How much of a difference does the donor’s age make?
What is the treatment plan for the recipient?
What is the treatment plan for the egg donor?
In vitro fertilization and embryo development
Introduction
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, premature ovarian failure, cancer survivor)
- Advanced age (above 42 years)
- Genetic abnormality
- Repetitive failure to conceive with other infertility treatments, including IVF with their own eggs
- Reduced ovarian reserve (inability to produce multiple healthy eggs).
Ironically, pregnancy initiation with donated eggs has turned out to be the single most effective assisted reproductive technology 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% and the combined fresh and frozen live birth rate per retrieval exceeds 60%. The pregnancy loss rate is generally low (< 10%) except in women with uterine abnormalities or auto-immune factors.
Who are the egg donors?
Young, healthy, fertile women under the age of 33 years are recruited and rigorously screened by our office on an ongoing basis. The screening includes genetic, medical and psychological testing as well as multiple interviews with our staff, a consulting psychologist and Dr. Richard Chetkowski. Some of out best donors are young mothers with a good support system 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. The majority of our donors are open to future contact with the child, should he or she desire such contact upon reaching maturity.
Occasionally, young infertility patients undergoing IVF are willing to donate some of the extra eggs produced during the ovarian stimulation for a reduction in the cost of their own treatment. 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 than compensated donors, the cost of these arrangements also tends to be lower.
Some couples strongly prefer to pursue conception with eggs donated by a family member or a close friend who then becomes their directed non-anonymous donor. We are open to such an arrangement provided that the prospective directed egg donor meets the screening criteria and that a thorough psychological evaluation is completed on the Intended Parents as well as their directed donor and her partner. In-family donation can be a highly satisfactory solution but it can have lasting effects on the family dynamics. Therefore, assessment by an experienced mental health professional is required for optimal outcome.Top of Page
How to select an egg donor?
Dr. Chetkowski believes that personalized medical guidance is of help to most patients facing the unfamiliar challenge of selecting an egg donor. Using the information provided by you about your preferences, priorities and exclusions, we try to identify donors within our pool who meet these requirements and who are available within your time frame. You are then provided with detailed personal, family, educational and medical information about several donors and the final selection is made by you and your partner.
You receive a written donor profile describing her physical characteristics, family and educational background, special interests, medical information and you have an opportunity to see her photographs. If you have a specific question, the donors are happy to provide an answer. Our aim is to give you as much information as needed to make you entirely comfortable with your selection.
If you do not find anyone you like in the pool of donors available through our office, we provide you with referral to select egg donor agencies and coordinate your search with their coordinators.
How much of a difference does the donor’s age make?
There is widespread belief that the younger the donor the higher the success rate. Unfortunately, at this time there is no donor-IVF data bearing on this issue. This belief represents an inappropriate extrapolation of data pertaining to the well-established decline in live birth rate in women undergoing IVF with their own eggs (What is Age Factor?). Close examination of the national IVF data over a period of 3 years (2003-05), as portrayed in the graph below, indicates that the age-related decline begins no earlier than the age of 33 years. Consequently, we advise our patients that up to the age of 32 years, the donor’s age has no discernible effect on the recipient’s chance of a live birth.
What is the treatment plan for the recipient?
The minimum pre-treatment evaluation of the recipient includes a semen analysis, an HSG (dye study of uterus) and a saline sonohysterogram (SHG) for evaluation of the uterine cavity. If one or both tubes are closed at the end near the ovaries, forming a hydrosalpinx, removal or ligation of the damaged tubes is recommended before IVF, because such closed tubes lower pregnancy rates (What Is a Hydrosalpinx?).Male partner is required to have the STD panel (Hepatitis B Antigen, Hepatitis C Antibody, HIV Antibody, HTLV Antibody and RPR) required by Health and Safety Code. The Intended Mother also has a prenatal panel in addition to the STD tests.
Since many of our recipients are beyond the usual childbearing age, a comprehensive medical and/or obstetrical pre-conception evaluation is advisable to assess the safety of initiating a pregnancy. A mammogram is recommended for all women above the age of 40. Above the age of 48 years a stress/exercise EKG or echocardiogram is required.
Preparation of the uterine lining for implantation (attachment of the fertilized dividing egg to the womb) is key to the success. In some cases a trial hormone replacement cycle with an endometrial biopsy are recommended. Recipients receive estrogen either as twice-a-week injections, as patches or oral pills in order to build up the lining. Blood tests and ultrasounds are done to assess endometrial response and adjust the dose. Once the date of donor’s egg retrieval is set, the recipient adds every-other-day injections of progesterone-in-oil and vaginal progesterone capsules.
The hormone preparations, estradiol and progesterone are identical to the hormones which your body would naturally produce during a 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.
What is the treatment plan 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 the right day for egg retrieval. Egg retrieval is performed in an 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 anesthesia.Top of Page
In Vitro Fertilization & Embryo Development
After eggs are retrieved, they are transferred to the embryology laboratory where they are kept in conditions that support their needs and growth. The embryos are placed in small dishes or tubes containing “culture medium,” which is special fluid developed to support development of the embryos made to resemble that found in the fallopian tube or uterus. The dishes containing the embryos are then placed in incubators, which control the temperature and atmospheric gasses the embryos experience.
A few hours after eggs are retrieved, sperm are placed in the culture medium with the eggs, or individual sperm are injected into each mature egg in a technique called Intracytoplasmic Sperm Injection (What is ICSI?). We inseminate all the mature eggs so that there will be an optimal chance of obtaining several healthy-appearing embryos. The day after the retrieval, the eggs are examined for presence of 2 circular structures within the eggs (pro-nuclei) which constitute evidence of normal fertilization (see picture below).
