Additional Fertility Links
- Transvaginal aspiration of eggs
- Additional information on ICSI
- Gonadotropin therapy
- Treatment with prednisone
- Medications prior to embryo transfer
- Cystic fibrosis testing
- Transfer of multiple embryos
- Risks of multiple gestations
TRANSVAGINAL ASPIRATION OF EGGS
Transvaginal aspiration of oocytes is performed by Dr. Nemiro, in order to recover oocytes (eggs) for fertilization. A local anesthesia, or light IV sedation is usually given, or in some cases no anesthesia is necessary. An aspirating needle is attached to an ultrasound guided vaginal probe in order to locate the follicles on the ovary. The needle is guided through the vagina into the abdominal cavity and then into the follicle(s) on the ovary(s) and the contents are removed. In most cases the fluid inside the follicle will contain an egg(s). It is possible that a follicle will not contain an egg. Complications from transvaginal aspiration of oocytes are very rare, but may include bleeding, infection or damage to surrounding tissues and organs.
In some cases it may be necessary to recover eggs by laparoscopy. A laparoscopy is done under general anesthesia. A small telescope is introduced through the umbilicus, allowing Dr. Nemiro to visualize the ovary(s) and follicle(s). The egg retrieval is then performed as described above. Complications from laparoscopy are very uncommon, but they can sometimes occur. Some of the risks associated with laparoscopy are bleeding, infection, damage to other internal organs, nerve injury, or other complications. In the unlikely event that an injury occurs, a repair may be done through the laparoscope or by a laparotomy (incision in the abdominal cavity).
All patients undergoing oocyte aspiration will have the opportunity to ask Dr Nemiro and/or his staff questions, to assure that they fully understand the risks and benefits of the above procedures. It should also be understood that it is not possible to list all unforeseeable complications that can occur from transvaginal aspiration and/or laparoscopy for egg retrieval.
ADDITIONAL INFORMATION ON ICSI
Intracytoplasmic sperm injection (ICSI) is a procedure designed to help the fertilization process. ICSI is performed by the embryologist, in the laboratory, after egg retrieval. The egg is held under the microscope and a single sperm is injected into the interior of the egg (ICSI). Thereafter, the newly formed zygote, which then becomes a developing embryo, must be cultured in an environment of constant temperature, with control of humidity and with strict limitations of oxygen and carbon dioxide levels. The culture medium containing salts and nutrients is altered and changed at intervals to promote cellular division.
Not all eggs retrieved will be mature or normal in appearance. The percentage of eggs achieving fertilization depends on many factors. Some eggs, which appear to be mature and normal in appearance, will not become fertilized even when exposed to normal looking sperm. Not all of those exposed to sperm will go on to division (cleavage). Not all transfers of embryos will result in pregnancy.
The biological mechanisms of ICSI are not completely understood. The selection of spermatozoa for ICSI is based solely on a cursory overview of morphology and may unwittingly result in the transmission of chromosomal abnormalities. Genetic data on children born as a result of ICSI is limited. It has been reported that ICSI performed with sperm from men with congenital bilateral absence of the vas deferens may pass on a cystic fibrosis mutation should pregnancy occur. It is suggested a couple undergo genetic screening and /or testing to assess their risk factors. In addition, the reproductive ability of the offspring of ICSI is not able to be determined at this time.
All patients having ICSI performed on their eggs will be provided with the above information and will have the opportunity to ask Dr Nemiro and/or his staff questions regarding this procedure to assure that they fully understand their options, and the risks and benefits of doing ICSI. Informed consent will be given by the couple to proceed with ICSI and agree to hold harmless ACFS, to include all staff that participate in the above procedure from any liability, damages, claims or costs, which may arise out of or relate to the procedure mentioned above.
