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Some Frequently Asked Questions
About Assisted Reproductive Technologies
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Who is a candidate for IVF and ART?
Assisted reproductive technologies (ART) include in vitro fertilization (IVF) which is the technique of fertilizing a woman’s eggs in the laboratory for the treatment of infertility. While it was designed originally for women with tubal disease, IVF has been extended with equal success to infertility due to endometriosis, poor cervical mucus and unexplained factors. A variant of IVF, the GIFT procedure is available to women with normal fallopian tubes. IVF has also been applied to male factor infertility. While the success rates of standard ART in these cases used to be low, the recent advances in assisted fertilization through ICSI can succeed even in couples with severe sperm abnormalities. ART attempts using the woman's own eggs are rarely successful above the age of 43 years. Fortunately, pregnancy initiation with donated eggs has proven highly effective in women who are no longer good candidates for traditional ART, including women without functioning ovaries.
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What are the chances of success with IVF?
Our current results in the main treatment categories can be found in the Results section.
The statistics of success can be confusing. The current standard measures of success are clinical pregnancy and live birth rates per retrieval, the difference between them being primarily due to miscarriages. For recent experience, ongoing pregnancy rate (defined by the presence of a viable fetus with heartbeat at 12 weeks) approximates closely the ultimate birth rate. The woman’s age is the main determinant of outcome. Our consistently high success rates result from combining extensive clinical experience with up-to date research and innovation.
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What should I expect during the IVF process?
IVF is a complex process consisting of several steps. First, fertility drugs are given over a period of ten days to stimulate the ripening of multiple eggs. Several blood tests and ultrasound examinations are done for precise monitoring of follicle development. At the appropriate time, the eggs are retrieved through the vagina. Egg retrieval is a non-surgical procedure performed under light sedation after which you return home after a couple of hours. Since the egg retrieval is performed in a hospital-based outpatient surgery center, we can offer you the full range of anesthesia options with a maximum of safety. Once the eggs have been obtained, the sperm is then added to the eggs in the laboratory where the eggs develop for 3 to 5 days. In cases requiring ICSI individual sperm are injected directly into the egg. When embryos are transferred on day 3 after retrieval, the embryos undergo Assisted Hatching.
Eight-cell embryo 3 days after retrieval
The embryos (fertilized dividing eggs) are placed in the womb by a simple non-surgical procedure similar to a pelvic examination. If a large number of eggs fertilize and develop normally, transfer is often delayed until day 5 to allow better selection of embryos at the blastocyst stage.
Spontaneously hatching blastocyst 5 days after retrieval
Expanded blastocyst 5 days after retrieval
When more embryos develop than are transferred, the additional embryos can be frozen and stored for replacement at a later date. Two weeks after retrieval, a pregnancy test is done. At the end of the first trimester, pregnant patients are referred back to their obstetricians for prenatal care and delivery. If pregnancy does not ensue, treatment can be repeated with an equal chance of conception in subsequent cycles.
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What are the risks of ART?
The assisted reproductive procedures have so far proven remarkably safe for both the would-be mother and her child, but long-term follow-up studies are not yet available. Occasionally, ovarian cysts may form in response to the fertility drugs. Some concern has been raised that the use of fertility medications may increase the future risk of ovarian tumor, including borderline tumors and cancer. However, this finding has not been confirmed and awaits further studies. Laparoscopy and anesthesia carry the same low risks as other surgical procedures, while ultrasound retrieval can occasionally result in a pelvic infection or bleeding. Apart from the increased chance of multiple birth, the risks of pregnancy and delivery are unchanged. With over forty thousand children born after standard IVF worldwide, there has been no increased risk of birth defects or abnormalities.
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How do I know if ART can help me?
Thorough evaluation by an infertility specialist familiar with ART is necessary to decide whether IVF or another treatment is appropriate for you. In many cases simpler treatments may also be successful. Tests previously done usually need not be repeated as long as past records are available. Alternative therapies are presented to you if another approach offers an equal or greater chance of success. These options include laser laparoscopy, tubal microsurgery, tubal cannulation, ovulation induction, hormonal supplementation, sperm washing and intrauterine insemination.
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What is Age Factor?
It is more difficult for all women as they become older to achieve a successful pregnancy resulting in delivery of a healthy infant. The reproductive aging process is complex and multi-faceted but the aspect which comes into play relatively early (in the mid 30s) pertains to decreasing viability of eggs and embryos (fertilized dividing eggs). This decrease in viability reflects higher frequency of deep-seated errors in chromosome number (aneuploidy) which arise during the development of immature eggs found in small ovarian follicles (fluid-filled sacs containing the eggs) into mature eggs found in large follicles at ovulation. These errors of chromosome number (i.e. too many or too few chromosomes) are not directly inherited from either parent both of whom have the correct number of chromosomes.
The primary adverse effect of such chromosomal disorders is not on ovulation or fertilization but on the embryo implantation or attachment of the 5-7 day old embryo to the uterus. Early division of the embryo is pre-programmed by the mother’s genes but subsequent development and implantation require activation of the embryo’s own genes at which point the errors manifest themselves. Needless to add, we do not currently have the ability to either prevent or repair such abnormalities. Clinically, these chromosomal abnormalities lead one or more of the following:
- infertility
- sub-fertility with infrequent conception
- early miscarriages
- elective terminations prompted by finding an abnormality on amniocentesis or chorionic villus sampling (CVS).
Whatever the scenario, there is no birth of a healthy child. Most of the disorders due to incorrect number of chromosomes are incompatible with fetal growth and only individuals with a handful of disorders, such as Down’s syndrome (extra chromosome 21) and Turner’s syndrome (one X chromosome missing), can be born and survive to adulthood.
The graph below portrays the decline in live births with advancing age in all women undergoing embryo transfers after IVF with their own eggs in the United States in year 2001 as reported by the CDC. While the IVF data are best documented, the same decline occurs in spontaneous conceptions in fertile couples as well as with other infertility treatments. You may want to note that the steep declining slope begins as early as the age of 33-34 years.
Since there are no direct interventions to counteract the age factor, the available therapeutic approaches are indirect and limited. One such strategy is to increase the total number of eggs being ovulated within a given period of time, such as a cycle or a year, by using FSH hormone to induce ovarian hyper-stimulation with simultaneous release of multiple eggs (What is an Ovulation Induction?). This strategy is central to IVF but it can also be used as a stand-alone approach in conjunction with intrauterine insemination (IUI) in couples where the woman’s tubes are open and the sperm is likely to fertilize the eggs in vivo. The success of this strategy is dependent upon the ability of the ovaries to respond to FSH by producing multiple follicles containing healthy eggs which is known as ovarian reserve (How do we Test Ovarian Reserve?). Ovarian hyper-stimulation does not create new eggs or follicles within the ovaries but merely induces simultaneous growth of several follicles thus overcoming the body’s natural tendency to select a single dominant follicle containing just one egg.
