LONDON: Sperm saved for a ''rainy day'' has given a British cancer survivor a daughter 22 years later, in a double first for IVF.
When Richard Pott developed testicular cancer at the age of 21, doctors advised that he freeze samples of his sperm before embarking on treatment that might leave him infertile.
As a university student, having children wasn't a priority but he took their advice. Two decades later, Mr Pott is profoundly grateful that he did after becoming a father to Vivienne in a remarkable first for IVF treatment in Britain.
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Vivienne, now 13 months old, was conceived using sperm frozen in 1987 – the oldest to create a child in Britain.
''I really want our story to give hope to other people who are in similar circumstances,'' Mr Pott said.
Once the embryos were created, using the thawed sperm, three were frozen before being transferred to the womb.
It is also thought to be the first time a baby has been born after this kind of double freezing.
Freezing sperm before having cancer treatment was relatively new in the 1980s but is now standard procedure for men.
Mr Pott, who works in banking, married Rebecca in 1999 and due to her problems with endometriosis in 2003 they were advised to start trying for a family soon. Despite his treatment, Mr Pott was able to produce fresh sperm and after two cycles of IVF, baby Henry, now five, was born.
The couple embarked on more IVF but after four failed cycles were on the verge of giving up. The couple then turned to what Mrs Pott called their ''rainy day sperm''. Dr Tarek El-Toukhy, of Guy's and St Thomas' assisted conception unit, in London, said: ''We believe this is the longest that sperm has been frozen and used successfully in Britain.''
Debbie and Lawrence Waller love their 11-year-old son, Keeden, but they believe he should never have been born.
Just days after Mrs Waller gave birth in August 2000 following IVF treatment, Keeden suffered a massive stroke that caused severe brain damage and meant he was never able to walk, talk or go to the toilet.
The stroke was the result of a rare blood clotting condition known as antithrombin deficiency which Keeden inherited from his father.
Tragically, the Wallers did not know there was a 50 per cent chance that Keeden would have the defective gene.
They are now suing the IVF specialist who oversaw Keeden's conception – Wollongong-based Christopher James – in the NSW Supreme Court for what is known as ''wrongful birth'' and seeking compensation in the order of $10 million for the lifelong care of their handicapped son.
''We love Keeden now that he's here, but if we had the right information and the right options we wouldn't have gone ahead with the birth, not in the way we did,'' Mrs Waller said from her home in Kangaroo Valley.
''Had things been done right, Keeden would never have been here. He would never have to go through the suffering he goes through – the seizures and all.''
The case raises a number of legal questions and could set a precedent for other parents whose children have disabilities.
The Wallers told Dr James about Lawrence's blood clotting condition, and they claim he breached his duty of care to them by failing to take proper steps to find out whether it could be passed on by just one parent.
In the first day of the hearing yesterday, Justice John Hislop heard that Dr James did not seek to find out the answer himself, but handed the couple the name and phone number of a genetic counsellor at Wollongong Hospital on a post-it note. It is alleged the note was given to the Wallers in the context of a discussion about fertility not genetics, and that the phone number was the main switchboard for the hospital rather than the counsellor's direct line.
When the phone went unanswered the Wallers did not call back, and it is alleged that Dr James did not mention the genetic counsellor again, and began the IVF process.
''There was a duty of care on the part of Dr James to ensure that both he and the Wallers understood that this problem could be passed on and for there to be proper counselling and discussion about the other options they had, including the option of an anonymous sperm donor,'' counsel for the Wallers, David Higgs, SC, said.
It is not the first time the Wallers have been to court in relation to their son. In 2006, they launched an unsuccessful ''wrongful life'' case in the High Court on Keeden's behalf, in which he sought compensation for future loss of earnings and opportunity.
Lawyers for Dr James will argue it is not the responsibility of an IVF specialist to find out whether rare genetic conditions such as antithrombin deficiency can be passed on from father to son.
They claim that such responsibility as does exist was met by the referral of the Wallers to the genetic counsellor.
Deborah and Lawrence Waller are suing their IVF doctor for the wrongful birth of their son. Picture: Stephen Cooper Source: PerthNow
A NSW couple are suing the doctor who provided their IVF treatment for $10 million because their 11-year-old son was born with a rare genetic defect and will suffer a lifelong handicap.
