Managing assisted reproduction in women over the age of 50 years: a clinical update

Abstract

For more than 20 years, women over 50 years of age have been able to achieve pregnancy and deliver babies using donor oocyte IVF (D-IVF). Pregnancy and live-birth delivery rates following D-IVF in these older patients are comparable with rates experienced by younger women undergoing IVF with either donor or autologous oocytes. While there are increased risks of adverse perinatal events occurring in this unique older age group of women, the current data infers the relative overall safety of attempting pregnancy in properly screened and selected patients. This article describes the history and current practice of D-IVF in women over 50 years of age and then concludes with expert commentary and current 5-year outlook on the future of this practice.

Keywords::

• advanced reproductive age
• donor IVF (D-IVF)
• donor oocyte
• egg donation
• menopausal pregnancy

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Release date: 28/11/2012; Expiration date: 28/11/2013;

Learning objectives

Upon completion of this activity, participants will be able to:

• • Evaluate the risks of D-IVF among women over the age of 50 years

• • Assess how to select women over age 50 years for D-IVF

• • Analyze the practice of embryo transfer among women over age 50 years

• • Evaluate the success rates of D-IVF among women over 50 years

Financial & competing interests disclosure

EDITOR

Elisa Manzotti

Publisher, Future Science Group, London, UK

Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

CME AUTHOR

Charles P Vega, MD

Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of California, Irvine, CA, USA

Disclosure: Charles P Vega, MD, has disclosed no relevant financial relationships.

AUTHORS AND CREDENTIALS

Lisa C Grossman, MD

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Center for Women's Reproductive Care at Columbia

University, NY, USA

Disclosure: Lisa C Grossman, MD, has disclosed no relevant financial relationships.

Daniel H Kort, MD

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Center for Women's Reproductive Care at Columbia

University, NY, USA

Disclosure: Daniel H Kort, MD, has disclosed no relevant financial relationships.

Mark V Sauer, MD

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Center for Women's Reproductive Care at Columbia

University, NY, USA

Disclosure: Mark V Sauer, MD, has disclosed no relevant financial relationships.

Figure 1. Synchronization scheme typically prescribed to perform egg donation from a young oocyte donor to a menopausal recipient.

GnRH: Gonadotropin-releasing hormone; hCG: Human chorionic gonadotropin; im.: Intramuscular; sc.: Subcutaneous.

History of oocyte & embryo donation

Oocyte and embryo donation in humans evolved from a series of scientific developments and animal studies dating back to the 19th century [1]. Embryo donation has long been used in mammals and was first reported in rabbits in 1890 [2]. In later studies, scientists recovered embryos fertilized in vivo through uterine lavage and transferred them to recipient animals. This technique became commonplace in animal husbandry and was used to reproduce cattle, prize horses and exotic animals. Researchers at the Harbor–UCLA Medical Center in Los Angeles (CA, USA) employed a modification of this method in 1983 in order to fertilize a spontaneously ovulated human oocyte in vivo after artificial insemination of a paid designated egg donor and then transfer the recovered embryo into the uterus of a menstrually synchronized recipient [3]. Fourteen insemination cycles resulted in two ongoing pregnancies [4], with the first delivery of a healthy male occurring in January 1984 [5].

During this same time period, researchers in Australia were able to surgically retrieve oocytes from a woman willing to donate an ‘extra egg’ from her own IVF attempt to a 25-year-old infertile woman with premature ovarian failure. They then performed fertilization in vitro upon the single donated egg and transferred the embryo to the infertile recipient who was hormonally synchronized to the egg donor using oral estrogen and vaginal progesterone [6]. Remarkably, this approach was successful, and ultimately led to the first live birth from egg donation and IVF, also occurring in 1984 [7]. With improvements in sonographic technology, transvaginal ultrasound-guided needle aspiration of oocytes soon replaced laparoscopy and remains the preferred method of egg retrieval used today.