Women who have infertility associated with both age factor and reduced ovarian reserve typically do not benefit from ovarian hyper-stimulation because their ovaries have few follicles and FSH does not result in the simultaneous growth of multiple follicles. In addition women above the age of 43 have generally low success rates with IVF and ovarian hyper-stimulation even if their ovaries are capable of producing multiple eggs at the same time. Patients in these categories are much more likely to achieve live birth with donor eggs than with their own gametes as shown in the graph below adapted from the 2001 national CDC report.
The graph above also demonstrates that the primary effect of aging is upon the ovaries and eggs rather than the uterus which is capable of carrying pregnancy long after the ovaries cease to function. While there is a mild decline in outcome of donor eggs cycles due to uterine factors its magnitude is relatively small and it does not occur till about 48-50 years of age.
Are men affected by age factor? While the effect of age on male fertility is slight, there is evidence of increased frequency of point mutations in chromosomes of men above the age of 45 years. By comparison with the errors in the number of chromosomes associated with advanced female age, such small mutations rarely cause a problem because most of time their effect is obscured by the presence of the other normal chromosome.
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How Do We Test Ovarian Reserve?
Ovarian reserve refers to the presence within the ovaries of follicles (fluid-filled sacs) containing healthy eggs in excess of the single dominant follicle destined to ovulate in a spontaneous cycle. Women whose ovaries possess good ovarian reserve typically respond to ovarian hyper-stimulation with FSH (What is an Ovulation Induction?) by developing multiple growing follicles and mature eggs capable of establishing a healthy pregnancy. Women with reduced reserve typically develop very few follicles even with higher doses of FSH injections. Even more importantly, multiple studies have established that women with diminished ovarian reserve (DOR) are much less likely to achieve a live birth than women with other infertility factors when undergoing IVF and other fertility therapies.
The graph below clearly illustrates that women with diminished ovarian reserve (DOR in red) had less than half the live birth rates achieved by patients with most other diagnoses (adapted from the national CDC Report on ART for 2001). Thus, next to the age factor, which itself is closely related to ovarian reserve (What is Age Factor?), reduction in ovarian reserve is the greatest determinant of the success of infertility treatment in women using their own eggs.
Ovarian reserve is assessed hormonally and anatomically. In our program all patients have a baseline cycle day 2,3 or 4 FSH and Estradiol blood tests. FSH levels above 10 mIU/mL and/or Estradiol levels above 80 pg/mL are indicative of reduction in ovarian reserve. High resolution vaginal ultrasound of the ovaries is used to determine the antral follicle count which is an anatomical correlate of ovarian reserve. Unless small antral follicles are present within the ovaries, fertility medications cannot make them grow and the woman will not exhibit the multi-follicular response which is key to the success of IVF and other treatments.
When the day 3 FSH/Estradiol and ultrasound examination do not agree a dynamic hormonal test known as clomiphene challenge may be helpful. In this test cycle day 2, 3 or 4 FSH/Estradiol are followed by oral clomiphene 100 mg daily on days 5-9 and the FSH/Estradiol tests are repeated seven days after the initial test. Under the stress of clomiphene (which is an anti-estrogen binding to estradiol receptors) the pituitary gland releases extra FSH hormone which in turn should hyper-stimulate ovaries possessing normal reserve to initiate production of several follicles each of which releases estradiol thus ultimately lowering the FSH level by cycle day 10. A significant percentage of women with diminished ovarian reserve exhibit normal day 3 FSH but markedly elevated day 10 FSH – a finding which carries similar prognostic implication to elevated baseline day 3 hormones, i.e. a much lower live birth rate regardless of the treatment.
The main reason for ovarian reserve testing is to define the exact likelihood of successful conception for each infertile couple so that they have best information in order to make an informed decision about different treatment options. In addition the information may be value in selecting ovarian stimulation regimen best suited for an individual patient.
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What is involved in Embryo Freezing?
If more eggs are normally fertilized and divide to form healthy-looking embryos than is advisable to replace during the treatment cycle, the additional embryos can be frozen and stored for replacement in the future. However, the embryos may not survive the freezing process or may be incapable of resuming growth after thawing. Offspring born from frozen embryos have the same rate of congenital abnormalities as the general population. When damage occurs during the freezing process, the pregnancy usually does not ensue. The likelihood of establishing a pregnancy following transfer of frozen- thawed embryos is about 15-20% per transfer.
Once frozen, the embryos can be maintained in storage for several years, but we encourage replacement within 2 years of fertilization whenever possible. The consent form for embryo freezing requests that you indicate how you would like to dispose of the frozen embryo(s) in case of divorce and death. The options include donating the embryos anonymously for the benefit of another infertile patient or discarding them. While the embryos remain in storage, you need to pay an annual fee. The amount of the fee increases sharply for each additional year of storage.
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What is Assisted Hatching?
Assisted hatching is a laboratory procedure designed to facilitate implantation or attachment of the dividing embryos to the wall of the uterus. In order for implantation and pregnancy to occur, the embryo must "hatch" out of the zona pellucida (the egg's outermost membrane). In some patients, failure to establish a pregnancy after IVF may be related to the inability of the embryos to get out of the zona. On the day of transfer, a small opening is created in the zona pellucida under microscopic control, thus aiding the hatching process.
Assisted Hatching 3 days after retrieval
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What are ICSI and MESA?
Couples with male factor infertility can use a powerful technique called intra-cytoplasmic sperm injection (ICSI) to realize their aim of parenthood. The ICSI procedure was initially developed for severe male factor cases when the number and/or functional capacity of sperm is not sufficient for standard IVF. The first baby from ICSI at the Alta Bates IVF Program was born in April 1995. Recently the use of ICSI has been extended to couples with milder forms of male-factor as well as couples with unexplained or multi-factorial infertility in order to avoid the low or absent fertilization which occurs in some of these cases and which can severely reduce the chance of success. The tests for functional capacity of the sperm (such as semen analysis, strict sperm morphology and the hamster egg penetration assay) do no always predict low or absent fertilization in the laboratory. While uncommon, this can happen even with sperm of men who had previously achieved pregnancy naturally and who have normal semen characteristics. Failed fertilization markedly reduces the number of embryos available and the likelihood of successful outcome. For this reason, we have recently extended the use of ICSI on some or all eggs to IVF cycles without obvious male factor with men who did not previously demonstrate normal fertilization rate in vitro.
During ICSI, a single sperm cell is injected directly into the egg. The procedure is carried out under a microscope while the eggs are kept on a warm stage at 30°C. During thee injection procedures, micromanipulators are used to reduce hand movements to microscopic movements. The sperm injection pipette is used to immobilize and then to inject the sperm into the egg while it is kept stationary using a holding pipette. After egg retrieval, about 80 to 100% of the eggs are expected to be mature for sperm injection. A small percentage of the eggs may be damaged by the ICSI procedure. Not all eggs will fertilize after ICSI and some fertilized eggs may not divide into a cleavage stage embryo. Overall, however, the live birth rates with ICSI equal those achieved by conventional IVF. For most couples with severe male factor infertility, ICSI is the only option available to achieve parenthood with their own gametes.