Debbie and Lawrence Waller, of Kangaroo Valley, 152km south of Sydney, told Fairfax they love their 11-year-old son Keeden but believe he should never have been born.
Days after Keeden was born in August 2000 he suffered a massive stroke causing brain damage and leaving him unable to walk, talk or go to the toilet unaided. The stroke was the result of a rare blood clotting condition he inherited from his father.
The Wallers are now suing IVF specialist Christopher James – who oversaw the conception of Keeden – in the New South Wales Supreme Court for what is known as “wrongful birth”.
They are seeking $10 million compensation for the lifelong care of their handicapped son, claiming the doctor breached his duty of care by not advising them of the risks of the clotting condition.
“We love Keeden now that he's here, but if we had the right information and the right options we wouldn't have gone ahead with the birth, not in the way we did,” Debbie Waller said. “Had things been done right, Keeden would never have been here. He would never have to go through the suffering he goes through – the seizures and all.”
This is the second damages claim against doctors brought by the Wallers. In 2006, the High Court rejected a “wrongful life” claim made on behalf of Keeden against Debbie Waller's two obstetricians and her IVF clinic.
Lifelong suffering … Debbie Waller says her disabled son, Keeden, 11, would not have been born if she had been warned about the chance of his hereditary condition. Photo: Quentin Jones
DEBBIE and Lawrence Waller love their 11-year-old son, Keeden, but they believe he should never have been born.
Just days after Mrs Waller gave birth in August 2000 following IVF treatment, Keeden suffered a massive stroke that caused severe brain damage and meant he was never able to walk, talk or go to the toilet.
The stroke was the result of a rare blood clotting condition known as antithrombin deficiency which Keeden inherited from his father.
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Tragically, the Wallers did not know there was a 50 per cent chance that Keeden would have the defective gene.
They are now suing the IVF specialist who oversaw Keeden's conception – Christopher James – in the NSW Supreme Court for what is known as ''wrongful birth'' and seeking compensation in the order of $10 million for the lifelong care of their handicapped son.
''We love Keeden now that he's here, but if we had the right information and the right options we wouldn't have gone ahead with the birth, not in the way we did,'' Mrs Waller said from her home in Kangaroo Valley yesterday.
''Had things been done right, Keeden would never have been here. He would never have to go through the suffering he goes through – the seizures and all.''
The case raises a number of legal questions and could set a precedent for other parents whose children have disabilities.
The Wallers told Dr James about Lawrence's blood clotting condition, and they claim he breached his duty of care to them by failing to take proper steps to find out whether it could be passed on by just one parent.
In the first day of the hearing yesterday, Justice John Hislop heard that Dr James did not seek to find out the answer himself, but handed the couple the name and phone number of a genetic counsellor at Wollongong Hospital on a post-it note. It is alleged the note was given to the Wallers in the context of a discussion about fertility not genetics, and that the phone number was the main switchboard for the hospital rather than the counsellor's direct line.
When the phone went unanswered the Wallers did not call back, and it is alleged that Dr James did not mention the genetic counsellor again, and began the IVF process.
''There was a duty of care on the part of Dr James to ensure that both he and the Wallers understood that this problem could be passed on and for there to be proper counselling and discussion about the other options they had, including the option of an anonymous sperm donor,'' counsel for the Wallers, David Higgs, SC, said.
It is not the first time the Wallers have been to court in relation to their son. In 2006, they launched an unsuccessful ''wrongful life'' case in the High Court on Keeden's behalf, in which he sought compensation for future loss of earnings and opportunity.
Lawyers for Dr James will argue it is not the responsibility of an IVF specialist to find out whether rare genetic conditions such as antithrombin deficiency can be passed on from father to son.
They claim that such responsibility as does exist was met by the referral of the Wallers to the genetic counsellor.
‘‘There is no question that Debbie and Lawrence Waller have experienced a tragedy event and that Keeden Waller situation is extremely sad,’’ counsel for Dr James Jeremy Kirk SC said.
‘‘But they are intelligent adults who were advised to speak ro a genetic counsellor. They chose not to take up that advice.’’
