Oocyte Donation: State of the Art doc

18 Oocyte Donation: State of the Art Anne Z. Steiner and Richard J. Paulson Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Women’s and Children’s Hospital, Keck School of Medicine, University of Southern California, Los Angeles, California, U.S.A. INTRODUCTION Oocyte donation is now an integral part of the armamentarium of the infertility specialist. At its inception, it was intended as therapy for women with premature ovarian failure, or those with heritable genetic defects. However, as experience accumulated, oocyte donation as a treatment has been extended to women with a variety of defects in oocyte production or function. The largest group of women now undergoing treatment with oocyte donation consists of those with age-related decline in fertility. Additionally, techniques learned from oocyte donation, including endometrial preparation and embryo-endometrial synchrony, have been applied to other infertility treatments, including frozen embryo transfer and in vitro maturation of immature oocytes. HISTORY The first successful human oocyte donation was reported in 1983. At the time of ovulation, a fertile donor was inseminated with the recipient partner’s sperm. Uterine lavage was performed on the fifth day after the luteinizing hormone (LH) peak. The recovered embryo was then transferred to the uterus of the infertile patient. After several attempts, a pregnancy was successfully initiated and a singleton birth at term was achieved (1,2). 381 Unfortunately, this method, known as ‘‘ovum transfer,’’ was inefficient (3). Attempts to enhance the efficiency of the process by administering fertility medications to the donors were unsuccessful and led to retained pregnancies in the donors (4). The first use of standard in vitro fertilization (IVF) methodology for oocyte donation was also reported in 1983; however, this pregnancy ended as a miscarriage (5). Subsequently, Lutjen et al. reported a successful pregnancy in a woman with ovarian failure. Donated oocytes were fertilized in vitro and the resulting embryos were transferred to the recipient’s uterus, which was prepared with a combination of oral estradiol and intramuscular progesterone (6). This landmark event substantiated the observation that exogenous estrogen and progesterone could reliably produce a receptive endometrium rather than relying on natural ovulatory cycles. In women with residual ovarian function, donor and recipient cycles could thus be syn- chronized with gonadotropin-releasing hormone (GnRH) agonists (7), and the recipi ent endometrium stimulated with exogenous steroids (8,9). These essential principles have remai ned the key components of the current practice of oocyte donation. INDICATIONS Oocyte donation is a therapy which allows women to conceive when their own oocytes are either not capable of producing a pregnancy or carry a heritable defect that the patient does not want to pass on to their children. Common indications for oocyte donation thus include premature ovarian failure secondary to chemotherapy in healthy cancer survivors (10), follicle- stimulating hormone (FSH) recepto r defects (11), or other causes. Patients with gonadal dysgenesis are also appropriate candidates for oocyte donation. Those with Turner’s syndrome may conceive; this group may be at some risk of obstetrical complications (12). Oocyte donation is also indicated in the cases of poor oocyte quality inferred by multiple failed cycles of conventional IVF or in women of advanced reproductive age with associated diminished ovarian reserve. Other patients may choose oocyte donation in an attempt to avoid passing heritable genetic diseases to their children, although pre-implantation gen etic diagnosis is increasingly being applied in these situations. FACTORS INFLUENCING SUCCESS Donor Age It has been established that female fertility hinges on the age of the oocyte provider. Thus, the chronological age of the oocyte donor would seem to play an intuitive role in the overall success of the process. Remarkably, most 382 Steiner and Paulson retrospective series do not demonstrate a major effect of donor age on pregnancy success (13–18). However, retrospective series suffer from selection bias; older donors may indeed have been chosen for inclusion because of their prior good track record. Some studies have confirmed that older donors may be less likely to produce a clinical pregnancy (19–21). Although prior fertility in a donor does not appear to play a role (19,21), previous successful cycles may improve the prognosis in subsequent ones (15). Recipient Age Recipient age per se does not appear to decrease the probability of pregnancy success with oocyte donation. Indeed, it was the observation that the age of the uterus does not influence the probability of the initiation of pregnancy that led to the conclusion that the age-related decline in human fertility was primarily due to the age of the oocyte (22–27). Supporting this conten- tion were physiological observations that uterine blood flow does not appear to decrease with age (28) and that the endometrial response to exogenous steroids also does not appear to diminish with age (29). It is not yet