ICSI Procedure
In cases where the ejaculate does not contain sperm, MESA (microsurgical epididymal sperm aspiration) is performed by a urologist specializing in infertility on the same day that the eggs are retrieved or in advance of the ICSI-IVF cycle. Epididymal and testicular sperm require ICSI for fertilization. During the MESA procedure it is common to obtain more sperm than needed for the ICSI treatment and the additional sperm can usually be frozen for future attempts.
The risk of genetic abnormalities in children born form ICSI has been of equal concern to patients and health professionals. Studies carried out world-wide showed that some forms of congenital abnormalities had a higher incidence in male babies born from ICSI but the most recent studies showed no difference between IVF with and without ICSI. Men with marked sperm abnormalities have a high chance of carrying mild genetic abnormalities which would then be transmitted to their offspring conceived through ICSI but would not be the result of the ICSI procedure itself. Specifically, men with very low sperm counts often have deletions or mutations in the long arm of the Y chromosome which would be passed on to their sons born from ICSI. Therefore, when the sons born form ICSI reach reproductive age, they may also find that they are sub-fertile or infertile due to the genes inherited from their fathers.
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What is an Intrauterine Insemination?
Intrauterine insemination, or IUI, is an infertility treatment which consists of placing prepared sperm within the uterus around the time of ovulation. IUI is used to treat infertility due to low sperm concentration or motility, poor cervical mucus, anti-sperm antibodies, and unexplained infertility. IUI can be done with partner's fresh or frozen sperm or with frozen donor sperm. The pregnancy rate per cycle is about 8-12%. The likelihood of success with IUIs depends on the type and severity of the infertility problem and the woman’s age. According to California Health and Safety Code Section 1644.5, male partners must be checked for the following infectious diseases: HIV (causative agent of AIDS), Hepatitis B & C, HTLV-I/II and syphilis (RPR).
Why is the Sperm Preparation Necessary?
The processing of sperm by gentle centrifugation accomplishes: 1. Removal of the seminal fluid which contains white cells, bacteria and prostaglandin hormones which can cause painful uterine contractions and allergic reaction; 2. Selection of sperm which are most active and vigorous. The active sperm are then suspended in a small volume for placement within the uterus.
How is the IUI Performed?
The IUI is an office procedure. A small tube or catheter with the sperm is passed through the cervix into the uterus, and the sperm are deposited in the uterine cavity. Most of the time, this is a simple procedure that causes minimal, if any, discomfort. Occasionally, it can be technically difficult and uncomfortable. IUIs are very safe, but they do carry a small risk of introducing infection into the uterus and tubes.
When is the IUI Performed?
IUI is timed as closely as possible to the day of ovulation. The sperm preparation takes about 1-1/2 hours after collection. On weekdays, the semen collection is usually scheduled in our office at 8 am or 1 pm. The IUI is scheduled either at 10:15 am or at 3:15 pm. On Saturday, the semen collection is usually at 8:30 am and the IUI is at 10:15 am. We do not perform IUIs on Sundays. Semen is collected by masturbation in the office. Men who reside close to the office may bring the semen after collection at home in a receptacle provided by our office with proper labeling. We must have specimen within 30 minutes of collection. It is best not to use a lubricant for collection. The man and woman are scheduled separately, so there is no need to wait in the office during the semen preparation.
How is the Day of IUI Determined?
OVU-QUICK urine LH-detection kit has been most extensively studies for prediction of ovulation, but other kits are similar: Clear Blue Easy, First Response, etc. Please use kits that give 24-36 hour notice for ovulation. Kits are sold without a prescription. When a rise in urine LH is detected, ovulation generally occurs a day or two later. A test is positive when your dot is close to, equal to or darker than the reference dot. Ovulation usually occurs 14 days before menses. For example, if you have a regular 28 day cycle, ovulation occurs around day 14 (28 minus 14 = 14). If you have a 30 day cycle ovulation occurs around day 16 (30 minus 14 = 16). Start testing about 3-4 days before you anticipate ovulation, e.g. day 10 for a 28 day cycle or day 12 for a 30 day cycle . If you are not certain when to begin testing, please ask us when you call us to let us know that your period began and that you wish to have an IUI in that cycle.
What If My LH Kit Does Not Turn Positive?
If the kit is still not positive after four days of testing or around the expected time of ovulation, please call the office to schedule an ultrasound to check whether there is a mature follicle in the ovary in which case ovulation can be induced with an injection. If your reference dot does not appear or if it is streaked, you probably need a new kit. Sometimes there is a question whether or not the kit is defective, in which case you need to call the manufacturer. A toll-free number is provided on your kit.
How Do I Schedule an IUI?
Please call us on the first business day after your period begins to let us know that you will be testing for an IUI. On Sunday through Friday you should test between 10 am and 2 pm so that you can call us no later than 2 pm when your test is positive. Arrangements will be made for the IUI the following day. On Saturdays only, you should LH test by 7 am; if the test is positive leave message on the answering machine and have your partner come for collection at 8:30 am the same Saturday; your IUI will be done about 10 am. Please ring the doorbell to the right of door (under plastic case) If no one answers, please wait, we will be with you as soon as possible. If the IUI cannot be done on Saturday, you should have intercourse that day.
What is the Cost of IUI?
The IUI costs $500 which includes the sperm preparation, office visit and IUI. The cost of LH kits or other methods of ovulation monitoring is separate. IUIs are usually not a covered benefit of most insurance companies. Therefore, payment is requested at the time of the visit.
How Do I Know if the IUI was Successful?
You can expect a period two weeks after the IUI if you are not pregnant. If two weeks have passed and you have not started bleeding, call the office to schedule a blood pregnancy test. HCG tests are usually done in our office on Mondays, Wednesdays and Fridays and blood needs to be drawn between 8:15 a.m. and 10:00 a.m. Please call our office if you wish to schedule the HCG test. If you start a period, call the office, so that we know when to expect you for another IUI. Generally, 3 to 5 IUIs are done before moving on to another treatment.
A pdf file with the above information on IUI can be downloaded by clicking here.
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What is an Ovulation Induction?
Gonadotropin Ovulation Induction (HMG)
Pergonal, Repronex, Follistim and Gonal-F are the brand names of gonadotropins currently available in the United States. Gonadotropins are used primarily in two groups of women: 1) those who do not ovulate regularly and/or have failed to ovulate and/or conceive with clomiphene; 2) women who ovulate on their own but may benefit from simultaneous ovulation of multiple eggs and the accompanying enhanced hormonal environment.
In most cases, gonadotropin ovulation induction is combined with an intrauterine insemination (IUI). IUI places a much larger number of sperm inside the uterine cavity than usually get there. Current California regulations require that male partners be tested for HIV (causative agent of AIDS), Hepatitis B and C, HTLV-I and syphilis before their sperm can be used for insemination.