The Waller's solicitor, Bill Madden from Slater and Gordon, said that the compensation claim was largely made up of the costs of accommodation, food and caring for the Keeden full-time.
“Neither parent have been able to work much, they've had to modify their home – the financial impact of something like this is huge.”
Couples have for centuries sought to influence the gender of their offspring. More than seven centuries ago the ancient Chinese developed a birth calendar said to be able to predict gender on the basis of when conception occurred. Later, the ancient Greeks suggested that by lying on her right side during intercourse, a woman could improve the likelihood of having a male child. And 300 years ago, the French suggested that placing a ligature around the right testicle would improve the chance of having a male child.
More recently in the U.S., methods such as timing intercourse, assuming different positions during sex, and (relatively recently) employing rapid sperm centrifugation in an attempt to separate male chromosome-bearing sperm from female sperm prior to artificial insemination were proposed. The fact is that none of these (as well as many other) such anecdotal assertions have been shown to have any real validity.
Currently, in spite of several well described medical approaches, the indisputable fact has emerged that it is only by way of IVF that reliable sex selection can be achieved. This allows for embryos to be screened for gender through preimplantation genetic diagnosis prior to transferring the embryo(s) of the desired gender to the uterus.
Nevertheless, it is an inescapable reality that the very idea of medical sex selection challenges moral and ethical beliefs at their very foundation. Many hold that the growing popularity of gender selection solely for the convenience of altering a family’s gender balance represents an unwanted example of how assisted reproductive technology is subject to abuse…and thus it should be outlawed. They also see it a an example of a disturbing trend towards “designer babies” where genetic engineering could be used to manipulate the intellect, body configuration, build, height, and the talents of future offspring. This assertion is commonly followed by the tantalizing question as to where all this would end and whether we as a society “would really want to live in such a world.”
There is, however, one clear exception to the apparent across-the-board opposition to sex selection that is well worthy of mention. This applies in cases where sex selection is used to avoid the occurrence of a serious medical disorder that selectively affects one gender or the other (e.g., Hemophilia, a life threatening bleeding disorder that selectively affects male offspring).
EVALUATING CURRENTLY USED METHODS FOR SEX SELECTION
Sperm Gradient Method (highly unreliable) This is one of the simplest methods that still (unfortunately) remains in widespread use. Here sperm is rapidly spun down (centrifuged) in the hope of separating the male sperm (those with Y-chromosomes) from the female sperm (those with X-chromosomes). It relies on the assumption that the X chromosome makes sperm heavier, allowing for separation of male from female chromosome-bearing sperm. Though this method is often touted as a low cost method for sex selection, the truth is that it simply does not work!
Flow Cytometry-The Microsort Technique (has certain problems) This method employs the use of a fluorescent dye that adheres to genetic material within the sperm. Because X-bearing sperm contain more genetic material, these sperm are supposed to pick up more dye than Y-bearing sperm. Thereupon, X and Y bearing sperm are then separated into two groups and used for intrauterine insemination (IUI) or IVF. This method has been touted as yielding a 60% to 70% accuracy rate with IUI. Some swear by this method, but my personal experience with its efficacy and reliability in the IVF setting has been rather disappointing. Significant to note is that approval of the Microsort method is still under review by the FDA and in the meantime, has only been granted approval for use in cases where it is necessary to prevent sex-linked or sex-limited genetic diseases in children.
Preimplantation Genetic Diagnosis (PGD) Preimplantation Genetic Diagnosis is the only approach that offers virtually a 100% chance of obtaining the desired gender. In PGD, one cell is removed from each “potentially competent” early embryo, and then DNA based genetic analysis is performed in highly-specialized laboratories. We recommend comparative genomic hybridization (CGH) using paternal/maternal controls (GSN) in such cases because it not only determines gender but also helps identify the most “competent” embryos (those that have the proper number of chromosomes) and thereby significantly enhances success per embryo transferred. CGH has all but replaced fluorescence in-situ-hybridization (FISH) for PGD because, while the latter accurately can determine gender, it lacks sufficient sensitivity/specificity to optimally identify competent embryos for transfer.