Normally fertilized egg 1 day after retrieval
The eggs are examined for evidence of cell division (cleavage) at two and/or three days after retrieval. Two days after insemination or ICSI, normal embryos have divided into about 4 cells.
Two-cell embryo 2 days after retrieval with sperm in zona
Four-cell embryo 2 days after retrieval
Three days after insemination or ICSI, normally developing embryos contain about 8 cells.
Eight-cell embryo 3 days after retrieval
Five days after insemination or ICSI, normally embryos have developed to the blastocyst stage, which is typified by an embryo that now has 80 or more cells, an inner fluid-filled cavity, and a small cluster of cells called the inner cell mass.
Blastocyst 5 days after retrieval
It is important to note that since many eggs and embryos are abnormal,it is expected that not all eggs will fertilize and not all embryos will divide at a normal rate. The chance that a developing embryo will produce a pregnancy is related to whether its development in the lab is normal, but this correlation is not perfect. This means that not all embryos developing at the normal rate are in fact also genetically normal, and not all poorly developing embryos are genetically abnormal. Nonetheless, their visual appearance is the most common and useful guide in the selection of the best embryo(s) for transfer.
Untoward Events in the IVF Laboratory
In spite of reasonable precautions, any of the following may occur in the lab that would prevent the establishment of a pregnancy:
- Fertilization of the egg(s) may fail to occur.
- One or more eggs may be fertilized abnormally resulting in an abnormal number of chromosomes in the embryo; these abnormal embryos will not be transferred.
- The fertilized eggs may degenerate before dividing into embryos, or adequate embryonic development may fail to occur.
- Bacterial contamination or a laboratory accident may result in loss or damage to some or all of theeggs or embryos.
- Laboratory equipment may fail, and/or extended power losses can occur which could lead to the destruction of eggs, sperm and embryos.
- Other unforeseen circumstances may prevent any step of the procedure to be performed or prevent the establishment of a pregnancy.
- Hurricanes, floods, or other ‘acts of God’ (including bombings or other terrorist acts) could destroy the laboratory or its contents, includingany sperm, eggs, or embryos being stored there.
Embryo Transfer
While transfer of multiple embryos increases the chance of pregnancy, it also increases the risk of multiple pregnancy (The Dilemma of Twins). The decision regarding the number of embryos to transfer can be difficult. In making a recommendation we take into account the donor’s age, the appearance of the embryos, the couple’s prior history, the advisability of embryo freezing and the couple’s concern about multiple pregnancy and the potential need for multi-fetal pregnancy reduction. In general, we transfer 2 embryos when the eggs are provided by a donor under that age of 35 years. Some couples may choose to have a single embryo transferred at the blastocyst stage because of concern about the risks of multi-fetal pregnancy.
The embryo transfer is done in a room adjacent to the laboratory. The transfer requires no anesthesia. If at all possible, we would like your partner to be present. We use an abdominal ultrasound to confirm that the catheter is within the uterine cavity. Therefore it is best if you drink extra fluid 1-2 hours and stop voiding about 1 hour before the transfer. In the usual position for a pelvic examination, a tiny catheter containing minute amount of fluid with the embryos is gently inserted into the uterus and the fluid is deposited. You then rest for 5-10 minutes before discharge. Following transfer you might notice light spotting for a couple of days.
The embryos not transferred are either frozen for future use or discarded (Embryo Freezing). If you have embryos which will be discarded, you may either permit us to study them first for research or quality control or you may choose to discard them without any study.
Post-Transfer Care
Individualized luteal phase support schedule is provided to you in advance of the actual embryo transfer procedures. Currently we use micronized progesterone capsules or tablets (Endometrin) vaginally, progesterone vaginal gel (Crinone 8%) and intramuscular injections of progesterone-in-oil 50 mg/mL. Progesterone supplementation usually begins in the morning on the day of egg retrieval.
It is our recommendation that you refrain from vaginal intercourse and orgasm, which can be associated with strong uterine contractions, for five days after the transfer until embryo implantation (attachment of the embryo(s) to the womb) has been completed. While there is direct data to this effect, uterine contractions could in theory expel the free-floating embryos from the uterine cavity. Otherwise, we leave it up to your discretion to what extent you may want to modify your usual activities. Bedrest after transfer is not required for high pregnancy rate.
Pregnancy Tests
About twelve days after transfer a sensitive blood pregnancy test (quantitative hCG) is performed to determine if implantation has taken place. It is important to have the test done even if you are spotting or bleeding. If the test is negative, luteal supplementation with progesterone is stopped and a period follows within a few days. If the test is positive, it is repeated in a couple of days to determine whether there is normal growth. In the presence of pregnancy, progesterone is often continued for several weeks until a blood test determines that the placenta is producing sufficient quantity of this hormone.
In some instances the first HCG test is higher than the second even in the absence of hCG injections during the luteal phase. These cases are classified as “biochemical” pregnancies, which do not progress to the clinical state. Biochemical pregnancies are not included in the calculation of the success rate in our program. If your pregnancy progresses normally, you will be scheduled for an ultrasound examination about 4 weeks after the retrieval in order to visualize the pregnancy. About 4-5% have been ectopic, i.e., in the tube. This complication usually requires either a laparoscopy to remove the ectopic pregnancy or medical treatment with methotrexate.
With intrauterine pregnancies there is still the risk of miscarriage which increases with advanced age. We usually perform a second ultrasound examination at 9-10 weeks to confirm normal development of the fetus. In the unlikely event that a high-order multi-fetal pregnancy, i.e. more than twins, is found, we discuss with you the relative benefits and risks of the multi-fetal pregnancy reduction procedure (The Dilemma of Twins). Top of Page