defini- tively established whether pregnancy success after the age of 50 remains unaltered. In our experience (30,31), no decline has been observed. However, an analysis of data derived from the national registry suggested a modest decline in live birth rates after 50 years of age (32). Maternal Factors The specific indication for oocyte donation does not appear to influence the success of the procedure (15,27,32). However, uterine pathology, such as Asherman’s syndrome or previous radiation therapy, may negatively impact uterine receptivity (33). Analogously, uterine fibroids or other endometrial lesions are thought to interfere in embryo implantation, regardless of whether or not oocyte donation is used (34). It should be noted that the incidence of uterine pathology increases with the chronological age of the recipient. Therefore, older recipients may require more careful screening for these factors. Hydrosalpinges in recipients also appear to negatively impact embryo implantation (35), and thus we recommend imaging of the fallopian tubes in all potential recipients. Obesity in recipients does not appear to impact pregnancy rates (36,37); one report suggested an increase in miscarriage rates (38). Endometriosis in recipients does not negatively impact embryo implantation (39). Pinopod expression, a marker of uterine receptivity, appears to be the same in recipients with endometriosis as in those without the disease (36). Repetitive Cycles Lack of success in one or more cycles does not negatively impact the outcome in subsequent cycles, and pregnancy rates appear to remain unaltered Oocyte Donation 383 on a per cycle basis (32) as long as the recipient has a normal uterine cavity and normal endometrial development was verified. However, in one series, patients who conceived during their first cycle of oocyte donation were more likely to conceive in subsequent cycles (40). Cycle fecundability also appears to be unaltered by the number of cycles that the donor has undergone. The donor response to gonadotropin therapy and pregnancy rates do not differ by the interval between donation cycles or the cycle rank (41,42). Donor complications are uncommon and do not appear related to the number of stimulation cycles. Nevertheless, the American Society for Reproductive Medicine (ASRM) recommends that an individual limit the number of donor cycles to no more than six (43). SCREENING OF DONORS The ASRM publishes and periodically updates its guidelines for donor screening (44). Screening guidelines include a personal and sexual history, with the intent of excluding those women at high risk for HIV, other sexu- ally transmitted disease, transmissible spongiform encephalopathy (44), or recent confi rmed or suspected West Nile virus infection (45). Serum screening for syphilis, hepatitis B and C, HIV-1, and HIV-2, as well as cervical cultures for Neisseria Gonorrhoea and Chlamydia, is recommended (44). Psychological screening should include family, sexual, substance use, psychiatric history, information on educational background, assessment of stability, motivation to donate, life stressors and coping skills, and interper- sonal relationships. The counselor should confirm that the donor has been informed of the medical treatment, discuss the psychological risks of oocyte donation, and evaluate for signs of coercion (46). Genetic screening should include a history with a specific focus on any major Mendelian disorders, major malformations due to multifactorial causes, or known karyotypic abnormalities in the potential donors or in any of their first-degree relatives (47). A screening test for cystic fibrosis is recommended for all donors. A heterozygote may be included as a donor if the recipient is aware and the recipient’s partner tests negative (48). Spe- cific ethnic groups known to be at high risk for carrying certain recessive genes should undergo additional screening tests (47). SCREENING OF RECIPIENTS As with donors, the ASRM periodically updates its guidelines for the screening of recipients (44). Routine screening includes a medical and reproductive history, physical exam, and standard preconception testing and counseling. These include blood type and Rh factor, rubella and varicella titers (with vaccination if not immune) along with infectious disease screening. Recipients 384 Steiner and Paulson should undergo counseling regarding the potential psychological implica- tions of becoming parents as a result of oocyte donation (46). The uterus should be examined by ultrasound and the cavity evaluated and pathology corrected prior to embryo transfer (36). Evaluation of the endometrial cavity can be achieved by saline-injection sonography (49), hys- teroscopy, or hystero salpingography (HSG). The advantage of the HSG lies in its ability to visualize the fallopian tubes and thus detect the presence of hydrosalpinges. All hydrosalpinges should be removed, as these have been shown to decrease implantation rates and increase the risk of infection as well as ectopic pregnancy in recipients of oocyte donation (50,51). If salpin- gectomy is not possible, interruption of the oviduct in a location proximal to the uterotubal junction also appears to prevent reflux