Upon completion of the GSN-CGH analysis, which takes about 24-36 hours, the couple can select which embryo(s) they will transfer to the uterus. If pregnancy results, there is almost a 100% chance it will result in the desired gender. This method is particularly helpful for couples where the risk of having a male child with an X-linked genetic disease is significant.
A Personal Opinion On the Use of Sex Selection for “Family Balancing”
Sex selection done simply for family balancing remains controversial, raising concern that if it became widely accessible and freely available, such practice could distort the natural sex ratio, leading to a population gender imbalance. However, for this to happen, there would have to be a significant population preference for sex selection. In reality, the contrary seems to apply, since studies conducted in western societies discount these concerns. In fact, the relatively high cost of IVF with the added cost of gender selection in the United States makes it unlikely that the demand would ever become large enough to impact overall population gender balance. In addition, several studies done in Western countries have shown that the majority of people do not seem to be concerned about the gender of their offspring, and that with a few notable exceptions, gender preference does not appear to be slanted in the direction of either male or female. Thus, from a practical standpoint, such concerns are overstated.
So, given that in the United States most do not care about the sex of their offspring, and only a minority are interested in selecting the sex of their children, it is my opinion that freedom of choice should prevail. As such, a service for sex selection for non-medical reasons should be freely available.
NEW YORK (Reuters Health) – Acupuncture may help some women conceive through in-vitro fertilization (IVF), a new analysis of past research concludes. But the true benefit in the real world, if any, remains unclear. The technique has been used for millennia in traditional Chinese medicine, for a whole range of ills. Ten years ago, a study in Germany was the first clinical trial to report that …
When a woman has been diagnosed as being a poor responder – or
has poor ovarian reserve – there is an increased risk that an IVF
cycle may be cancelled due to poor response. Cancelled cycles can
be very costly and frustrating but a 2011 study (1) has found a
new way of predicting which women may have trouble getting to the
egg retrieval and embryo transfer stages of IVF. This study
discovered that a woman's testosterone level on day three of her
menstrual cycle can be very predictive of how her IVF will
progress.
The study was extremely large following one-thousand two
hundred and sixty Chinese women who were undergoing their first
IVF who were free of endometriosis and PCOS. The women were
divided into two groups: those who had diminished ovarian
reserve (FSH>10 IU/L) comprising one hundred and eighty
seven women and those with normal ovarian reserve. All women
underwent the same IVF protocol.
In women with poor ovarian reserve a testosterone level greater
than 47.85 ng/dl was able to predict pregnancy outcome (with a
sensitivity of 52.8% and specificity of 65.3%). Day three
testosterone was correlated with the numbers of mature
follicles on the day of the hCG trigger and also indicated the
total number of days of gonadotropin stimulation and the total
dose of gonadotropins that would be required. The study
concluded that:
“In women with diminished ovarian reserve, basal T
(testosterone) level was a predictor for the number of large
follicles on HCG day and pregnancy outcome; but could not in
those with normal serum FSH.”
“Basal T (testosterone) levels were associated with both days
of stimulation and total dose of gonadotropins, indicating that
lower level of T might relate with potential ovarian poor
response.”
Interestingly there have been recent studies showing that women
with poor ovarian reserve who receive a pre-treatment phase of
testosterone and DHEA (another androgen) have better IVF
success rates. Your day three testosterone, if low, may
indicate that you may benefit from some form of androgen
pre-treatment to help your IVF to be more successful. The study
further concludes that:
“Basal T level is a good predictor for pregnancy outcome and
number of large follicles on HCG day in women with diminished
ovarian reserve. Basal T level is equally helpful in tailoring
the dosage of gonadotropins to individual and identifying
potential poor ovarian responders, subsequently, making
individualized COH (controlled ovarian hyperstimulation)
strategy before entering IVF cycles. It also gives evidence to
androgen supplementation in infertile women. Those women with
lower basal T (testosterone) levels would benefit from T
supplementation during COH such as improving response,
decreasing the amount of gonadotropins used and the cost
accordingly.”
Your doctor will usually evaluate your FSH (follicle
stimulating hormone) and estradiol on day three to assess
ovarian reserve before IVF, asking for a testosterone test too
could help to fine-tune your IVF for greater success.
