The phrase “third-party reproduction” refers to the use of eggs, sperm, or embryos that have been donated by a third person (donor) to enable an infertile individual or couple (intended recipient) to become parents. Donors may be known or anonymous to the intended recipient. “Third-party reproduction” also includes traditional surrogacy and gestational carrier arrangements. Traditional surrogacy refers to a treatment in which a woman is inseminated with sperm for the purpose of conceiving for an intended recipient. The surrogate in this scenario has a genetic and biological link to the pregnancy she might carry. In contrast, a gestational surrogate (also called a gestational carrier [GC] or uterine carrier) is an individual in which embryos created by the intended parents are transferred into the surrogate’s uterus, which has been prepared hormonally to carry a pregnancy. The gestational surrogate has no genetic link to the fetus she is carrying. Traditional surrogacy arrangements often are perceived as controversial with the potential to be complicated both legally and psychologically. Despite the requirement for in vitro fertilization (IVF) to create embryos, the utilization of a gestational surrogate, legally, is a lower-risk procedure and is the more common approach conducted in the United States.
Third-party reproduction is a complex process requiring consideration of social, ethical, and legal issues. The increased use of egg donation has required a reconsideration of the social and ethical impact this technology has had on prospective parents, their offspring, and the egg donors themselves. Surrogacy has been acknowledged within the reproductive-medicine community as well as by the American Society for Reproductive Medicine (ASRM). Surrogacy arrangements nevertheless remain controversial and are subject to both legal and psychosocial scrutiny. This booklet will discuss the options for third-party reproduction, reviewing sperm donation, egg donation, embryo donation, and both traditional surrogacy and gestational surrogacy.
The first pregnancy achieved with egg donation was reported in 1984. Since that time, there has been increasing use of egg donation to help infertile couples/individuals conceive. Egg donors are identified, and, through the process of IVF, eggs are obtained from the donor’s ovaries and donated to the intended recipient. Sperm obtained from the recipient’s partner (or a sperm donor) is used to fertilize these eggs, and embryos are transferred into the recipient’s uterus. If pregnancy occurs, the recipient will have a biological but not genetic relationship to the child; her partner (if he provided the sperm) will be both biologically and genetically related.
Egg donation initially was intended for women with ovarian failure. Typically, women were prematurely menopausal as a result of disease, chemotherapy, radiation therapy, or surgical removal of their ovaries. Egg donation is appropriate for women who were born without ovaries. Due to the success of the procedure, as well as the improvements in IVF technology, these indications have been expanded. Egg donation may be offered to women who are known to be affected by or be the carrier of a significant genetic disease who would prefer not to pass this disease on to her offspring. This indication includes women who have a significant family condition where their carrier status cannot be determined. Normal-ovulatory women who appear to have an egg factor as the cause of their infertility often are candidates for egg donation. In many instances, this includes women with multiple failures to conceive after IVF, women of advanced reproductive age, and women with inadequate response to ovulation induction.
There Are Several Ways Of Obtaining Donor Oocytes (Eggs).
Anonymous donors: Women who are not known to the recipient. Donors may be recruited through established egg donation programs or may be identified through agencies.
Known or directed donors: Women who are known to the recipient. The donor is generally a close relative or friend. In some instances, recipients advertise directly for donors in newspapers or on the Internet. In these circumstances, the recipient couple and the donor are known to each other in a limited way, having met without an intermediary program or agency. Recipients should exercise caution about recruiting donors directly without having an intermediary program or agency screen donors or without seeking legal counsel.
IVF programs: Women undergoing IVF may agree to donate their excess eggs to infertile patients. This source of donors is limited, probably because of the perceived coercive nature of the donation, particularly if the women are offered a financial discount on their own IVF cycle.
All donors, both anonymous and known, should be screened according to the most recent guidelines recommended by the ASRM. Donors should have attained their state’s age of legal majority and preferably should be between the ages of 21 and 34. The rationale for the lower age limit is to ensure that the donor is mature enough to provide true informed consent. The rationale for the age of less than 34 is that younger women typically respond favorably to ovulation induction, produce more eggs and high-quality embryos with high implantation, and have subsequent higher pregnancy rates than older women. If the donor is over the age of 34, recipients should be informed as to the cytogenetic risk of having a child with a chromosomal abnormality such as Down syndrome and the impact of donor age on pregnancy rates.
Both anonymous and known donors should complete an extensive medical questionnaire that details their personal and family medical history. Included in this questionnaire should be a detailed sexual history, substance abuse history, history of family disease, and psychological history. In the United States, the Food and Drug Administration (FDA) requires that all egg donors be screened for risk factors for, and clinical evidence of, communicable infections and diseases. A donor is ineligible if either screening or testing indicates the presence of a risk factor for, or clinical evidence of, a communicable infection or disease. For anonymous donors, the questionnaire should assess the donor’s motivation for donating her eggs and provide insight into the donor personality, her hobbies, educational background, and life goals. This document ultimately will be shared with the recipient and provides her with insight into a donor she will never meet. A medical professional reviews this history with the donor and conducts a comprehensive physical examination.
Generally, each donor completes a written psychometric test prior to meeting with a mental health professional (MHP). In addition to reviewing the psychometric test, the MHP has the opportunity to further evaluate the donor, discuss the many complex ethical and psychosocial issues she may encounter, and confirm the donor truly is able to provide informed consent for egg donation.