of hydrosalpingeal fluid and thus to mitigate the adverse effects of the hydrosalpinx (52). As a special group, patients with Turner’s syndrome should undergo echocar- diography because they are thought to have as high as a 2% risk of aortic rupture or dissection with a risk of death during pregnancy (12). The screening of partners of recipients of oocyte donation should include a semen analysis, blood type and Rh screen, and a genetic screen along with infectious disease screenin g for syphilis, hepatitis B and C, cytomegalovirus antibody, and HIV. Screening should also include psychological counseling. PRACTICE CYCLE When oocyte donation first began, all recipients underwent practice cycles to ensure an adequate response of the recipi ent’s endometrium to exogenous steroids. Although this practice has recently become somewhat controversial in that some programs feel that it is not necessary, our program continues to rely on the information the cycle provides. In a practice cycle, recipients undergo a regim en of exogenous estrogen and progest erone, which is identical to the actual recipient cycle. Our practice utilizes the regimen depicted in Table 1. Endometrial thickness is noted at the beginning of the cycle and prior to the initiation of progesterone. On the seventh day of progesterone administration, endometrial thickness is again documented and the recipient undergoes a practice embryo transfer as well as endometrial biopsy. We have found that ultrasound measurement of en dometrial thickness does not always correlate with biopsy findings (54). The biopsy may the document a lack of adequate estrogen priming or out-of-phase endometrium (55). Practice cycles also provide additional information on patient’s ability to comply with the hormone therapy protocol. In one large study, 5.8% of women had difficulty in follo wing the instructions (54). A recent report has suggested that local injury to the endometrium during non-transfer cycles may improve subsequent implantation rates during IVF, although the mechanism is not clear (56). Oocyte Donation 385 In contrast, programs that no longer require endometrial biopsies rely on information from studies indicating that an in-phas e e ndometrial biopsy does not predict pregnancy (57) and an out-of-phase biopsy does not neces- sarily predict failure (58). Pregnancy rates in one small study did not differ whether a biopsy was or was not performed (57). It has also been argued that measurement of the endometrial thickness may be a better predictor of outcome (58) and one study did find that it correlates with biopsy (59). OVARIAN STIMULATION Oocyte donors undergo controlled ovarian hyperstimulation in a manner similar to that of conventional IVF. The most common method is the so-called ‘‘long protocol,’’ which relies on pre-stimulation pituitary downregulation using GnRH a gonists in daily intermittent or depot formulations. More recently, short protocols using GnRH antagonist during the late fol- licular phase of the stimulation cycle have been utilized. Studies comparing agonists and antagonists have not shown a significant difference in pregnancy rates achieved with protocols using agonists or antagonists (60,61). As with conventional IVF, the use of antagonists appears to reduce the amount of gonadotropins required and the duration of treatment (60,62). When utilizing antagonists, gonadotropin dosage may need to be adjusted to prevent a potential decline in estradiol levels, which has been correlated with decreased pregnancy and implantation rates (63). Others have advo- cated adding recombinant LH to recombinant FSH protocols, when starting antagonists, as a strategy to increase oocyte yield and improve pregnancy rates (64). In agonist cycles, controlled ovarian hyperstimulation follows pituitary downregulation in the standard fashion as per conventional IVF using recombinant or purified gonadotropins. The addition of recombinant LH to recombinant FSH in donors on agonists with an LH value of less than Table 1 Standard Estrogen and Progesterone Replacement Regimen Micronized estradiol (oral administration) Micronized progesterone (vaginal administration) Days 1–4 1 mg BID Days 5–9 2 mg BID Days 10–14 2 mg TID Days 15–28 (through 13th week of gestation) 2 mg BID 200 mg TID Source: From Ref. 53. 386 Steiner and Paulson 1 IU/L during downregulation may increase the number of mature oocytes and the implantation rate (65). Dosages are individualized based on donor characteristics. For example, non-hirsute fertile women with polycystic- appearing ovaries may require fewer ampoules to meet criteria for oocyte retrieval compared to donors without polycystic-appearing ovaries; fertilization rates tend to be similar (66). During the stimulation phase, serum estradiol levels on day 5 (67) and at peak (68) have been reported to correlate with the number of oocytes as well as with the implantation rate. In our practice, donors are most commonly prescribed an overlapping regimen of oral contraceptives and GnRH agonists in a long protocol. Oral contraceptives are begun one week before the initiation of leuprolide acetate. Both medications are continued for one week, and the oral contraceptives are then