declining ovarian reserve after age 35, and menopause between 40 and 50 years of age, this can occur much earlier. In fact, some women will go into a premature menopause with declining ovarian reserve beginning as early in their mid 20’s or early 30’s. In such cases, there will usually be no clear warning signs in the early stages. This serves to underscore the need for early baseline evaluation of ovarian reserve, and regular (at least biannual) monitoring of these same parameters after the age of 30.
With a few notable exceptions, most causes of female infertility will often be picked up in the course of regular physical and ultrasound examinations. The exceptions are endometriosis (the development of endometrial implants on pelvic organs), which can only be definitively diagnosed by direct visualization by open surgery or laparoscopy, and damage to the fallopian tubes, which can only be recognized through invasive tests such as a dye x-ray evaluation (hysterosalpingogram) or laparoscopy. It follows that failure to conceive after a year of trying should prompt evaluation of 1) fallopian tubal function and 2) endometriosis. Both are treatable surgically or through assisted reproduction (e.g., IVF).
In my opinion, all men should have a semen analysis performed immediately prior to, or upon committing to a relationship in which they wish to father a child. The sooner this is done, the better; in doing so the man would have a better idea as to the existence and severity of fertility issues. Men with a history of undescended testicles at birth, testicular injury or swelling, prior venereal infection, mumps causing testicular enlargement, exposure to heavy metals, or pain in the testicular region should probably undergo a semen analysis even before contemplating fatherhood.
Always remember that even in the absence of any symptoms or signs of male or female infertility, there is always the possibility that a woman’s cervical secretions might be hostile to the man’s sperm. That is why, along with a comprehensive reproductive evaluation, I recommend the performance of a post-coital test around the time of natural ovulation when clear mucus is exuding from the cervix (the opening to the uterus) . The test is ideally performed soon after intercourse to evaluate sperm-mucus interaction. Failure of sperm to survive in this environment often points towards a significant barrier to fertility…. one that requires (and is often quite amenable to) medical correction.
National Infertility Awareness Week should serve as a strong reminder that reproductive potential is highly vulnerable to internal and external influences and should never be taken for granted. Information represents empowerment and without it comes both disappointment and heartache.
Posted on April 27, 2010 | Filed under IVF Treatment | Permalink
In the mid?1990s a group at Monash University in Melbourne, Australia, reported the world’s first baby born from an embryo derived from an immature egg that had been matured in the embryology laboratory, and then fertilized and transferred to the uterus. The process has come to be known as In vitro maturation (IVM) of eggs. In so doing, these researchers in fact opened the door to retrieving numerous healthy eggs from women who had not received fertility drugs at all in advance of the egg retrieval, and so potentially transforming the entire IVF arena. More recently, Sean Ling Tan, MD from Mc Gill University in Montreal, Canada reported on impressive results using IVM, claiming success rates that are comparable to those being reported for conventional IVF. A few other centers are reporting a similar experience.
How is the IVM process conducted?
Within 6-8 days of a natural menstruation, an ultrasound examination is done to see how many early follicles have developed. A few days later, 10,000 units of hCG is administered, and approximately 36 hours after that, an egg retrieval is performed and eggs are aspirated from the follicles. These eggs are then allowed to mature in special media and under special conditions. Many of them develop into mature (M2) eggs. The eggs can then be fertilized in the embryology lab and transferred to the uterus as embryos/blastocysts (3-6 days after fertilization), or vitrified (frozen) as eggs or embryos and cryobanked for subsequent dispensation.
At SIRM we are in the process of undertaking a study that will combine IVM with CGH testing of all M2 (matured) eggs. We believe that by doing so we might be able to further improve success rates associated with IVM.
What are the possible benefits and advantages of IVM?
Immediate benefits of IVM would be seen in the arena of Fertility Preservation (FP) where women who for medical or personal reasons would bank their frozen eggs for future dispensation. This would be most applicable in cases where women who have certain types of cancer need to undergo chemotherapy or radiotherapy that could damage their eggs and/or launch them into premature ovarian failure. IVM could also be used to access large numbers of donor eggs for dispensation to women who require egg donor-IVF. It would definitely simplify the entire process to the benefit of all.
No doubt, the ability to generate and acquire viable eggs and embryos without using fertility drugs to stimulate multiple follicle development would constitute a major breakthrough in the field of IVF. It would reduce cost dramatically (for IVF drugs often constitute more than one third of the total cost). It would eliminate side effects from, and all risk of serious complications associated with, use of fertility drugs, and it would expand the reproductive choices available to women.
Simply stated, IVM is a much needed approach in view of the physiological, emotional, and financial costs associated with the administration of fertility drugs. Frankly, the widespread introduction of IVM could herald the end of the era of fertility drugs being required to perform IVF. Wouldn’t that be a blessing?