What are gonadotropins and how do they work?
Gonadotropins (FSH and LH) are natural hormones that induce the development of multiple eggs. Their use is generally safe but requires experience and close monitoring. In the natural cycle, without any medications, a woman ovulates one or two eggs under the influence of her own gonadotropins. The eggs are contained in fluid-filled sacs called follicles. The recruitment, maturation, and release of the eggs from these follicles is influenced by the sequential release of two hormones: Follicle Stimulating Hormone (FSH), and Luteinizing Hormone (LH), both of which are secreted by the pituitary gland.
When a woman becomes menopausal, her pituitary gland secretes large amounts of these hormones in an attempt to stimulate the ovaries that no longer function. The older gonadotropin preparations (Pergonal and Repronex) are manufactured by extracting these hormones from the urine of post-menopausal women, carefully purifying the material and placing the freeze-dried extract in sterile glass containers. The newer preparations (Follistim and Gonal F) are made in the laboratory using biotechnology techniques. These hormones cannot be taken orally because they would be digested in the stomach.
Pergonal and Repronex contain both FSH and LH; Follistim and Gonal-F contain only the FSH hormone. Pergonal is given as intramuscular (IM) injections; Repronex can be given either IM or subcutaneously (SC) whereas Follistim and Gonal-F are given SC.
Like all medications, gonadotropins have side effects. Ovarian enlargement, known as the hyperstimulation syndrome, is uncommon and can usually be treated by bed rest at home, but in severe cases, intravenous fluids or even hospitalization might be necessary. Close monitoring of your response with blood tests and ultrasound helps avoid severe hyperstimulation. If too many follicles develop, a decision may be made either to forego ovulation by withholding HCG to avoid hyperstimulation or additional measures may need to be taken. The risk of multiple births after gonadotropins is approximately 20%, with the majority being twins. Some reports have linked the use of fertility medications, such as gonadotropins and clomiphene, with possible increased risk of developing ovarian cancer later in life although other reports have not supported this link and the causality is not established. The magnitude of the increased risk, if any, is also uncertain. Ovarian cancer is a relatively uncommon but often life-threatening malignancy.
You may experience soreness or local irritation from the injections. Warm soaks with wet washcloths may help alleviate the discomfort. Some women report fatigue and/or headaches. While on gonadotropins, you can take Tylenol (acetaminophen but not aspirin) if you have a headache.
In some cases gonadotropins are used in conjunction with an oral medication, clomiphene citrate (Clomid, Serophene). In other cases, gonadotropins may be combined with an injectable medication, leuprolide acetate (Lupron) or an intranasal medication, nafarelin (Synarel), both of which inhibit premature ovulation. Antagon is another new medication that is at times added to the gonadotropins to prevent premature ovulation.
Treatment Cycle
Several days before the first treatment cycle, you and your partner or (designee) need to learn the injection technique. It is not a difficult procedure to learn and it can be mastered after a few practice injections with an orange or grapefruit. You can check out a VHS videotape demonstrating the injection technique from our office. Please be sure to return the tape within 2-3 days. One of the nurses will supervise your first injection and answer any additional questions at that time.
Gonadotropins are usually started 2-5 days after the onset of menses. If your period starts before 4:00 p.m., call our office at (510) 649-0440 in order to schedule a baseline ultrasound. If your period starts after 4:00 p.m., call the office the next day. On weekends and holidays, leave a message on the answering machine. The first day of your period is the first day of regular flow, not just spotting. Prior to beginning the injections, a baseline ultrasound is done to detect any pre-existing ovarian cysts. A vaginal probe is used so a full bladder is not necessary. Simple ovarian cysts are common and they usually resolve on their own. However, if a cyst is found, the treatment cycle may be delayed.
At the baseline ultrasound, the nurse will dispense your supplies -- syringes, extra needles, and alcohol wipes. You will be instructed when to begin your injections (typically that same evening or the next day). Response to gonadotropins varies greatly from woman to woman. The particular protocol, start date, dosage and length of treatment will be tailored specifically for you. Please make sure we have your current phone numbers, as frequent communication is often necessary.
Two to four days of injections are prescribed before you return for your next visit--which is usually a blood test (estradiol). Estradiol hormone is secreted by the growing follicles. The blood is drawn in our office at 2999 Regent Street, #101-A between 8:00 and 10:00 AM Monday through Friday. Ultrasounds are generally scheduled between 8:30 and 10:00 AM. On weekends, blood tests and ultrasounds are done by appointment only.
In the afternoon of the days on which you have a blood test, you receive instructions about the dose of gonadotropins for that evening and possibly the following day as well as the time of your next blood test and/or ultrasound. These instructions are recorded on an answering machine which can be reached by calling (510) 649-0717 after 3:00 PM. This number is exclusively for picking up your instructions and cannot be used for leaving messages for the office. If you have a question about the recorded instructions, please call our office by 4:30 p.m. at (510) 649-0440. In providing all instructions we talk of ampules which refers to single (75 units) ampoules or vials.
The fluid-filled sacs (follicles) containing the microscopic eggs (follicles) are visualized and measured by ultrasound. Ultrasound is harmless to you and your developing eggs. Depending on the growth of the follicles and the estradiol levels, variable doses of gonadotropins are given for a total of 7-10 days. When the ultrasounds and blood tests indicate that the follicles are mature, a single injection of HCG (human chorionic gonadotropin) is given to trigger ovulation. Based on when you receive your HCG injection, you will be given instructions about the timing of intercourse or scheduling of an intrauterine insemination. HCG is a natural hormone produced by the placenta and is similar to the LH hormone which triggers ovulation in a spontaneous cycle. The preferred brands are Pregnyl, Profasi and Novarel. If you have another HCG preparation, it is probably fine as long as the powder and the fluid are in two separate vials. Please don't accept HCG in a plunger-type bottle containing both powder and fluid.
Following insemination many patients receive progesterone in the form of vaginal suppositories twice daily. Your menses may be delayed even in the absence of pregnancy if you are taking progesterone. If you are not pregnant, your menses are expected about 14 days after the day of insemination. If your period is more than 2 to 3 days late, please call the office to schedule a blood pregnancy test (quantitative HCG) before stopping progesterone supplementation. Our laboratory usually runs HCG tests on Mondays, Wednesdays and Fridays. Blood needs to be drawn between 8:00 a.m. and 10:00 a.m. to ensure same day results. Please call our office in advance of coming for this test, so that we know to expect you.
What is the cost of gonadotropin ovulation induction?
Gonadotropin ovulation induction is an expensive treatment and insurance coverage varies widely. The cost of the medications is high. We can provide you with the names of pharmacies that sell these medications. It may be worth your while to call several pharmacies and inquire about the prices as they may vary. To avoid confusion, it is important that you let us know what exact medications you have obtained at the baseline ultrasound, but for most patients all the gonadotropin preparations are equally effective.