1. Association of basal serum testosterone levels with ovarian
response and in vitro fertilization outcome
Qin, Yingying1; Zhao, Zhiyi1; Sun, Mei1; Geng, Ling1; Che, Li2;
Chen, Zi-Jiang1
Reproductive Biology and Endocrinology 2011, 9:9
ISSN:?1477-7827, DOI:?10.1186/1477-7827-9-9
Boston IVF, a medical practice providing specialized infertility treatment, today said it has introduced the first needle-free saliva test that will replace daily blood tests needed to monitor infertility treatment.
Until recently, for many infertile older women and those with diminished ovarian reserve (DOR) who wanted to have a baby, IVF using donated eggs offered the only realistic option. Many who were unwilling to use donor eggs often nonetheless attempted IVF (often repeatedly) with their own eggs, only rarely succeeding in having a baby. The recent introduction of selectively banking genetically tested, “competent” embryos over several IVF cycles and subsequently (in a later cycle) transferring only those found to be chromosomally normal, could offer many such women/couples a realistic alternative to IVF with egg donation, while offering them an opportunity to have their own genetic offspring.
It is mainly the chromosomal integrity of the egg, rather than the sperm that determines whether the embryo will be “competent” (i.e. have the potential to develop into a normal baby). It is the age of the woman that most profoundly impacts the likelihood that the mature egg will have a full contingent of chromosomes (a “euploid” egg), necessary to achieve embryo “competency.” By way of example, up until about 35 years of age, fewer than 50% of a woman’s mature eggs will be euploid, and thus upon fertilization, more than half will have an irregular chromosome component (i.e. “aneuploid”) and thus be “incompetent.”
Incompetent embryos either will fail to develop normally, fail to attach (implant) in the uterine lining, miscarry, or even result in a chromosomally abnormal baby (e.g. Down syndrome). As a woman ages beyond her mid-30’s the incidence of egg/embryo aneuploidy increases such that by the time she reaches her mid forties, more than 90% of her eggs/embryos will be aneuploid and incompetent.
To make matters worse, the older the woman, the closer she gets to the time that her ovaries run out of eggs and she stops ovulating and menstruating (i.e. menopause). The 6-8 years prior to menopause (i.e. the climacteric or pre-menopause) which is characterized by 1) diminishing ovarian reserve (DOR) with an associated progressive reduction in the number of available number of mature eggs at the time of egg retrieval, and 2) building resistance to fertility drugs.
To complicate matters further, it becomes ever more difficult in the face of DOR, to protect developing eggs during stimulation with fertility drugs in the hope of minimizing the incidence of egg/embryo aneuploidy. This is why, unless a very customized and individualized approach to ovarian stimulation is used in older women and those with DOR, the incidence of egg/embryo aneuploidy may even approach 100%. It also serves to explain why IVF success rates plummet with diminishing ovarian reserve and with advancing age, and why the relentlessly ticking biological clock often creates in them a profound sense of urgency and even desperation to have a baby before their time runs out.
Confronted with the reality that advancing age and diminishing ovarian reserve will inevitably reduce the likelihood of an IVF pregnancy, as well as increasing the risk of miscarriage, in all probability, come at considerable emotional and financial cost, many such women often choose to undergo IVF using the eggs derived from a younger egg donor.
Embryo banking offers many older women an those with DOR a realistic and cost-efficient alternative to IVF with Egg Donation: The recent introduction of Embryo Banking at SIRM now offers an alternative to egg donation for many older women, as well as those with prematurely diminishing ovarian reserve (DOR) who otherwise would have a very small chance of having a baby with their own eggs. This is provided, of course, that they still have an ability to produce some ovarian follicles in response to fertility drugs.
Embryo banking involves a process whereby several blastocysts are accumulated (stockpiled) over two or more IVF cycles. After each such cycle, the embryos are biopsied for CGH analysis, taken to the blastocyst stage of development and then vitrified (ultra-rapidly frozen and banked). All biopsy specimens accumulated over several such cycles are held for as long as it takes to complete the scheduled IVF egg retrieval cycles, whereupon they are collectively dispatched for a single CGH analysis (to reduce testing costs). When the results return, the “incompetent” (CGH-abnormal) embryos are discarded while the “competent” ones are stored (cryobanked) for a subsequent embryo transfer. With this method, the transfer of even a single “competent” embryo is capable of achieving almost a 70% chance of a viable pregnancy, regardless of the age of the woman.