stopped, whereas leuprolide is continued. Oral contraceptives allow for coordination of recipient and donor cycles. Donors are evaluated approximately one week after cessation of oral contraceptives prior to stimulation to confirm downregulation by ultrasound evaluation of the ovaries and endometrium and by measurement of serum estradiol. Stimulation is then performed using human menopausal gonadotropins alone or in con- junction with recombinant FSH. Donor cycles require vigilance on the part of the nursing staff. One study showed that despite thorough and repetitive instructions, 2% of donors were found to have difficulties adhering to the protocol and 7% become pregnant after stimulation, despite instructions to use barrier meth- ods of contraception (69). We now advise donors to abstain from intercourse from the onset of stimulation until the following menses. In addition, donors are given a prescription for oral contraceptives to initiate with menses. DONOR SAFETY Serious complications of oocyte donation are relative ly rare. Less than 1% of donors have events requiring hospitalization or emergent intervention during or foll owing aspiration as a result of any cause, including severe ovarian hyperstimulation syndrome (OHSS), reactions to anesthesia, or intra-abdominal bleeding (70). Severe OHSS is uncommon (71); however, mild forms should be anticipat ed as a majority of donors experience abdominal discomfort and bloating to some extent. The symptoms usually resolve by the time of menstrual flow. As the severity of OHSS is correlated with estradiol levels on the day of human chorionic gonadotropin, oversti- mulation of donors should be avoided (72). Other general principles in the prevention and management of OHSS apply in donors a s in infertility patients with the significant advantage that donors do not become pregnant and thus avoid pregnancy-related exacerbation of OHSS (73). Additional intravenous fluid and/or albumin may be administered at the time of follicle aspiration (74). In our practice, donors are evaluated in our office two days Oocyte Donation 387 after follicle aspiration. If necessary, additional intravenous fluids (1000– 2000 mL of normal saline) may be administered. Rarely, paracentesis may be required (75). A small retrospective study showed that ‘‘coasting’’ in an attempt to prevent OHSS does not affect pregnancy rates unless coasting lasts for more than four days (76). Little is known about the effect of oocyte donation on future health and fertility. However, in a study of eight donors who each underwent 4 to 12 cycles, laparoscopy confirmed no pelvic pathology except minimal endometriosis in one patient (77). ENDOMETRIAL PREPARATION The goal of endometrial preparation is to prepare the uterine cavity for implantation and to synchronize endometrial progress with embryo development. In general, preparation of the recipient endometrium with estrogen and progest erone occurs in fashion identical to the recipient practice cycle (Table 1). Women with ovarian failure can initiate a cycle at any time, whereas those with residual ovarian function should undergo pituitary downregulation with agonists to avoid untimely uterine bleeding associated with fluctuating steroid levels. Additionally, premature progesterone production by the recipients’ ovaries can disrupt synchrony between embryos and endometrium. Using agonist therapy allows coordination of the oocyte donor and recipient and prevents ovulation, but does not appear to affect implantation rates (78). One study (79) suggested that downregulation in the recipient with residual functio n may not always be necessary. In that trial, 4 mg of oral estradiol daily starting on cycle day 1 suppressed ovulation (as determined by serum progesterone levels) until day 14 of the cycle in 97% of patients. Unfortunately, this regimen limits the flexibility for syn- chronization with donor stimulation in fresh cycles and is thus primarily used in frozen-thawed embryo transfer cycles. Ever since Navot et al. showed that in-phase endometrium could be obtained with a variable estrogen and progesterone regimen, designed to mimic the natural cycle (80), variations on this combination have been used. To date, no study has demonstrated that a better endometrial environment can be generated by any other means. In other words, although many other biochemical substances are involved in the actual implantation process, their production is secondary to the steroid stimulation of the endometrial cells. Estrogen stimulation can be achieved by a variety of regimens utilizing different routes of administration as well as different duration of administration. Estrogen may be delivered via an oral, transdermal, or vaginal route in a fixed or variable regimen. Oral or transdermal estradiol is most commonly used. In one study comparing a transdermal 0.1 mg patch to 6 mg of oral estradiol daily, less of a delay in glandular histology was noted despite lower serum estradiol levels (81). 