Please secure the medications before the expected start date. Once your period starts, things move quickly.
In order to make it easier for self-pay patients to budget their expenses, we have developed a cash package for gonadotropin ovulation induction with or without intrauterine insemination. This package represents the maximum price which will not be exceeded for self-pay patients even if the number of ultrasounds and blood tests is greater than the expected number of five. The package is not designed for billing insurance and patients who have insurance coverage are billed on a line-by-line basis for the exact services provided. Self-pay patients who do not complete the entire treatment or whose monitoring is less extensive than provided for in the package are also billed for the actual service provided, not the entire package. Payment is expected at the time of the service. All prior charges must be paid up before another treatment cycle can be started.
| Gonadotropin Ovulation Induction Self-Pay Package: |
| Serial Ultrasounds |
$ 1,000
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| Monitoring |
$ 200
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| Medical supplies |
$ 25
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| Estradiol blood tests |
$ 535
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Subtotal
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$ 1,760
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| Intrauterine Insemination |
| Sperm washing |
$ 150
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| Intrauterine insemination |
$ 250
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| Brief visit |
$ 100
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Subtotal
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$ 500
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| Total cost without medications |
$ 2,260
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| Medications (highly variable) |
$1,300 - $3,000
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| IUI's performed using an ultrasound tech at Alta Bates will incur an additional $140 fee from the hospital. |
The above prices are subject to change without prior notification. If you have any questions about the billing, please contact Maria Castillo at 510-649-0440.
(An informational brochure on Gonadotropin Ovulation Induction can be downloaded by clicking here.) |
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What is the Donor Egg Program?
This program was developed to help women who otherwise have little chance of achieving a successful birth because of one or more of the following:
- Non-functioning ovaries (Turner Syndrome, early menopause)
- Advanced age (above 42 years)
- Genetic abnormality
- Repetitive failure to conceive with other infertility treatments, including IVF and GIFT, with their own eggs
- Reduced ovarian reserve (inability to produce multiple healthy eggs).
PRIDE (Pregnancy Initiation with Donated Eggs) has turned out to be one of the most effective assisted reproductive technologies to date and its high success rate is largely independent of the recipient's age. The mean age of our donor egg recipients has been 45 years. The live birth rate per fresh embryo transfer has been over 50%. The pregnancy loss rate is generally low (< 10%) except in women with uterine abnormalities.
Who are the egg donors?
Our office has an ongoing donor recruitment and screening program. Young, healthy, fertile women under the age of 35 years are recruited in a variety of ways, such as advertising in community journals. The candidates go through a rigorous screening process before they are accepted for our program. The screening includes medical and psychological testing as well as multiple interviews with our staff, a consulting psychologist and the Medical Director, Dr. Richard Chetkowski. We have found that the majority of women who become egg donors are young mothers who are motivated not just by monetary gain, but who also have an altruistic desire to help infertile women.
Our program has primarily followed the anonymous model which has been standard for sperm donation for decades. While no identifying information about the donor is revealed, detailed personal, medical and family profiles are provided to recipients in the process of selecting a donor. In most cases, anonymity best protects the privacy and interests of both parties. Most donors are open to future contact with the child, should he or she desire it upon reaching maturity. If the donor is married or in a stable relationship, full support and consent of her partner is also obtained.
At times, young infertility patients undergoing IVF are willing to donate some of the extra eggs produced during the ovarian stimulation for a reduction in their own expense. If a satisfactory match can be made between such a donor and a recipient, this arrangement can be mutually highly rewarding. Whereas such patient-donors are available less frequently, the cost of these arrangements tends to be less than that of compensated donors.
Some couples strongly prefer to pursue conception with eggs donated by a family member or a close friend who then becomes their designated non-anonymous donor. We are open to this type of arrangement provided that the prospective donors meet our standard screening criteria and provided that thorough psychological counseling and evaluation are completed on the recipient couple as well as the designated donor and her partner. In-family donation can be a satisfactory solution for many couples but it may also have profound effects on long-term family dynamics. Therefore, assessment by an experienced mental health professional is required for optimal outcome.
How do we select our egg donor?
We make every effort to find a donor that the recipient will feel entirely comfortable with and we guide you through this difficult and unique process. Using the information provided by you about your preferences, priorities and exclusions, we try to identify donors who meet these requirements in a general way and who are available within your time frame. We then provide you with detailed personal, family, educational and medical information about several donors and the final selection is made by you. We also provide you with a written donor profile describing her physical characteristics, educational background, special interests, medical and family background, etc. We give you as much information as we can without compromising confidentiality.
What is the treatment plan for the recipient?
The minimum pre-treatment evaluation of the recipient couple includes a current semen analysis and either an HSG (dye study of uterus) or hysteroscopy for evaluation of the uterine cavity within 2 years. Blood tests for both partners include: Hepatitis B and C, HIV antibody (AIDS test), HTLV-1 and RPR which are required by California law. Additional tests for the woman include blood type, rubella and chlamydia IgG antibody tests.
Since many of our recipients are beyond the usual childbearing age, a comprehensive medical and/or obstetrical evaluation is required to assess the safety of pregnancy. A mammogram is recommended for all women above the age of 40. Above the age of 45 years an exercise/treadmill EKG and blood chemistry tests are also required.
Preparation of the uterine lining for implantation (attachment of the fertilized dividing egg to the womb) is key to the success. Recipients receive either twice-a-week intramuscular injections of estradiol valerate (Del-Estrogen) or estradiol patches or daily oral estrogen (Estrace) pills in order to build up the lining. One or two blood tests and ultrasounds are done in our office to assess her response and adjust the medication dose. An individualized printed schedule of injections will be provided for your convenience. Once the date of egg retrieval is set, the recipient adds daily injections of progesterone-in-oil and vaginal progesterone suppository at bedtime.
The hormone preparations, estradiol and progesterone are identical to the hormones which your body would naturally produce during spontaneous pregnancy. Consequently, you need not worry about their possible adverse effects on the developing fetus because these hormones are the same as the ones produced in all human (and for that matter all mammalian) pregnancies.
How do I know how much medicines to take?
In advance of the treatment cycle you receive a preliminary schedule of medications. In most cases this schedule will need to be modified somewhat during the actual treatment cycle to achieve perfect synchronization with the egg donor's cycle. Occasionally we perform a trial cycle to test whether the standard protocol results in good uterine lining in your particular case. In most cases, however, the standard protocol prepares the uterine lining so well, that a trial cycle is not necessary.
What is the treatment for the egg donor?
The donors undergo the first two phases of in vitro fertilization: controlled ovarian hyperstimulation and egg retrieval. They receive a series of daily injections of gonadotropins to stimulate their ovaries to produce multiple eggs over a period of 10 to 12 days. During that time they are closely monitored with blood tests and ultrasounds to determine what is the right day to collect the eggs. Egg retrieval is performed in the outpatient operating room and involves passing a long needle into the ovaries and removing the fluid containing the eggs from the ovarian follicles under light sedation for anesthesia.