Posted on April 21, 2010 | Filed under IVF Treatment | Permalink
In the mid?1990s a group at Monash University in Melbourne, Australia, reported the world’s first baby born from an embryo derived from an immature egg that had been matured in the embryology laboratory, and then fertilized and transferred to the uterus. The process has come to be known as In vitro maturation (IVM) of eggs. In so doing, these researchers in fact opened the door to retrieving numerous healthy eggs from women who had not received fertility drugs at all in advance of the egg retrieval, and so potentially transforming the entire IVF arena. More recently, Sean Ling Tan, MD from Mc Gill University in Montreal, Canada reported on impressive results using IVM, claiming success rates that are comparable to those being reported for conventional IVF.
How is the IVM process conducted?
Within 6-8 days of a natural menstruation, an ultrasound examination is done to see how many early follicles have developed. A few days later, 10,000 units of hCG is administered, and approximately 36 hours after that, an egg retrieval is performed and eggs are aspirated from the follicles. These eggs are then allowed to mature in special media and under special conditions. Many of them develop into mature (M2) eggs. The eggs can then be fertilized in the embryology lab and transferred to the uterus as embryos/blastocysts (3-6 days after fertilization), or vitrified (frozen) as eggs or embryos and cryobanked for subsequent dispensation.
We are in the process of undertaking a study that will combine IVM with CGH testing of all M2 (matured) eggs. We believe that by doing so we might be able to further improve success rates associated with IVM.
What are the possible benefits and advantages of IVM?
Immediate benefits of IVM would be seen in the arena of Fertility Preservation (FP) where women who for medical or personal reasons would bank their frozen eggs for future dispensation. This would be most applicable in cases where women who have certain types of cancer need to undergo chemotherapy or radiotherapy that could damage their eggs and/or launch them into premature ovarian failure. IVM could also be used to access large numbers of donor eggs for dispensation to women who require egg donor-IVF. It would definitely simplify the entire process to the benefit of all.
No doubt, the ability to generate and acquire viable eggs and embryos without using fertility drugs to stimulate multiple follicle development would constitute a major breakthrough in the field of IVF. It would reduce cost dramatically (for IVF drugs often constitute more than one third of the total cost). It would eliminate side effects from, and all risk of serious complications associated with, use of fertility drugs, and it would expand the reproductive choices available to women.
Simply stated, IVM is a much needed approach in view of the physiological, emotional, and financial costs associated with the administration of fertility drugs. Frankly, IVM could soon herald the end of the era when fertility drugs were indispensable to the removal of a sufficient number of eggs from a woman’s ovaries….Wouldn’t that be a blessing?
Posted on April 19, 2010 | Filed under IVF Treatment | Permalink
Of the estimated five million infertile couples in the U.S., approximately two million are unable to conceive without IVF treatment. The majority have no insurance coverage for IVF, since only a quarter of employers or less offer insurance plans with infertility benefits. As a result, as many as 50 percent of American Infertile couples do not seek treatment for financial reasons. The fact is that per capita, utilization of IVF in the united states is about half that of the United Kingdom, 3 times less than in the rest of Europe and almost five times less than in Asia. The reason for this is the lack of insurance coverage for IVF in the United States, unlike other 1st world countries where there is often insurance reimbursement for IVF. For the vast majority of these Americans the $10,000 to $20,000 fee per IVF treatment cycle is simply cost prohibitive. This must change.
The main reasons why Health Insurance providers are reluctant to pay for IVF services are:
- They have no reliable data on IVF outcome statistics in the U.S.A. so they can’t accurately gauge the true cost of providing IVF services. With reported IVF success rates varying so greatly between programs, there isn’t an industry-wide standard upon which to base reimbursement.
- The unacceptably high incidence of IVF multiple births brought about by the indiscriminate transfer of multiple embryos at a time exacts a high financial toll. The cost of treating pregnancy complications as well as the short and long-term costs of care for premature babies can be extensive.
A Proposed Solution
In my opinion, the solution might lie in linking payment by insurance companies to IVF outcome.
The first step would be to establish acceptable standards of performance in terms of live birth rates for different categories of IVF patients (age, FSH, etc.).
Second, IVF programs would be required to meet those standards to obtain full reimbursement for services rendered. Those whose performance exceeds the required standard would be bonused, while those that do not would be penalized by receiving reduced reimbursement. Consistent failure to achieve acceptable outcomes might ultimately disqualify such programs from participating altogether.
As a check to assure that success rates aren’t boosted at the expense of good judgment, programs that report an unacceptably high incidence of multiple births would be penalized. Such an approach would serve to motivate IVF centers to achieve the highest standard of excellence in care so as to optimize outcomes. It would almost certainly lead to fewer IVF cycles having to be conducted in order to achieve a live birth and, at the same time, reduce the number of multiple pregnancies.