Donor egg IVF (D-IVF) was initially considered only for younger patients, such as those suffering from premature ovarian insufficiency, which is best defined as women <40 years of age with persistent amenorrhea and elevated gonadotropins [8]. While most of these cases were idiopathic in etiology, premature ovarian insufficiency was also often secondary to autoimmune disease, endocrinopathies or iatrogenic treatments using chemotherapy and/or radiation therapy. D-IVF was also used to treat patients with a variety of other reproductive disorders, such as repeated IVF failure, decreased ovarian reserve/poor response to gonadotropins and age-related infertility [9,10]. By the late 1980s, D-IVF was extended to women 40 years of age and older, and successful attainment of high pregnancy rates in these older women received much attention following the preliminary series report in the New England Journal of Medicine in 1990 [11,12].

While the success of D-IVF in achieving pregnancies in older, pre- and peri-menopausal women was firmly established by the early 1990s, strong concerns regarding whether or not to offer this treatment to even older recipients with natural menopause over the age of 50 years remained. Specifically, many clinicians thought that the receptivity of a menopausal uterus, even when hormonally prepared, would be inadequate for implantation and development of the transplanted embryo. Animal studies had demonstrated lower implantation and pregnancy rates with increasing maternal age [13,14], with a decrease in the number of implantation sites and resorption of embryos in several mammalian species. However, this phenomenon was not evident in humans, as demonstrated in a subsequent report published in 1992 of even older recipients, including menopausal women over 50 years of age [15]. In fact, the endometrial biopsies of advanced reproductive-age women that were appropriately primed with hormones before transfer had normal histological appearance and were not demonstrably different from biopsies obtained from younger women [16]. The ability of the menopausal endometrium to respond to hormonal preparation with exogenously delivered steroid, regardless of the woman’s age, provided the opportunity to extend reproductive potential well beyond the natural boundaries created by age. The stage was set for D-IVF to be offered to even older women wishing to become mothers following natural menopause.

The first clinical series reporting D-IVF in women over 50 years of age were published in the early 1990s [15,17]. In these initial reports, both embryo implantation and ongoing pregnancy rates were similar in women 50 years of age and older compared with their younger counterparts undergoing D-IVF [15,17,18]. However, these observations were based upon only a few dozen cases. By contrast, in a much larger retrospective review of 3089 donor egg cycles, recipient women >45 years old had lower pregnancy rates (44 vs 49%), lower implantation rates (17 vs 21%) and higher miscarriage rates (23 vs 17%) compared with younger recipients [19]. This phenomenon was also similarly noted in the compiled annual CDC/SART database, which demonstrated a slightly declining pregnancy rate with advancing age of recipients. However, in a 10-year review of postmenopausal women at the University of Southern California (CA, USA) with mean age 52.8 ± 2.9 years, 121 embryo transfers (89 fresh, 32 frozen) using D-IVF were performed and a pregnancy rate of 45.5% with a live-birth rate of 37.2% was achieved, results not different from rates in younger recipients seen there [18]. Regardless of whether or not minor decreases in embryo implantation and clinical pregnancy rates actually occurred, these various studies clearly demonstrated promising outcomes in this advanced-reproductive-age group of women.

Risks

While oocyte donation may be used successfully in helping older women become pregnant and deliver babies after menopause, it is not without risk. Women of advanced maternal age (AMA), as defined as mothers 35 years of age and older, have long been known to be at an increased risk for developing pregnancy-related complications, such as hypertensive disorders, gestational diabetes, abnormal placentation, preterm deliveries, stillbirths and cesarean section delivery [20–22]. Studies have shown that neonates born to AMA women also have an increased risk of being small for gestational age, and are more likely to develop respiratory distress syndrome, be admitted to the neonatal intensive care unit and experience a greater overall mortality rate [22]. It is therefore not surprising that as the age of mothers increases beyond 50 years, so do perinatal problems that contribute to maternal and neonatal morbidity and mortality.

