Conceiving with Egg Donation: Is it right for you? by Andrew J. Levi, M.D.

Conceiving with Egg Donation: Is it right for you? 
by Andrew J. Levi, M.D.

Oocyte (egg) donation has become an exciting option for women who otherwise would not be able to conceive. Because the eggs used in oocyte donation are usually from young, healthy donors, pregnancy rates are extremely high, exceeding those of all other fertility therapies available. As a rule, only the age of the egg donor is important in the establishment of a pregnancy in donor egg recipients. As long as the recipient’s uterus is capable of carrying a pregnancy (which is typically not age-dependent), she can have children using this revolutionary therapy. 
While many patients and clinicians view the use of donated eggs to assist conception as a new fertility modality, its roots trace back over 100 years – in animals. In fact, in 1890, an English physician first described the replacement of a fertilized rabbit egg back to a “recipient” rabbit. This technique of using donor embryos then extended to the cattle industry, where it was performed routinely, starting in the 1950s. In the late 1960s, the transfer of donor embryos was then extended to monkeys. These animal models taught scientists an important point: pregnancy rates using donor embryos were extremely high, as long as there was appropriate menstrual cycle synchronization between the egg donor and the embryo recipient. When the menstrual cycles between the donor and recipient were physiologically in line, pregnancy was more often than not achieved; when significant menstrual cycle asynchrony was present, pregnancies were far and few between. 
The first successful egg donation cycle was performed in the United States in 1983. At that time, the egg was actually fertilized in the donor’s reproductive tract and then washed from her uterus. The recovered early embryo was then transferred transcervically to the recipient. While this first successful donor egg cycle was a landmark achievement, it was far from optimal. Firstly, recovering the fertilized egg from the donor posed many technical dilemmas as well as the risk of transmission of infectious diseases. Secondly, recovery of a single embryo was inefficient compared to the potential of surgically removing the donor eggs and fertilizing those eggs in vitro. In that same year, the first donor egg pregnancy was achieved after the laparoscopic removal of a donor’s eggs, fertilization of those eggs in vitro, and subsequent intrauterine embryo transfer. Since that time, tremendous strides have been made in the arena of egg donation, resulting in exceptional pregnancy rates, extremely low miscarriage rates, and thousands of live births to couples that otherwise would have been unable to conceive and bear children. 
The indications for oocyte donation have grown considerably since its inception. Many women can successfully have children using donor eggs, including: (1) women who are unable to bear children because they no longer produce eggs, either because of natural menopause or because of premature ovarian failure; (2) women who produce eggs monthly, but whose eggs are not robust enough to be fertilized and lead to a pregnancy; (3) women who are carriers of genetic diseases and choose not to become pregnant with their own eggs (since they would be at risk for having a child affected with that disease); (4) women who have undergone multiple cycles of fertility therapies using their own eggs without success; and (5) patients who have undergone medical or surgical treatments (chemotherapy, radiation, or surgical removal of their ovaries) that have rendered them unable to conceive using their own eggs. Thus, both women with or without functional ovaries are candidates for egg donation. Fortunately, for all of these women, oocyte donation is an option that can lead to the birth of a healthy child. 
Egg donation itself is most frequently performed anonymously, although “known” egg donation can be facilitated by agencies. In addition, nonanonymous donation can be achieved through relatives or directed donors. Ideally, egg donors should be between the ages of 21-34 years old and should have attained their state’s age of legal majority; utilizing a donor who is less than 35 years old maximizes pregnancy rates while eliminating the need to consider amniocentesis or chorionic villus sampling in cases of a successful singleton pregnancy. An older donor, however, is acceptable, provided the recipient couple is counseled appropriately regarding the cytogenetic risks and the effect of donor age on pregnancy rates. Egg donors can also be “split” between potential recipients; in these cases, the eggs are equally divided between two recipient couples as are the costs related to the egg donor. Pregnancy rates in “split” cycles are the same as those in standard egg donation cycles, although there is a tend towards having less embryos available to freeze. Nonetheless, in all of these cases, thorough screening of the oocyte donor prior to the initiation of an egg donation cycle is of great import. 