HMG is a combination of two naturally occurring hormones, FSH (follicle stimulating hormone) 75 IUs, and LH (luteinizing hormone) 75 IUs. Follistim, Gonal F or other pure FSH drugs consist of 75 IUs of FSH. Both these medications are used for the correction of ovulatory dysfunction. Other indications are an ovulation, luteal phase defect, as well as repeat pregnancy loss, and unexplained infertility. Gonadotropins may also be used to induce the production of more than one follicle (the fluid filled sac the egg grows in), this response is dosage dependent, and not guaranteed to result in the production of multiple follicles.
Patients using gonadotropin therapy should understand and consent to the following general steps involved in the use of gonadotropin treatment.
- Administration of gonadotropins by intramuscular or subcutaneous injection. The injection may be given by myself, my partner, or a person I choose. I will be instructed on injection technique and medication preparation depending on which medications I use.
- Monitoring the growth and development of a follicle(s) will be done by vaginal ultrasound.
- Serum estradiol level will be done when follicles reach optimal maturity as determined by ultrasound.
- Timed administration of HCG in order to complete the maturation process of the eggs, and then allow them to be released, (ovulation).
- Intercourse, IUI (intrauterine insemination), or ART (assisted reproductive technique will be timed appropriately).
There are potential risks and side effects of gonadotropins, which may include, but are not limited to the following:
- The use of gonadotropins may result in over stimulation of the ovaries, the production of too many follicles (eggs), or hyperstimulation; which may cause pain and fluid retention due to enlargement of one or both ovaries. In its' most severe form hyperstimulation may result in hospitalization for management. This is extremely rare.
- The use of gonadotropins may result in the formation of ovarian cysts. These are usually detected by ultrasound and may result in the need to "skip" a cycle, as gonadotropins should not be administered in the presence of an ovarian cyst. Sometimes birth control pills are used in the "skip" cycle to quiet the ovaries in an attempt to eliminate the cysts.
- Multiple gestations may occur from the use of gonadotropins at ACFS 80-90% of the pregnancies following the use of gonadotropins will be single births. The multiple gestation rate is approximately 10-20%, the majority of which are twins, less than 1% of total pregnancies result in triplets, and 0.3% quadruplets. Over the age of 35 these statistics begin to decrease, and after 40 multiple birth rate is much less common.
- If too many mature follicles develop (when doing timed intercourse or IUI) and/or the serum estradiol level is too high, the cycle will be cancelled. In some cases provera will be given to induce an ovulatory withdrawal bleed and protection with intercourse will be suggested. However, without HCG ovulation should not occur.
- Other possible adverse reactions that have been reported with gonadotropin use are: allergic sensitivity, rash, swelling or irritation at the injection site, headaches, irritability, restlessness, depression and fatigue. As with any attempt at pregnancy, ectopic pregnancy may result.
- Genetic defects or congenital malformations that may result have not been linked to the use of gonadotropins.
- Ovarian cancer has not been linked to gonadotropin usage.
TREATMENT WITH PREDNISONE
Prednisone is an adrenocortical steroid that occurs naturally or can be produced synthetically. They tend to have a short duration of action. They are used as replacement therapy in adrenocortical deficiency states as well as for their potent anti-inflammatory effects in disorders of many organ systems. In addition, they modify the body's immune responses to diverse stimuli.
In the field of reproductive endocrinology and infertility, steroids or prednisone, can be used for the treatment of antisperm antibodies; and in females, for the treatment of repeated pregnancy loss as well as antisperm antibodies. It is usually given in low doses 5 or 10 mg daily, and for short periods of time, 6 months.
The mechanism of action is to decrease the immune systems' production of either antisperm antibodies or the elevated phospholipid antibodies found in some patients with repeated pregnancy loss. There is some evidence that empiric treatment with low dose steroids may be beneficial in repeated pregnancy loss, even when the autoimmune testing has been negative. There are a few reports of subclinical (not detected by present laboratory testing) autoimmune causes of habitual abortion.