Suzanne Gaskell, from Warrington, had been trying for six years to have a baby with husband Chris, but was told she would have to lose weight in order to have treatment.
09-12-2011 17:48 Kelly and Ryan Key had all but given up on having a baby. At the suggestion of friends, they scheduled an appointment with the infertility experts in UAB’s Division of Reproductive Endocrinology and Infertility.
Unique program for infertility patients includes quality treatment AND medications, with discounts up to 50% for each treatment cycle is now available to patients in the greater Atlanta area.WHITE PLAINS, NY (PRWEB) January 18, 2012 WINFertility, Inc., the leader in Infertility Management Programs for insurers and employers, today announced the extension of its consumer offering to the greater …
For an ever-increasing number of infertile women, advancing age or diminished ovarian reserve (DOR) associated with the onset of menopause or ovarian disease precludes them from producing the “competent” eggs that are necessary to achieving a viable pregnancy. In the vast majority of cases, such women will usually have a healthy uterus and thus, provided that they are free of medical disorders that would compromise a pregnancy, will usually be quite capable of bearing a child once “competent embryos” are transferred to their uterus. Accessing “competent” embryos will usually require utilizing eggs taken from the ovaries of young egg donors.
The choice of treatment is highly personal and should be considered in light of the financial and emotional costs involved. The further the woman’s age advances beyond 40 yrs and/or the closer she gets to the menopause, the more likely it becomes that she would require multiple attempts at IVF to have even a reasonable chance of achieving a viable pregnancy with her own eggs. However, after the age of 43, the adverse effect of age on the egg’s chromosomal integrity (“competence”) so reduces the likelihood of successful IVF, that egg donation represents the most rational choice. The effect of age on IVF outcome is largely negated through the use of donor eggs. This is because the donor eggs derived from a younger woman (usually less than 35 years of age) are usually healthy. In addition, newer methods for preparing the embryo recipient’s uterine lining help optimize the chance of healthy implantation.
IVF with egg donation involves preparing the uterus of the embryo recipient (the “intended mother”) with hormones while stimulating the donor’s ovaries with fertility drugs. The eggs are harvested and then fertilized with designated sperm in an embryology laboratory. One or more embryos are then transferred to the uterus of the embryo recipient. Upon conceiving, the embryo recipient then carries the baby(ies), hopefully to full term.
There several ways by which Egg Donation can be conducted, and the steps taken in preparing for the process are profoundly affected by the approach chosen:
Conventional Egg Donation: This is the basic format used for conducting the process of egg donor IVF. It involves synchronizing the menstrual cycles of both the recipient and the donor by placing the donor and the recipient on a birth control pill, so that both parties start stimulation with fertility drugs simultaneously. This ultimately allows for precise timing of the fresh embryo transfer.
Staggered-IVF Egg Donation: With this approach, there is no need for the egg donor and recipient cycles to be synchronized. Here, the donor’s cycle of stimulation and egg retrieval are conducted in advance. Her eggs are fertilized with designated sperm and the resulting blastocysts are frozen (vitrified & cryobanked) for subsequent transfer to an embryo recipient’s uterus in a subsequent cycle. The ability to separate the ER cycle from the ET cycle, markedly increases the convenience for all parties, and at the same time, removes a great deal of stress from the equation because it provides the embryo recipient with confidence that there will almost certainly be blastocysts available when she comes for ET.
Moreover, the ET cycle can be scheduled to be performed at the convenience of recipient, and the time needed at our center to perform ET is virtually cut in half. Most important of all is the fact that embryo vitrification by and large will not compromise good quality embryos. This means that the freeze/thaw survival rate of previtrified blastocysts is >95% and the pregnancy rate per transferred pre-vitrified blastocyst is at least the same as for fresh transfers. The cost for Staggered IVF-ED is also not greater than is the case with Conventional Egg Donation. Staggered IVF with Egg Donation is best suited to those couples/individuals whose location (usually from afar) and/or calendar, requires much tighter scheduling of their egg donation experience.