Screening involves three major areas of testing: medical, genetic, and psychological screening. Centers that provide egg donation services generally screen donors in accordance with the guidelines set forth by the American Society for Reproductive Medicine (ASRM). First and foremost, a comprehensive history and physical and pelvic examination is necessary to identify factors that might make a donor unsuitable for donation; contraindications to egg donation are most often discerned from both personal and family histories. Medical screening of the donor typically involves the following testing: a complete blood count, blood type and screen to assure Rh compatibility, infectious disease testing for human immunodeficiency virus, hepatitis B and C, syphilis (RPR), and cytomegalovirus (CMV) antibodies, as well as cervical cultures for Neisseria gonorrhoeae and Chlamydia trachomatis. 
Genetic screening of anonymous or unrelated directed donors is performed at the discretion of the screening physician and is frequently tailored to the egg donor’s ethnic background and risk for carrying certain genetic diseases. Groups at higher risk for being a carrier of a genetic disease include Ashkenazi Jews, Americans of African descent, Mediterranean people, and Southeast Asians and Chinese people. Testing may include a genetic karyotype as well as screening for more common diseases, including Tay-Sachs disease, Canavan disease, Sickle cell anemia, a-Thalassemia, ß-Thalassemia, and cystic fibrosis. More intensive genetic screening of the donor may be warranted based on the donor’s ethnic background and family history. Screening for cystic fibrosis should be in accordance of that set forth by the American College of Obstetrics and Gynecology (ACOG). Genetic screening of relatives is advised if there is a family of any heritable diseases or any major congenital malformations.
Psychological screening of egg donors is an extremely important part of the screening process. Appropriate psychological evaluation is necessary for three major reasons: (1) to be certain that egg donation is a suitable elective process for the potential egg donor; (2) to ascertain that the donor has no psychological contraindications for egg donation; and (3), that once started, the potential egg donor will fulfill her responsibilities for the cycle. As per ASRM guidelines, psychological assessment (performed by a qualified mental health professional) should include a psychosocial history focusing on the potential donor’s family history, educational background, assessment of stability, motivation to donate, current life stressors and coping skills, difficult or traumatic reproductive history, interpersonal relationships, sexual history, history of major psychiatric and personality disorders, substance abuse in donor or first-degree relatives, legal history, and history of abuse or neglect. Potential egg donors may be excluded from donating when there is a history of any of the following: heritable psychiatric disorders, substance abuse, two or more first-degree relatives with substance abuse, current use of psychoactive medications, sexual or physical abuse with no professional treatment, excessive stress, marital instability, impaired cognitive functioning, mental incompetence, or high-risk sexual practices. Perhaps most importantly, psychological evaluation for the potential egg donor affords the potential egg donor the opportunity to better consider the possible short- and long-term impacts of egg donation, which may in turn have potential subsequent physical, mental, and ethical ramifications. 
Recipients of donor eggs should also undergo screening prior to an egg donation cycle. In accordance with ASRM guidelines, potential donor egg recipients should have a thorough history taken and should undergo a comprehensive physical exam; depending on the patient’s age, a mammogram, colonoscopy, and/or electrocardiogram may be indicated. Blood testing should include blood type and Rh factor, and rubella and varicella titers. Recipients should be offered immunization if nonimmune to these viruses. Other screening tests may include testing for syphilis (RPR), hepatitis B and hepatitis C, cytomegalovirus (CMV) antibodies, and human immunodeficiency virus (HIV). The partner of the donor egg recipient should have a semen analysis performed and should undergo screening for blood type and Rh factor, serologic testing for syphilis (RPR), hepatitis B and C antibody, cytomegalovirus antibodies, and HIV. Genetic screening and testing should be offered when indicated. The recipient should also undergo evaluation of her uterine cavity (either by hysterosalpingogram, sonohysterogram, or hysteroscopy) to rule out any uterine factors (such as polyps, fibroids, synechiae, of congenital abnormalities) that may hinder embryo implantation. In regards to the psychological evaluation, all couples using an egg donor to conceive should be offered psychological counseling; in some cases, at the discretion of the physician, psychological evaluation may be strongly advised prior to embarking upon an egg donation cycle. 
The coordination of anonymous egg donors with potential donor egg recipients is performed either by fertility physicians and their supporting staff, or by an agency. In cases where donors are “known” but not directed, matching with a potential recipient is frequently facilitated by an agency. In cases of anonymous donation, healthy, thoroughly screened donors are first anonymously “matched” with women who desire to be recipients of donor eggs. This is often based upon genetic and ethnic backgrounds, as well as upon other characteristics. Once the matching process is completed, the process of preparation of the donor egg recipient followed by stimulation of the egg donor ensues.