ICSI micro-fertilization and MESA procedure
Couples with severe male factor infertility that cannot be treated with standard IVF procedures, can now use a powerful new technique called intracytoplasmic sperm injection (ICSI) to realize their aim of parenthood. The first baby from successful ICSI at the Alta Bates Medical Center was born in April 1995. The ICSI procedure is used primarily in cases when the number of motile sperm in the ejaculate is not sufficient for fertilization with standard IVF.
During ICSI, a single sperm cell is injected directly into the egg. The procedure is carried out under a microscope. Due to the small size of the eggs and sperm, micromanipulators are used to reduce hand movements to microscopic movements. The holding pipette keeps the egg stationary by slight suction applied to its shell, the zona pellucida. The sperm injection pipette is used to immobilize and then to inject the sperm into the egg. The holding pipette is 80 to 100 micron (1 micron = 1/1,000 mm) in diameter and the sperm injection pipette has a diameter of 7 microns. Before injection, the maturation of the egg is assessed. About 65% of the fully mature eggs are expected to fertilize with ICSI but about 1 in 20 eggs may be damaged during this invasive procedure.
In cases where the ejaculate does not contain sperm, MESA (microsurgical epididymal sperm aspiration) is performed by a urologist specializing in infertility on the same day that the eggs are retrieved or in advance of the ICSI-IVF cycle. Epididymal and testicular sperm require ICSI for fertilization. During the MESA procedure it is common to obtain more sperm than needed for the ICSI treatment and the additional sperm can usually be frozen for future attempts.
You need to consider the following information about the risk of genetic abnormalities in children born from ICSI. It is reassuring that the frequency of congenital abnormalities following ICSI are not increased over that seen in the general population. However, there are three separate areas of concern with genetic abnormalities observed in babies born from the ICSI procedure:
- Children conceived through ICSI appear to have an 8/1000 chance of have either an extra or a missing sex (X or Y) chromosome. This is a higher chance than seen in the general population (2/1000). Similarly, the incidence of abnormalities in non-sex chromosomes in children born from ICSI may also be increased from 2/1000 in the general population to 8/1000. At present, we do not know why children conceived through ICSI appear to have this risk. Two possibilities exist:
1. Sperm used for ICSI may be abnormal.
2. The ICSI procedure itself may lead to an increased risk of chromosome abnormalities.
Some of the sex chromosome abnormalities are associated with an increased risk of miscarriage, heart problems that may require surgery, behavior or learning difficulties and infertility in adulthood. Based on the above information, we recommend that you consider genetic counseling and a careful consideration of prenatal diagnosis procedure, such as chorionic villus sampling (CVS) or amniocentesis for detection of these sex chromosome abnormalities. If a child does not have a sex chromosome abnormality, studies to date show that the medical and health risks to ICSI offspring are not greater than with IVF or intercourse. The above risk applies even to couples where man had prior fertility and underwent vasectomy.
- A second, separate issue with ICSI is much more controversial. One study from Australia suggests a higher rate of developmental delay at one year of age for children conceived with ICSI compared to traditional IVF. However, these data have been disputed by two other groups who found no developmental delay after ICSI. Although these results are preliminary, we want to share this information with you. Hopefully, further research will clarify this issue.
- Finally, there is another source of genetic abnormality which is associated with the nature of infertility in men who require ICSI because of low sperm count and/or motility. A proportion of these men carry small changes (micro-deletions) in the long arm of the Y chromosome. These minor genetic abnormalities are not detectable on standard chorionic villus sampling (CVS) or amniocentesis but are expected to be passed on to male offspring born from ICSI. When sons born from ICSI reach reproductive age, they may find that they are also sub-fertile or infertile due to genes inherited from their father. This risk does not apply to previously fertile men with vasectomy but only to men with very abnormal sperm count, motility and morphology.
Out-of-town recipients
Since the treatment of the donors is much more time-consuming than preparation of the recipients, PRIDE lends itself singularly well to patients coming for treatment from outside Northern California. With a world-wide shortage of qualified egg donors, many of our recipients travel from out of state or abroad. We have developed a system of evaluating potential recipients through review of past medical records and telephone interviews with them and their local gynecologists. This system has allowed most of them to travel to Berkeley for only 5 to 7 days during the actual treatment cycle. Accommodations close to Alta Bates Medical Center are available for your convenience. Berkeley is about 10 miles from the San Francisco airport and 4 miles from the Oakland airport.
Financial considerations of donor egg treatment
When undergoing pregnancy initiation with donated eggs (PRIDE) with one of the donors recruited through our program, the total costs include the recruitment and screening of the donors which are often excluded by many outside donor broker agencies. These brokers often charge significant fees in addition to the donor compensation and ART clinic fees. Our donors are compensated $5,000 and their compensation is included in the total fee. However, recently some donors have requested higher compensation. In such cases prospective recipients can decide whether or not they agree to pay the higher compensation in order to work with a particular donor. With rare exceptions, insurance coverage does not include PRIDE (especially since all but about $3,000 of the total cost represents treatment expenses for the donor, not the recipient). Full pre-payment of the projected total expense is required several weeks in advance of the scheduled treatment cycle. Prices are subject to change without prior notice.
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What do I need to know about screening for Cystic Fibrosis?
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Planning for a Healthy Baby: Screening for Cystic Fibrosis
Richard Chetkowski, M.D. and Ulrike Zenke, M.D.
Perhaps the one and only benefit of infertility is that it gives you time to plan carefully for the pregnancy. With the explosion in genetic knowledge in the past couple of decades, heritable conditions have come to play an increasingly important role in pre-conception counseling. Gene identification, characterization of disease-causing changes (mutations), and advances in genetic technology have led to a number of tests for the diagnosis of genetic disorders. Physicians seeing infertile couples have a unique opportunity to screen for and prevent life-threatening conditions before conception occurs. Yet many doctors have been slow to incorporate genetic screening into their practices so the burden of inquiry often falls upon the patient. The common autosomal recessive diseases include cystic fibrosis, sickle cell anemia, Tay Sachs and the thalassemias each of which has maximal frequency in different racial and ethnic groups. The following discussion is designed to introduce you to the most common but also the most complex of these conditions – cystic fibrosis.
What is an autosomal recessive (AR) disease?
AR conditions require that an individual with the disease inherits two deleterious mutations in the same gene, one from each genetic parent. Carriers have just one abnormal mutation and are not affected. Currently most people do not know whether or not they are carriers. Family genetic and medical history is of limited value in assessing the risk of AR diseases because the chance of a match between two carriers for CF is only 1 in 841. Therefore, screening for carriers of AR diseases is a clear example of how new technology can provide would-be parents with information which may influence their reproductive choices.