The maternal and perinatal outcome data of women 50 years of age and above remains limited by the small number of patients who elect to undergo D-IVF each year. While the majority of these patients experience uncomplicated pregnancies and go on to deliver healthy babies, current published information indicates significant risks of hypertensive disorders of pregnancy (~20–35% of all pregnancies), gestational diabetes (~5–10% of pregnancies) and cesarean section (typically over half or more of all deliveries) [18,23–25]. However, we recently published the largest consecutive series of patients from a single treatment center, comprising 101 delivered pregnancies in women aged 50 years and above, and actually found no major differences in obstetric and neonatal outcomes compared with patients 42 years of age and younger also achieving pregnancy through D-IVF [24].

Perhaps of greater concern are reports of maternal deaths in women undergoing D-IVF. In our large series, one patient suffered cardiac arrest in the late first trimester and died [24]. Her only known risk factor was a significant smoking history (one pack per day for 30 years, undisclosed to her physicians). A case report of a maternal death following worsening HELLP syndrome developing in a 49-year-old woman after delivering twins further illustrates the cause for concern related to underlying cardiovascular disease in this age group [26]. While difficult to estimate the incidence of mortality following D-IVF, it is fair to say that death remains a rare complication. In hope of minimizing the risk of serious injury to mothers and their children, we require extensive medical screening to be performed prior to performing D-IVF in this population (Box 1). Attention is focused on discovering conditions and diseases known to be more prevalent with advancing age, including hypertension, diabetes, obesity, hypothyroidism and uterine leiomyomata; all of which are known to further complicate pregnancy. Optimization of health should occur preconceptually and in consort with interdisciplinary support from specialists in internal medicine and fetal maternal medicine.

Multiple pregnancies & increased risks

Limiting the number of multiple births in older patients through the judicious use of small numbers of embryos for transfer (1–2 per embryo transfer) is essential in order to lessen complications. While this has been advocated for many years, multiple gestation pregnancies have always plagued this subset of patients. Ironically, the maintenance of uterine receptivity in the hormonally replaced menopausal woman places her at heightened risk for higher order births following embryo transfer.

The first woman over the age of 50 years to carry and deliver triplets was published in 1995 at the University of Southern California. She had four day-2 embryos transferred, the standard of care at that time, and three embryos successfully implanted. She was counseled regarding the high-risk nature of the pregnancy and given the option of multifetal pregnancy reduction but declined and ultimately she delivered by cesarean section at 33 weeks gestation [27]. Interestingly, all three children had unremarkable clinical courses and the two girls and one boy are presently entering their freshman year of college. In another similar case, a 51-year-old patient had four early cleavage-stage embryos transferred and all four successfully implanted. However, in this case the patient elected to undergo multifetal pregnancy reduction to twins and subsequently experienced an uncomplicated pregnancy with cesarean delivery at 38 weeks [28].

Given the potential for serious maternal and neonatal complications resulting from multiple gestation, we advise strict adherence to the American Society for Reproductive Medicine (ASRM) guidelines with regard to the number of embryos transferred to recipients of egg donation [29]. Since donors are usually below 35 years of age, we typically transfer two day-3 cleavage-stage embryos or 1–2 blastocyst-stage embryos. Figure 1 illustrates the prescribed regimen of treatment scheme used to synchronize the egg donor and the menopausal recipient. Pregnant recipients are maintained on full hormone replacement of estrogen and progesterone until approximately 12 weeks of pregnancy, at which time they are discontinued, since by then the placenta produces all requisite hormones to support the gestation.

With continued improvements in clinical outcome measures from D-IVF, consideration of transferring even fewer embryos should be entertained and may be the preferred management strategy. In a single-institution study of 10,537 donor cycles from 1995 to 2005, the mean number of embryos transferred decreased from 3.6 ± 0.8 to 1.9 ± 0.3 per attempt while increasing ongoing pregnancy rates from 31 to 44.3% over a 10-year time period were witnessed [30]. Improved clinical outcomes and reduced multiple gestation rates are largely secondary to the increasingly popular choice of extended culture for embryo growth and development leading to blastocyst transfer. A well-selected single blastocyst will provide pregnancy rates on par with the transfer of three day-3 cleavage-stage embryos, yet without the associated risk of multiple gestation.