Prednisone is not an anabolic (testosterone-like) steroid and will not cause masculinization. It is a glucocorticoid and thus has salt retaining properties. Side effects generally are minimal and mild when given in low dose, short term use. These include: fluid retention, high blood pressure, muscle weakness, increased sweating, allergic dermatitis, headache, dizziness, menstrual irregularities, weight gain, increased appetite, nausea and fatigue. The more serious side effects, which are rare and generally related to long term use, include: aseptic necrosis of the hip bones, agranulocytosis (the bone marrow stops making white blood cells) cardiomyopathy (damage to the heart muscle), osteoporosis and steroid psychosis.
Withdrawal from steroids should be slow, generally over a 3 week period, gradually decreasing the dose.
MEDICATIONS PRIOR TO UTERINE EMBRYO TRANSFER
It is recommended by the American College of Obstetricians and Gynecologists to be on a minimum of 400 micrograms of folic acid if you are low risk. If you are a high-risk patient i.e., prior history of spina bifida or other neural tube defects, taking anti-epileptic medications or have an elevated homocysteine level, than you should be on 1000 micrograms (which is in prescription prenatal medications). Also the newer prenatal vitamins have omega-3 fatty acids, which have been shown to be important for the development of the baby's eyes and brain in the third trimester.
DOSAGE: Prescription for Duet DHA-EC or Prenate DHA or Prenexa
Baby aspirin is shown to improve blood flow to the uterus and ovaries. It has been shown to help reduce the risk of miscarriages. Generally, there are no disadvantages to taking this medication unless otherwise specified by Dr. Nemiro.
DOSAGE: One baby aspirin to start day one of the gonadotropins (hMG and/or FSH) until 12 weeks pregnant.
Antibiotics have been shown to be protective against the small risk of infection during egg retrieval and subsequent tubal or uterine embryo transfer.
DOSAGE: The antibiotic is Zithromax. Take 500 mg starting the night before your retrieval and continue every night through the night after the tubal or uterine transfer. You should not be taking this if you have an allergy to Erythromycin so please let us know if this is the case. Zithromax may cause mild stomach upset. An alternative antibiotic would be Vibramycin.
This medication is a steroid, like cortisone, and has been shown to possibly protect the embryo(s) from attack by the immune system after transfer. Serious side effects from this medication are rare especially from low dose, short-term use. Please see package insert.
DOSAGE: The steroid is Medrol (Methylprednisolone). Take 32 mg starting the morning before your egg retrieval, (you will take it after your retrieval so bring it with you) and continue every morning through the morning after the tubal or uterine embryo transfer.
CYSTIC FIBROSIS CARRIER SCREENING
Cystic fibrosis (CF) is a genetic disorder developed by having two changed copies of the CF gene. If both partners are carriers of CF any child they have has a 25% chance of inheriting two changed copies of CF, thereby developing CF. Anyone having one changed copy of the CF gene is a carrier, but does not have CF. CF is a life-long illness usually diagnosed in the first few years of life, causing problems with digestion and breathing. It does not affect intelligence or appearance. Digestive problems can usually be treated with daily medications. Breathing problems are usually treated with daily respiratory therapy to help clear mucus from the lungs. Lung infections can develop resulting in treatment in a hospital. Infections tend to become worse over time and more difficult to treat. Treatment is costly and may become burdensome financially. Not all people with cystic fibrosis have the same symptoms. Symptoms can be mild in some people and severe in others. The reason for this is not completely understood. It's not always possible to predict the severity of symptoms based on prenatal testing. In general, people with cystic fibrosis have a shortened life span. Some die in childhood while others live into their 40s or even longer. There is no cure for cystic fibrosis, but research continues for more effective treatments. Cystic fibrosis carrier testing is provided to see if a couple is at risk for having a child who will have cystic fibrosis. Testing is done on a sample of blood to determine carrier status. The illness cannot be treated before birth. If both parents are carriers, additional testing on the developing baby can be done so you can decide how to proceed and prepare for the future. Anyone can be a carrier of CF even if no one in your family has CF and even if you already have children without CF. The following table show the chance of being a CF carrier depending on race/ethnicity.