388 Steiner and Paulson Estradiol therapy can be provided in a fixed or variable regimen with comparable efficacy (82). Although fixed regimens using 1 mg of estradiol a day appear to be ineffective (82), fixed regimens using 4 or 8 mg/day without downregulation have been used to achieve an endometrial thickness greater than 6 mm in an average of seven days with good pregnancy rates. Navot et al. found that such small administration of fixed dosage estradiol compared favorably to a longer variable regimen (83); however, others have noted higher miscarriage rates with such short duration of estradiol therapy (84). In contrast, prolonged duration of estr adiol therapy does not appear to have a negative impact (83,85). Serum estradiol measurements during estradiol therapy appear to be unnecessary (27,86). However, multiple studies have shown that mid-cycle thickness correlates with pregnancy success (36,85,87). Although pregnancies occur in patients with a thinner endometrium measurement (88,89), it appears that endometrial thickness of !7 mm offers superior results. The presence of a multilayer endometrial echo complex may (90) or may not matter (91). In patients who cannot achieve an adequate endometrial thickness with oral or transdermal estradiol alone, vaginal estradiol may be used. The vaginal route of steroid administration results in high endometrial tissue levels and these appear to increase the endometrial thickness (85,92). Low-dose aspirin (81 mg/day) has also been reported to increase the endometrial thickness (93). A combination of pentoxifylline 800 mg and tocopherol (Vitamin E) 1000 IU for nine months prior to hormone therapy has also been reported as therapy to enhance endometrial respon- siveness in some women (94). Following adequate estrogen priming of the endometrium, it is progesterone that prepares the endometrium for implantation. However, progesterone cannot act in the absence of adequate priming. Thus, an endometrial biopsy taken during a practice cycle, which shows no progestational effect has, in our experience, generally been reflective of inadequate estrogen priming rather than inadequate progesterone delivery to the endometrium. This effect may be observed in women after long episodes of amenorrhea, such as that occurs in agonadal women in the absence of estrogen stimulation, or after prolonged hormonal replacement with combination of estrogen and progesterone replacement in which menstrual sloughing does not take place. It is tempting to speculate that prolonged continuous progesterone stimulation of the endometrium produces a profound downregulation of estrogen receptors and that these may require priming prior to attaining an appropriate response. To achieve lutei nization of the endometrium, progesterone is started either on the day of oocyte retrieval or one day prior. Progesterone may be administered by the intramuscular or vaginal route, but progesterone delivery modes are more complex than those of estradiol. The reasons for Oocyte Donation 389 this are (i) much larger quantities of progesterone are necessary to achieve luteinization in the endometrium and (ii) progesterone is susceptible to metabolism by 5a-reductase in the skin, making transdermal delivery even more impractical due to the large size of the patch that would be required. In addition, oral progesterone is ineffective because it is rapidly metabo- lized. The advantages of the intramuscular route include higher serum progesterone levels and emotionally reassuring sense that the progesterone has been delivered to the body of the recipient. Many programs in the United States still utilize this mode of delivery with a dose of 50 to 100 mg daily. Even lower doses of 25 to 50 mg/day results in luteal phase serum levels of progesterone, a secretory endometrium, and good pregnancy rates (95). Supra-physiological doses of intramuscular progesterone do not appear to have an adverse effect on the maturation process (83), but doses lower than the standard result may have a negative impact (96). Vaginal progesterone has generally been formulated in three ways: capsules containing micronized progesterone powder, a silastic ring that gradually releases progesterone, and a cream formulation. When compared with intramuscular administration of progesterone, vaginal micronized progesterone results in lower serum levels, but higher endometrial levels of progesterone. Its administration results in similar histological findings (97,98). For this reason, we have all but abandoned the intramuscular route, reserving it only for those patients who dislike the use of vaginal suppositories. Results from Europe on the use of a vaginal ring releasing 10 to 20 nmol/L of progesterone for 90 days have been favorable (99). In the United States, Crinone 1 , formulated as a cream, and administered vaginally twice daily, has been shown to result in in-phase biopsies (100) and pregnancy rates similar to those achieved with intramuscular progesterone (101). EMBRYO TRANSFER Embryo transfer is performed in the same manner as in conventional IVF. Pregnancies have been reported after transfer of embryos at any stage in development and after zygote intrafallopian transfer and tubal embryo transfer. In general, the recipient starts progesterone the day of or day prior to oocyte retrieval (102,103). As with conventional IVF cycles, the use of transabdominal ultrasound guidance during transcervical embryo transfer appears to improve the pregnancy and implantation rates (104). Embryos derived from oocytes donated by young oocyte donors have very good implantation potential. Therefore, it is reasonable to limit the number of embryos that are transferred at one time. Recent studies have reported that the transfer of two versus three embryos results in similar pregnancy and implantation rates and a lower triplet and multiple rate 390 Steiner and Paulson [...]