Long-term consequences to family & society

While the clinical attention has most often been focused on the pregnancy success and safety of D-IVF in women 50 years of age and above, the social ramifications of becoming a new mother at this age are equally important to consider. New questions arise surrounding the physical condition and stamina needed by an older woman to properly attend to a child, the emotional depth and patience required to guide appropriate growth and development, and of course the overall life expectancy of one or both of the intended parents. Older parents tend to also have older peers, and social supports and concern over the welfare of a child when parents become sick, debilitated or die has been voiced by critics of D-IVF since it was offered to menopausal women. These issues were raised by the Ethics Committee of the ASRM in its 2004 report on oocyte donation to postmenopausal women, and led to their generalized recommendation that, although no medical or ethical reason is compelling enough to label the practice as ‘unethical’, sufficient concerns existed to ‘discourage’ the practice [31].

Interestingly, one study of 49 women over the age of 50 years did not find reduced parenting capacity due to physical ability, mental ability or parental stress in AMA mothers [32]. However, clearly more data are needed to fully address the important issues related to safety of both mother and child, and family welfare. However, presently there are no data to suggest that these families are harmed or compromised owing to the age of the parents raising their children. Therefore, it is our belief, congruent with the Ethics Committee recommendation, that physicians should carefully assess each prospective case, and decide on offering care without an arbitrary cutoff of age based upon the merits of the patient’s profile.

Screening & selection

The key to best ensuring a successful pregnancy in this older age group relates to the medical, reproductive and psychosocial screening and selection of potential mothers prior to conception. Along with the standard fertility testing and counseling that is normally undertaken by younger women interested in D-IVF, patients over 50 years of age should also undergo additional medical surveillance that utilizes a variety of blood tests, chest x-rays, electrocardiograms and routine healthcare maintenance examinations to ensure that they are healthy enough to carry a baby to term (Box 1) [33]. This also includes mammography and, when appropriate, cardiac stress tests [17]. We believe that patients should be seen for preconception counseling by a maternal fetal medicine specialist who will also review with the patient the various risks that she may face during the ante-, intra- and post-partum period, and discuss how such problems, if encountered, will be managed. In a 12-year review of 2729 women aged 45–63 years seen at one center in Rome (Italy), only 42% of the women evaluated were suitable candidates for pregnancy, using strict medical screening criteria. Despite heightened screening, 23.6% of women who then underwent D-IVF experienced antenatal complications including gestational hypertension, gestational diabetes and preterm labor [34]. However, it is reasonable to assume that with careful screening and patient selection, the incidence of antenatal and postpartum complications can be decreased and women with very high-risk conditions identified prior to establishing the pregnancy.

A psychosocial evaluation of the woman and couple is also important to perform during the precycle evaluation. Parenting is emotionally stressful and physically demanding, and it is reasonable to ensure, as best as possible, that patients receive adequate counseling about the potential problems that may arise. In addition, treatment failures are also common, as well as pregnancy losses, and adequate supports need to be in place to manage the grief associated with these events. Finally, issues related to the identity of the egg donor, and disclosure or nondisclosure to the child and family, are challenging and evolving, and need to be openly addressed and discussed in advance by a trained mental healthcare professional with appropriate time and focus. Again, not different from the physical examination and laboratory testing that occurs in these patients, there are rarely absolutes in the mental health assessment that will govern acceptance or rejection from a program. Rather, the focus should be on attempting to address the complex moral, ethical and psychological issues that confront these unique families, and facilitate discussion of difficult topics that might otherwise go unchallenged.

Ethical concerns

After examining the use of D-IVF for postmenopausal women, the Ethics Committee of the ASRM concluded that, while the practice is not necessarily unethical, it should not necessarily be encouraged. Cases might be best performed in academic centers in which Institutional Review Board oversight exists, and preferably in league with an Ethics Committee recommendation. However, the ASRM does encourage physicians to carefully consider cases on an individual basis and acknowledges that older women have a right to access care [31]. Other professional societies such as the International Federation of Gynecology and Obstetrics and the European Society of Human Reproduction and Embryology do not specifically address advanced reproductive age in their Task Force recommendations on gamete and embryo donation, although the ethical challenges of treating older women has been an international focus of attention, particularly since the practice is outlawed in much of Europe and Asia [35–37].