The inheritance of AR diseases follows the classic Mendelian patterns you may remember from your high school biology class. When both partners are carriers, 1 in 4 children inherit two defective genes and have the disease; half of the offspring inherit one defective gene and thus are unaffected carriers; 1 in 4 children inherit two normal genes. If only one partner is a carrier, half of the children are also carriers but none should have the disease.
The clinical facts about cystic fibrosis (CF)
Cystic fibrosis (CF) is the most common AR disease in the Caucasian population. Most children with CF are born to couples who do not even know that they are at high risk, because mass pre-conception screening has not been widely utilized. Like other AR conditions, the carrier frequency varies in different ethnic groups. In whites of European extraction, the carrier frequency is 1/29 and the frequency of children with CF is 1/3,300. Close to 1,000 children with CF are born in the United States each year.
Cystic fibrosis is a multisystem disorder, affecting glands which produce sweat, mucus, tears, saliva and digestive juices. There is a remarkable variability in the severity of the disease. The most serious manifestation is recurrent pulmonary infections progressively destroying the lung tissue. More than 95% of men with CF are infertile, because they are born with a ?natural vasectomy? called congenital absence of the vas deferens (CAVD): sperm are produced in the testes but do not get into the ejaculate. Otherwise healthy infertile men with isolated CAVD have 2 mutations one of which is typically of a milder variety than those which cause full-blown CF. CF usually presents in early childhood, although approximately 4% of patients are diagnosed as adults. Currently, there is no cure and the average life span is about 30 years.
Screening for CF and its limitations
It was only in October 2001 that the American College of Obstetricians and Gynecologists and the American College of Medical Genetics recommended that CF screening be offered to all “couples in whom one or both partners are Caucasian and are planning a pregnancy or seeking prenatal care” even in the absence of family history. Screening programs for CF carriers must take into account the varying frequency of different mutations in diverse ethnic groups as well as the limited detection rate with most tests. Over 900 different mutations have been described but the standard panel includes just the 25 commonest ones. Thus, even when a person tests negative for CF, there always remains a small risk that he or she is in fact a carrier for a rare mutation which was not included in the test.
The enclosed tables show the benefit of screening when both partners belong to one of several ethnic groups listed. Table 1 provides the risk of being a carrier before testing, the detection rate, and the residual risk of being a carrier after testing negative. Table 2 lists the risk of having a child with CF before and after negative testing of just one parent when both partners belong to the same ethnic group. With ever increasing ethnic diversity, the limited data available for many groups and the frequent intermarriages between members of different ethnic backgrounds, you can appreciate that difficulty may be encountered in quantifying the exact risks facing a given couple.
What to do if one partner is a CF carrier?
First of all, the other partner should also be screened for CF, because it takes two carriers to have a child with CF. However, having a negative CF screening test, does not mean that the risk of having an affected child is zero. Since the standard test fails to detect some carriers, there is a residual risk of being a carrier despite a negative test. As you can see in the Table 1, this residual risk ranges from a low of 1/930 to high of 1/105. The corresponding risk of having an affected offspring when one genetic parent is a known carrier and the other tests negative on the standard test also varies widely from a low of 1/3,720 for Ashkenazi Jews to a high of 1/420 for Hispanic Americans. For sake of comparison, the risks of having a child with Down syndrome when the woman providing the eggs is 30, 35 and 40 years of age are 1/952, 1/385 and 1/106, respectively.
Only you can decide what odds are acceptable to you. Fortunately, a more extensive test for almost all the 900 known mutations in the CF gene has become available recently. While more expensive, in this test the entire gene is sequenced so it can provide reassurance to couples where one partner is a carrier.
How can two carriers build a healthy family?
If both would-be genetic parents are carriers for CF, the likelihood of having an affected child is 1 in 4 which is unacceptably high for almost most couples. Such patients have three medical options:
- They can use sperm or donor eggs from a donor who tests negative.
- They can initiate a pregnancy and then abort the fetus if it is shown to be affected through amniocentesis or chorionic villus sampling.
- They can turn to the high tech option of in vitro fertilization (IVF) in conjunction with pre-implantation genetic diagnosis (PGD) by embryo biopsy. Here the genetic testing and selection of healthy embryos for transfer take place before implantation and pregnancy have occurred. However, IVF with PGD has its drawbacks too. Since PGD tests just a single cell, it is less reliable than amniocentesis and errors have been reported. Obviously, the live birth rate from a single IVF cycle is far from 100% while the procedures are complex, invasive and expensive. The high tech PGD option is of most interest to infertile couples who already require IVF to conceive, such as couples where the man infertile because of CAVD.
Screening egg and sperm donors for CF
Few reproductive decisions are as carefully premeditated as the selection of an egg or sperm donor. Whereas genetic screening of sperm donors has been nearly universal for many years, a survey of donor egg programs published in 1999 revealed that 78% of ART programs did not screen egg donors for CF. The guidelines of the American Society for Reproductive Medicine (ASRM) have recommended testing for CF since 1993 but the adoption of screening by practitioners has lagged in part because of the unique complexity of CF tests.
The current 1998 ASRM guidelines not only recommend screening for the common AR diseases including CF, but also state that carriers need not automatically be excluded from donor pools. We have recently published an analysis of our initial experience with screening of donor egg applicants for CF at the Alta Bates IVF Program and the response of recipients to the inclusion of CF positive donors within the donor pool. While CF positive donors were about half as likely to be selected as non-carriers, some recipients did choose donors who were carriers for CF provided the recipient’s partner tested negative. One of the donor applicants who turned out to be a carrier had previously donated in another California program without having ever been tested. Regardless of whether CF carriers are included in the donor pool, screening Caucasian egg donor applicants should be universal.
Making reproductive choices
In contrast to screening for genetic disease in newborns and adults, screening for carriers has, as its main purpose, the identification of individuals who, while themselves healthy, are at risk for having children with a severe disease. Screening is appropriate in specific ethnic groups in which the carrier frequency is high enough to justify the cost. For cystic fibrosis that group comprises the entire Caucasian population. Although genetic testing for CF is not 100% reliable, the residual risk of having an affected child can be calculated and discussed with the couple seeking conception. Assessment of risks by patients seldom coincides with expert opinion. However, the experts in the field of risk assessment wisely conclude that “in our democracy, people are final arbiters of how safe is safe enough”. Since the future child’s well-being must be the touchstone of policy and the would-be parents are the best guardians of their child’s welfare, the policy at Alta Bates has been to leave the decisions whether or not to test and what to do with the results of testing to fully informed consumers of our medical services.
| Table 1: The detection rate and the probability of being a carrier for cystic fibrosis before and after testing in different populations |
| Ethnic Group |
Risk of Being
a CF Carrier
|
Detection
Rate |
Risk of being
a CF carrier
after negative testing |
|
Ashkenazi Jews
|
1/29
|
97%
|
1/930
|
|
Northern Europeans
|
1/29
|
90%
|
1/290
|
|
Southern Europeans
|
1/29
|
74%
|
1/111
|
|
Hispanics
|
1/46
|
57%
|
1/105
|
| Table 2: The probability of having a child with CF before testing and after one partner tests negative in different populations |
| Ethnic Group |
Risk of having
a child with CF
without testing
|
Risk of having
a child with CF
if one partner
tests negative |
|
Ashkenazi Jews
|
1/3,364
|
1/101,880
|
|
Northern Europeans
|
1/3,364
|
1/33,640
|
|
Southern Europeans
|
1/3,364
|
1/12,876
|
|
Hispanics
|
1/8,464
|
1/12,876
|
Additional Readings:
The American College of Obstetricians and Gynecologists and American College of Medical Genetics. Preconception and prenatal carrier screening for cystic fibrosis: Clinical and laboratory guidelines. October 2001.