Preparation of the donor egg recipient involves a series of processes that act to prepare the recipient’s uterus for eventual embryo transfer and subsequent embryo implantation. This hormonal preparation seeks to mimic the physiologic events that occur in a normal menstrual cycle, i.e., a period of estrogen stimulation of the uterine lining following by a period of concomitant progesterone stimulation prior to embryo implantation. In women who have ovarian function, a gonadotropin-releasing hormone (GnRH) agonist is typically used to prevent the recipient’s hypothalamus and pituitary gland (in the brain) from stimulating ovarian follicular development and subsequent endometrial maturation. In this way, the recipient’s uterine lining can be stimulated in a controlled manner and a predictable “window” for implantation created; when performed in a natural menstrual cycle, this window of opportunity can be missed for a variety of physiologic reasons. Thus, the use of a GnRH agonist allows the physician to control the physiologic events necessary to ensure an optimal outcome. Once the communication between the recipient’s brain and ovary has been hormonally suppressed by the GnRH agonist, the recipient takes estrogen, which stimulates the uterine lining, paralleling the endometrial development seen prior to ovulation. Estrogen can be administered orally, vaginally, transdermally, or by injection with equal success. In patients who have complete cessation of ovarian function, a GnRH agonist is not necessary; typically, recipients without ovarian function can begin a course of estrogen without concern for hypothalamic-pituitary interaction. In either case, response to the administered estrogen is measured in most cases by both serum estrogen levels as well as by endometrial thickness and differentiation as visualized by transvaginal ultrasound. When the recipient’s uterine lining appears well-differentiated and amenable to implantation and pregnancy, the egg donor begins a regimen of injectable gonadotropins for controlled ovarian stimulation in preparation for egg retrieval. The donor egg recipient remains on estrogen until her embryo transfer. Studies suggest that the donor egg recipient can remain on estrogen for up to 6-8 weeks prior to her transfer, although the period of time spent on estrogen is typically closer to 4-5 weeks. 
The egg donor can only be successful in making multiple follicles if the drive for the recruitment of a single dominant ovulatory follicle is prevented. Like the case of the donor egg recipient, a GnRH agonist can block this hypothalamic drive; in addition, a GnRH antagonist can be utilized (typically following a short suppressive course of birth control pills) to achieve this same goal. Once the egg donor’s hypothalamic-pituitary-ovarian axis is suppressed (as typified by low estrogen levels), the egg donor begins a course of injectable gonadotropins, which usually consists of recombinant or urinary-derived follicle stimulating hormone (FSH) with or without human menopausal gonadotropins (hMG, a combination of FSH and luteinizing hormone [LH]). The egg donor’s progress is monitored every few days by ultrasound and blood work (just as a patient using her own eggs undergoing IVF would). Thirty four to thirty six hours after an appropriately-timed injection of hCG, the egg retrieval is performed, and the eggs are inseminated with the sperm from the recipient’s partner; after the egg donor is deemed stable post-retrieval, her job is done. Coincidentally, the recipient begins progesterone (administered intramuscularly and/or vaginally) the day before the egg retrieval to assure appropriate synchrony between the cleaving embryo and endometrium development. Typically, an embryo transfer is performed three or five days after retrieval. Extranumerary embryos can be cryopreserved in most cases if desired. The donor egg recipient continues taking estrogen and progesterone with a positive pregnancy test, and these hormonal supplements are then continued through 8-10 weeks gestation. The donor egg recipient transitions here care to her obstetrician at the end of her first trimester of pregnancy, and as a rule can expect a “normal” pregnancy. Throughout the entire process of anonymous egg donation cycles, all office visits, testing, and procedures are performed discretely, and anonymity between the donor and recipient is preserved.
This is an exciting era in the treatment of infertility, as now almost all women who desire to have children can do so. With the advent of the use of donor eggs, women who once could not bear children are now able to conceive and deliver healthy babies. Recipients of donor eggs can be assured that their chances of having a healthy child are excellent, and that the entire process can be performed in a discrete and confidential manner if anonymous egg donation is desired. It is indeed a thrilling option for women who wish to conceive who otherwise would not be able to do so.

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