Extending care to women beyond menopause also impacts directly upon society at large, and social sensitivities need to be carefully considered when treating these patients. Many people find births to older women offensive and in defiance of the natural laws of nature. This is particularly true when women as old as 70 years give birth, as recently occurred in India. Concerns over the welfare of the child and accusations of abuse of assisted reproductive technology seem most justified in these extreme cases. With continued difficulty in recruiting egg donors for younger patients (there remains much greater demand than supply) and critics continuing to suggest that egg donors are being exploited by wealthy older recipients, the debate surrounding egg donation is not likely to soon subside. Many people view menopausal women as not worthy of this scarce resource [38]. Generally speaking, we see this view as discriminatory, particularly since men in this age group are not given restrictions on procreation [39]. However, as the practice of D-IVF in older women grows, these debates will most certainly continue.

Expert commentary

As discussed above, oocyte and embryo donation has proven to be a safe and viable option for addressing the infertility needs of women with ovarian failure for nearly 30 years. Interestingly, during 20 of those 30 years, the focus has been primarily upon age-related problems, and managing the reproductive desires of postmenopausal women in their late forties and fifties. There were grave concerns voiced early on regarding the need to extend care to these older patients. In the late 1980s, ‘old’ would have been women in their early to mid-40s, who were known to perform poorly compared with younger patients undergoing traditional assisted reproduction. It was suggested that women of advanced reproductive age would likely experience lower implantation rates, higher miscarriage rates and poorer obstetrical outcomes. Thankfully, this generally turned out not to be true; however, despite the high pregnancy rates per embryo transfer, the pregnancy complication rates of older recipients remained on par with the few peers who conceived naturally; thus, egg donation did not totally spare older recipients from the inevitable consequences of advanced age. Higher rates of: gestational hypertension and diabetes; preterm labor and small-for-gestational-age infants; abnormal placentation and placenta accreta; and stillbirth were seen consistently in series after series report and continue to define the pregnancies experienced by these patients as truly high risk.

Despite the aforementioned concerns, on balance the treatment has served the great majority of interested parties very well. This is certainly true for women over 50 years of age. Few would argue with the fact that women in their sixth decade of life are hopelessly infertile. However, many of them have valid reasons for pursuing fertility care, and, unless deemed medically unfit to carry a baby, arguments to deny them access to treatment underscores a strong sexual bias and prejudice as men of similar age or older are welcomed by most, if not all, fertility doctors. The implantation rate per embryo transfer, ongoing and delivered pregnancy rates and normalcy of the offspring birthed speak for the validity of the method. There are little if any data to suggest that older parents are unfit to raise their offspring, and families appear to be thriving. Ironically, multiple gestation pregnancy remains the biggest problem experienced by these older mothers and this is really unacceptable since it is largely preventable. Knowing the high-risk nature of the older gravidarum, recommendations promoting single-embryo transfer in order to reduce the iatrogenic complication of multiple birth in these patients must be vigilantly followed. Understandably, both patients and their doctors are reluctant to cut back on the number of embryos transferred for fear of lowering success rates, but twins and triplets should not be viewed as a success. Not only are these pregnancies complicated, they lead to the creation of complicated families and tax the resources of any woman or couple who must manage over 20 or more years.

As outlined in this article, the key to continued success requires a careful pretreatment screening of the perspective patient. It is anticipated that underlying conditions will often be found that may be further exacerbated by pregnancy and adversely affect the gestation. This is particularly true for women known to be hypertensive prior to pregnancy. These individuals present the greatest risk for adverse outcomes. Problems may also be anticipated in preclinical and frankly diabetic patients, who are typically also grossly overweight. Finally, a large proportion of women over 50 years of age have leiomyomata and, although their fibroid tumors may be relatively innocuous in the nonpregnant state, the high estrogenic environment of pregnancy promotes their growth. Implantation rates are lower, miscarriage rates are higher, and complications of carriage and delivery are known to exist in patients with myomatous uteri, which necessitates a frank discussion regarding the possible necessity for myomectomy prior to attempting pregnancy. This is a particularly difficult discussion in the relatively asymptomatic woman who has been told by her gynecologist that she will not need surgery once reaching menopause.