Such an approach would create a win-win situation for all parties:
- The insurance provider would save money through an inevitable reduction in the number of per patient IVF cycles needed a live birth, as well as by a decline in the number of IVF multiple births.
- The IVF program would win from increased productivity brought about by growing insurance referrals.
- The patient would win from improved access to IVF and higher standards of care.
- Science would win through accelerated growth of IVF technology, in part related to incentivization of IVF programs to improve their results.
Health care providers are obliged to strive to improve the human condition and alleviate suffering. Thus, for the millions of infertile couples who have little hope of conceiving without access to IVF, and for the majority who need IVF but simply cannot afford it, the medical-scientific community and health insurance providers must rise to the occasion and strive to promote the accessibility, affordability and quality of IVF services in the United States.
Posted on April 12, 2010 | Filed under IVF Treatment | Permalink
Public trust is the single greatest factor that has allowed the miracles of medicine to evolve. The public has allowed the medical community a great deal of latitude to decide where to go and how to get there. It is unfortunate that we have not in all cases returned that respect with an equal degree of explanation and understanding by addressing the fears and concerns of the public in general. Even within our industry, we are not of a single mind as to the appropriate course or the end?point in decision?making with regard to the ethics of in vitro fertilization therapy and research.
How should the IVF medical community respond to that public trust? I believe the first step should be to make IVF more accessible to all consumers. This can be achieved by:
1) cooperatively working to improve standards of care such that ultimately, consumers can expect about the same chance of having a baby regardless of the IVF program they choose.
2) willingly providing consumers with access to reliable and understandable data regarding IVF outcome statistics.
3) working with consumers, health insurance companies and legislators to make IVF more affordable.
A proactive approach on the part of the medical community toward compiling and disseminating IVF information would go a long way toward educating members of the media, who all too often misunderstand and consequently misrepresent what IVF is all about. We are faced with too many contentious newspaper editorials and oversimplified TV reports that paint an inaccurate and sometimes alarmist picture about the success of IVF. Reversing the harmful trend of bad press by being openly accountable is one giant step that could be undertaken immediately.
Standards must be established for all IVF programs in the United States, and consumers must have easy access to understandable data about success rates. Consumers deserve to have similar outcomes from every IVF program in the United States. Presently, a patient seeking IVF might have more than double the chance of having a baby through one program versus another. To make matters worse, such a patient would presently have no reliable way of knowing which program was the better one to go to. This (as explained elsewhere on this blog), is because IVF outcome statistics published annually by the Centers for Disease Control (CDC) and the Society for Assisted Reproductive Technology (SART) are currently reported through an unaudited/non-validated process and are thus of questionable reliability. It is not right that patients/couples should pay such huge amounts when they don’t know what their prospect of success will be.
One way in which IVF programs can meet minimum standards is by learning from and replicating the performance of proven programs. The general factors that contribute to a successful IVF program can be viewed as a triangle, with each side of the triangle representing a crucial ingredient: (1) technical expertise, (2) proven, standardized clinical and laboratory protocols and techniques, and (3) rigid quality assurance. Commitment, teamwork, and determination comprise the “glue” that holds the walls of the triangle together
Ultimately, consumers can control the debate. They may have to band together to make their voices heard against the forces of the marketplace, but they can bring about change. Now is the time for IVF consumers to be outspoken. If they don’t participate in the campaign to put the IVF house in order, they have only themselves to blame if progress comes slowly. One of the most promising lobbying avenues would be to join an infertility support group such as the International Council on Infertility Information Dissemination (INCIID)(http://www.inciid.org/ ) both to become more informed and to speak with a louder voice before the medical profession, legislative groups, and the insurance industry.
Posted on April 7, 2010 | Filed under IVF Treatment | Permalink
Public trust is the single greatest factor that has allowed the miracles of medicine to evolve. The public has allowed the medical community a great deal of latitude to decide where to go and how to get there. It is unfortunate that we have not in all cases returned that respect with an equal degree of explanation and understanding by addressing the fears and concerns of the public in general. Even within our industry, we are not of a single mind as to the appropriate course or the end?point in decision?making with regard to the ethics of in vitro fertilization therapy and research.
How should the IVF medical community respond to that public trust? I believe the first step should be to make IVF more accessible to all consumers. This can be achieved by:
1) cooperatively working to improve standards of care such that ultimately, consumers can expect about the same chance of having a baby regardless of the IVF program they choose.
2) willingly providing consumers with access to reliable and understandable data regarding IVF outcome statistics.
3) working with consumers, health insurance companies and legislators to make IVF more affordable.