... finding, therefore, that the high success rates with oocyte donation observed in the younger age group were mirrored in the women over 40 (22) The concept of offering fertility therapy to women over the age of 40 was not novel; rather, it was the observation that the success rates were not influenced by the age of the recipient that was remarkable Several reports confirmed the efficacy of oocyte donation in the. .. can be obtained (32) One of the concerns about this type of therapy was the issue of obstetrical complications that might arise as a result of the advanced age of the new mothers In a study of 77 postmenopausal women !50 years, we found that pregnancy rates, multiple gestation rates, and spontaneous abortion rates were similar to those of younger recipients (124) The incidence of gestational diabetes,... visualization of fetal heart motion has been reported to occur in 5.7% of singleton pregnancies after oocyte donation (108) In the setting of multiple gestation, the probability of absorption of one or more embryos is 19% to 28% (108,109) The risk of fetal loss appears to correlate with the number of gestational sacs Although patients with multiple gestations are more likely to have bleeding, their miscarriage... fertility caused by oocyte problems The details of an oocyte donation cycle are very similar to those of the standard IVF Stimulation of the donor is similar to the standard IVF, yet may be simpler, because poor responder protocols are rarely, if ever, needed and concerns about hyperstimulation are at least partially mitigated by the fact that donors do not become pregnant Preparation of the recipient endometrium... emotional involvement with the child compared to parenting after natural conception (119) ADVANCED REPRODUCTIVE AGE Prior to 1990, no series had specifically addressed the issue of oocyte donation to women of advanced reproductive age Oocyte donation was primarily conceived of as a therapy for young women with premature ovarian failure, rather than as a means of overcoming the age-related decline in... Age of Pregnancy-induced Gestational Cesarean subjects hypertension (%) diabetes mellitus (%) section (%) !50 35 20 78 !50 22 11 — !45 10.8 8 64.8 !45 11.8 0.8 75 !45 42 8 64 Oocyte Donation 395 of these older parents To date, there have been no studies showing any adverse impact, thus concerns are only theoretical at this time point SUMMARY Oocyte donation is a logical extension of the technology of. .. Lindheim SR, Paulson RJ, et al Efficacy of oocytes donated by older women in an oocyte donation programme Hum Reprod 1996; 11:820 18 Stolwijk AM, Zielhuis GA, Sauer MV, Hamilton CJCM, et al The impact of the woman’s age on the success of standard and donor in vitro fertilization Fertil Steril 1997; 67:702 19 Faber BM, Mercan R, Hamacher P, Muasher SJ, et al The impact of an egg donor’s age and her prior... discovered in the future Donors as well as recipients should be medically screened and offered psychosocial counseling to address issues of thirdparty parenting As oocyte donation bypasses all oocyte problems, it has increasingly been applied to the age-related block to conception in women of advanced reproductive age It is possible to establish pregnancies in menopausal women over 50 years of age, although... Effect of aging on the female reproductive system: evidence for a role of uterine senescence in the decline of female fecundity Fertil Steril 1995; 64:584 26 Abdalla HI, Wren ME, Thomas A, Korea L Age of the uterus does not affect pregnancy or implantation rates; a study of egg donation in women of different ages sharing oocytes from the same donor Hum Reprod 1997; 12:827 27 Garcia-Velasco JA, Isaza V,... Steiner and Paulson 43 Practice Committee of the American Society for Reproductive Medicine Repetitive oocyte donation Fertil Steril 2004; 82(suppl 1):S158 44 The American Society for Reproductive Medicine Guidelines for oocyte donation Fertil Steril 2004; 82(suppl 1):S13 45 Practice Committee of the Society for Assisted Reproductive Technology, Practice Committee of the American Society for Reproductive . obtained (32). One of the concerns about this type of therapy was the issue of obstetrical complications that might arise as a result of the advanced age of the new mothers. In a study of 77 postmenopausal. female fertility hinges on the age of the oocyte provider. Thus, the chronological age of the oocyte donor would seem to play an intuitive role in the overall success of the process. Remarkably,. that the age of the uterus does not influence the probability of the initiation of pregnancy that led to the conclusion that the age-related decline in human fertility was primarily due to the

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