In many respects, it boils down to a matter of informed consent. Evidence-based results define the relative safety of the method. It is not without risk, but pregnancy at any age is a risk to health. Patients should undergo a very thorough medical screen, concentrating on organ systems known to be at greatest risk for age-related pathology (i.e., cardiovascular, endocrinology particularly thyroid, renal, breast and reproductive tract), and, when problems are detected, a frank discussion of the possible worsening of these conditions during pregnancy may, or may not, dissuade the patient and her doctor from proceeding. However, in most cases the relative health of women attempting pregnancy will be good and care will proceed; and for the majority, yes the majority, they will succeed in achieving their dream of delivering a healthy baby.

Five-year view

It is always difficult to predict advances in our field but there are some interesting changes on the horizon related to egg donation. Most significant are the development of ‘egg banks’, made possible through technological improvements in the cryopreservation of eggs using vitrification rather than slow-freezing methodology. Avoiding intra- and extra-cellular ice crystals through vitrification has led to demonstrable improvements in outcomes and several large series reports speak for the efficiency of the method [40,41]. Egg banking would greatly simplify the method, avoiding the need to synchronize recipients and donors in ‘real time’; allowing for a more judicious allocation of resources (commonly six eggs per patient rather than giving over an entire harvested cohort); reducing the increasing number of stored supernumerary embryos resulting from donor–recipient cycles (embryos that ultimately are usually not used and later destroyed); and perhaps creating regional repositories that would allow better and more affordable availability of eggs for the growing population of aging women seeking this type of therapy.

Better selection of embryos for transfer will probably occur over time as well. We now know that differentiation to blastocyst provides much-improved pregnancy rates than the more traditional approach of transferring cleavage-stage embryos. However, even blastocysts implant and develop into a fetus in only approximately 50% of cases. Most failed blastocyst transfers are probably a result of genetic or epigenetic abnormality, and efforts at surveillance beyond the presently used visual grading system may further enhance success. This will probably include methods such as embryo biopsy and comparative genomic hybridization, proteomics of cultured growth media, and cleavage development using video surveillance. All have been suggested as significantly improved methods of detecting which embryo to place, and may further avoid the need for transferring multiple embryos leading to twins and triplets.

Finally, there will undoubtedly be more and stricter regulation. This would include not only the present oversight of the FDA, but increasing involvement of individual state tissue banking licensing or agencies such as the College of American Pathology or the Centers for Medicine and Medicaid Services who regulate laboratory testing through Clinical Laboratory Improvement Amendments. The public is demanding more quality assurance and safety, and the policing of assisted reproductive technology practices will likely be mandated, as already occurs in many other countries. Physicians are always going to protest further regulation of their facilities; however, given the epidemic of multiple births, the escalating payment provided to younger and younger donors often viewed by a skeptical public as exploitive, and the sensationalized abuses of egg donation (pregnancies announced in 2011 involving 70-year-old women), it seems reasonable that changes are going to come. The ASRM continues to publish both practice and ethical guidelines to responsibly conduct egg and embryo donation. It would serve us all well if everyone involved with assisted reproduction and gamete donation would read them and adhere to their recommendations.

Box 1. Screening recommendations for women over 50 years of age prior to attempting pregnancy.