The laboratory testing of all donors should include screening and testing for syphilis, hepatitis B and C, human immunodeficiency virus (HIV)-1 and HIV-2, Neisseria gonorrhoeae, and Chlamydia trachomatis, as well as screening for human transmissible spongiform encephalopathy and testing when risk factors for it exist. All infectious-disease testing must be done and noted to be negative within 30 days before egg donation. Donors also should have documentation of their blood type and Rh status, complete blood count, and rubella titer. Genetic screening of donors should be based on ethnicity. All donors should be tested for the presence of a cystic fibrosis (CF) mutation. Donors of Asian, African, and Mediterranean descent should undergo a hemoglobin electrophoresis as a screen for sickle cell trait and thalassemias. If the donor is of Ashkenazi Jewish origin, CF mutation analysis and screening for Tay-Sachs disease, Canavan disease, familial dysautonomia, Gaucher disease, and other genetic diseases is indicated. Donors who are of French Canadian descent should be screened for CF as well as Tay-Sachs disease. Additional genetic testing and karyotyping of the donor is not required but may be offered by individual programs as part of their standard procedure or upon the request of the recipient couple.
Evaluation of the recipient couple is similar to that of couples undergoing routine IVF. The physician should obtain a comprehensive medical history from both partners. In addition, the female assessment will include a comprehensive gynecologic history and complete physical exam. From a laboratory perspective, the female should have an assessment of ovarian reserve, when appropriate, blood type and Rh, and rubella and cytomegalovirus (CMV) testing. A Pap smear and cultures for Neisseria gonorrhoeae and Chlamydia trachomatis should be obtained.
The female partner should have an evaluation of her uterine cavity with a hysterosalpingogram (HSG), sonohysterogram (SHG), or hysteroscopy. If the female recipient is over the age of 45 years, a more thorough evaluation with assessment of cardiac function, risk for pregnancy-induced hypertension, and gestational diabetes should be considered. A high-risk obstetrical consultation is recommended to discuss the impact of advanced maternal age on pregnancy, as well as any medical conditions that may impact a pregnancy. The male assessment will include a semen analysis, blood type and RH factor, and genetic testing as indicated. The intended recipient couple should be screened for syphilis, hepatitis B and C, HIV-1, and HIV-2.
In order to retrieve multiple eggs from the donor’s ovaries, the donor must be given a combination of hormonal medications to stimulate the development of multiple eggs within the ovary. This technique is called ovulation induction. The medications may include a gonadotropin-releasing hormone agonist (GnRH-a) or gonadotropin-releasing hormone antagonist (GnRH-ant) to prevent the donor from spontaneously ovulating, and either human menopausal gonadotropin (hMG) or recombinant follicle-stimulating hormone (r-FSH), both of which are able to induce egg development. Development of eggs is monitored by ultrasound and measurement of hormones in blood. When the egg development is at the appropriate size, ovulation is triggered by an injection of human chorionic gonadotropin (hCG).
The eggs are harvested from the ovary approximately 34-36 hours after hCG administration through a process called transvaginal ultrasound aspiration (Figure 1). This is done by placing a transvaginal ultrasound probe, which has a needle guide, into the vagina. A needle is placed into this guide, through the vaginal wall, and into the ovary. The eggs are obtained, evaluated for maturity, and then are inseminated with the male partner’s sperm (donor sperm also may be used), which has been processed in the laboratory. For further details regarding the types of ovulation induction medications and the IVF procedure, please refer to the ASRM patient information booklet titled Assisted Reproductive Technologies.
In order for embryos to implant into the recipient’s uterus, the endometrium (uterine lining) must be prepared and synchronized with the donor reproductive cycle. Numerous methods of endometrial preparation have been described; however, the principle of hormonal preparation is similar. Women who have ovarian function are given a GnRH-a to temporarily suppress their menstrual cycle. When the donor starts her hormonal medications to stimulate her ovaries, the recipient is given estradiol to stimulate the endometrium to develop. Estradiol may be given in the form of an oral pill, transdermal patch, or injection. Ultrasound assessment of the endometrium and blood tests may occur during this time. The recipient begins progesterone on the day after the donor receives hCG. Progesterone causes specific maturational changes within the endometrium that enable the embryo to implant. Progesterone may be given by intramuscular injection, vaginal gel, or tablet.
Embryos are transferred into the recipient’s uterus, usually within three to five days after the eggs are fertilized in the laboratory. The embryo transfer (Figure 2) is performed by placing a small catheter with the embryos through the cervix and into the uterus. If the recipient couple has extra embryos, these embryos may be cryopreserved (frozen) for use at a later time in additional attempts to achieve a pregnancy.
The hormonal replacement regimen of estradiol and progesterone is continued until the recipient achieves a positive pregnancy test. If the pregnancy test is positive, estradiol and progesterone are continued through the first trimester to support the early pregnancy.
The pregnancy rate with egg donation depends on many factors but is generally independent of the age of the recipient. Success rates compiled by the Centers for Disease Control (CDC) for the year 2009 show the average live-birth rate per fresh embryo transfer is 55.1% for all egg-donor programs. The major risk for egg-donor programs is multiple gestations. In 2009, of the 6,553 pregnancies conceived with egg donation, 5,595 resulted in a live birth. Of these, the multiple pregnancy rate was 39.9% with 37.1% being twins and 2.8% being triplets or greater. Because many of the pregnancies miscarry before the actual number of fetuses can be determined, the percentage of multiple pregnancies actually may be higher. The current trend is to reduce the number of embryos transferred in an effort to reduce the risk of multiple gestations. Most programs will limit the number of embryos transferred to two if the donor is between the ages of 21 and 34.
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