Ulrike Zenke and Richard Chetkowski. Inclusion of heterozygotes for cystic fibrosis in the egg donor pool. Fertility and Sterility September 2002; volume 73, pages 557-561.
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What is Embryo Donation?
Embryo donation, also at times called embryo adoption, entails the transfer of eggs previously fertilized by one woman's partner (or sperm donor of her choice) into the uterus of another infertile woman. From a technical point of view embryo donation is analogous to egg donation except that the donation takes place after fertilization. From a genetic point of view embryo donation is analogous to adoption inasmuch neither rearing parent provides the gametes (egg and sperm); thus the child has no genetic link to the rearing parents. Whereas in theory both fresh and frozen embryos can be donated, in practice, most donated embryos have been frozen.
It is unknown how many embryo donation transfers are done each year in the United States. The annual national SART reports which go back to 1987 and the clinic-specific reports which go back to 1989 do not designate embryo donation as a separate ART procedure. Thus embryo donation is subsumed within the much larger category of frozen embryo transfers. The exact success rate of embryo donation is also unknown but is likely to be comparable to the live birth rate per frozen transfer which in 1996 was about 17% nationally. Historically, embryo donation is a by-product of embryo freezing technology which in turn was necessitated by the widespread use of vigorous ovarian stimulation with production of multiple eggs and embryos.
One of the common misconceptions is that thousands of frozen embryos have been donated and are available in ART clinics throughout the world. On March 16, 1997 the New York Times published a front-page article entitled "Surplus of human embryos is the fruit of doctors' labor". Certainly, our experience at Alta Bates and the experience of other Bay Area infertility clinics has been just the opposite: many potential recipients inquire about the few donated embryos. In order to understand the long-term disposition of frozen embryos and to estimate the availability of donated embryos, we conducted a study of the fate of embryos frozen after IVF and after donor egg treatments in our program. As one would expect, about 60% of the embryos were thawed for replacement into the original intended recipient. However, the fate of the "spare embryos", which were not used by the original patients, was very different depending on the source of the eggs. Following IVF with the woman's own eggs, the spare embryos were four times more likely to be destroyed than donated. After treatment with donor eggs, on the other hand, spare embryos were much more likely to be donated than destroyed (Fertility & Sterility 1997; 69:350-2). Extrapolating the above observations, one can estimate that the total number of transfers of donated embryos in the United States is probably less that 400 per year making it one of the rarest ART procedures. By comparison, in 1996, there were 48,7266 IVF and GIFT cycles with the woman's own eggs and 3,345 transfers of donor eggs.
Embryo donation is seldom the infertility procedure of first choice. It is rare that a couple would turn to embryo donation as their preferred method of establishing a family. Embryo donation makes most intuitive sense for single women who require the use of both donor eggs and donor sperm. Couples who undergone multiple failed infertility therapies with their own gametes may wish to try embryo donation before moving on to adoption. Since most of the work and expense involved in assisted fertilization has already been incurred, donated embryos are also relatively less expensive than other ARTs. Waiting lists for donated embryos are common. An informal survey of programs in the Bay Area revealed that most centers tend to reserve the scarce donated embryos for established patients rather than to offer them to new patients. This trend may reflect the fact that, in the process of embryo donation, ART clinics act as fiduciaries entrusted with the proper placement of the donor embryos.
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What is Reversal of Tubal Ligation?
While tubal ligation is generally considered a permanent procedure, some women desire to have children afterwards. The two options for pregnancy after tubal ligation are: microsurgical tubal reversal and in vitro fertilization (IVF).
Tubal reversal is performed by carefully reattaching the cut segments of the tubes to restore tubal integrity and patency. Reviewing the operative and pathology reports from the tubal ligation procedure is the first step in estimating the feasibility and success rate of tubal reversal. If at least 4-5 cm (2 inches) of the tubes are present after the reversal, women under 37 years achieve a pregnancy rate of up to 70% over a period of one to two years after the procedure. However, certain types of tubal sterilization, such as fimbriectomy, are not amenable to surgical reversal and require IVF.
At Alta Bates Medical Center, microsurgical tubal reversal is usually an outpatient procedure with overnight 23-hour stay. The surgery is performed in the morning and you go home the next morning. A small incision (“bikini cut”) is made in the lower abdomen close to pubic hairline to expose the tubes for repair. The surgery takes about three hours and a microscope is used to carefully reattach the tubes with very fine sutures. Most women are able to return to work within two weeks after surgery. Surgical complications are uncommon.
The total cost of tubal reversal at Alta Bates Medical Center is $9,944. Charges are subject to change without prior notification.
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Experimental Protocol of Cryopreservation of Ovarian Tissue
A novel research protocol for freezing of ovarian tissue is open to women under the age of 35 years who are likely to develop ovarian failure and infertility as a result of intensive chemotherapy. The protocol offers them the possibility, but certainly no assurance, of conceiving with their own eggs after they have been cured. Unlike standard in vitro fertilization with freezing of all the embryos after fertilization (which is available on non-experimental basis), this new protocol does not require that the woman have a male partner prepared to make a commitment to fatherhood.
The treatment involves removal of the ovarian tissue at laparoscopy (a minor surgical procedure done under general anesthesia on outpatient basis) followed by controlled freezing and cryo-storage of the tissue until the woman has been cured and is ready to pursue family building. In designing our study, we have followed the pioneering animal and human studies of Dr. Robert Gosden. Our preliminary experience indicates good microscopic survival of ovarian tissue after short-term freezing. To date healthy offspring have been born from replaced cryopreserved ovarian tissue in sheep and mice but no pregnancies have been reported in the human. Therefore, it needs to be fully understood by all the women and their referring physicians that the safety and efficacy of transfer of ovarian tissue into the woman have yet to be established. Our protocol, as approved by the Committee for the Protection of Human Subjects at Alta Bates Medical Center, covers the removal and freezing of ovarian tissue but does not include the transfer of the tissue which will require a separate research protocol to be developed in the future. Since this is an experimental protocol not covered by insurance and since patients undergoing bone marrow transplantation are likely to incur other major expenses, we have made a special effort to minimize the cost of this service.
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