A proactive approach on the part of the medical community toward compiling and disseminating IVF information would go a long way toward educating members of the media, who all too often misunderstand and consequently misrepresent what IVF is all about. We are faced with too many contentious newspaper editorials and oversimplified TV reports that paint an inaccurate and sometimes alarmist picture about the success of IVF. Reversing the harmful trend of bad press by being openly accountable is one giant step that could be undertaken immediately.
Standards must be established for all IVF programs in the United States, and consumers must have easy access to understandable data about success rates. Consumers deserve to have similar outcomes from every IVF program in the United States. Presently, a patient seeking IVF might have more than double the chance of having a baby through one program versus another. To make matters worse, such a patient would presently have no reliable way of knowing which program was the better one to go to. This (as explained elsewhere on this blog), is because IVF outcome statistics published annually by the Centers for Disease Control (CDC) and the Society for Assisted Reproductive Technology (SART) are currently reported through an unaudited/non-validated process and are thus of questionable reliability. It is not right that patients/couples should pay such huge amounts when they don’t know what their prospect of success will be.
One way in which IVF programs can meet minimum standards is by learning from and replicating the performance of proven programs. The general factors that contribute to a successful IVF program can be viewed as a triangle, with each side of the triangle representing a crucial ingredient: (1) technical expertise, (2) proven, standardized clinical and laboratory protocols and techniques, and (3) rigid quality assurance. Commitment, teamwork, and determination comprise the “glue” that holds the walls of the triangle together
Ultimately, consumers can control the debate. They may have to band together to make their voices heard against the forces of the marketplace, but they can bring about change. Now is the time for IVF consumers to be outspoken. If they don’t participate in the campaign to put the IVF house in order, they have only themselves to blame if progress comes slowly. One of the most promising lobbying avenues would be to join an infertility support group such as the International Council on Infertility Information Dissemination (INCIID) (http://www.inciid.org/ ) both to become more informed and to speak with a louder voice before the medical profession, legislative groups, and the insurance industry.
Posted on April 5, 2010 | Filed under IVF Treatment | Permalink
Public trust is the single greatest factor that has allowed the miracles of medicine to evolve. The public has allowed the medical community a great deal of latitude to decide where to go and how to get there. It is unfortunate that we have not in all cases returned that respect with an equal degree of explanation and understanding by addressing the fears and concerns of the public in general. Even within our industry, we are not of a single mind as to the appropriate course or the end?point in decision?making with regard to the ethics of in vitro fertilization therapy and research.
How should the IVF medical community respond to that public trust? I believe the first step should be to make IVF more accessible to all consumers. This can be achieved by:
1) cooperatively working to improve standards of care such that ultimately, consumers can expect about the same chance of having a baby regardless of the IVF program they choose.
2) willingly providing consumers with access to reliable and understandable data regarding IVF outcome statistics.
3) working with consumers, health insurance companies and legislators to make IVF more affordable.
A proactive approach on the part of the medical community toward compiling and disseminating IVF information would go a long way toward educating members of the media, who all too often misunderstand and consequently misrepresent what IVF is all about. We are faced with too many contentious newspaper editorials and oversimplified TV reports that paint an inaccurate and sometimes alarmist picture about the success of IVF. Reversing the harmful trend of bad press by being openly accountable is one giant step that could be undertaken immediately.
Standards must be established for all IVF programs in the United States, and consumers must have easy access to understandable data about success rates. Consumers deserve to have similar outcomes from every IVF program in the United States. Presently, a patient seeking IVF might have more than double the chance of having a baby through one program versus another. To make matters worse, such a patient would presently have no reliable way of knowing which program was the better one to go to. This (as explained elsewhere on this blog), is because IVF outcome statistics published annually by the Centers for Disease Control (CDC) and the Society for Assisted Reproductive Technology (SART) are currently reported through an unaudited/non-validated process and are thus of questionable reliability. It is not right that patients/couples should pay such huge amounts when they don’t know what their prospect of success will be.
One way in which IVF programs can meet minimum standards is by learning from and replicating the performance of proven programs. The general factors that contribute to a successful IVF program can be viewed as a triangle, with each side of the triangle representing a crucial ingredient: (1) technical expertise, (2) proven, standardized clinical and laboratory protocols and techniques, and (3) rigid quality assurance. Commitment, teamwork, and determination comprise the “glue” that holds the walls of the triangle together
Ultimately, consumers can control the debate. They may have to band together to make their voices heard against the forces of the marketplace, but they can bring about change. Now is the time for IVF consumers to be outspoken. If they don’t participate in the campaign to put the IVF house in order, they have only themselves to blame if progress comes slowly. One of the most promising lobbying avenues would be to join an infertility support group such as the International Council on Infertility Information Dissemination (INCIID) (http://www.inciid.org/ ) both to become more informed and to speak with a louder voice before the medical profession, legislative groups, and the insurance industry.
Posted on April 5, 2010 | Filed under IVF Treatment | Permalink
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