CGH Embryo Selection in IVF with Egg Donation: The introduction of Comparative Genomic Hybridization (CGH) allows full embryo chromosome analysis (karyotyping) and confidence that CGH-normal embryos so selected will have a high likelihood of being “competent” (i.e. capable of producing a healthy baby). In fact, CGH-normal embryos will each provide >60% chance of a baby per embryo transferred. Combining CGH embryo selection with Staggered IVF Egg Donation thus further enhances the efficiency of the process and allows us to limit the number of embryos transferred to 1 or 2, thus virtually eliminating the risk of “high order” multiple pregnancies (triplets or greater).
Use of a Donor Egg Bank: Another imminent advance in the arena of IVF with egg donation is the emergence of donor egg banking. Being able to freeze and bank donor eggs would solve most of these challenges. By using vitrification to freeze eggs, we are now capable of improving the birth rate per warmed/thawed egg by a factor of 7 (from a previous average of 1-4% per egg to about 27%). In the future, through an electronic catalog, recipients will be able to select and purchase CGH-normal eggs that have been retrieved from donors, genetically tested, then frozen. Thereupon, the selective transfer of 1 or 2 embryos derived from these chromosomally normal eggs could achieve a >60% pregnancy rate without the risk of initiating high-order multiple pregnancies in the process. At the same time, this approach will drive down the cost while reducing both risk and inconvenience to the patient.
Egg donation is associated with several benefits. First, in most instances, more eggs are retrieved from the young donor than are required for a single attempt at achieving a pregnancy, so that there are often several embryos left over for storage (cryopreservation/freezing) and use in a future IVF cycle. Second, because of the relatively high level of “competency” of the younger donor’s eggs the risk of miscarriage is also considerably reduced. Third, the low occurrence of chromosomal birth defects (e.g. Down Syndrome) when embryos that are derived from the eggs of a young donor implant, diminishes the necessity for the performance of invasive preimplantation genetic testing such as amniocentesis or chorionic villus sampling (CVS).
The indications for egg donation/IVF are:
Severely diminished ovarian reserve (DOR) as might be evidenced by ovarian resistance or failure to respond to stimulation with fertility drugs.
Ovarian failure due to menopause, surgery, radiation, or chemotherapy for malignant diseases.
The presence of chromosomal or genetic disorders that have a high likelihood of being transmitted via the woman’s eggs to the offspring.
Most IVF programs employ the services of a reputable egg donor/surrogacy agency with access to many donors and surrogates. All egg donors are thoroughly screened before entering a cycle of treatment (see below).
While we strongly recommend to aspiring parents that the identity of the ovum donor be anonymous, we do accommodate the needs of those individuals/couples who prefer to use a known donor. However, the arrangements to use a known donor must be clearly defined and agreed upon at the outset.
Every attempt is made to find a matched donor that meets the embryo recipients’ needs. Issues such as physical characteristics, race, ethnic background, religion, etc. are all taken into consideration and fully disclosed. The donor is screened and undergoes detailed medical evaluation, as do the sperm provider and embryo recipient. (See below)
Finally, the couple and the egg donor independently visit with our clinical coordinator, who will outline the exact process step-by-step and develop a calendar that outlines every step they will go through. Once all the evaluations have been completed, a date to begin treatment will be selected.
Stimulating with Fertility Drugs and Monitoring the Egg Donor The egg donor is treated with one or more gonadotropins (e.g., Recombinant FSH [FSHr], e.g. Follistim, Gonal F, Luveris) and/or Menotropins (e.g., Menopur) in order to stimulate development of enough follicles to optimize the number of mature eggs available at egg retrieval. In preparation for this treatment, the donor will be asked to commence taking a combined (monophasic) birth control pill (BCP) for ten days or longer. Thereupon, she will receive daily GnRHa (e.g., Lupron, Buserelin, Decapeptyl) injections in combination with the BCP for about 2 days. At this point, the BCP will be discontinued and the GnRHa therapy continued. About 5-8 days later, with the subsequent onset of menstruation, the donor will have her blood tested for estradiol and usually (especially if her blood estradiol level is >70pg/ml), will have a baseline ultrasound examination to exclude the presence of ovarian cysts and to confirm that her ovaries are ready to be stimulated with gonadotropins.