• • Medical and reproductive history including general physical examination and pelvic examination

• • Laboratory tests:

  • – Standard preconception testing and counseling including blood type, Rh factor and antibody screen

  • – Rubella and varicella titers; offer immunization if not immune

  • – Complete blood count

  • – Complete metabolic panel

  • – Fasting lipid screen

  • – Thyroid-stimulating hormone

  • – Coagulation studies

  • – Oral glucose tolerance test or hemoglobin A_1c blood test

  • – Pap smear, cervical cultures or nucleic acid-based test on urine or swab obtained from the cervix, urethral meatus or vagina for Neisseria gonorrhoeae and Chlamydia trachomatis

  • – Infectious disease panel (HIV-1 and -2 tests, hepatitis B surface antigen and hepatitis B core antibody, hepatitis C antibody, syphilis serology)

  • – Stool guaiac for occult blood

• • Imaging:

  • – Electrocardiogram and/or echocardiogram; stress test is abnormal or at-risk factors exist

  • – Mammogram

  • – Chest x-ray

  • – Transvaginal pelvic ultrasound anatomic survey

  • – Assessment of uterine cavity by saline sonohysterogram or hysterosalpingogram

  • – Colonoscopy

  • – Skin cancer survey

• • Mental health and psychosocial assessment

Key issues

• • Donor IVF (D-IVF) is a feasible option for menopausal women.

• • After a long history of experimentation in animals, the first baby conceived by donor IVF was born in 1984.

• • Success rates for D-IVF in women over 50 years of age are comparable with younger recipient patients, and today are over 50% birth rates per embryo transfer attempt.

• • There are increasing ante- and post-partum maternal and neonatal risks associated with increased age, including hypertensive disorders, gestational diabetes, preterm labor, need for cesarean section, small-for-gestational-age infants and other neonatal morbidities related to prematurity.

• • Strict adherence to the American Society for Reproductive Medicine guidelines on the number of embryos to transfer should be encouraged, given the further increased risks for a patient in this age group with a multiple gestation pregnancy.

• • Stringent screening and selection of recipient candidates is crucial to limiting risk in this special population.

• • D-IVF in women over 50 years of age will probably continue, given the increased demand for services by this age group and the reasonable clinical outcomes reported to date.

• • Development of techniques focused on improving embryo selection, combined with enhancements in extended culture media, promises to provide most women with the opportunity for single-embryo transfer of a blastocyst.

• • The banking of unfertilized donor eggs through a process of vitrification should greatly simplify the method while also improving the efficiency of the technique.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Managing assisted reproduction in women over the age of 50 years: a clinical update

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Activity Evaluation: Where 1 is strongly disagree and 5 is strongly agree

	1	2	3	4	5
1. The activity supported the learning objectives.
2. The material was organized clearly for learning to occur.
3. The content learned from this activity will impact my practice.
4. The activity was presented objectively and free of commercial bias.

1. You are counseling a 51-year-old woman and her husband regarding donor-oocyte in vitro fertilization (D-IVF). Which of the following complications may be most prevalent if she achieves pregnancy with D-IVF?

• □ A Large-for-gestational-age infant

• □ B Congenital cardiac malformations

• □ C Failure to progress in labor

• □ D Hypertension

2. What should you consider regarding screening this patient for acceptability for D-IVF at her age?

• □ A It is biased and unfair to order additional screening studies on women based on their age

• □ B Mammography should be avoided until after pregnancy

• □ C More intensive screening leads to rates of antenatal complications of less than 5%

• □ D Issues related to the identity of the egg donor should be addressed in advance of D-IVF

3. It is decided to proceed with D-IVF for this patient. What is the maximum number of embryos that should be transferred?

• □ A One cleavage-stage embryo or 1 blastocyst-stage embryo

• □ B Two cleavage-stage embryos or 1 to 2 blastocyst-stage embryos

• □ C Three cleavage-stage embryos or 2 blastocyst-stage embryos

• □ D Four cleavage-stage embryos or 2 blastocyst-stage embryos

4. What can you tell this woman about the success of D-IVF among women over age 50?

• □ A There is little difference between the success rates of implantation of blastocyst-stage embryos and cleavage-stage embryos

• □ B Cleavage-stage embryos tend to result in higher rates of deliveries at term vs blastocyst-stage embryos

• □ C The success rates of D-IVF for women over 50 years are less than one tenth those of younger women

• □ D The success rates for women over the age of 50 years now exceed 50%