|Race/Ethnicity||Chance of being a
|Chance both partners are
|European Caucasian or Ashkenazi Jewish||1 in 29||1 in 841|
|Hispanic American||1 in 46||1 in 2,116|
|African American||1 in 65||1 in 4,225|
|Asian American||1 in 90||1 in 8,100|
Your chance is higher if there is a carrier or a relative with CF in your family. Screening to determine CF carrier status is voluntary. It may be right for some people and not right for others based on many factors, including your level of risk, family situation, plans and needs, and religious and spiritual beliefs. Current testing is limited as there are some mutations of the CF gene that cannot be found. Many labs test for only 32 mutations. Here at ACFS, we use a lab that is able to test for 97 mutations. Due to the fact that there are some unknown mutations, it is best to test for as many as possible. However, it is important to know that this still will not guarantee you are not a carrier. The likelihood of you still being a CF carrier is very small if your results are normal. If your test shows you are a carrier, your partner should be tested as well. CF testing only has to be done once as the result is definite and will not change. If CF seems like a serious disorder to you, if the chance of being a carrier seems high to you, if you have a family history or are related to someone with the disorder, if both partners found to be carriers would consider amniocentesis or CVS testing (to show if the baby will develop CF & decide to keep/terminate the pregnancy), if test results are reassuring to you, or if the cost of testing is covered by insurance, you might consider testing. If you feel any of the above does not affect you, you might consider declining testing.
TRANSFER OF MULTIPLE EMBRYOS
A transfer of multiple embryos increases the possibility of multiple births, and the associated obstetrical, maternal and financial risks. While each embryo transferred has a chance of implanting, it is possible that all embryos transferred may implant.
Selection of the number of embryos transferred at ACFS is based on the guidelines set up by the American Society of reproductive Medicine (ASRM) and the Society of Assisted Reproductive Technology (SART), and is dependent on the woman's age, quality of embryos, and the number of cells in each embryo.
Since obstetrical complications, including prematurity, occur at a higher percentage in multiple gestations, high multiples can be reduced. The procedure involved is called Selective Reduction. This involves insertion of a needle, guided by ultrasound, through the abdomen and into the gestational sac(s). A toxic solution is injected into the sac(s) reducing the pregnancy. Selective Reduction appears to be an effective and safe procedure with a 3% to 5% chance of complications including pregnancy loss.
RISK OF MULTIPLE GESTATION
If you have elected a prescribed course of treatment, which utilizes fertility drugs, you are at a potential known risk for multiple gestation (twins, triplets, quadruplets, etc). These are inherently difficult pregnancies, which may be further complicated by underlying health problems or age (when >35 years). Conditions associated with multiple gestations include: premature labor, premature birth, stillbirth (death of one or more of the fetuses), incompetent cervix (opening of the cervix and loss of the pregnancy prior to estimated date of delivery), diabetes, placenta previa (placenta blocking the exit from the uterus), and thrombophlebitis (blood clots). Cesarean section is commonly required to deliver these babies safely, and at a much higher incidence than what is normally seen in singletons.
Any of these problems may require you to be hospitalized, and the care needed may be prolonged (weeks or months). Occasionally babies will be born so premature that they cannot survive. In other cases the problems of prematurity are very severe leaving the child permanently and severely disabled. The total expense of health care for you and your babies may be high. This may be further compounded by the loss of wages from time off work.
Dr. Nemiro can neither predict nor prevent a patient from experiencing any of these events once the pregnancy has been established. The only way to minimize risk is to limit the number of embryos entering the uterus. Even then, there is a slight chance of multiple gestation (i.e., identical twins form when the embryo divides into two spontaneously prior to implantation, occurring 1 out of 250 pregnancies).