Sequential ultrasound examinations and blood estradiol levels are monitored starting on the 7th day of gonadotropin therapy. Usually, one to four additional days of gonadotropin therapy will be required to allow the follicles to develop optimally, at which time she will receive a “trigger” injection of hCG 10,000U intramuscularly. About 36 hours later the egg retrieval will be performed with the donor under conscious sedation.
Central to conducting conventional IVF-egg donation, is the need that the embryo recipient’s and egg donor’s cycles be synchronized as closely as possible so that the endometrial lining of the embryo recipient’s uterus can be optimally prepared for embryo implantation. This is achieved by administering the BCP and Lupron to the recipient in the same manner as for the donor (see above). By lengthening or shortening the duration of BCP treatment, it is a relatively easy matter to synchronize the cycles of the embryo donor and recipient. When Staggered IVF egg donation is used, such synchronization becomes redundant and unnecessary (see above).
Preparing for ET by Building the Embryo Recipient’s Uterine Lining
Hormonal Injections: The embryo recipient receives estrogen in the form of biweekly injections of estradiol valerate (E2V) (on Tuesdays and Fridays). The embryo recipient’s blood is drawn one day prior to each scheduled E2V injection to measure E2 concentrations in order to determine the subsequent dosage. The recipient also undergoes ultrasound examinations to evaluate the development of her endometrial lining.
Special considerations in women with estrogen deprivation (non-menstruating): Women with estrogen deprivation due to Ovarian Failure, who have not been receiving hormone replacement therapy (HRT) for more than 2 months should, in my opinion, first receive estrogen priming for a few months before undergoing ET. This is because in such cases, the few weeks of estrogen administration prior to ET is insufficient to prepare the lining of their uteri for ET without prior estrogen priming for 2 or more months. The reason for this is that in the absence of regular estrogen administration through HRT, the endometrial linings of many such women will have reduced responsiveness to estrogen, making them far less likely to conceive following ET. Those that do are much more likely to miscarry.
Thus, in my opinion, it is important for women with prior prolonged estrogen deprivation, first to receive cyclical estrogen HRT for at least 2 months in order to grow the uterus and prime the endometrium so as to render it more receptive to subsequent implantation HRT for ET. In the process, both implantation and pregnancy potential will be enhanced.
Selective Use of Sildenafil (Viagra) to Improve Endometrial Development
In some cases, a thin (<9mm) endometrium can be successfully treated by administering vaginal sildenafil (Viagra) suppositories until progesterone therapy begins. The sildenafil will in many cases enhance response to estrogen by improving uterine blood flow, which is capable of improving the uterine lining.
Preparatory Tests That should Be Performed
A. EMBRYO RECIPIENT Examination, PAP smear and mammogram; TSH; prolactin; Rubella antibodies; Blood group (ABO/Rh); Hep B; Hep C; HIV; Chlamydia antibodies; Syphilis; Natural Killer (NK) cell Activity (K-562-target cell test); Cervical cultures (ureaplasma and gonococcus); Sonohysterogram (saline sonogram).
B. SPERM PROVIDER History & Physical Examination; Semen Analysis; Semen Cultures (gonococcus, ureaplasma); TSH; Blood group (ABO/Rh); Hep B; Hep C; HIV; Chlamydia antibodies; Syphilis.
C. EGG DONOR History & Examination; PAP smear; FSH; E2; AMH (on cycle day-3); TSH; prolactin; Rubella antibodies; Blood group (ABO/Rh); Hep B; Hep C; HIV; Chlamydia antibodies Syphilis; Natural Killer; cervical cultures (gonococcus & ureaplasma); Genetic tests (e.g. cystic fibrosis and Tay Sachs disease, Sickle Cell disease, Thalassemia, etc).
*Next week I will address Embryo Banking; an exciting alternative to Egg donation for women who have DOR but are unwilling to consider IVF- Egg Donation as an option.
